SEC Form 10-Q filed by IDEAYA Biosciences Inc.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
(Mark One)
QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES AND EXCHANGE ACT OF 1934 |
For the quarterly period ended
OR
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES AND EXCHANGE ACT OF 1934 |
For the transition period from to
Commission File Number:
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Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
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Accelerated filer |
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Non-accelerated filer |
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Smaller reporting company |
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Emerging growth company |
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No
As of November 1, 2024, the registrant had
NOTE REGARDING FORWARD-LOOKING STATEMENTS
This Quarterly Report on Form 10-Q contains forward-looking statements. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements other than statements of historical facts contained in this Form 10-Q, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations and future results of anticipated products, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements.
In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this Quarterly Report on Form 10-Q are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this Quarterly Report on Form 10-Q and are subject to a number of risks, uncertainties and assumptions described under the sections in this Quarterly Report on Form 10-Q entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in this Quarterly Report on Form 10-Q. These forward-looking statements are subject to numerous risks, including, without limitation, the following:
1
Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties.
Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not occur or be achieved, and actual results could differ materially from those projected in the forward-looking statements. We qualify all of our forward-looking statements by these cautionary statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.
2
IDEAYA Biosciences, Inc.
Form 10-Q for Quarterly Period Ended September 30, 2024
Table of Contents
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Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations |
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Item 3. Quantitative and Qualitative Disclosures About Market Risk |
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Item 1. Legal Proceedings |
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Item 2. Unregistered Sales of Equity Securities and Use of Proceeds |
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3
PART I—FINANCIAL INFORMATION
Item 1. Financial Statements (UNAUDITED).
IDEAYA Biosciences, Inc.
Condensed Balance Sheets
(in thousands, except share and per share amounts)
(Unaudited)
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September 30, |
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December 31, |
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2024 |
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2023 |
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Assets |
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Current assets |
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Cash and cash equivalents |
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Short-term marketable securities |
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Accounts receivable |
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Prepaid expenses and other current assets |
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Total current assets |
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Restricted cash |
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Long-term marketable securities |
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Property and equipment, net |
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Right-of-use assets |
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Other non-current assets |
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Total assets |
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$ |
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Liabilities and Stockholders’ Equity |
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Current liabilities |
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Accounts payable |
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$ |
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Accrued liabilities |
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Operating lease liabilities, current |
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Total current liabilities |
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Long-term operating lease liabilities |
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Total liabilities |
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Stockholders’ equity |
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Preferred stock, $ |
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Common stock, $ |
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Additional paid-in capital |
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Accumulated other comprehensive income |
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Accumulated deficit |
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Total stockholders’ equity |
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Total liabilities and stockholders’ equity |
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$ |
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The accompanying notes are an integral part of these condensed financial statements.
4
IDEAYA Biosciences, Inc.
Condensed Statements of Operations and Comprehensive Loss
(in thousands, except share and per share amounts)
(Unaudited)
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Three Months Ended |
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Nine Months Ended |
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2024 |
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2023 |
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2024 |
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2023 |
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Collaboration revenue |
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$ |
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Total revenue |
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Operating expenses |
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Research and development |
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General and administrative |
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Total operating expenses |
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Loss from operations |
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Other income |
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Interest income and other income, net |
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Net loss |
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$ |
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$ |
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$ |
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Unrealized gains on marketable securities |
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Comprehensive loss |
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$ |
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$ |
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$ |
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Net loss per common share, basic and diluted |
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$ |
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$ |
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$ |
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Weighted-average common shares outstanding, basic and diluted |
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The accompanying notes are an integral part of these condensed financial statements.
5
IDEAYA Biosciences, Inc.
Condensed Statements of Stockholders’ Equity
(in thousands, except share amounts)
(Unaudited)
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Accumulated |
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Additional |
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Other |
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Total |
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Common Stock |
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Paid-In |
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Comprehensive |
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Accumulated |
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Stockholders' |
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Shares |
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Amount |
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Capital |
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Income (Loss) |
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Deficit |
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Equity |
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Balances as of June 30, 2024 |
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$ |
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$ |
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$ |
( |
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$ |
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$ |
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Issuance of common stock upon follow-on public offering, net of issuance costs |
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— |
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— |
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Issuance of pre-funded warrants to purchase common stock |
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— |
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— |
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— |
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Exercise of pre-funded warrants |
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— |
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— |
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— |
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— |
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— |
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Issuance costs related to at-the-market offering program |
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— |
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— |
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— |
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— |
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Issuance of common stock upon exercise of stock options |
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— |
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— |
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— |
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Stock-based compensation |
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— |
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— |
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— |
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— |
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Other comprehensive income |
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— |
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— |
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— |
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— |
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Net loss |
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— |
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— |
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— |
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— |
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( |
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Balances as of September 30, 2024 |
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$ |
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$ |
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$ |
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$ |
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$ |
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Balances as of June 30, 2023 |
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$ |
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$ |
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$ |
( |
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$ |
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$ |
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Issuance of common stock related to at-the-market offering program, net of issuance costs |
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— |
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— |
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— |
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Issuance of common stock upon exercise of stock options |
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— |
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— |
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— |
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Stock-based compensation |
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— |
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— |
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— |
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— |
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Other comprehensive income |
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— |
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— |
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— |
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— |
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Net loss |
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— |
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— |
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— |
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— |
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( |
) |
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( |
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Balances as of September 30, 2023 |
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$ |
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$ |
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$ |
( |
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$ |
( |
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$ |
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The accompanying notes are an integral part of these condensed financial statements.
IDEAYA Biosciences, Inc.
6
Condensed Statements of Stockholders’ Equity
(in thousands, except share amounts)
(Unaudited)
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Accumulated |
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Additional |
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Other |
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Total |
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Common Stock |
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Paid-In |
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Comprehensive |
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Accumulated |
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Stockholders' |
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Shares |
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Amount |
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Capital |
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Income (Loss) |
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Deficit |
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Equity |
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Balances as of December 31, 2023 |
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$ |
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$ |
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$ |
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$ |
( |
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$ |
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Issuance of common stock upon follow-on public offering, net of issuance costs |
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— |
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— |
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Issuance of pre-funded warrants to purchase common stock |
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— |
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— |
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— |
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— |
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Exercise of pre-funded warrants |
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— |
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— |
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— |
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— |
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— |
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Issuance of common stock related to at-the-market offering program, net of issuance costs |
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— |
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— |
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Issuance of common stock upon exercise of stock options |
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— |
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— |
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— |
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Employee stock purchase plan (ESPP) purchase |
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— |
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— |
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— |
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Stock-based compensation |
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— |
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— |
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— |
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— |
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Other comprehensive income |
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— |
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— |
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— |
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— |
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Net loss |
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— |
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— |
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— |
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— |
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( |
) |
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( |
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Balances as of September 30, 2024 |
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$ |
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$ |
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$ |
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$ |
( |
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$ |
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Balances as of December 31, 2022 |
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$ |
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$ |
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$ |
( |
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$ |
( |
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$ |
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Issuance of common stock upon follow-on public offering, net of issuance costs |
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— |
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— |
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Issuance of pre-funded warrants to purchase common stock |
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— |
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— |
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— |
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— |
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Issuance of common stock related to at-the-market offering program, net of issuance costs |
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— |
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— |
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— |
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Issuance of common stock upon exercise of stock options |
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— |
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— |
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— |
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Employee stock purchase plan (ESPP) purchase |
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— |
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— |
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— |
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Stock-based compensation |
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— |
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— |
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— |
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— |
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Other comprehensive income |
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— |
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— |
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— |
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— |
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Net loss |
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— |
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— |
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— |
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— |
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( |
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( |
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Balances as of September 30, 2023 |
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$ |
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$ |
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$ |
( |
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$ |
( |
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$ |
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The accompanying notes are an integral part of these condensed financial statements.
7
IDEAYA Biosciences, Inc.
Condensed Statements of Cash Flows
(in thousands)
(Unaudited)
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Nine Months Ended September 30, |
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2024 |
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2023 |
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Cash flows from operating activities |
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Net loss |
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( |
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$ |
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Adjustments to reconcile net loss to net cash used in operating activities |
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Depreciation and amortization |
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Net amortization (accretion) of premiums (discounts) on marketable securities |
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Stock-based compensation |
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Amortization of right-of-use assets |
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Changes in assets and liabilities |
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Accounts receivable |
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Prepaid expenses and other assets |
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Accounts payable |
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Accrued and other liabilities |
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( |
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Contract liabilities |
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Lease liabilities |
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Net cash used in operating activities |
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Cash flows from investing activities |
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Purchases of property and equipment, net |
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Purchases of marketable securities |
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Maturities of marketable securities |
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Net cash used in investing activities |
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Cash flows from financing activities |
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Proceeds from issuance of common stock upon public offering, net of issuance costs |
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Proceeds from issuance of pre-funded warrants to purchase common stock, net of issuance costs |
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Proceeds from issuance of common stock related to at-the-market offering program, net of issuance costs |
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Proceeds from ESPP purchase |
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Proceeds from exercise of common stock options |
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Net cash provided by financing activities |
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Net increase in cash, cash equivalents and restricted cash |
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Cash, cash equivalents and restricted cash |
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Cash, cash equivalents and restricted cash, at beginning of period |
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Cash, cash equivalents and restricted cash, at end of period |
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$ |
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$ |
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Reconciliation of cash, cash equivalents and restricted cash |
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Cash and cash equivalents |
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$ |
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$ |
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Restricted cash |
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Cash, cash equivalents and restricted cash |
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$ |
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$ |
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Supplemental disclosure of cash flow information: |
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Cash paid for interest |
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$ |
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$ |
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Supplemental non-cash investing and financing activities: |
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Right-of-use asset obtained in exchange for a new operating lease liability |
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Purchases of property and equipment in accounts payable and accrued liabilities |
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Unpaid offering costs |
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Unpaid at-the-market offering program costs |
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$ |
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$ |
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The accompanying notes are an integral part of these condensed financial statements.
8
IDEAYA Biosciences, Inc.
Notes to Condensed Financial Statements (Unaudited)
1. Organization
Description of the Business
IDEAYA Biosciences, Inc. (the “Company”) is a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. The Company is headquartered in South San Francisco, California and was incorporated in the State of Delaware in June 2015. To date, the Company has been primarily engaged in business planning, research, development, recruiting and raising capital.
Follow-On Offering
On July 11, 2024, the Company completed an underwritten public follow-on offering. The offering consisted of
On October 27, 2023, the Company completed an underwritten public follow-on offering. The offering consisted of
On April 27, 2023, the Company completed an underwritten public follow-on offering. The offering consisted of
At-the-Market Offering
On January 19, 2024, the Company entered into a new Open Market Sales Agreement (the “January 2024 Sales Agreement”) with Jefferies relating to an at-the-market offering program under which the Company may offer and sell, from time to time at its sole discretion, shares of common stock having aggregate gross proceeds of up to $
During the three months ended September 30, 2024, pursuant to the January 2024 Sales Agreement, the Company sold
The Company may cancel its at-the-market program at any time upon written notice, pursuant to its terms.
Liquidity
9
The Company has incurred significant losses and negative cash flows from operations in all periods since inception and had an accumulated deficit of $
The Company has financed its operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK.
To date, none of the Company’s product candidates have been approved for sale, and the Company has not generated any revenue from commercial products since inception. Management expects operating losses to continue and increase for the foreseeable future, as the Company progresses clinical development activities for its lead product candidates. The Company’s prospects are subject to risks, expenses and uncertainties frequently encountered by companies in the biotechnology industry as discussed under Risks and Uncertainties in Note 2. While the Company has been able to raise multiple rounds of financing, there can be no assurance that in the event the Company requires additional financing, such financing will be available on terms which are favorable or at all. Failure to generate sufficient cash flows from operations, raise additional capital or reduce certain discretionary spending would have a material adverse effect on the Company’s ability to achieve its intended business objectives.
As of September 30, 2024, the Company had cash, cash equivalents and marketable securities of $
2. Summary of Significant Accounting Policies
Basis of Presentation
These condensed financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“GAAP”) and the rules and regulations of the United States Securities and Exchange Commission (“SEC”) for interim reporting.
Unaudited Condensed Financial Statements
The accompanying financial information for the three and nine months ended September 30, 2024 and September 30, 2023 are unaudited. The unaudited condensed financial statements have been prepared on the same basis as the annual audited financial statements and, in the opinion of management, reflect all adjustments, which include only normal recurring adjustments, necessary to present fairly the Company’s financial position as of September 30, 2024 and its results of operations for the three and nine months ended September 30, 2024 and September 30, 2023 and cash flows for the nine months ended September 30, 2024 and September 30, 2023. The results for interim periods are not necessarily indicative of the results expected for the full fiscal year or any other periods.
Use of Estimates
Risks and Uncertainties
The Company operates in a dynamic and highly competitive industry and is subject to risks and uncertainties common to early-stage companies in the biotechnology industry, including, but not limited to, development by competitors of new technological innovations, protection of proprietary technology, dependence on key personnel, contract manufacturers, contract research organizations and collaboration partners, compliance with government
10
regulations and the need to obtain additional financing to fund operations. Product candidates currently under development will require significant additional research and development efforts, including extensive preclinical studies and clinical trials and regulatory approval, prior to commercialization. These efforts require significant amounts of additional capital, adequate personnel infrastructure and extensive compliance and reporting. The Company believes that changes in any of the following areas could have a material adverse effect on the Company’s future financial position, results of operations, or cash flows: ability to obtain future financing; advances and trends in new technologies and industry standards; results of clinical trials and collaboration activities; regulatory approval and market acceptance of the Company’s products; development of sales channels; certain strategic relationships; litigation or claims against the Company based on intellectual property, patent, product, regulatory, or other factors; and the Company’s ability to attract and retain employees necessary to support its growth.
Products developed by the Company require approvals from the U.S. Food and Drug Administration (“FDA”) or other international regulatory agencies prior to commercial sales. There can be no assurance that the Company’s research and development will be successfully completed, that adequate protection for the Company’s intellectual property will be obtained or maintained, that the products will receive the necessary approvals, or that any approved products will be commercially viable. If the Company was denied approval, approval was delayed or the Company was unable to maintain approval, it could have a materially adverse impact on the Company. Even if the Company’s product development efforts are successful, it is uncertain when, if ever, the Company will generate revenue from product sales. The Company operates in an environment of rapid change in technology and substantial competition from other pharmaceutical and biotechnology companies. In addition, the Company is dependent upon the services of its employees, consultants and other third parties.
The Company has expended and will continue to expend substantial funds to complete the research, development and clinical testing of product candidates. The Company also will be required to expend additional funds to establish commercial-scale manufacturing arrangements and to provide for the marketing and distribution of products that receive regulatory approval. The Company may require additional funds to commercialize its products. The Company is unable to entirely fund these efforts with its current financial resources. If adequate funds are unavailable on a timely basis from operations or additional sources of financing, the Company may have to delay, reduce the scope of or eliminate one or more of its research or development programs which would materially and adversely affect its business, financial condition and operations.
Concentration of Credit Risk
Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents and marketable securities. Substantially all the Company’s cash, cash equivalents and marketable securities are held by three financial institutions that management believes are of high credit quality. Such deposits may, at times, exceed federally insured limits.
The Company’s investment policy addresses credit ratings, diversification, and maturity dates.
Summary of Significant Accounting Policies
There have been no material changes in the accounting policies from those disclosed in the financial statements and the related notes included in the Company’s Annual Report on Form 10-K, filed with the SEC on February 20, 2024.
Recent Accounting Pronouncements
From time to time, new accounting pronouncements are issued by the Financial Accounting Standards Board (“FASB”) under its accounting standard codifications (“ASC”) or other standard setting bodies and adopted by the Company as of the specified effective date, unless otherwise discussed below.
11
New Accounting Pronouncements, Not yet Adopted
In October 2023, the FASB issued ASU 2023-06, Disclosure Improvements: Codification Amendments in Response to the SEC’s Disclosure Update and Simplification Initiative, which modifies the disclosure or presentation requirements related to variety of FASB Accounting Standard Codification topics. The effective date for each amendment will be the date on which the SEC’s removal of that related disclosure from Regulation S-X or Regulation S-K is effective. If by June 30, 2027, the SEC has not removed the applicable requirement from Regulation S-X or Regulation S-K, the pending content of the associated amendment will be removed from the Codification and will not become effective for any entities. The Company is currently evaluating the effect of adopting this ASU.
In November 2023, the FASB issued ASU 2023-07, Segment Reporting (Topic 280): Improvements to Reportable Segment Disclosures, which improves reportable segment disclosure requirements through enhanced disclosures about significant segment expenses. These amendments enhance interim disclosure requirements, require disclosure of the title and position of the chief operating decision maker (“CODM”), require disclosure of significant segment expenses that are regularly provided to the CODM, clarify circumstances for disclosure of more than one segment profit or loss measure and require that a public entity that has a single reportable segment provide all disclosures required by ASC 280 and amendments. This ASU update is effective for fiscal years beginning after December 15, 2023 for the Company’s annual report, and interim periods within fiscal years beginning after December 15, 2024. The Company is currently evaluating the effect of adopting the ASU, but does not expect any material impact upon adoption.
On December 14, 2023, the FASB issued ASU 2023-09, Improvements to Income Tax Disclosures, which amends the guidance in ASC 740, Income Taxes. The ASU is intended to improve the transparency of income tax disclosures by requiring (1) consistent categories and greater disaggregation of information in the rate reconciliation and (2) income taxes paid disaggregated by jurisdiction. It also includes certain other amendments to improve the effectiveness of income tax disclosures. The ASU’s amendments are effective for public business entities for annual periods beginning after December 15, 2024. Entities are permitted to early adopt the standard “for annual financial statements that have not yet been issued or made available for issuance.” Adoption is either prospectively or retrospectively; the Company will adopt this ASU on a prospective basis. The Company is currently evaluating the impact of the ASU, but does not expect any material impact upon adoption.
3. Fair Value Measurement and Marketable Securities
The Company applies fair value accounting for all financial assets and liabilities and non-financial assets and liabilities that are recognized or disclosed at fair value in the financial statements on a recurring basis. Fair value is an exit price, representing the amount that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants. As such, fair value is a market-based measurement that should be determined based on assumptions that market participants would use in pricing an asset or liability. As a basis for considering such assumptions, a three-tier fair value hierarchy has been established, which prioritizes the inputs used in measuring fair value as follows:
Level 1—Observable inputs, such as quoted prices in active markets for identical assets or liabilities at the measurement date.
Level 2—Observable inputs other than Level 1 prices such as quoted prices for similar assets or liabilities, quoted prices in markets that are not active, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities.
Level 3—Unobservable inputs which reflect management’s best estimate of what market participants would use in pricing the asset or liability at the measurement date. Consideration is given to the risk inherent in the valuation technique and the risk inherent in the inputs to the model.
In determining fair value, the Company utilizes valuation techniques that maximize the use of observable inputs and minimize the use of unobservable inputs to the extent possible as well as consider counterparty credit risk in its assessment of fair value.
12
As of September 30, 2024, financial assets measured and recognized at fair value are as follows (in thousands):
|
|
|
|
September 30, 2024 |
|
||||||||||
|
|
|
|
Amortized |
|
Gross |
|
Gross |
|
Estimated |
|
||||
Assets |
|
|
|
|
|
|
|
|
|
|
|
||||
U.S. government securities(1) |
|
Level 2 |
|
$ |
|
$ |
|
$ |
( |
) |
$ |
|
|||
Corporate bonds |
|
Level 2 |
|
|
|
|
|
|
( |
) |
|
|
|||
Commercial paper(2) |
|
Level 2 |
|
|
|
|
|
|
( |
) |
|
|
|||
Marketable securities |
|
|
|
|
|
|
|
|
( |
) |
|
|
|||
Money market funds(3) |
|
Level 1 |
|
|
|
|
— |
|
|
— |
|
|
|
||
Total fair value of assets |
|
|
|
$ |
|
$ |
|
$ |
( |
) |
$ |
|
|||
As of December 31, 2023, financial assets measured and recognized at fair value are as follows (in thousands):
|
|
|
|
December 31, 2023 |
|
||||||||||
|
|
|
|
Amortized |
|
Gross |
|
Gross |
|
Estimated |
|
||||
Assets |
|
|
|
|
|
|
|
|
|
|
|
||||
U.S. government securities(1) |
|
Level 2 |
|
$ |
|
$ |
|
$ |
( |
) |
$ |
|
|||
Corporate bonds |
|
Level 2 |
|
|
|
|
|
|
( |
) |
|
|
|||
Commercial paper(2) |
|
Level 2 |
|
|
|
|
|
( |
) |
|
|
||||
Marketable securities |
|
|
|
|
|
|
|
|
( |
) |
|
|
|||
Money market funds(3) |
|
Level 1 |
|
|
|
|
— |
|
|
— |
|
|
|
||
Total fair value of assets |
|
|
|
$ |
|
$ |
|
$ |
( |
) |
$ |
|
|||
As of September 30, 2024 and December 31, 2023, all marketable securities had a remaining maturity of less than
The Company considers available evidence in evaluating potential other-than-temporary impairments of its marketable securities, including the duration and extent to which fair value is less than cost, and the Company’s ability and intent to hold the investment. As of September 30, 2024 and December 31, 2023, the Company held certain securities in an unrealized loss position. These unrealized losses were considered to be temporary as the Company expects to recover the entire amortized cost basis on the securities in unrealized loss positions based on the creditworthiness of the underlying issuer, and the Company neither intends to sell these securities nor considers it more likely than not that the Company would be required to sell any such security before its anticipated recovery. As a result, the Company did not consider any of these investments to be other-than-temporarily impaired at September 30, 2024 and December 31, 2023.
13
4. Balance Sheet Components
Property and Equipment, Net
Property and equipment, net consisted of the following (in thousands):
|
Useful Life |
|
September 30, |
|
December 31, |
|
||
|
(In Years) |
|
2024 |
|
2023 |
|
||
Laboratory equipment |
|
$ |
|
$ |
|
|||
Computer equipment |
|
|
|
|
|
|||
Software |
|
|
|
|
|
|||
Leasehold improvements |
|
|
|
|
|
|||
Furniture and fixtures |
|
|
|
|
|
|||
Total property and equipment |
|
|
|
|
|
|
||
Less: Accumulated depreciation and amortization |
|
|
|
( |
) |
|
( |
) |
Property and equipment, net |
|
|
$ |
|
$ |
|
||
Depreciation and amortization expense was $
Accrued Liabilities
Accrued liabilities consisted of the following (in thousands):
|
|
September 30, |
|
December 31, |
|
||
|
|
2024 |
|
2023 |
|
||
Accrued research and development expenses |
|
$ |
|
$ |
|
||
Accrued salaries and benefits |
|
|
|
|
|
||
Legal and professional fees |
|
|
|
|
|
||
Other |
|
|
|
|
|
||
Accrued liabilities |
|
$ |
|
$ |
|
||
14
5. Operating Leases
In June 2023, the Company entered into a lease agreement for approximately
In May 2024, the Company amended its 5000 Shoreline Court facility lease agreement to expand the size of the original premises by adding approximately
The Company's lease at 7000 Shoreline Court, South San Francisco, California, expired in September 2024.
In November 2023, the Company entered into a lease agreement for approximately
Future minimum lease payments under operating leases included on the Company's condensed balance sheet are as follows:
As of September 30, 2024 |
|
Operating Leases |
|
|
2024 |
|
$ |
|
|
2025 |
|
|
|
|
2026 |
|
|
|
|
2027 |
|
|
|
|
2028 |
|
|
|
|
Thereafter |
|
|
|
|
Total future minimum lease payments |
|
|
|
|
Less: imputed interest |
|
|
( |
) |
Total operating lease liabilities |
|
$ |
|
|
The following table summarizes other information about the Company’s operating leases:
|
|
As of |
|
|||||
|
|
September 30, 2024 |
|
|
December 31, 2023 |
|
||
Remaining Lease Term |
|
|
|
|
|
|
||
Discount Rate |
|
|
% |
|
|
% |
||
15
Operating lease costs were $
Variable lease costs were $
During the nine months ended September 30, 2024 and September 30, 2023, cash paid for amounts included in the measurement of lease liabilities were $
6. Commitments and Contingencies
Contingencies
From time to time, the Company may be involved in litigation related to claims that arise in the ordinary course of its business activities. The Company accrues for these matters when it is probable that future expenditures will be made and these expenditures can be reasonably estimated. As of September 30, 2024, the Company does not believe that any such matters, individually or in the aggregate, will have a material adverse effect on the Company’s financial position, results of operations or cash flows.
Indemnification
The Company enters into standard indemnification arrangements in the ordinary course of business with vendors, clinical trial sites and other parties. Pursuant to these arrangements, the Company indemnifies, holds harmless and agrees to reimburse the indemnified parties for losses suffered or incurred by the indemnified party. The term of these indemnification agreements is generally perpetual any time after the execution of the agreement. The maximum potential amount of future payments the Company could be required to make under these arrangements is not determinable. The Company has never incurred costs to defend lawsuits or settle claims related to these indemnification agreements. Accordingly, the Company has not recorded a liability related to such indemnification agreements as of September 30, 2024.
7. Income Taxes
For the three and nine months ended September 30, 2024 and September 30, 2023, the Company did
The Company is under audit in California for tax years 2020-2021.
8. Common Stock
As of September 30, 2024 and December 31, 2023, the Company’s certificate of incorporation authorized the Company to issue
On July 11, 2024, the Company completed an underwritten public follow-on offering. The offering consisted of
16
On October 27, 2023, the Company completed an underwritten public follow-on offering. The offering consisted of
On April 27, 2023, the Company completed an underwritten public follow-on offering. The offering consisted of
As of September 30, 2024, the following aggregate warrants to purchase shares of the Company’s common stock were issued and outstanding:
Issue Date |
|
Expiration Date |
|
Exercise Price per Share |
|
|
Number of Shares subject to Outstanding Warrants |
|
||
|
None |
|
$ |
|
|
|
|
|||
|
None |
|
$ |
|
|
|
|
|||
|
None |
|
$ |
|
|
|
||||
(1) In September 2024,
The warrants are classified as a component of Stockholders’ Equity within Additional Paid-in-Capital. The warrants
are classified as equity because they are freestanding financial instruments that are legally detachable and separately exercisable from the equity instruments, are immediately exercisable, do not embody an obligation for the Company to repurchase its shares, are indexed to the Company’s common stock and meet the equity classification criteria. The warrants will not expire until they are fully exercised.
The Company had reserved common stock for future issuance as follows:
|
|
September 30, |
|
December 31, |
|
|
2024 |
|
2023 |
Outstanding options under the 2015, 2019 and 2023 Plans |
|
|
||
Shares available for grant under the 2019 Plan |
|
|
||
Shares available for grant under the 2023 Inducement Plan |
|
|
||
Shares available under the Employee Stock Purchase Plan |
|
|
||
Pre-funded warrants issued and outstanding |
|
|
||
Total |
|
|
17
9. Stock-Based Compensation
2023 Inducement Plan
On February 24, 2023, the Company adopted the IDEAYA Biosciences, Inc. 2023 Employment Inducement Award Plan (the “2023 Inducement Plan”), pursuant to which the Company reserved
On June 25, 2024, the Company amended the 2023 Employment Inducement Award Plan, increasing the number of shares available for issuance by
As of September 30, 2024, the number of shares available for issuance under the 2023 Inducement Plan was
2019 Incentive Award Plan
In May 2019, the Company’s board of directors adopted and the Company’s stockholders approved the 2019 Incentive Award Plan (the “2019 Plan”), under which the Company may grant cash and equity-based incentive awards to the Company’s employees, consultants and directors. Following the effectiveness of the 2019 Plan, the Company will not make any further grants under the 2015 Equity Incentive Plan (the “2015 Plan”). However, the 2015 Plan continues to govern the terms and conditions of the outstanding awards granted under it. Shares of common stock subject to awards granted under the 2015 Plan that are forfeited or lapse unexercised and which following the effective date of the 2019 Plan are not issued under the 2015 Plan will be available for issuance under the 2019 Plan.
Options granted under the 2019 Plan may be either incentive stock options (“ISOs”) or nonqualified stock options (“NSOs”). ISOs may be granted only to Company employees (including officers and directors who are also employees). NSOs may be granted to Company employees, directors and consultants.
The 2019 Plan is subject to an annual increase on the first day of each year beginning in 2020 and ending in 2029, equal to the lesser of
As of September 30, 2024, the number of shares available for issuance under the 2019 Plan was
2015 Equity Incentive Plan
In 2015, the Company established its 2015 Plan which provides for the granting of stock options to employees, directors and consultants of the Company. Options granted under the 2015 Plan may be either ISOs or NSOs.
2019 Employee Stock Purchase Plan
In May 2019, the Company’s board of directors adopted and the Company’s stockholders approved the 2019 Employee Stock Purchase Plan (the “ESPP”). The ESPP provides eligible employees with the opportunity to acquire an ownership interest in the Company through periodic payroll deductions up to
The ESPP is intended to constitute an “employee stock purchase plan” under Section 423(b) of the Internal Revenue Code of 1986, as amended. A total of
18
As of September 30, 2024, the number of shares available for issuance under the ESPP was
Stock-Based Compensation Expense
Total stock-based compensation expense recorded related to awards granted to employees and non-employees was as follows (in thousands):
|
|
Three Months Ended September 30, |
|
Nine Months Ended September 30, |
|
||||||||
|
|
2024 |
|
2023 |
|
2024 |
|
2023 |
|
||||
Research and development |
|
$ |
|
$ |
|
$ |
|
$ |
|
||||
General and administrative |
|
|
|
|
|
|
|
|
|
||||
Total stock-based compensation expense |
|
$ |
|
$ |
|
$ |
|
$ |
|
||||
Stock Options
Activity under the Company’s 2015 and 2019 Plans and 2023 Inducement Plan is set forth below:
|
Outstanding Options |
|
|
|
|
|
||||||
|
Shares |
|
Weighted- |
|
Weighted- |
|
Aggregate Intrinsic Value (Millions) |
|
||||
Balance, January 1, 2024 |
|
|
$ |
|
|
|
$ |
|
||||
Options granted |
|
|
$ |
|
|
|
|
|
||||
Options exercised |
|
( |
) |
$ |
|
|
|
|
|
|||
Options canceled |
|
( |
) |
$ |
|
|
|
|
|
|||
Balance, September 30, 2024 |
|
|
$ |
|
|
|
$ |
|
||||
Exercisable as of September 30, 2024 |
|
|
$ |
|
|
|
$ |
|
||||
Vested and expected to vest as of |
|
|
$ |
|
|
|
$ |
|
||||
19
The weighted-average grant-date fair value of options granted during the nine months ended September 30, 2024 and September 30, 2023 was $
As of September 30, 2024 and December 31, 2023, total unrecognized stock-based compensation expense for stock options was $
Black-Scholes Assumptions
The fair values of options were calculated using the assumptions set forth below:
|
|
Three Months Ended September 30, |
|
Nine Months Ended September 30, |
||||
|
|
2024 |
|
2023 |
|
2024 |
|
2023 |
Expected term |
|
|
|
|
||||
Expected volatility |
|
|
|
|
||||
Risk-free interest rate |
|
|
|
|
||||
Dividend yield |
|
|
|
|
||||
Expected term. The expected term represents the weighted-average period the stock options are expected to remain outstanding and is based on the options’ vesting terms, contractual terms and industry peers, as the Company does not have sufficient historical information to develop reasonable expectations about future exercise patterns and post-vesting employment termination behavior.
Expected Volatility. The expected volatility is based on the Company’s historical stock price volatility. The historical stock price volatility is calculated based on a period of time commensurate with the expected term assumption for each grant.
Risk-Free Interest Rate. The risk-free rate assumption is based on U.S. Treasury instruments whose term was consistent with the expected term of the Company’s stock options.
Expected Dividend Rate. The Company has not paid and does not anticipate paying any dividends in the near future. Accordingly, the Company has estimated the dividend yield to be
The Company accounts for forfeitures as they occur.
Fair Value of Common Stock
The fair value of the Company’s common stock is determined based on the market price on the date of grant.
10. Significant Agreements
GSK Collaboration, Option and License Agreement
In June 2020, the Company entered into the Collaboration, Option and License Agreement (the “GSK Collaboration Agreement”), with an affiliate of GSK plc, GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO. 4) LIMITED (“GSK”), pursuant to which the Company and GSK have entered into a collaboration for its synthetic lethality programs targeting MAT2A, Pol Theta and Werner Helicase (“WRN”). On July 27, 2020, the Company and GSK received Hart-Scott-Rodino Antitrust Improvements Act clearance, and the GSK Collaboration Agreement became effective.
Pursuant to the GSK Collaboration Agreement, GSK paid the Company $
GSK Collaboration - Pol Theta Program
20
Pursuant to the GSK Collaboration Agreement, GSK holds a global, exclusive license to develop and commercialize Pol Theta products arising out of the Pol Theta program. The Company and GSK collaborated on preclinical research for the Pol Theta program, and GSK is leading clinical development for the Pol Theta program. GSK is responsible for all research and development costs for the Pol Theta program.
The Company will be eligible to receive total development and regulatory milestones of up to $
In June 2022, the Company announced the nomination of a Pol Theta Helicase Inhibitor development candidate (“DC”), and in August 2022, the Company announced the achievement of an initial preclinical development milestone in connection with ongoing investigational new drug (“IND”)-enabling studies to support evaluation of Pol Theta Helicase Inhibitor DC, triggering a $
An IND was submitted and was cleared by the FDA in August 2023 to enable clinical evaluation in combination with niraparib, triggering a $
The Company has the potential to achieve an additional $
GSK Collaboration - Werner Helicase Program
Pursuant to the GSK Collaboration Agreement, GSK holds a global, exclusive license to develop and commercialize WRN products arising out of the WRN program. The Company and GSK are collaborating on ongoing preclinical research for the WRN program, and GSK will lead clinical development for the WRN program, with the Company responsible for
The Company will be eligible to receive total development milestones of up to $
In October 2023, the Company earned a $
The Company has the potential to earn up to an additional $
GSK Collaboration – General
Under the terms of the GSK Collaboration Agreement, subject to certain exceptions, the Company and GSK will not, directly or through third parties, develop or commercialize other products whose primary and intended
21
mechanism of action is the modulation of WRN or Pol Theta for an agreed upon period of time. The Company and GSK have formed a joint steering committee, joint development committees, and joint commercialization committees responsible for coordinating all activities under the GSK Collaboration Agreement. Ownership of intellectual property developed under the GSK Collaboration Agreement is allocated between or shared by the parties depending on development and subject matter.
GSK’s royalty obligations continue with respect to each country and each product until the later of (i) the date on which such product is no longer covered by certain intellectual property rights in such country and (ii) the 10th anniversary of the first commercial sale of such product in such country.
Each party has the right to sublicense its rights under the GSK Collaboration Agreement subject to certain conditions.
The GSK Collaboration Agreement will continue in effect on a product-by-product and country-by-country basis until the expiration of the obligation to make payments under the GSK Collaboration Agreement with respect to such product in each country, unless earlier terminated by either party pursuant to its terms. Either party may terminate the GSK Collaboration Agreement for the other party’s insolvency or certain uncured breaches. The Company may terminate the GSK Collaboration Agreement if GSK or any of its sublicensees or affiliates challenge certain patents of the Company. GSK may terminate the GSK Collaboration Agreement in its entirety or on a target-by-target basis upon
Novartis License Agreement
In September 2018, the Company entered into a license agreement with Novartis to develop and commercialize Novartis’ LXS196 (also known as IDE196), a Phase 1 PKC inhibitor, for the treatment of cancers having GNAQ and GNA11 mutations. The Company renamed Novartis’ LXS196 oncology as IDE196, and which has a non-proprietary name of darovasertib. Under the license agreement, Novartis granted to the Company a worldwide, exclusive, sublicensable license to research, develop, manufacture, and commercialize certain defined compounds and products, including IDE196 and certain other PKC inhibitors as well as companion diagnostic products, collectively referred to as the licensed products, for any purpose.
The Company paid Novartis an upfront payment of $
Pfizer Clinical Trial Collaboration and Supply Agreements
In March 2020, the Company entered into a clinical trial collaboration and supply agreement with Pfizer, Inc. (as amended in September 2020, April 2021, September 2021 and May 2023, the “Pfizer Agreement”). Pursuant to the Pfizer Agreement, Pfizer supplies the Company with their MEK inhibitor, binimetinib, and their cMET inhibitor, crizotinib, to evaluate combinations of darovasertib independently with each of the Pfizer compounds, in patients with tumors harboring activating GNAQ or GNA11 mutations. Under the Pfizer Agreement, the Company is the sponsor of the combination studies and will provide darovasertib and pay for the costs of the combination studies. Pfizer will provide binimetinib and crizotinib for use in the clinical trial at no cost to the Company. The Pfizer Agreement provides that the Company and Pfizer will jointly own clinical data generated from the clinical trial and will also jointly own inventions, if any, relating to the combined use of darovasertib and binimetinib, or independently, to the combined use of darovasertib and crizotinib. The Company and Pfizer have formed a joint development committee responsible for coordinating all regulatory and other activities under the agreement.
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In March 2022, the Company and Pfizer entered into a second clinical trial collaboration and supply agreement (as amended in May 2023, the “Second Pfizer Agreement”), pursuant to which the Company is evaluating darovasertib and crizotinib as a combination therapy in MUM in a planned Phase 2/3 potential registration-enabling clinical trial. Pursuant to the Second Pfizer Agreement, the Company is the sponsor of the combination trial and the Company will provide darovasertib and pay for the costs of the combination trial; Pfizer will provide crizotinib for the planned combination trial at no cost to the Company for up to an agreed-upon number of MUM patients. The Company and Pfizer will jointly own clinical data from the planned combination trial and all inventions relating to the combined use of darovasertib and crizotinib. The Company and Pfizer have formed a joint development committee responsible for coordinating all regulatory and other activities under the Second Pfizer Agreement.
Separately, in March 2022, the Company and Pfizer also entered into a third clinical trial collaboration and supply agreement (the “Third Pfizer Agreement”), pursuant to which the Company could, subject to preclinical validation and FDA feedback and guidance, evaluate darovasertib and crizotinib, as a combination therapy in cMET-driven tumors such as NSCLC and/or HCC in a Phase 1 clinical trial. Pursuant to the Third Pfizer Agreement, the Company was the sponsor of the planned combination trial, and the Company would provide darovasertib and pay for the costs of the combination trial; Pfizer would provide crizotinib for the planned combination trial at no cost to the Company. Pursuant to Amendment No. 1 to the Second Pfizer Agreement, as described below, the Company and Pfizer terminated the Third Pfizer Agreement.
In May 2023, the Company continued its relationship with Pfizer by entering into Amendment No. 4 to the Pfizer Agreement relating to the supply of crizotinib in support of this Phase 2 clinical trial, pursuant to which Pfizer will continue to provide the Company with an additional defined quantity of crizotinib at no cost.
The Company also expanded its relationship with Pfizer in May 2023 under an Amendment No. 1 to the Second Pfizer Agreement to support the Phase 2/3 registrational trial to evaluate darovasertib and crizotinib as a combination therapy in MUM. Under the as-amended Second Pfizer Agreement, Pfizer will provide the Company with a first defined quantity of crizotinib at no cost, as well as an additional second defined quantity of crizotinib at a lump-sum cost. Under Amendment No. 1 to the Second Pfizer Agreement, the Company and Pfizer also terminated the Third Pfizer Agreement.
Cancer Research UK and University of Manchester Exclusive Option and License Agreement
In January 2022, the Company exercised its option for an exclusive worldwide license covering a broad class of PARG inhibitors from Cancer Research Technology Ltd. (“CRT”) and the University of Manchester, and in connection therewith, paid a one-time option exercise fee of £
In April 2023, the Company incurred an obligation to pay milestone payments in an aggregate amount of £
The Company will be obligated to make additional payments to CRT aggregating up to £
Amgen Clinical Trial Collaboration and Supply Agreement
In July 2022, the Company entered into a clinical trial collaboration and supply agreement with Amgen Inc. (the “Amgen CTCSA”), to clinically evaluate IDE397 in combination with AMG 193, the Amgen investigational MTA-cooperative PRMT5 inhibitor, in patients having MTAP-null solid tumors, in a Phase 1/2 clinical trial. Under the
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mutually non-exclusive Amgen CTCSA, the Company will provide IDE397 drug supply to Amgen, who will be the sponsor of the Phase 1 clinical combination trial evaluating IDE397 and AMG 193. Each party will pay for fifty percent (
Gilead Clinical Study Collaboration and Supply Agreement
In November 2023, the Company entered into a clinical study collaboration and supply agreement with Gilead Sciences, Inc. (“Gilead”) (the “Gilead CSCSA”), to clinically evaluate IDE397 in combination with Trodelvy (sacacituzumab-govitecan-hziy), a Trop-2 directed ADC, in patients having MTAP-deletion urothelial cancer, in a Phase 1 clinical trial. Under the mutually non-exclusive Gilead CSCSA, the Company will receive Trodelvy drug supply from Gilead and will sponsor the Phase 1 clinical combination trial evaluating ID397 and Trodelvy. Gilead will bear internal or external costs incurred in connection with its supply of Trodelvy. The Company will bear all internal and external costs and expenses associated with the conduct of the combination study. The Company and Gilead will jointly oversee clinical development of the combination therapy through a Joint Steering Committee responsible for coordinating all regulatory and other activities under the Gilead CSCSA. The Company and Gilead each retain commercial rights to its respective compounds, including with respect to use as a monotherapy agent or combination agent.
Merck Clinical Trial Collaboration and Supply Agreement
In March 2024, the Company entered into a Clinical Trial Collaboration and Supply Agreement (the “Merck CTCSA”), with Merck (known as MSD outside of the US and Canada) to evaluate the combination of IDE161 with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with microsatellite instability (“MSI”)-high and MSS endometrial cancer. Pursuant to the Merck CTCSA, the Company is the sponsor of the combination study, and the Company will provide the IDE161 compound and pay for the costs of the combination study. Merck will provide KEYTRUDA at no cost to the Company. The Company and Merck will jointly own clinical data from the combination. Each party retains commercial rights to its respective compounds, including with respect to use as a monotherapy or combination agent.
Biocytogen Option and License Agreement
In July 2024, the Company entered into an option and license agreement for a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program with Biocytogen Pharmaceuticals (Beijing) Co., Ltd. (“Biocytogen”). The agreement grants the Company an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program (the “Option”). Under the terms of the agreement, the Company will pay Biocytogen an upfront fee and, upon the Company’s potential exercise of the Option, an exercise fee totaling up to $
11. Revenue Recognition
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The Company recognizes revenue in accordance with ASC 606 for the GSK Collaboration Agreement (see Note 10, Significant Agreements).
Disaggregation of Revenue
The Company recognized
The Company recognized
The Company completed all performance obligations related to the upfront payment under the GSK Collaboration Agreement as of December 31, 2023. Future collaboration revenue recognized under the GSK Collaboration Agreement will be related to future milestone payments as they are earned.
Contract Balances
As of September 30, 2024 and December 31, 2023, the Company had
The Company has identified the following
(i) Preclinical and Phase 1 Monotherapy clinical research and development services under the MAT2A program (“MAT2A R&D Services”)
(ii) Preclinical research services and the related license to IDEAYA-owned technology under the Pol Theta program (“Pol Theta R&D Services”)
(iii) Preclinical research services and the related license to IDEAYA-owned technology under the WRN program (“WRN R&D Services”)
(iv) Material right associated with the option to license IDEAYA-owned technology under the MAT2A program (“Option”)
(v) Material right associated with the option to license to IDEAYA-owned technology under the MAT2A program to the extent necessary for preclinical activities in preparation for the MAT2A Combination Trial (“Preclinical MAT2A License”)
(vi) Material right associated with the supply of MAT2A product for the MAT2A Combination Trial (“MAT2A Supply”)
The Company recognizes revenue related to amounts allocated to the MAT2A R&D services as the underlying services are performed over the period through the delivery of the Option data package, which is generated from its conduct of the dose escalation portion of the MAT2A Phase 1 monotherapy clinical trial. The Company uses its internal research and development capability and also engages third-party clinical research organizations (“CROs”), for which the Company acts as a principal. The Company has delivered the Option data package to GSK. Accordingly, the performance obligation related to the MAT2A R&D services has been fulfilled.
With respect to the Pol Theta and WRN programs, the Company identified two promises: (1) granting of the license to develop and commercialize Pol Theta and WRN products, respectively, and (2) the preclinical research services. The Company has determined that these two promises are not distinct within the context of the contract.
For the Pol Theta product, the Company achieved and earned a $
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For the WRN product, the Company achieved and earned a $
The Company recognized revenue related to amounts allocated to the Pol Theta R&D Services and WRN R&D Services as the underlying services are performed over the period through the completion of the Pol Theta and WRN preclinical research programs, respectively. Within
Since December 31, 2023, there have been no remaining performance obligations related to the WRN, Pol Theta and MAT2A programs.
Significant Judgments
In applying ASC 606 to the GSK Collaboration Agreement, the Company made the following judgments that significantly affect the timing and amount of revenue recognition:
(i) Determination of the transaction price, including whether any variable consideration is included at inception of the contract
The transaction price is the amount of consideration that the Company expects to be entitled to in exchange for transferring promised goods or services to the customer. The transaction price must be determined at inception of a contract and may include amounts of variable consideration. However, there is a constraint on inclusion of variable consideration in the transaction price, if there is uncertainty at inception of the contract as to whether such consideration will be recognized in the future.
The decision as to whether or not it is probable that a significant reversal of revenue will occur in the future, depends on the likelihood and magnitude of the reversal and is highly susceptible to factors outside the Company’s influence (for example, the Company cannot determine the outcome of clinical trials; the Company cannot determine if or when the counterparty will initiate or complete clinical trials; and the Company cannot determine if or when an regulatory agency provides any approval). In addition, the uncertainty is not expected to be resolved for a long period and finally, the Company has limited experience in the field. Therefore, at inception of the GSK Collaboration Agreement, development and regulatory milestones were fully constrained and were not included in the transaction price based on the factors noted above.
The Company constrains estimates of other variable consideration, such as reimbursable program costs, to amounts that are not expected to result in a significant revenue reversal in the future. The Company re-evaluates the transaction price, including the estimated variable consideration included in the transaction price and all constrained amounts, in each reporting period and as uncertain events are resolved or other changes in circumstances occur.
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12. Net Loss Per Share Attributable to Common Stockholders
The following table sets forth the computation of basic and diluted net loss per share attributable to common stockholders (in thousands, except share and per share data):
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Net loss attributable to common stockholders |
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$ |
( |
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$ |
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Denominator: |
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Weighted-average common shares outstanding, basic and diluted(1) |
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Net loss per share attributable to common stockholders, basic and diluted |
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$ |
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$ |
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$ |
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$ |
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(1) The shares underlying the pre-funded warrants to purchase shares of the Company’s common stock have been included in the calculation of the weighted-average number of shares outstanding, basic and diluted, for the three and nine months ended September 30, 2024.
The following outstanding shares of potentially dilutive securities were excluded from the computation of diluted net loss per share attributable to common stockholders for the periods presented because including them would have been antidilutive:
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As of September 30, |
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2024 |
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2023 |
Options to purchase common stock |
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Total |
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13. Subsequent Events
In October 2024, the Company, in collaboration with GSK, received IND clearance for IDE275 (GSK959), a potential first-in-class WRN inhibitor, to enable first-in-human clinical evaluation of IDE275 (GSK959) for patients having tumors with high MSI. GSK will lead clinical development for the Werner Helicase program. As a result of the IND clearance, the Company earned a $
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Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations.
The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q. Some of the information contained in this discussion and analysis or set forth elsewhere in this Quarterly Report on Form 10-Q, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section of this Quarterly Report on Form 10-Q, our actual results could differ materially from the results described, in or implied, by these forward-looking statements. Please also see the section of this Quarterly Report on Form 10-Q titled “Forward-Looking Statements.”
Overview
We are a precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. Our approach integrates small molecule drug discovery with extensive capabilities in identifying and validating translational biomarkers to develop targeted therapies for select patient populations that are most likely to benefit from these targeted therapies. Our small molecule drug discovery expertise includes discovery and development of small molecule therapeutics. We are applying these capabilities to develop a robust pipeline in precision medicine oncology.
Our clinical pipeline includes five potential first-in-class clinical-stage product candidates – darovasertib (PKC), IDE397 (MAT2A), IDE161 (PARG), IDE705 / GSK101 (Pol Theta Helicase), and IDE275 / GSK959 (Werner Helicase). We own or control all commercial rights of the three most-advanced of these product candidates: darovasertib, IDE397, and IDE161. In July 2024, we entered into an Option and License Agreement with Biocytogen Pharmaceuticals (Beijing) Co., Ltd., or Biocytogen, pursuant to which Biocytogen granted to us an option for an exclusive worldwide license to develop and commercialize products in connection with a potential first-in-class B7H3/PTK7 topo-I-payload bispecific antibody drug conjugate program for which we are targeting a development candidate in the fourth quarter of 2024. We also have multiple earlier-stage preclinical programs. We are targeting development candidate nominations in the fourth quarter of 2024 for multiple new targets, or NTs, including a development candidate to treat MTAP-deletion solid tumors to enable a potential wholly-owned clinical combination with IDE397, and we are separately targeting a development candidate for a potential first-in-class program in the KAT6 pathway. We have established selective, value-accretive collaborations with leading pharmaceutical companies to support our clinical development activities.
Darovasertib – PKC Inhibitor Clinical Candidate in Uveal Melanoma and GNAQ/11 Melanomas
Darovasertib (IDE196) is our most advanced clinical-stage product candidate, which we in-licensed from Novartis. Darovasertib is a potent, selective small molecule inhibitor of protein kinase C, or PKC, which we are developing for genetically-defined cancers having GNAQ or GNA11 gene mutations. PKC is a protein kinase that functions downstream of the GTPases GNAQ and GNA11.
We have enrolled over 150 patients as of October 31, 2024, and have opened multiple clinical sites, including international sites, in our potential registration-enabling Phase 2/3 clinical trial, designated as IDE196-002. The purpose of the clinical trial is to evaluate darovasertib in combination with crizotinib, Pfizer’s investigational cMET inhibitor, in patients having metastatic uveal melanoma, or MUM, with human leukocyte antigen-, or HLA-A*02:01 negative, or HLA-A2(-), serotype, as part of a second Clinical Trial Collaboration and Supply Agreement, or Second Pfizer agreement, with Pfizer.
We are planning to enroll additional HLA-A*02:01 positive, or HLA-A2(+), patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001.
We have enrolled over 75 patients as of October 31, 2024, in our Phase 2 clinical trial, designated as IDE196-009, evaluating darovasertib as single-agent neoadjuvant and adjuvant therapy in patients having primary uveal melanoma, or UM, with ongoing enrollment and multiple clinical sites open. In September 2024, we announced interim clinical data from the ongoing Phase 2 company-sponsored trial and provided a regulatory update on a registrational trial based on a Type C meeting held with the U.S. Food and Drug Administration, or FDA.
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We are also supporting evaluation of darovasertib as single-agent neoadjuvant and adjuvant therapy in primary UM in an ongoing investigator-sponsored clinical trial, or IST, captioned as “Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma”, or NADOM, led by St. Vincent’s Hospital in Sydney with the participation of Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne.
In June 2024, we announced interim clinical data from the ongoing investigator-sponsored Phase 2 trial of darovasertib as neoadjuvant/adjuvant treatment in UM, which was included in an oral presentation at the American Society of Clinical Oncology, or ASCO, 2024 Annual Meeting, and preliminary clinical data from our Phase 2 trial of darovasertib for neoadjuvant UM.
ASCO Clinical Data from Investigator-Sponsored Phase 2 Trial
In our ongoing investigator-sponsored Phase 2 trial of darovasertib as neoadjuvant/adjuvant treatment in UM, 15 patients planned for enucleation with localized UM were treated twice daily with a 300 mg dose of darovasertib in the Phase 2 investigator-sponsored clinical trial as of May 14, 2024. An initial safety cohort of three patients was treated for one month, and the remaining 12 patients were treated in an expansion cohort for up to six months with darovasertib as neoadjuvant treatment prior to their primary intervention (enucleation, plaque brachytherapy or external beam radiotherapy, or EBRT) across three Australian centers. As of May 14, 2024, 13 patients had completed neoadjuvant darovasertib treatment, 11 patients received adjuvant darovasertib treatment after primary treatment of UM, with five patients completing the planned six months of therapy. As of May 14, 2024, 75% (nine out of 12 enucleation patients) had confirmed preservation of the eye, by conversion from planned enucleation to plaque brachytherapy or EBRT, and approximately 67% (eight out of 12 enucleation patients) observed greater than 30% tumor shrinkage (maximum tumor volume change) after six months. Median tumor shrinkage (maximum tumor volume change) in the 12 enucleation patients was approximately 47% after six months. The darovasertib monotherapy neoadjuvant treatment had a manageable adverse event, or AE, profile with no drug-related serious adverse events, or SAEs, observed in the investigator-sponsored Phase 2 trial. Drug-related AEs in the trial were predominantly Grade 1 or Grade 2 and 20% of patients reported at least one drug-related Grade 3 AE.
Company-Sponsored Phase 2 Trial
In September 2024, we provided another clinical data update in which we observed encouraging clinical activity in our Phase 2 company-sponsored trial. Collectively with the IST trial, the clinical efficacy data from the Phase 2 company-sponsored trial substantiate clinical proof of concept for the use of darovasertib in the neoadjuvant uveal melanoma setting. The Phase 2 company-sponsored trial used a data cutoff date of August 15, 2024, with an enrollment cutoff date of May 13, 2024.
We evaluated 31 enucleation and 18 plaque brachytherapy UM patients who were treated with darovasertib neoadjuvant therapy in the Phase 2 company-sponsored and IST trials. We observed approximately 59%, or 29 of the 49 total evaluable patients, with greater than or equal to 20% ocular tumor shrinkage by product of diameters and approximately 49%, or 24 of the 49 total evaluable patients, with greater than or equal to 30% ocular tumor shrinkage by product of diameters. We also observed an approximately 61% eye preservation rate in enucleation patients. We found evidence predicting visual preservation by reducing the amount of radiation associated with plaque brachytherapy.
We observed a manageable AE profile from the Phase 2 company-sponsored trial. In 38 patients, 11% of patients experienced a Grade 3 or higher AE and 5% of patients experienced a serious AE rate. We also observed a discontinuation rate of 3%. The most common AEs observed included diarrhea, nausea, vomiting and fatigue.
We are pursuing a clinical strategy for darovasertib to broadly address uveal melanoma, alternatively referred to as ocular melanoma, in both primary and metastatic settings. Greater than 90% of uveal melanoma patients have tumors harboring GNAQ or GNA11 mutations. There are no FDA-approved systemic therapies for primary UM, as either neoadjuvant or adjuvant therapies. There are likewise no FDA-approved therapies for patients having MUM with HLA-A*02:01 negative, or HLA-A2(-), serotype. These primary UM patients and HLA-A2(-) MUM patients collectively represent approximately 85% of all ocular melanoma patients. We have a separate, independent clinical strategy to address HLA-A*02:01 positive, or HLA-A2(+), MUM patients.
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The potentially addressable patient population for MUM is estimated to include an annual incidence of approximately 4,500 patients across the United States, or U.S., and Europe. (Neo)Adjuvant UM represents a significant expansion opportunity for darovasertib – with a potential annual incidence of approximately 12,000 patients aggregate in North America, Europe and Australia.
We own or control all commercial rights in our darovasertib program in uveal melanoma, including in MUM and in primary UM, subject to certain economic obligations pursuant to our exclusive, worldwide license to darovasertib with Novartis.
Darovasertib – Potential Registration-Enabling Clinical Trial in First-Line HLA-A2(-) MUM
The protocol of the Phase 2/3 clinical trial design incorporates guidance and feedback following our Type C meeting with the FDA in March 2023. This protocol includes an integrated Phase 2/3 open-label study-in-study design in first-line MUM patients with an HLA-A2(-) serotype. The clinical trial design employs a Phase 2 portion with median progression free survival, or PFS, as a primary endpoint for potential accelerated approval. Patients enrolled in Phase 2 will continue on treatment within the same study and will be considered, together with additional enrolled patients, to evaluate overall survival, or OS, as the primary endpoint of the Phase 3 portion of the clinical trial to support a potential confirmational approval.
In the Phase 2 portion of the clinical trial, approximately 230 patients will be randomized on a 2:1 basis for treatment with the darovasertib and crizotinib combination in the treatment arm or investigators choice in the control arm, selected from (a) a combination of ipilimumab (ipi) and nivolumab (nivo), (b) PD1-targeted monotherapy or (c) dacarbazine. The treatment arm of the Phase 2 portion of the clinical trial includes a nested study to confirm the move forward combination dose for the integrated Phase 2/3 clinical trial – including cohorts at the Phase 2 expansion doses of (i) darovasertib 300 mg BID + crizotinib 200 mg BID and (ii) darovasertib 200 mg BID + crizotinib 200 mg BID. Under the nested study design, patients enrolled in the cohort at the move forward dose will be included within the Phase 2/3 registrational clinical trial. The Phase 2 portion of the clinical trial contemplates an efficacy and safety data set of approximately 200 patients randomized 2:1 with the treatment arm at the move forward dose to support a potential accelerated approval based on median PFS by blinded independent central review, or BICR, as a primary endpoint. Accelerated approval is intended to allow for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a demonstration of effectiveness on a surrogate endpoint.
Patients enrolled in Phase 2 at the selected dose would continue on treatment and be included in the Phase 3 study analysis, supplemented by enrollment of approximately 120 additional patients into the Phase 3 portion of the clinical trial, with 2:1 randomization on the same basis as the Phase 2 portion. Efficacy data from the Phase 3 could support potential approval using median OS as a primary endpoint.
In May 2023, we expanded our relationship with Pfizer to support the Phase 2/3 registrational trial to evaluate darovasertib and crizotinib as a combination therapy in MUM by entering into Amendment No. 1 to the Second Pfizer Agreement. Under the as-amended Second Pfizer Agreement, Pfizer will provide us with a first defined quantity of crizotinib at no cost, as well as an additional second defined quantity of crizotinib at a lump-sum cost. We anticipate that the supply of crizotinib under the Second Pfizer Agreement, as amended, will be sufficient to support the planned Phase 2 and Phase 3 portions of the Phase 2/3 potentially registrational clinical trial.
In parallel, we are continuing to evaluate darovasertib in our ongoing Phase 2 clinical trial, designated as IDE196-001, as a combination therapy with crizotinib in HLA-A2(+) MUM patients. We are the sponsor of this Phase 2 clinical trial and are collaborating with Pfizer on this Phase 2 clinical trial pursuant to the Pfizer Agreement.
Prevalence of HLA-A2*02:01 Negative Serotype in MUM
Data from darovasertib clinical trials in MUM demonstrate that approximately 70% of MUM patients with known HLA-A*02:01, or HLA-A2 status were HLA-A2(-). As reported at ESMO 2023, the HLA-A2 status was known in subsets of patients enrolled in clinical trials evaluating darovasertib. Prevalence of HLA-A2(+) and HLA-A2(-) in MUM patients was determined from a first data set of n=149 MUM patients treated with darovasertib as
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monotherapy or in a combination arm of a clinical trial, and separately in a second data set of n=118 MUM patients treated with the darovasertib and crizotinib combination. These data include 102 of 149 (68%) of patients in the all-treatment subset and 81 of 118 (69%) patients in the darovasertib and crizotinib combination treatment subset.
Darovasertib – Strategy for HLA-A*02:01 Positive MUM
Based on clinical data from the Phase 2 clinical trial evaluating darovasertib and crizotinib in MUM as reported at ESMO 2023, and based on the darovasertib mechanism of action, we anticipate darovasertib will have clinical activity independent of HLA-A2 status in GNAQ/11-mutation cancers.
We are planning to enroll additional HLA-A2(+) MUM patients as an independent clinical strategy to address HLA-A2(+) MUM patients, in our ongoing Phase 2 clinical trial, designated as IDE196-001. This strategy demonstrates our commitment to fully address the high unmet medical need in MUM. Such clinical trial data from darovasertib and crizotinib combination treatment in HLA-A2(+) MUM could support publication and potential inclusion in NCCN Clinical Practice Guidelines in Oncology.
Darovasertib – Orphan Drug Designation in UM and Fast Track Designation in MUM
In April 2022, the FDA designated darovasertib as an Orphan Drug in UM, including primary and metastatic disease under 21 C.F.R Part 316. Under an Orphan Drug designation, darovasertib may be entitled to certain tax credits for qualifying clinical trial expenses, exemption from certain user fees and, subject to FDA approval of a New Drug Application, or NDA, for darovasertib in UM, eligibility for seven years of statutory marketing exclusivity. As an FDA-designated Orphan Drug, darovasertib may also be excluded from certain mandatory price negotiation provisions of the 2022 Inflation Reduction Act, if approved.
In November 2022, the FDA granted Fast Track designation to our development program investigating darovasertib in combination with crizotinib in adult patients being treated for MUM. The Fast Track designation makes our darovasertib and crizotinib development program eligible for various expedited regulatory review processes, including generally more frequent FDA interactions, such as meetings and written communications, potential eligibility for rolling review of a future NDA and potential accelerated approval and priority review of an NDA.
Darovasertib – Phase 2 Trials in Neoadjuvant and Adjuvant Therapy in Uveal Melanoma (UM)
We are clinically evaluating the potential for darovasertib as neoadjuvant or adjuvant therapy, or both, also referred to as (neo)adjuvant therapy, in primary, non-metastatic UM patients. We previously reported preliminary clinical data in the neoadjuvant setting showing evidence of anti-tumor activity that we believe supports further clinical evaluation of darovasertib to determine its potential as a neoadjuvant therapy to either save the eye by avoiding enucleation, or to reduce the tumor thickness in the eye, enabling treatment with less radiation to preserve vision, and as an adjuvant therapy, to potentially extend relapse free survival.
We have initiated and achieved double-digit patient enrollment in our company-sponsored Phase 2 clinical trial designated as IDE196-009, with ongoing enrollment and multiple clinical sites open. The purpose of the clinical trial is to evaluate single-agent darovasertib as neoadjuvant treatment of primary UM prior to primary interventional treatment of enucleation or radiation therapy and also as adjuvant therapy following the primary treatment. An amendment to the study protocol was submitted to the FDA in July 2024 to enable dosing of darovasertib therapy up to 12 months.
We are additionally supporting evaluation of darovasertib as (neo)adjuvant therapy in primary UM in the ongoing NADOM IST. Pursuant to an as-amended protocol for the NADOM study, uveal melanoma patients who would otherwise undergo enucleation are instead treated with single agent darovasertib as neoadjuvant treatment for up to six months or maximum benefit. This reflects an increase in potential treatment duration versus the initial approach of one month neoadjuvant therapy, following which these patients will undergo a primary interventional treatment. Patients will subsequently be treated with darovasertib for up to six months as follow-up adjuvant therapy after the primary interventional treatment.
Darovasertib – Potential Registration-Enabling Clinical Trial in Neoadjuvant UM
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A Type C meeting was held with the FDA for the clinical trial design of a potential Phase 3 registration-enabling clinical trial in neoadjuvant UM patients. For the potential Phase 3 clinical trial, we currently project approximately 400 patients will be randomized for treatment with darovasertib in the treatment arm or the control arm, with potential modifications pending further feedback from the FDA. Based on the currently targeted clinical trial design, there will be two cohorts enrolled, including plaque brachytherapy eligible UM patients and enucleation eligible UM patients. For the plaque brachytherapy cohort, the randomization will be darovasertib followed by plaque brachytherapy versus plaque brachytherapy alone. For the enucleation cohort, the randomization will be with or without darovasertib as neoadjuvant therapy.
Based on FDA guidance and information provided in our FDA briefing book, we expect that time to vision loss will be the primary endpoint for plaque brachytherapy UM patients. Eye preservation rate will be the primary endpoint for enucleation UM patients for the target registrational trial design in neoadjuvant UM. The FDA briefing book noted an objective to exceed lower bound of 10% eye preservation rate with a 95% confidence interval for this primary endpoint. No detriment to Event-Free-Survival, or EFS, in the treatment arms will be a secondary endpoint.
Pending ongoing discussions with the FDA, we are evaluating potential surrogate and composite endpoints to support earlier approval scenarios. The registrational study will enroll UM patients with a high risk for metastatic disease. Based on the FDA meeting, there is a potential for consideration of a broad indication label in neoadjuvant UM for subjects with low, intermediate and high risk for metastatic disease. We anticipate approximately two years of data maturity to initial readout for no detriment to EFS in the treatment arms for this high-risk patient population based on preliminary projections. 300mg BID darovasertib was noted in the FDA briefing book as the move-forward dose for the registrational trial. We are currently finalizing the trial protocol and are targeting to initiate the study in the first half of 2025.
IDE397 – MAT2A Inhibitor in Tumors with MTAP Deletion
IDE397 is a clinical-stage, potent, selective small molecule inhibitor of methionine adenosyltransferase 2a, or MAT2A, which we are developing for patients having solid tumors with MTAP deletion. The prevalence of methylthioadenosine phosphorylase, or MTAP, gene deletion is estimated to be approximately 15% of human solid tumors. MTAP deletion in patient tumors is identified by commercial or institutional next generation sequencing, or NGS, panels or by MTAP immunohistochemistry, or IHC, assay with confirmation by NGS.
MTAP-null cells lack the ability to metabolize 5-methylthioadenosine, or MTA, which is an essential step in a biochemical pathway involved in salvaging the metabolite S-adenosyl methionine, or SAM. Increased levels of MTA partially inhibit the methyltransferase PRMT5 for which SAM is the methyl-donor substrate for methylation of various proteins. This partial inhibition of PRMT5 by increased levels of MTA renders MTAP-null cells more dependent on the activity of MAT2A, an enzyme that is responsible for the synthesis of SAM. Because of this enhanced dependence, loss of MTAP results in synthetic lethality when MAT2A is pharmacologically inhibited.
We are enrolling patients into a Phase 1/2 clinical trial designated as IDE397-001 to evaluate IDE397 for patients having certain tumors with MTAP gene deletion. We are proceeding with enrollment of MTAP-deletion patients into a monotherapy Phase 1/2 expansion cohort with an initial focus on high priority solid tumor types, including urothelial cancer, or UC, and non-small cell lung cancer, or NSCLC. We have selected a move-forward Phase 1/2 expansion dose for IDE397 monotherapy in MTAP-deletion UC and NSCLC, based on adverse event profile and preliminary clinical efficacy observed, including multiple partial responses by RECIST 1.1. The estimated U.S. MTAP-deletion annual incidence in UC and NSCLC is approximately 48,000 patients.
Company-Sponsored Phase 1/2 Monotherapy Expansion in MTAP-Deletion Urothelial and Lung Cancer
In July 2024, we announced clinical data for the IDE397 Phase 1/2 monotherapy expansion dose demonstrating preliminary clinical efficacy in heavily pre-treated MTAP-deletion UC and NSCLC patients. The patients evaluated had a median of two prior lines of therapy, ranging from one to seven prior lines of treatment. The reported Phase 1/2 clinical data were based on 18 evaluable MTAP-deletion patients, including seven UC patients, four adenocarcinoma squamous NSCLC patients, and seven squamous NSCLC patients at the expansion dose of 30 mg once-a-day, or QD, of IDE397. In the interim update for 18 evaluable patients, with a data analysis cutoff date of
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June 21, 2024, we reported an overall response rate of approximately 39% (one complete response and six partial responses by RECIST 1.1 evaluation), which included two unconfirmed partial responses (one UC patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment and one adenocarcinoma squamous NSCLC patient which were both confirmed in the Company's October 2024 update). We also observed a disease control rate of 94%, including one complete response, six partial responses and ten stable disease by RECIST 1.1 evaluation. In addition, we observed tumor shrinkage in 14 of the 18 evaluable patients. 11 of the evaluable patients are still on treatment and five of the seven responses by RECIST 1.1 evaluation remain in response. We also reported a ctDNA molecular response, or MR, rate of 81%, representing 13 of 16 reportable patients with 50% or greater ctDNA reduction (several quality control failures of patient samples precluded the other patients from MR analysis).
Regarding safety data, we also reported a favorable AE profile at the 30 mg QD expansion dose. Approximately 5.6% of patients experienced a Grade 3 or higher drug-related AE at the 30 mg QD dose, represented by one instance of Grade 3 asthenia, and no drug-related SAEs were observed. We observed no drug-related AEs leading to discontinuations, and one non-evaluable patient discontinued due to rapid clinical progression of cancer fatigue and drug-unrelated adverse events in the first cycle of treatment. We anticipate that the favorable AE profile and dosing convenience of a 30 mg QD tablet has the potential to enable long-term dosing and combination development.
In October 2024, we announced Phase 1 expansion data for IDE397 in MTAP-deletion UC and NSCLC patients in a late breaker abstract oral presentation at the 36th edition of the EORTC-NCI-AACR Symposium, or ENA 2024, in Barcelona, Spain. The patients evaluated had a median of two to three prior lines of therapy, ranging from one to seven prior lines of treatment. The reported clinical data were based on 27 evaluable MTAP-deletion patients, including 10 UC patients, nine adenocarcinoma NSCLC patients, and eight squamous NSCLC patients at the expansion dose of 30 mg QD of IDE397. In the update of 27 evaluable patients, with a data analysis cutoff date of August 22, 2024, we reported an overall response rate of approximately 33% (one complete response and eight partial responses by RECIST 1.1 evaluation). Nine of nine responses were confirmed by RECIST 1.1, including four UC patients, of which one was a complete response, three squamous NSCLC patients, and two adenocarcinoma NSCLC patients. Two patients were confirmed after the data cutoff date. We also observed an overall response rate by RECIST 1.1 evaluation by solid tumor type. For MTAP-deletion urothelial cancer patients, the confirmed overall response rate was 40%, or 4 out of 10 patients, for MTAP-deletion squamous NSCLC patients, the confirmed overall response rate was approximately 38%, or 3 out of 8 patients, and for MTAP-deletion adenocarcinoma NSCLC patients, the confirmed overall response rate was approximately 22%, or 2 out of 9 patients. In addition, we observed a disease control rate of 93%, including one complete response, eight partial responses and 16 stable disease by RECIST 1.1 evaluation, reflecting 25 of 27 evaluable patients with stable disease or better. Of the 27 evaluable patients, 15 are still on treatment. The median duration of treatment has not been reached and is greater than 6.2 months. The median time to response is approximately 2.7 months. The median duration of response and median progression free survival data is still immature. Three UC patients were on treatment greater than 250 days, four squamous NSCLC patients were on treatment greater than 200 days, and three adenocarcinoma NSCLC patients were on treatment greater than 200 days. We also reported a ctDNA MR rate of 81%, representing 17 of 21 reportable patients with 50% or greater ctDNA reduction and approximately 33%, representing 7 of 21 reportable patients, with a deep 90% or greater ctDNA reduction (several quality control failures of patient samples precluded the other patients from MR analysis). All 17 MRs were rapid occurring at the first ctDNA sample analysis.
We continued to report favorable AE profile at the 30 mg QD expansion dose. Approximately 18% of patients experienced a Grade 3 or higher drug-related AE at the 30mg QD dose and no drug-related SAEs were observed. No drug-related AEs leading to discontinuations were observed. We anticipate that the favorable AE profile and dosing convenience of a 30 mg QD tablet has the potential to enable long-term dosing and combination development, including with MTA-cooperative PRMT5 inhibitors and topoisomerase payload antibody-drug conjugates, or ADCs.
We are collaborating with Amgen to clinically evaluate IDE397 in combination with AMG 193, the Amgen investigational MTA-cooperative PRMT5 inhibitor, in patients having tumors with MTAP deletion, in an Amgen-sponsored clinical trial pursuant to our Clinical Trial Collaboration and Supply Agreement with Amgen, or the Amgen CTCSA.
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The combination of IDE397 with AMG 193 is a novel and potential first-in-class synthetic lethality combination which targets two distinct and mechanistically complementary nodes of the MTAP methylation pathway – MAT2A and PRMT5, providing a complementary approach for targeting MTAP-null tumors.
In August 2023, Amgen initiated and dosed a first patient in the IDE397 /AMG 193 combination study, following FDA authorization to proceed with the clinical trial. This Phase 1/2 clinical trial (NCT: 05975073) will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of IDE397 in combination with AMG 193, with an initial focus for expansion in NSCLC patients and an estimated enrollment of approximately 180 patients. Enrollment is ongoing in the dose escalation portion of this Phase 1/2 clinical trial [and are targeting an expansion in MTAP-deletion NSCLC in late 2024 to early 2025]. We presented a preclinical poster presentation on the antitumor activity by combinatorial inhibition of MAT2A and PRMT5 in MTAP-deleted tumors at ENA 2024.
We are separately collaborating with Gilead Sciences, Inc., or Gilead, to clinically evaluate IDE397 and Trodelvy (sacituzumab-govitecan-hziy), Gilead’s Trop-2 directed ADC combination, in patients having MTAP-deletion UC, in our Phase 1 clinical trial pursuant to a Clinical Study Collaboration and Supply Agreement, or Gilead CSCSA, with Gilead. A first patient was dosed for the Phase 1 trial in June 2024.
In October, we reported the first preliminary clinical case study of the IDE397 and Trodelvy combination in MTAP-deletion UC at ENA 2024, including a partial response by RECIST 1.1 in a patient case report with a genetic co-alteration of MTAP-deletion and a FGFR3-TACC3 fusion, and rapid and deep first-evaluation MRs with ctDNA reduction of greater than 95% observed. The partial response reported at ENA 2024 has confirmed by RECIST 1.1. We are targeting to initiate the IDE397 and Trodelvy Phase 1/2 combination expansion in MTAP-deletion UC patients in the fourth quarter of 2024.
We are also advancing multiple preclinical stage MTAP-deletion programs to enable wholly-owned combinations with IDE397, including a program targeting a development candidate nomination in the second half of 2024. We own all rights, title, and interest in and to IDE397 and the MAT2A program, including all worldwide commercial rights thereto.
IDE161 – PARG Inhibitor in Tumors with Homologous Recombination Deficiency
We are evaluating IDE161, a small molecule inhibitor of poly (ADP-ribose) glycohydrolase, or PARG, being evaluated in a Phase 1/2 clinical trial designated as IDE161-001 for patients having tumors with homologous recombination deficiency, or HRD, and potentially other genetic and/or molecular signatures. PARG is a novel target in a clinically validated biological pathway. PARG functions as a regulator of DNA repair in the same biochemical pathway as poly-(ADP-ribose) polymerase, or PARP. PARG hydrolyzes poly (ADP-ribose), or PAR, chains that are polymerized by PARP enzymes, completing the PAR cycle. Small molecule inhibitors of PARG result in a dose dependent increase in cellular PAR after DNA damage. PARG is a mechanistically distinct target relative to PARP.
We are progressing with enrollment of patients having tumors with HRD into the Phase 1 expansion portion of the Phase 1/2 clinical trial in selected priority tumors. In parallel, we are also continuing with Phase 1 dose optimization to confirm a move-forward expansion dose for the planned Phase 2 portion of the clinical trial. We are targeting an initial Phase 2 monotherapy expansion in HRD solid tumors in the fourth quarter of 2024.
The expansion portion of the Phase 1 trial has a strategic focus in estrogen receptor positive, or ER+, human epidermal growth factor receptor 2 negative, or Her2(-), breast cancer with HRD, as well as other solid tumors with HRD, such as endometrial cancer, colorectal cancer and prostate cancer. The ER+, Her2-, HRD+ breast cancer focus represents approximately 10% to 14% of breast cancer patients.
In September 2023, we received Fast Track Designation from the FDA for IDE161 for ovarian cancer and breast cancer indications. Specifically, for IDE161, Fast Track Designation was received for the treatment of adult patients having advanced or metastatic ovarian cancer with germline or somatic BRCA 1/2 mutations who are platinum resistant and have received prior antiangiogenic and PARP inhibitor therapies. The Fast Track Designation was also received for IDE161 for the treatment of adult patients having advanced or metastatic HR+, Her2- breast cancer with
34
germline or somatic BRCA 1/2 mutations who have progressed following treatment with at least one line of a hormonal therapy, a CDK4/6 inhibitor therapy and a PARP inhibitor therapy.
We entered into an exclusive license under the Evaluation, Option and License Agreement, by and among the Company, Cancer Research Technologies Ltd., also known as Cancer Research United Kingdom, or CRT, and the University of Manchester, pursuant to which we hold exclusive worldwide license rights covering a broad class of PARG inhibitors.
In April 2023, we incurred an obligation to pay milestone payments in an aggregate amount of £750,000 to CRT based upon the achievement of certain milestones relating to first and second tumor histologies in connection with the Phase 1 portion of the IDE161-001 Phase 1/2 clinical trial in oncologic diseases. We will be obligated to make additional payments to CRT aggregating up to £18.75 million upon the achievement of specific development and regulatory approval events for development of a PARG inhibitor in oncologic diseases, including an aggregate of up to £1.5 million and up to £2.25 for the achievement of certain Phase 2 and Phase 3 development milestones, respectively, in each case as relating to first and second tumor histologies.
In March 2024, we entered into the Merck CTCSA with Merck (known as MSD outside of the US and Canada). We are planning to evaluate the combination of IDE161 and KEYTRUDA® (pembrolizumab) in patients with high microsatellite instability, or MSI, and microsatellite stable, or MSS, endometrial cancer. We are targeting a first-patient dosing for this study in the fourth quarter of 2024.
We own or control all commercial rights in our PARG program, subject to certain economic obligations pursuant to our exclusive, worldwide license to certain PARG inhibitors, including IDE161, with CRT and University of Manchester.
IDE705 (GSK101) – Pol Theta Helicase Inhibitor in tumors with Homologous Recombination Deficiency
We discovered IDE705 (GSK101), our DNA Polymerase Theta, or Pol Theta, Helicase inhibitor clinical development candidate, and evaluated IDE705(GSK101) in preclinical studies in collaboration with GSK. IDE705 (GSK101) targets the helicase domain of the Pol Theta protein for patients having solid tumors with BRCA or other mutations associated with HRD.
Pol Theta is involved in a DNA repair process called microhomology mediated end joining, or MMEJ, that is utilized when homologous recombination mediated repair is compromised, as happens in the case of certain BRCA1 or BRCA2 mutations. The expression of Pol Theta is largely absent in normal cells, but tumor cells harboring double strand break repair defects, such as BRCA1 or BRCA2 mutations, show higher Pol Theta expression and synthetic lethality when Pol Theta is inhibited. Pol Theta is a large protein with two functional domains: a DNA polymerase domain and an ATP-dependent DNA helicase domain, sometimes referred to as an ATPase domain, linked by a RAD51 central region.
GSK is evaluating IDE705 (GSK101) in combination with niraparib, the GSK small molecule inhibitor of PARP for the treatment of patients having tumors with BRCA or other HR mutations, or HRD, in a GSK-sponsored Phase 1 clinical trial. GSK has dosed the first patient and enrollment is ongoing in the dose escalation portion of this study.
GSK is leading clinical development of IDE705 (GSK101) pursuant to the Collaboration, Option and License Agreement with GSK, or GSK Collaboration Agreement. GSK is responsible for all research and development costs for the Pol Theta program.
We have the potential to receive an additional $10.0 million milestone payment upon initiation of Phase 1 clinical dose expansion. In August 2023, we achieved and earned a $7.0 million milestone based on acceptance of the IND by the FDA, for which payment was received in October 2023. An earlier preclinical development $3.0 million milestone payment from GSK was achieved in August 2022 in connection with ongoing IND-enabling studies to support evaluation of IDE705 (GSK101).
We have the potential to earn further aggregate late-stage development and regulatory milestones of up to $465.0 million. Upon commercialization, we will be eligible to receive up to $475.0 million of commercial milestones, and
35
tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.
IDE275 (GSK959) - WRN Inhibitor in Tumors with High Microsatellite Instability
We discovered IDE275 (GSK959), our Werner Helicase, or WRN, inhibitor clinical development candidate, and evaluated IDE275 (GSK959) in preclinical studies in collaboration with GSK. IDE275 (GSK959) targets WRN for patients having tumors with high MSI.
WRN protein is a RecQ enzyme involved in the maintenance of genome integrity. Germline loss of function mutations in WRN lead to premature aging and pre-disposition to cancer. MSI is a change in the DNA content of a tumor cell in which the number of repeats of microsatellites, short repeated sequences of DNA, differ as cells divide. High MSI is present in about 15% of gastrointestinal tumor cancers, including in approximately 22% of stomach adenocarcinoma and 16% of colorectal cancer. Tumors with high MSI are routinely assessed in multiple diagnostic profiling tests.
WRN is a protein having several functional domains, and we have shown that the helicase functional domain of WRN is responsible for this synthetic lethal interaction, as reflected in our publication in Cell Press - iScience, Werner Syndrome Helicase is Required for the Survival of Cancer Cells with Microsatellite Instability (March 2019).
We have demonstrated in vivo efficacy with tumor regression and PD response in a relevant high MSI model. We have observed selectivity of our Werner Helicase inhibitor and validation of the synthetic lethal relationship to tumors with high MSI over tumors with MSS based on a lack of in vivo pharmacological response in relevant MSS xenograft models.
We, in collaboration with GSK, received IND clearance for IDE275 (GSK959), a potential first-in-class WRN inhibitor, in October 2024 to enable first-in-human clinical evaluation of IDE275 (GSK959) for patients having tumors with high MSI. GSK will lead clinical development for the Werner Helicase program. GSK is responsible for 80% of global research and development costs and we are responsible for 20% of such costs. GSK holds a global, exclusive license to develop and commercialize the Werner Helicase Inhibitor DC.
In October 2023, we achieved and earned a $3.0 million milestone in connection with IND-enabling studies. In October 2024, we earned a $7.0 million milestone payment for the IND clearance of IDE275 (GSK 959). We have the potential to earn up to an additional $10.0 million milestone payment upon initiation of Phase 1 clinical dose expansion. We are also eligible to receive additional future aggregate total development milestones of up to $465.0 million. Upon commercialization, we will be eligible to receive up to $475.0 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase Inhibitor DC – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.
B7H3/PTK7 topo-I-payload bispecific antibody drug conjugate (BsADC) program with Biocytogen
In July 2024, we entered into an option and license agreement with Biocytogen, pursuant to which Biocytogen granted us an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program, or the Option. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in our pipeline targeting DDR-based therapies, including our PARG inhibitor IDE161. A development candidate nomination for the B7H3/PTK7 topoisomerase-I-inhibitor payload BsADC program is targeted for the fourth quarter of 2024.
Under the terms of the agreement, we will pay Biocytogen an upfront fee and, upon our potential exercise of the Option, an exercise fee totaling up to $6.5 million. We may exercise the Option within a specified time period after we obtain all data and results from certain non-GLP toxicology studies specified in the Agreement, which we will conduct at our own cost.
36
Subject to our exercise of the Option, Biocytogen will be eligible to receive an option exercise fee, development and regulatory milestone payments and commercial milestone payments, as well as low to mid single-digit royalties on net sales. Total potential milestone payments equal an aggregate of $400.0 million, including development and regulatory milestone payments of up to $100.0 million. Our royalty obligations continue with respect to each country and each product until the later of (i) the date on which such product is no longer covered by certain intellectual property rights in such country and (ii) the 10th anniversary of the first commercial sale of such product in such country.
Next-Generation Precision Medicine Pipeline Programs
We have initiated early preclinical research programs focused on pharmacological inhibition of several new targets, or NTs, for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures. We believe these research programs have the potential for discovery and development of first-in-class or unique-in-class or best-in-class therapeutics. We are targeting development candidate nominations in the fourth quarter of 2024 for multiple NTs, including a development candidate to treat MTAP-deletion solid tumors to enable a potential wholly-owned clinical combination with IDE397, and separately a development candidate for a potential first-in-class program in the KAT6 pathway. Collectively, we believe these efforts will further advance our multi-pronged clinical and business strategy. We own or control all commercial rights in our next-generation NT programs.
New Target and Biomarker Discovery Platform
Since the inception of the company, our core research has and continues to be focused on precision medicine oncology, with synthetic lethality as a central tenet. We have invested significantly and continue to invest in capabilities for identification and validation of new precision medicine targets and biomarkers for patient selection. For targets of interest, we advance our research to discover therapeutic drugs and to further qualify relevant biomarkers.
Small and Medium Enterprise Status from the European Medicines Agency
In June 2024, we were granted Small and Medium Enterprise, or SME, status by the European Medicines Agency, or EMA. This enables us to have access to administrative, regulatory and financial support, including fee reductions for scientific advice and regulatory procedures across all our programs.
Prospectus Supplement - At-the-Market Facility
On January 19, 2024, we entered into a new Open Market Sales Agreement, or January 2024 Sales Agreement, with Jefferies, or Jefferies, relating to an at-the-market offering program under which we may offer and sell, from time to time at our sole discretion, shares of common stock, par value $0.0001 per share, or common stock, having aggregate gross proceeds of up to $350.0 million through Jefferies as sales agent.
During the three months ended September 30, 2024, pursuant to the January 2024 Sales Agreement, we sold no shares of common stock through at-the-market offerings. As of September 30, 2024, approximately $182.1 million of common stock remained available to be sold pursuant to the January 2024 Sales Agreement.
We may cancel our at-the-market program at any time upon written notice, pursuant to its terms.
Corporate Update
We do not have any products approved for sale and have not generated any product revenue since inception. We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK. As of September 30, 2024, we had cash, cash equivalents and marketable securities of $1.2 billion, consisting primarily of money market funds, U.S. government securities, commercial paper, and corporate bonds.
Since our inception in June 2015, we have devoted substantially all of our resources to discovering and developing our product candidates. We have incurred significant operating losses to date and expect that our operating expenses
37
will increase significantly as we advance our product candidates through preclinical and clinical development; seek regulatory approval, and prepare for, and, if approved, proceed to commercialization; acquire, discover, validate and develop additional product candidates; obtain, maintain, protect and enforce our intellectual property portfolio; and hire additional personnel. Certain program costs that contribute to our operating expenses have been and/or will be reimbursed by GSK pursuant to the GSK Collaboration Agreement, including 100% of costs we incur for research we perform in connection with the Pol Theta program and 80% of the aggregate program costs incurred by us and GSK for research each of us performs for the Werner Helicase program. We anticipate that payments which we may make to Amgen will also contribute to our operating expenses as they are reimbursed by us pursuant to the Amgen CTCSA, including 50% of external costs Amgen incurs in connection with the Amgen-sponsored and executed IDE397 / AMG 193 Combination Study. We anticipate that we will also incur costs in accordance with the Gilead CSCSA. Gilead will bear internal or external costs incurred in connection with its supply of Trodelvy. We will bear all internal and external costs and expenses associated with the conduct of the combination study. We further anticipate that we will also incur costs in accordance with the Merck CTCSA. Merck will provide KEYTRUDA for the study at no cost to us. We will bear all internal and external costs and expenses associated with the conduct of the study. In addition, we expect to incur additional costs associated with operating as a public company.
Our net losses were $144.2 million and $79.0 million for the nine months ended September 30, 2024 and September 30, 2023, respectively. As of September 30, 2024, we had an accumulated deficit of $492.5 million.
Our ability to generate product revenue will depend on the successful development, regulatory approval and eventual commercialization of one or more of our product candidates, ourselves, or for some programs, in collaboration with our strategic partners.
Until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through the sale of equity, debt financings, or other capital sources, including potential collaborations with other companies or other strategic transactions. Adequate funding may not be available to us on acceptable terms, or at all. If we fail to raise capital or enter into such agreements as and when needed, we may have to significantly delay, scale back or discontinue the development and commercialization of our product candidates.
As of September 30, 2024, we had cash, cash equivalents, and short-term and long-term marketable securities of $1.2 billion.
We believe that our cash, cash equivalents, and short-term and long-term marketable securities will be sufficient to fund our planned operations for at least 12 months from the date of the issuance of our Quarterly Report on Form 10-Q filed November 4, 2024.
These funds will support our efforts through potential achievement of multiple preclinical and clinical milestones across multiple programs.
Components of Operating Results
Collaboration Revenues
To date, we have not generated any revenue from product sales, and we do not expect to generate any revenue from product sales unless and until we are able to initiate a registrational clinical trial, obtain regulatory approval and commercialize one of our product candidates in the future. Our revenue consists exclusively of collaboration revenue under the GSK Collaboration Agreement, including amounts that are recognized related to previously received upfront payments and amounts due and payable to us for research and development services. The amount of revenue recognized related to the GSK Collaboration Agreement, including as related to the previously received upfront payment or to certain development milestone payments, may vary considerably by period and certain components thereof may generally decrease year-over-year as we satisfy remaining performance obligations, for example, relating to the Pol Theta and WRN R&D Services. As of September 30, 2024, we have fully recognized the contract liabilities related to the upfront payment and reimbursements for the research and development performance obligations under the GSK Collaboration Agreement. There are no remaining contract liabilities as of September 30, 2024 as we concluded all the research and development performance obligations under the GSK Collaboration Agreement. The future revenue recognition will be contingent on additional milestones earned, profit sharing and royalties on any net product sales under our collaborations. We expect that any revenue we recognize or generate under the GSK Collaboration Agreement will fluctuate from period to period due to period to period variability in milestone payments and other payments.
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Operating Expenses
Research and Development Expenses
Substantially all of our research and development expenses consist of expenses incurred in connection with the discovery and development of our product candidates. These expenses include certain payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expenses for our research and product development employees, fees to third parties to conduct certain research and development activities on our behalf including fees to CMOs and CROs in support of manufacturing and clinical activity for darovasertib, IDE397, IDE161 and WRN, consulting costs, costs for laboratory supplies, costs for product licenses and allocated overhead, including rent, equipment, depreciation, information technology costs and utilities. We expense both internal and external research and development expenses as they are incurred.
We have entered into various agreements with CMOs and CROs. Our research and development accruals are estimated based on the level of services performed, progress of the studies, including the phase or completion of events, and contracted costs. The estimated costs of research and development provided, but not yet invoiced, are included in accrued liabilities on the balance sheet. If the actual timing of the performance of services or the level of effort varies from the original estimates, we will adjust the accrual accordingly. Payments made to CMOs and CROs under these arrangements in advance of the performance of the related services are recorded as prepaid expenses and other current assets until the services are rendered.
Costs of certain activities, such as preclinical studies, are generally recognized based on an evaluation of the progress to completion of specific tasks. Nonrefundable payments made prior to the receipt of goods or services that will be used or rendered for future research and development activities are deferred and capitalized as prepaid expenses and other current assets on our balance sheet. The capitalized amounts are recognized as expense as the goods are delivered or the related services are performed.
We do not allocate our internal costs by product candidate, including internal costs, such as payroll and other personnel expenses, laboratory supplies and allocated overhead. With respect to internal costs, several of our departments support multiple product candidate research and development programs, and therefore the costs cannot be allocated to a particular product candidate or development program. The following table summarizes our external clinical development expenses by program:
|
|
Three Months Ended |
|
||||
|
|
September 30, 2024 |
|
June 30, 2024 |
|
||
External clinical development expenses (1): |
|
|
|
|
|
||
Darovasertib |
|
$ |
13,216 |
|
$ |
14,895 |
|
IDE397 (2) |
|
|
5,062 |
|
|
4,064 |
|
IDE161 |
|
|
2,434 |
|
|
2,059 |
|
Personnel related and stock-based compensation |
|
|
14,350 |
|
|
14,534 |
|
Other research and development expenses |
|
|
22,090 |
|
|
18,981 |
|
Total research and development expenses |
|
$ |
57,152 |
|
$ |
54,533 |
|
|
|
Nine Months Ended |
|
||||
|
|
September 30, 2024 |
|
September 30, 2023 |
|
||
External clinical development expenses (1): |
|
|
|
|
|
||
Darovasertib |
|
$ |
28,112 |
|
$ |
17,794 |
|
IDE397 (2) |
|
|
9,126 |
|
|
8,474 |
|
IDE161 |
|
|
4,493 |
|
|
3,961 |
|
Personnel related and stock-based compensation |
|
|
41,138 |
|
|
28,735 |
|
Other research and development expenses |
|
|
71,621 |
|
|
31,774 |
|
Total research and development expenses |
|
$ |
154,490 |
|
$ |
90,738 |
|
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We are focusing substantially all of our resources on the development of our product candidates. We expect our research and development expenses to increase substantially during the next few years, as we seek to initiate and/or advance clinical trials for our product candidates, complete our clinical program, pursue regulatory approval of our product candidates and prepare for a possible commercial launch. Predicting the timing or the cost to complete our clinical program or validation of our commercial manufacturing and supply processes is difficult and delays may occur because of many factors, including factors outside of our control. For example, if the FDA or other regulatory authorities were to require us to conduct clinical trials beyond those that we currently anticipate, or if we experience significant delays in enrollment in any of our clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development. Furthermore, we are unable to predict when or if our product candidates will receive regulatory approval with any certainty.
General and Administrative Expenses
General and administrative expenses consist primarily of payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expense, professional fees for legal, patent, consulting, accounting and tax services, allocated overhead, including rent, equipment, depreciation, information technology costs and utilities, and other general operating expenses not otherwise classified as research and development expenses.
We anticipate that our general and administrative expenses will increase, as a result of increased personnel costs, including salaries, benefits and stock-based compensation expense, patent costs for our product candidates, expanded infrastructure and higher consulting, legal and accounting services associated with maintaining compliance with our Nasdaq stock exchange listing and requirements of the Securities and Exchange Commission, or the SEC, investor relations costs and director and officer insurance policy premiums associated with being a public company.
Other Income (Expense)
Interest Income and Other Income (Expense), Net
Interest income and other income (expense), net consists primarily of interest income earned on our cash, cash equivalents and marketable securities.
Results of Operations
A discussion regarding our financial condition and results of operations for the three months ended September 30, 2024 compared to the three months ended June 30, 2024 and nine months ended September 30, 2024 compared to the nine months ended September 30, 2023 is presented below.
Comparison of Three Months Ended September 30, 2024 and June 30, 2024
The following table summarizes our results of operations for the periods indicated (in thousands):
|
|
Three Months Ended |
|
|
|
|
|
||||||
|
|
September 30, 2024 |
|
June 30, 2024 |
|
Change |
|
% Change |
|
||||
Revenue: |
|
|
|
|
|
|
|
|
|
||||
Collaboration revenue |
|
$ |
— |
|
$ |
— |
|
$ |
— |
|
|
— |
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
||||
Research and development |
|
|
57,152 |
|
|
54,533 |
|
|
2,619 |
|
|
5 |
% |
General and administrative |
|
|
9,741 |
|
|
10,394 |
|
|
(653 |
) |
|
(6 |
%) |
Loss from operations |
|
|
(66,893 |
) |
|
(64,927 |
) |
|
(1,966 |
) |
|
3 |
% |
Interest income and other income, net |
|
|
15,072 |
|
|
12,155 |
|
|
2,917 |
|
|
24 |
% |
Net loss |
|
$ |
(51,821 |
) |
$ |
(52,772 |
) |
$ |
951 |
|
|
(2 |
%) |
Collaboration Revenue
40
There was no collaboration revenue recognized for the three months ended September 30, 2024 and for the three months ended June 30, 2024. We completed all performance obligations related to the upfront payment under the GSK Collaboration Agreement as of December 31, 2023. Future collaboration revenue recognized under the GSK Collaboration Agreement will be related to future milestone payments as they are earned.
Research and Development Expenses
Research and development expenses increased by $2.6 million, or 5%, during the three months ended September 30, 2024 compared to the three months ended June 30, 2024 due to an increase of $2.1 million primarily driven by fees paid to CROs, CMOs and consultants related to the advancement of our lead product candidates through preclinical and clinical studies and an increase of $0.9 million related to facility expenses, partially offset by a decrease of $0.4 million in costs for laboratory supplies.
General and Administrative Expenses
General and administrative expenses decreased by $0.7 million, or 6%, during the three months ended September 30, 2024 compared to the three months ended June 30, 2024. The decrease in general and administrative expense was primarily due to a decrease in stock-based compensation expense.
Interest Income and Other Income, Net
Interest income increased by $2.9 million, or 24%, during the three months ended September 30, 2024 compared to the three months ended June 30, 2024, primarily due to higher investment balances.
Comparison of Nine Months Ended September 30, 2024 and September 30, 2023
The following table summarizes our results of operations for the periods indicated (in thousands):
|
|
Nine Months Ended September 30, |
|
|
|
|
|
||||||
|
|
2024 |
|
2023 |
|
Change |
|
% Change |
|
||||
Revenue: |
|
|
|
|
|
|
|
|
|
||||
Collaboration revenue |
|
$ |
— |
|
$ |
19,463 |
|
$ |
(19,463 |
) |
|
(100 |
%) |
Operating expenses: |
|
|
|
|
|
|
|
|
|
||||
Research and development |
|
|
154,490 |
|
|
90,738 |
|
|
63,752 |
|
|
70 |
% |
General and administrative |
|
|
28,347 |
|
|
21,237 |
|
|
7,110 |
|
|
33 |
% |
Loss from operations |
|
|
(182,837 |
) |
|
(92,512 |
) |
|
(90,325 |
) |
|
98 |
% |
Interest income and other income, net |
|
|
38,672 |
|
|
13,506 |
|
|
25,166 |
|
|
186 |
% |
Net loss |
|
$ |
(144,165 |
) |
$ |
(79,006 |
) |
$ |
(65,159 |
) |
|
82 |
% |
Collaboration Revenue
There was no collaboration revenue recognized for the nine months ended September 30, 2024 compared to $19.5 million for the nine months ended September 30, 2023. We completed all performance obligations related to the upfront payment under the GSK Collaboration Agreement as of December 31, 2023. Future collaboration revenue recognized under the GSK Collaboration Agreement will be related to future milestone payments as they are earned.
Research and Development Expenses
Research and development expenses increased by $63.8 million, or 70%, during the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023. The increase in research and development expenses was primarily due to increases of $46.9 million in fees paid to CROs, CMOs and consultants related to the advancement of our lead product candidates through preclinical and clinical studies, increases of $12.4 million in personnel-related expenses, including stock-based compensation and salaries and benefits to support our
41
growth, and increases in $4.5 million in costs for laboratory supplies, facilities, and software to support our research and development programs.
General and Administrative Expenses
General and administrative expenses increased by $7.1 million, or 33%, during the nine months ended September 30, 2024 compared to nine months ended September 30, 2023. The increase in general and administrative expenses was primarily due to increases of $2.7 million of consulting and legal services and increases in $4.4 million of personnel-related expenses, including stock-based compensation and salaries and benefits to support our growth.
Interest Income and Other Income, Net
Interest income increased by $25.2 million, or 186%, during the nine months ended September 30, 2024 compared to the nine months ended September 30, 2023, primarily due to higher investment balances and interest rates.
Liquidity and Capital Resources; Plan of Operations
Sources of Liquidity
We have funded our operations primarily through the sale and issuance of common stock and the upfront payment and certain milestone payments received from GSK. As of September 30, 2024, we had cash, cash equivalents and marketable securities of $1.2 billion, consisting primarily of money market funds, U.S. government securities, commercial paper, and corporate bonds.
Material Cash Requirements
We have incurred net losses since our inception. For the nine months ended September 30, 2024 and September 30, 2023, we had net losses of $144.2 million and $79.0 million, respectively, and we expect to incur substantial additional losses in future periods. As of September 30, 2024, we had an accumulated deficit of $492.5 million. Based on our current business plan, we believe that our existing cash, cash equivalents and marketable securities will be sufficient to fund our planned operations for at least the next 12 months from the issuance date of this Quarterly Report on Form 10-Q.
To date, we have not generated any product revenue. We do not expect to generate any meaningful product revenue unless and until we obtain regulatory approval of and commercialize any of our product candidates, and we do not know when, or if, it will occur. We expect to continue to incur significant losses for the foreseeable future, and we expect the losses to increase as we continue the development of, and seek regulatory approvals for, our product candidates and begin to commercialize any approved products. We are subject to all of the risks typically related to the development of new product candidates, and we may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business. Moreover, we expect to incur additional costs associated with operating as a public company.
We will continue to require additional capital to develop our product candidates and fund operations for the foreseeable future. We may seek to raise capital through private or public equity or debt financings, collaboration or other arrangements with corporate sources, or through other sources of financing. Adequate additional funding may not be available to us on acceptable terms or at all. Our failure to raise capital as and when needed would have a negative impact on our financial condition and our ability to pursue our business strategies. We anticipate that we will need to raise substantial additional capital, the requirements for which will depend on many factors, including:
42
A change in the outcome of any of these or other variables with respect to the development of any of our product candidates could significantly change the costs and timing associated with the development of that product candidate. Furthermore, our operating plans may change in the future, and we will continue to require additional capital to meet operational needs and capital requirements associated with such operating plans. If we raise additional funds by issuing equity securities, our stockholders may experience dilution. Any future debt financing into which we enter may impose upon us additional covenants that restrict our operations, including limitations on our ability to incur liens or additional debt, pay dividends, repurchase our common stock, make certain investments or engage in certain merger, consolidation or asset sale transactions. Any debt financing or additional equity that we raise may contain terms that are not favorable to us or our stockholders. If we are unable to raise additional funds when needed, we may be required to delay, reduce, or terminate some or all of our development programs and clinical trials. We may also be required to sell or license to others rights to our product candidates in certain territories or indications that we would prefer to develop and commercialize ourselves.
In June 2023, we entered into a lease agreement for approximately 44,000 square feet of laboratory and office facilities at 5000 Shoreline Court, South San Francisco, California. The lease term is 120 months, and we have an option to extend the lease term for a total of two consecutive five-year periods. The lease commenced in August 2024.
In May 2024, we amended our 5000 Shoreline Court facility lease agreement to expand the size of the original premises by adding approximately 11,321 rentable square feet of additional space. The lease term has not yet commenced as of September 30, 2024.
Our lease at 7000 Shoreline Court, South San Francisco, California, expired in September 2024.
In November 2023, we entered into a lease agreement for approximately 5,700 square feet of space at 11710 El Camino Real, San Diego, California for corporate office space. The lease commenced in December 2023 and expires in March 2028. We have an option to renew the lease for three years.
We enter into contracts in the normal course of business with third-party contract organizations for preclinical and clinical studies and testing, manufacture and supply of our preclinical and clinical materials and providing other services and products for operating purposes. These contracts generally provide for termination following a certain period after notice, and therefore we believe that our non-cancelable obligations under these agreements are not material.
Pursuant to the GSK Collaboration Agreement, GSK holds a global, exclusive license to develop and commercialize WRN products arising out of the WRN program. We and GSK are collaborating on ongoing preclinical research for the WRN program, and GSK will lead clinical development for the WRN program, with us responsible for 20% and GSK responsible for 80% of such global research and development costs. The cost-sharing percentages will be adjusted based on the actual ratio of U.S. to global profits for WRN products, as measured three and six years after global commercial launch thereof.
In September 2018, we entered into a license agreement with Novartis to develop and commercialize Novartis’ LXS196 (also known as IDE196), a Phase 1 PKC inhibitor, for the treatment of cancers having GNAQ and GNA11 mutations. We renamed Novartis’ LXS196 oncology as IDE196, and which has a non-proprietary name of darovasertib. Under the license agreement, Novartis granted to us a worldwide, exclusive, sublicensable license to research, develop, manufacture, and commercialize certain defined compounds and products, including IDE196 and
43
certain other PKC inhibitors as well as companion diagnostic products, collectively referred to as the licensed products, for any purpose.
We paid Novartis an upfront payment of $2.5 million and issued 263,615 shares of our Series B redeemable convertible preferred stock concurrently with the execution of the license agreement. Subject to completion of certain clinical and regulatory development milestones, we agreed to make milestone payments in the aggregate of up to $9.0 million, and subject to achievement of certain commercial sales milestones, we agreed to make milestone payments in the aggregate of up to $20.0 million. We also agreed to pay mid to high single-digit tiered royalty payments based on annual worldwide net sales of licensed products, payable on a licensed product-by-licensed product and country by country basis until the latest of the expiration of the last to expire exclusively licensed patent, the expiration of regulatory exclusivity, and the ten year anniversary of the first commercial sale of such product in such country. The royalty payments are subject to reductions for lack of patent coverage, loss of market exclusivity, and payment obligations for third-party licenses.
In March 2020, we entered into the Pfizer Agreement. Pursuant to the Pfizer Agreement, as amended in September 2020, April 2021, September 2021 and May 2023, Pfizer supplies us with their MEK inhibitor, binimetinib, and their cMET inhibitor, crizotinib, to evaluate combinations of darovasertib independently with each of the Pfizer compounds, in patients with tumors harboring activating GNAQ or GNA11 mutations. Under the Pfizer Agreement, we are the sponsor of the combination studies and will provide darovasertib and pay for the costs of the combination studies. Pfizer will provide binimetinib and crizotinib for use in the clinical trial at no cost to us. We have further expanded the scope of our relationship with Pfizer, entering into additional agreements to facilitate evaluation of darovasertib in combination with crizotinib in a potential registrations clinical trial in MUM and separately, in combination with crizotinib in other cMET-driven tumor indications.
In March 2022, we and Pfizer entered into the Second Pfizer Agreement pursuant to which we may, subject to FDA feedback and guidance, evaluate darovasertib and crizotinib as a combination therapy in MUM in a planned Phase 2/3 potential registration-enabling clinical trial. Pursuant to the Second Pfizer Agreement, we are the sponsor of the planned combination trial and we will provide darovasertib and pay for the costs of the combination trial; Pfizer will provide crizotinib for the planned combination trial at no cost to us for up to an agreed-upon number of MUM patients. Separately, in March 2022, we and Pfizer also entered into the Third Pfizer Agreement pursuant to which we may, subject to preclinical validation and FDA feedback and guidance, evaluate darovasertib and crizotinib, as a combination therapy in cMET-driven tumors such as NSCLC and/or HCC in a Phase 1 clinical trial. Pursuant to the Third Pfizer Agreement, we are the sponsor of the planned combination trial, and we will provide darovasertib and pay for the costs of the combination trial; Pfizer will provide crizotinib for the planned combination trial at no cost to us. In May 2023, we continued our relationship with Pfizer by entering into Amendment No. 4 to the Pfizer Agreement relating to the supply of crizotinib in support of this Phase 2 clinical trial, pursuant to which Pfizer will continue to provide us with an additional defined quantity of crizotinib at no cost.
We also expanded our relationship with Pfizer in May 2023 under an Amendment No. 1 to the Second Pfizer Agreement to support the Phase 2/3 registrational trial to evaluate darovasertib and crizotinib as a combination therapy in MUM. Under the as-amended Second Pfizer Agreement, Pfizer will provide us with a first defined quantity of crizotinib at no cost, as well as an additional second defined quantity of crizotinib at a lump-sum cost. Under Amendment No. 1 to the Second Pfizer Agreement, we also terminated the Third Pfizer Agreement.
In January 2022, we exercised our option for an exclusive worldwide license rights covering a broad class of PARG inhibitors from CRT and the University of Manchester, and in connection therewith, paid a one-time option exercise fee of £250,000.
In addition to an upfront fee of £100,000 and the one-time option exercise fee of £250,000, each of which have been paid, we have certain potential milestone-dependent financial obligations, including: (a) subject to completion of specific development and regulatory approval events for development of a PARG inhibitor in oncologic diseases, payments of up to £19.5 million per broad disease classification block – for example, in oncologic diseases, up to £13.0 million aggregate for a first achievement of such clinical and regulatory milestones and up to £6.5 million aggregate for a second achievement of such clinical and regulatory milestones; (b) subject to certain sales-based milestones based on net sales of licensed products. payments of up to £9.0 million per broad disease classification block – for example, in oncologic diseases, up to £6.0 million aggregate for a first achievement of such sales milestones and up to £3.0 million aggregate for a second achievement of such sales milestones; and (c) low single-digit tiered royalty payments based on aggregate worldwide net sales of al products, payable on a
44
product-by-product and country-by-country basis until the later of the last-to-expire patent covering such product in such country and the ten year anniversary of the first commercial sale of such licensed product in such country. The royalty payments are subject to reductions for payment obligations in the event third-party licenses are required to develop or commercialize the product or if the product is not covered by certain patents.
In April 2023, we incurred an obligation to pay milestone payments in an aggregate amount of £750,000 to CRT based upon the achievement of certain milestones relating to first and second tumor histologies in connection with the Phase 1 portion of the Phase 1/2 clinical trial in oncologic diseases. After the achievement of this milestone, we will be obligated to make future milestone payments to CRT aggregating up to £18.75 million upon the achievement of specific development and regulatory approval events for development of a PARG inhibitor in oncologic diseases. This includes an aggregate of up to £1.5 million and up to £2.25 million for the achievement of certain Phase 2 and Phase 3 development milestones, respectively, in each case as relating to first (e.g., a breast cancer) and second (e.g., ovarian cancer) tumor histologies.
We pay all expenses associated with prosecution and maintenance and each party bears its own costs for enforcement. If we abandon the patents covering inventions developed under the agreement as project intellectual property, Cancer Research UK will thereafter be responsible for prosecuting and maintaining such patents. If we abandon such patents, Cancer Research UK and University of Manchester will be responsible for paying the expenses associated with the prosecution and maintenance of such patents.
Following our exercise of the option, if we sublicense certain intellectual property developed under the agreement or Cancer Research UK background patents specifically relating to PARG, we will also have an obligation to pay to Cancer Research UK low double digit percentage of sublicense revenue we receive, if any. If the agreement is terminated due to our material breach, then we are eligible to receive a percentage of sublicensing revenue that Cancer Research UK receives for licensing intellectual property.
In July 2022, we entered into the Amgen CTCSA to clinically evaluate IDE397 in combination with AMG 193 in patients having MTAP-null solid tumors, in a Phase 1/2 clinical trial. Under the mutually non-exclusive Amgen CTCSA, we will provide IDE397 drug supply to Amgen, who will be the sponsor of the Phase 1 clinical combination trial evaluating IDE397 and AMG 193. Each party will pay for fifty percent (50%) of the external third-party costs of the combination study. Each party will be responsible for its own internal costs and expenses in support of the combination study. We and Amgen will jointly oversee clinical development of the combination therapy through a Joint Oversight Committee responsible for coordinating all regulatory and other activities under the Amgen CTCSA. The parties will jointly own collaboration data and combination-related intellectual property, if any, arising from the combination clinical trial. We and Amgen each retain commercial rights to our respective compounds, including with respect to use as a monotherapy agent or combination agent.
In November 2023, we entered into the Gilead CSCSA with Gilead to clinically evaluate IDE397 in combination with Trodelvy (sacituzumab-govitecan-hziy), a Trop-2 directed ADC, in patients having MTAP-deletion UC, in a Phase 1 clinical trial. Under the mutually non-exclusive Gilead CSCSA, we will receive Trodelvy drug supply from Gilead and will sponsor the Phase 1 clinical combination trial evaluating ID397 and Trodelvy. Gilead will bear internal or external costs incurred in connection with its supply of Trodelvy. We will bear all internal and external costs and expenses associated with the conduct of the combination study. We and Gilead will jointly oversee clinical development of the combination therapy through a Joint Steering Committee responsible for coordinating all regulatory and other activities under the Gilead CSCSA. We and Gilead each retain commercial rights to our respective compounds, including with respect to use as a monotherapy agent or combination agent.
In March 2024, we entered into the Merck CTCSA with Merck (known as MSD outside of the US and Canada). We are planning to evaluate the combination of IDE161 and Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with MSI-high and MSS endometrial cancer. Pursuant to the Merck CTCSA, we are the sponsor of the combination study, and we will provide the IDE161 compound and pay for the costs of the combination study. Merck will provide KEYTRUDA at no cost to us. We will jointly own clinical data from the combination and all inventions relating to the combined use of IDE161 and KEYTRUDA. Each party retains commercial rights to its respective compounds, including with respect to use as a monotherapy or combination
45
agent. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
In July 2024, we entered into an option and license agreement with Biocytogen, pursuant to which Biocytogen granted us an option for an exclusive worldwide license for a potential first-in-class B7H3/PTK7 topoisomerase-I-inhibitor-payload BsADC program. Under the terms of the agreement, we will pay Biocytogen an upfront fee and, upon our potential exercise of the Option, an exercise fee totaling up to $6.5 million. We may exercise the Option within a specified time period after we obtain all data and results from certain non-GLP toxicology studies specified in the Agreement, which we will conduct at our own cost. Subject to our exercise of the Option, Biocytogen will be eligible to receive an option exercise fee, development and regulatory milestone payments and commercial milestone payments, as well as low to mid single-digit royalties on net sales. Total potential milestone payments equal an aggregate of $400.0 million, including development and regulatory milestone payments of up to $100.0 million.
Adequate additional funding may not be available to us on acceptable terms or at all.
See the section of this Quarterly Report on Form 10-Q titled “Part II, Item 1A. – Risk Factors” for additional risks associated with our substantial capital requirements.
Off-Balance Sheet Arrangements
We have not entered into any off-balance sheet arrangements as defined in the rules and regulations of the SEC.
Summary Statement of Cash Flows
The following table sets forth the primary sources and uses of cash, cash equivalents, and restricted cash for each of the periods presented below (in thousands):
|
|
Nine Months Ended September 30, |
|
||||
|
|
2024 |
|
2023 |
|
||
Net cash provided by (used in): |
|
|
|
|
|
||
Operating activities |
|
$ |
(125,929 |
) |
$ |
(91,476 |
) |
Investing activities |
|
|
(305,450 |
) |
|
(46,513 |
) |
Financing activities |
|
|
674,798 |
|
|
221,823 |
|
Net increase in cash, cash equivalents and restricted cash |
|
$ |
243,419 |
|
$ |
83,834 |
|
Cash Flows from Operating Activities
Net cash used in operating activities was $125.9 million for the nine months ended September 30, 2024. Cash used in operating activities was primarily due to the use of funds in our operations to develop our product candidates resulting in a net loss of $144.2 million, adjusted for net non-cash charges of $10.1 million and changes in net operating assets and liabilities of $8.1 million. Our non-cash charges consisted of $25.3 million in stock-based compensation, $1.8 million in depreciation and $1.4 million of the amortization of right of use assets, partially offset by $18.3 million accretion of discounts on marketable securities. The net change in our operating assets and liabilities consisted primarily due to cash inflows from $5.3 million in accounts payable and $8.5 million accrued and other liabilities due to CRO fees in support of research and manufacturing activities, partially offset by outflows of $4.4 million in prepaid and other assets and $1.3 million in lease liabilities.
Net cash used in operating activities was $91.5 million for the nine months ended September 30, 2023. Cash used in operating activities was primarily due to the use of funds in our operations to develop our product candidates resulting in a net loss of $79.0 million, adjusted for net non-cash charges of $9.0 million and changes in net operating assets and liabilities of $21.5 million. Our non-cash charges consisted of $13.7 million in stock-based compensation, $1.8 million in depreciation and $1.1 million amortization of right-of-use assets, partially offset by $7.7 million accretion of discount on marketable securities. The net change in our operating assets and liabilities consisted primarily of decreases of $12.3 million in contract liabilities due to revenue recognized under the GSK Collaboration Agreement, an increase of $6.5 million in accounts receivable, $1.4 million decrease in lease liabilities, and $1.3 million increase in prepaid and other current assets.
46
Cash Flows from Investing Activities
Net cash used in investing activities was $305.5 million for the nine months ended September 30, 2024, which consisted primarily of $854.3 million used to purchase marketable securities and $2.8 million used to purchase property and equipment, partially offset by $551.6 million provided by maturities of marketable securities.
Net cash used in investing activities was $46.5 million for the nine months ended September 30, 2023, which consisted of $374.4 million used to purchase marketable securities and $1.5 million used to purchase property and equipment, partially offset by $329.4 million provided by maturities of marketable securities.
Cash Flows from Financing Activities
Net cash provided by financing activities was $674.8 million for the nine months ended September 30, 2024, which consisted primarily of $379.9 million of net proceeds from at-the-market offerings, $274.7 million of proceeds from issuance of common stock upon public offering, $9.4 million of proceeds from issuance of pre-funded warrants, $10.0 million of proceeds from exercise of common stock options and $0.8 million of proceeds from ESPP purchase.
Net cash provided by financing activities was $221.8 million for the nine months ended September 30, 2023, which consisted primarily of $153.6 million of proceeds from issuance of common stock upon public offering, $35.1 million of proceeds from issuance of pre-funded warrants, $28.8 million of proceeds from ATM offering, and $3.7 million of net proceeds from exercise of common stock options and $0.6 million of proceeds from ESPP purchase.
Critical Accounting Policies
Our financial statements have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of these financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the financial statements and the reported revenue recognized and expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. We believe that the accounting policies discussed below are critical to understanding our historical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates.
For more detail on our critical accounting policies, refer to Note 2 in the unaudited interim condensed financial statements appearing elsewhere in this Quarterly Report on Form 10-Q, and the notes to the financial statements appearing elsewhere in our Annual Report on Form 10-K filed with the SEC on February 20, 2024. For the nine months ended September 30, 2024, there were no material changes to our critical accounting policies from those disclosed in our Annual Report on Form 10-K filed with the SEC on February 20, 2024.
47
Item 3. Quantitative and Qualitative Disclosures About Market Risk.
Interest Rate Sensitivity
The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates or exchange rates. As of September 30, 2024, we had cash, cash equivalents and marketable securities of $1.2 billion, consisting of bank deposits, interest-bearing money market funds, investments in U.S. government securities, commercial paper, and corporate bonds, for which the fair value would be affected by changes in the general level of U.S. interest rates. Even if the fair value of certain government securities, commercial paper, and corporate bonds is affected by changes in U.S. interest rates, the principal of such instruments will be due to us upon maturity.
The primary objective of our investment activities is to preserve capital to fund our operations. We also seek to maximize income from our investments without assuming significant risk. Because our investments are primarily short-term in duration and our holdings in U.S. government treasury bonds mature prior to our expected need for liquidity, we believe that our exposure to interest rate risk is not significant.
While we are seeing, and expect to continue to see, record inflation due to geopolitical and macroeconomic events, such as the ongoing Ukraine-Russia conflict and related sanctions, the Israel-Hamas conflict, and the banking sector volatility, we do not believe that inflation, or exchange rate fluctuations have had a significant impact on our results of operations for any periods presented herein.
Item 4. Controls and Procedures.
Limitations on Effectiveness of Controls and Procedures
In designing and evaluating our disclosure controls and procedures, management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design of disclosure controls and procedures must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the benefits of possible controls and procedures relative to their costs.
Evaluation of Disclosure Controls and Procedures
Our management, with the participation of our Principal Executive Officer and Principal Financial and Accounting Officer, evaluated, as of the end of the period covered by this Quarterly Report on Form 10-Q, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act. Based on that evaluation, our Principal Executive Officer and Principal Financial and Accounting Officer concluded that our disclosure controls and procedures were effective at the reasonable assurance level as of September 30, 2024.
Changes in Internal Control over Financial Reporting
There was no change in our internal control over financial reporting identified in connection with the evaluation required by Rule 13a-15(e) and 15d-15(e) of the Exchange Act that occurred during the period covered by this Quarterly Report on Form 10-Q that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.
48
PART II—OTHER INFORMATION
Item 1. Legal Proceedings.
From time to time, we may become involved in litigation or other legal proceedings. We are not currently a party to any litigation or legal proceedings that, in the opinion of our management, are likely to have a material adverse effect on our business. Regardless of the outcome, litigation can have an adverse impact on our business, financial condition, results of operations and prospects because of defense and settlement costs, diversion of management resources and other factors.
Item 1A. Risk Factors.
In addition to other information contained elsewhere in this Quarterly Report on Form 10-Q, you should carefully consider the risk factors discussed in Part I, Item 1A. Risk Factors in our Annual Report on Form 10-K filed with the SEC on February 20, 2024, or the Annual Report, which could materially affect our business, financial condition, or future results. As of the date of this Quarterly Report on Form 10-Q, there have been no material changes to the risk factors disclosed in our Annual Report.
49
Item 2. Unregistered Sales of Equity Securities and Use of Proceeds.
Unregistered Sales of Equity Securities
None.
Use of Proceeds from the Sale of Registered Securities
Not applicable.
Issuer Purchases of Equity Securities
None.
Item 3. Defaults Upon Senior Securities.
Not applicable.
Item 4. Mine Safety Disclosures.
Not applicable.
Item 5. Other information.
Trading Plans
During the three months ended September 30, 2024, our Section 16 officers and directors
Name and Title |
|
|
Trading Arrangement |
|
|
|
Rule 10b5-1* |
Non-Rule 10b5‑1** |
|||||
X |
|
|||||
Head of Finance and Investor Relations |
X |
|
||||
* Intended to satisfy the affirmative defense of Rule 10b5-1(c) ** |
||||||
50
Exhibit Index
Item 6. Exhibits.
Exhibit Number |
|
Exhibit Description |
|
Incorporated by Reference |
|
Filed Herewith |
||||
|
|
Form |
|
Date |
|
Number |
|
|||
|
|
|
|
|
|
|
|
|
|
|
3.1 |
|
|
8-K |
|
5/28/2019 |
|
3.1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
3.2 |
|
|
8-K |
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5/28/2019 |
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3.2 |
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4.1 |
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4.2 |
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S-1/A |
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5/13/2019 |
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4.2 |
|
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4.3 |
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|
10-K |
|
2/20/2024 |
|
4.3 |
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|
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4.4 |
|
|
8-K |
|
4/27/2023 |
|
4.1 |
|
|
|
|
|
|
|
|
|
|
|
|
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|
4.5 |
|
|
8-K |
|
10/27/2023 |
|
4.1 |
|
|
|
|
|
|
|
|
|
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|
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|
4.6 |
|
|
8-K |
|
7/11/2024 |
|
4.1 |
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10.1† |
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X |
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10.2† |
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|
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X |
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31.1 |
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X |
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31.2 |
|
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X |
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32.1* |
|
|
|
|
|
|
|
|
X |
|
|
|
|
|
|
|
|
|
|
|
|
101.INS |
|
Inline XBRL Instance Document – the instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document. |
|
|
|
|
|
|
|
X |
|
|
|
|
|
|
|
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|
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101.SCH |
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Inline XBRL Taxonomy Extension Schema with Embedded Linkbase Documents. |
|
|
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|
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|
X |
|
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|
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104 |
|
Cover Page Interactive Data File (embedded with the Inline XBRL document). |
|
|
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|
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|
X |
51
† Certain information in this exhibit has been excluded pursuant to Regulation S-K, Item 601(b)(10).
* The certification attached as Exhibit 32.1 that accompanies this Quarterly Report on Form 10-Q is not deemed filed with the SEC and is not to be incorporated by reference into any filing of IDEAYA Biosciences, Inc. under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, whether made before or after the date of this Form 10-Q, irrespective of any general incorporation language contained in such filing.
52
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereto duly authorized.
|
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IDEAYA Biosciences, Inc. |
||
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Date: November 4, 2024 |
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By: |
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/s/ Yujiro Hata |
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Yujiro Hata |
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President and Chief Executive Officer |
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(Principal Executive Officer) |
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Date: November 4, 2024 |
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By: |
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/s/ Andres Ruiz Briseno |
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Andres Ruiz Briseno |
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Senior Vice President, Head of Finance and Investor Relations |
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(Principal Financial and Accounting Officer) |
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53