Immuneering Announces Positive Initial Phase 2a Data Including Complete and Partial Responses with IMM-1-104 in Combination with Chemotherapy in First-Line Pancreatic Cancer Patients

- In Phase 2a arm investigating IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel, complete or partial responses have been observed in the first two patients (2/5) to date, for an initial response rate of 40% and an initial disease control rate of 80%, with all five patients continuing on treatment -

- Initial data are at 240 mg QD (safety lead-in dose) of IMM-1-104; additional patients have now been dosed at 320 mg QD in this arm; IMM-1-104 has been well-tolerated to date in combination with gemcitabine/nab-paclitaxel -

- Initial data are consistent with preclinical data presented at AACR, which demonstrated that IMM-1-104 combined with chemotherapy induced deeper responses than either agent alone -

- Clear path forward expected for clinical development of IMM-1-104 in combination with gemcitabine/nab-paclitaxel for pancreatic cancer, assuming initial data is representative; FDA previously granted IMM-1-104 Fast Track designation for the treatment of first- and second-line pancreatic ductal adenocarcinoma -

- Enrollment progressing in all Phase 2a arms with further data expected by year end -

- Company to hold webcast today at 4.30 pm ET /1.30 pm PT -

CAMBRIDGE, Mass., Sept. 12, 2024 (GLOBE NEWSWIRE) -- Immuneering Corporation (NASDAQ:IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, today announced positive initial response data from the first five patients treated with IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel in first line pancreatic cancer as part of its ongoing Phase 2a clinical trial.

"We are delighted to share today's initial data on IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel. While the initial ORR of 40% and Disease Control Rate of 80% are very encouraging – and both more than would be expected for gemcitabine/nab-paclitaxel alone- we are still in the early stages of this trial, with more scans for all five of these initial patients and for additional patients planned to come. Nevertheless, it was encouraging to see a complete response in the very first pancreatic cancer patient treated with IMM-1-104 in this combination, with the patient now on treatment for over six months," said Ben Zeskind, Ph.D., Co-Founder and CEO of Immuneering. "Looking at the bigger picture, our Phase 2a trial aims to evaluate the efficacy of IMM-1-104 in multiple settings across various tumor types, to identify the highest priority opportunities for future development. If the early trends with IMM-1-104 in combination with modified gemcitabine/nab-paclitaxel continue, we will have an exciting direction for potential future development of IMM-1-104, which could greatly improve the prognosis for a drastically underserved patient population."

Initial Results from Phase 2a Arm Evaluating IMM-1-104 with Modified Gemcitabine/nab-Paclitaxel in First Line Pancreatic Cancer as of September 12, 2024

Patient

MAPK Mutation Variant

Dose (p.o.) Level for IMM-1-104

% Change in SLD 1st Scan

% Change in SLD 2nd Scan

% Change in SLD 3rd Scan

% Change in SLD 4th Scan

% Change in SLD 5th Scan

ORR/ RECIST

1

GNAS-T105Vfs*3 (*)

240mg QD

-100%

-100%

-100%

-100%

next scan

CR

2

KRAS-G12V*

240mg QD

-8%

-10%

-40%

next scan

uPR°

3

KRAS-G12V*

240mg QD

-4%

next scan

SD

4

Unk.#

240mg QD

+6%

next scan

SD

5

KRAS-G12R*

240mg QD

-9%

next scan

eqPD**

Initial Overall Response Rate (ORR):

40%

Initial Disease Control Rate (DCR):

80%

* Detected in plasma cfDNA or prior genomic test.

^# Unknown (Unk.); MAPK pathway variant not detected in plasma cfDNA or prior genomic test.

° Partial response result classified as "unconfirmed" pending subsequent scan.

**Equivocal (eq); Patient not dosed for over two weeks during hospitalization for a preexisting condition. Scans showed ascites and a pleural effusion categorized by radiology as equivocal new lesions per RECIST 1.1. The investigator determined these to be related to the recent placement of a hepatic stent, not disease progression, and stated that the patient is improving and remains on therapy.

Source: Immuneering Corporation

• To date, the first two patients in the Phase 2a arm evaluating IMM-1-104 with modified gemcitabine/nab-paclitaxel in first-line pancreatic cancer have recorded complete or partial responses for an initial response rate of 40% (2/5) and disease control rate of 80% (4/5), with the other three patients earlier in the course of treatment and all five continuing on treatment.
• Benchmarks for gemcitabine/nab-paclitaxel alone in first-line pancreatic cancer patients were established by the Phase 3 MPACT study, which included 1 Complete Response (CR) out of 431 patients, a 23% Overall Response Rate, and a 48% Disease Control Rate¹. Benchmarks for modified (m) Gemcitabine/nab-Paclitaxel include an 18.6% ORR².
• To date, the combination of IMM-1-104 plus modified gemcitabine/nab-paclitaxel was observed to be well tolerated, with an emerging safety profile in line with known data for both therapeutics respectively.
• Based on safety data to date, the trial's Data and Safety Monitoring Board (DSMB) has approved enrolling additional patients into this arm at 320mg QD p.o., the first of which have already been dosed and are awaiting first scans.

^[1] Von Hoff, et al. N Engl J Med. 2013;369:1691-1703, ^[2] Ahn DH, et al. Therapeutic Advances in Medical Oncology. 2017;9(2):75-82

"These exciting early clinical findings are consistent with the preclinical data we shared at AACR earlier this year, which pointed to synergies between IMM-1-104 and chemotherapeutics - driving deeper more durable responses than either can achieve alone," said Brett Hall, Ph.D., Chief Scientific Officer, Immuneering Corporation. "If the combination data for IMM-1-104 continues to be positive – and taking into account the excellent emerging safety profile for IMM-1-104 – one can imagine the drug's potential inclusion in various vertical drug combinations, immune-modifying combinations, and orthogonal combinations with therapeutics with non-overlapping mechanisms of action, which Immuneering may in the future develop both on its own and in partnership with third parties."

"There is a high unmet need in pancreatic cancer for novel therapies that meaningfully improve outcomes. With current therapies in pancreatic cancer, we rarely see complete responses, and as such any treatment that leads to one is exciting and deserves further investigation, particularly when observed in the setting of a well-tolerated agent such as IMM-1-104," said Tanios Bekaii-Saab, M.D., Leader of the Gastrointestinal Cancer Disease Group for the Mayo Clinic Cancer Center enterprise wide and Medical Oncology consultant in Mayo Clinic in Phoenix, Arizona.

In the Phase 2a portion of Immuneering's ongoing IMM-1-104 Phase 1/2a clinical trial, IMM-1-104 is being evaluated as both monotherapy and in combination with approved chemotherapeutic agents. The Phase 2a portion includes five arms, one of which focuses on patients with RAS mutant melanoma, another on patients with RAS mutant non-small cell lung cancer (NSCLC), and three arms focused on patients with pancreatic cancer. Immuneering previously announced that IMM-1-104 received fast track designation for the treatment of first- and second-line pancreatic cancer.

Near-Term Milestone Expectations

IMM-1-104

Initial data from at least one additional arm of the Phase 2a portion of the Company's Phase 1/2a trial is expected by year end.

IMM-6-415

Initial pharmacokinetic (PK), pharmacodynamic (PD) and safety data from the Phase 1 portion of the Company's Phase 1/2a trial is expected by year end.

Conference Call

Immuneering will host a conference call and live webcast at 4:30 p.m. ET / 1:30 p.m. PT on September 12, 2024, to discuss the results and provide a business update. Individuals interested in listening to the live conference call may do so by dialing (800) 715-9871 for U.S callers and (646) 307-1963 for other locations and reference conference ID 8890310, or from the webcast link in the "investors" section of the company's website at www.immuneering.com A webcast replay will be available in the investor relations section on the company's website for 90 days following the completion of the call.

About IMM-1-104

IMM-1-104 aims to achieve universal-RAS activity that selectively impacts cancer cells to a greater extent than healthy cells, through Deep Cyclic Inhibition of the MAPK pathway with once-daily dosing. IMM-1-104 is currently being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations (NCT05585320).

About Immuneering Corporation

Immuneering is a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients with an initial aim to develop a universal-RAS therapy. The Company aims to achieve universal activity through Deep Cyclic Inhibition of the MAPK pathway, impacting cancer cells while sparing healthy cells. Immuneering's lead product candidate, IMM-1-104, is an oral, once-daily Deep Cyclic Inhibitor currently in a Phase 1/2a trial in patients with advanced solid tumors harboring RAS mutations. IMM-6-415 is an oral, twice-daily Deep Cyclic Inhibitor currently in a Phase 1/2a trial in patients with advanced solid tumors harboring RAS or RAF mutations. The company's development pipeline also includes several early-stage programs. For more information, please visit www.immuneering.com.

Forward-Looking Statements

This press release contains forward-looking statements, including within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding: Immuneering's plans to develop, manufacture and commercialize its product candidates; the treatment potential of IMM-1-104, alone or in combination with other agents, including chemotherapy; the design, enrollment and conduct of the Phase 1/2a IMM-1-104 clinical trial; the translation of preclinical data into human clinical data; the future development path of IMM-1-104 in combination with gemcitabine/nab-paclitaxel in first-line pancreatic cancer patients; and the timing of additional results from the Phase 2a portion of the trial for IMM-1-104 and the Phase 1 portion of the trial for IMM-6-415.

These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but 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, including, but not limited to, the following: the risks inherent in oncology drug research and development, including target discovery, target validation, lead compound identification, and lead compound optimization; we have incurred significant losses, are not currently profitable and may never become profitable; our projected cash runway; our need for additional funding; our unproven approach to therapeutic intervention; our ability to address regulatory questions and the uncertainties relating to regulatory filings, reviews and approvals; the lengthy, expensive, and uncertain process of clinical drug development, including potential delays in or failure to obtain regulatory approvals; our reliance on third parties and collaborators to conduct our clinical trials, manufacture our product candidates, and develop and commercialize our product candidates, if approved; failure to compete successfully against other drug companies; protection of our proprietary technology and the confidentiality of our trade secrets; potential lawsuits for, or claims of, infringement of third-party intellectual property or challenges to the ownership of our intellectual property; our patents being found invalid or unenforceable; costs and resources of operating as a public company; and unfavorable or no analyst research or reports.

These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the three month period ended June 30, 2024, and our other reports filed with the U.S. Securities and Exchange Commission, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

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Investor Contact:

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