Vincerx Pharma Announces Compelling Clinical Efficacy of Enitociclib in Combination with Venetoclax and Prednisone in Lymphoma

Investigators from the National Institutes of Health (NIH) report 2 partial responses (PR) in 3 peripheral T-cell lymphoma (PTCL) patients and 1 PR in 2 double-hit diffuse large b-cell lymphoma (DH-DLBCL) patients in ongoing dose-escalation trial of enitociclib in combination with venetoclax and prednisone

Vincerx remains on target to report early clinical data from lead VersAptx™ platform compounds, VIP236 (early 2024) and VIP943 (mid 2024)

PALO ALTO, Calif., Jan. 07, 2024 (GLOBE NEWSWIRE) -- Vincerx Pharma, Inc. (NASDAQ:VINC) ("Vincerx"), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, today announced promising clinical results from a Phase 1 NIH-sponsored study of enitociclib in combination with venetoclax and prednisone for the treatment of relapsed/refractory lymphoma.

"Enitociclib continues to differentiate itself in the CDK9 inhibitor field," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx.  "Enitociclib is well tolerated, making it ‘the partner of choice' for novel combinations. We are pleased to see the high response rate and tolerability of enitociclib in combination with venetoclax and prednisone in patients with hard-to-treat types of non-Hodgkin's lymphoma such as peripheral T-cell lymphoma (PTCL) and double-hit diffuse large B-cell lymphoma (DH-DLBCL).  Previous reports of venetoclax monotherapy in PTCL show low response rates; thus, we believe we are seeing compelling evidence for synergism between enitociclib and venetoclax in this patient population."  

Ian Flinn, M.D., Ph.D., Vincerx Scientific Advisory Board member and Chief Scientific Officer of One Oncology, commented, "Outcomes for patients with PTCL are extremely poor, with median progression-free survival and overall survival of 3.1 and 5.5 months, respectively. Currently, clinical trials are considered the best standard of care for patients with relapsed/refractory PTCL, underscoring the substantial unmet medical need in this population."

Dr. Hamdy continued, "In addition to the exciting results with enitociclib, VIP236 and VIP943, the lead drugs from our cutting-edge VersAptx platform, are rapidly progressing through dose-escalation studies. To date, 15 patients with relapsed/refractory advanced or metastatic solid tumors have been treated with VIP236, and we are observing a promising safety profile and preliminary evidence of clinical activity with once every 3-week dosing. Enrollment in the second cohort of the VIP943 trial is nearly complete. Preliminary pharmacokinetic results from the first cohort of our VIP943 antibody drug conjugate (ADC) trial show very little free payload in circulation, consistent with the favorable safety profile observed to date. ADCs and bi-specifics have been limited by numerous safety and efficacy challenges, so the profile we are observing in these initial dose levels is exciting."

About Enitociclib

Enitociclib is a highly selective CDK9 inhibitor that prevents activation of RNA polymerase II, resulting in reduction of known oncogenes MYC and MCL1 (Frigault 2023). It is currently in a dose-escalation Phase 1 trial (NTC05371054), in collaboration with the National Institutes of Health, evaluating the combination of enitociclib, venetoclax, and prednisone in DLBCL and PTCL. Two patients out of three (67%) with PTCL have had a best response of PR. A subject with angioimmunoblastic T-cell lymphoma treated in the first dose level of enitociclib had a PR with a 91% reduction in tumor burden and remains on study for follow-up. A second subject with PTCL who received the second dose level of enitociclib remains on study with a PR with an 86% reduction in pulmonary lesions and resolution of skin lesions. In addition, on the second dose cohort of enitociclib, one patient with DH-DLBCL has achieved a PR after only one cycle of treatment—highlighting the faster response rate with the combination, compared with enitociclib monotherapy. Investigators are pleased with the safety profile of this novel combination (no DLTs have been observed so far) and continue with enrollment. Early-stage clinical studies (n=95) in patients with hematologic malignancies and solid tumors provided enitociclib monotherapy proof-of-concept. Additional combination studies will be determined based on financing/partnering support.

About VIP236

VIP236, the first-in-class small molecule drug conjugate (SMDC) from our VersAptx Platform, consists of an αvβ3 integrin binder, a neutrophil elastase linker cleaved in the tumor microenvironment, and a camptothecin payload optimized for high permeability and low efflux. VIP236 was designed to deliver its payload to advanced/metastatic tumors that express αvβ3. Preclinical data show enhanced efficacy, independent of HER2 status, in patient-derived and cell line-derived gastric cancer models compared with ENHERTU^®, an approved ADC. VIP236 is being evaluated in a Phase 1 dose-escalation trial treating patients with advanced or metastatic solid tumors (NTC05371054). As VIP236 is a first-in-class drug, the Phase 1 trial is evaluating various dosing schedules. To date, 15 patients with advanced or metastatic disease that has relapsed or is refractory to standard of care have received VIP236; the early safety profile of once every three-week dosing is promising. This schedule also shows early signs of clinical activity. We expect to report preliminary clinical trial data in early 2024.

About VIP943

VIP943, the first ADC from our VersAptx platform, consists of an anti-CD123 antibody, a unique linker cleaved intracellularly by legumain, and a novel kinesin spindle protein inhibitor (KSPi) payload enhanced with our CellTrapper^® technology. Our proprietary effector chemistry (linker + payload) was designed to reduce non-specific release of the payload and ensure payload accumulation in cancer cells versus healthy cells. The increased therapeutic index has the potential to address challenges associated with many ADCs by improving efficacy and reducing severe toxicities. VIP943 is in a Phase 1 dose-escalation trial evaluating patients with relapsed/refractory acute myeloid leukemia, myelodysplastic syndrome, and B-cell acute lymphoblastic leukemia who have exhausted standard therapeutic options (NCT06034275). Preliminary pharmacokinetic data from the first cohort shows low levels of unconjugated payload (VIP716) in the circulation as predicted from preclinical experiments. Reduced nonspecific release of payload is one of many features engineered into VIP943 to increase the therapeutic index compared with existing technologies. We expect to expand into additional CD123-positive indications, including TP53 mutated AML, both as monotherapy and in combination, as safety and efficacy data are generated. Preliminary Phase 1 data are expected in mid-2024.

About VersAptx Platform

VersAptx is our versatile and adaptable, next-generation bioconjugation platform. The modular nature of this innovative platform allows us to combine different targeting, linker, and payload technologies to develop bespoke bioconjugates to address different cancer biologies. With this platform (i) antibodies and small molecules can be used to target different tumor antigens, (ii) linkers can be designed to reduce non-specific release of the payload, cleave intracellularly or extracellularly, and conjugate to single or multiple payloads, and (iii) payloads can be designed with reduced permeability using our CellTrapper^® technology to ensure accumulation in cancer cells or to be permeable for release in the tumor microenvironment. The VersAptx platform allows us to optimize these technologies to a specific target and develop bioconjugates designed to address the safety and efficacy challenges of many ADCs and the needs of cancer patients.

About Vincerx Pharma, Inc.

Vincerx Pharma, Inc. is a clinical-stage biopharmaceutical company committed to developing differentiated and novel therapies to address the unmet medical needs of patients with cancer. Vincerx has assembled a seasoned management team with a proven track record of successful oncology drug development, approvals, and value creation. Vincerx's diverse pipeline consists of the next-generation antibody-drug conjugate, VIP943, in Phase 1; small molecule-drug conjugate, VIP236, in Phase 1; preclinical antibody-drug conjugate, VIP924; CDK9 inhibitor, enitociclib, in an NIH-sponsored Phase 1; and VersAptx, its versatile and adaptable, next-generation bioconjugation platform.

Vincerx is based in Palo Alto, California, and has a research facility in Monheim, Germany. For more information, please visit www.vincerx.com.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of 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, that are intended to be covered by the "safe harbor" created by those sections. Forward-looking statements, which are based on certain assumptions and describe future plans, strategies, expectations and events, can generally be identified by the use of forward-looking terms such as "believe," "expect," "may," "will," "should," "would," "could," "suggest," "seek," "intend," "plan," "goal," "potential," "on-target," "on track," "project," "estimate," "anticipate," or other comparable terms. All statements other than statements of historical facts included in this press release are forward-looking statements. Forward-looking statements include, but are not limited to: Vincerx's business model, pipeline, strategy, timeline, product candidates and attributes, and preclinical and clinical development, timing, and results. Forward-looking statements are neither historical facts nor assurances of future performance or events. Instead, they are based only on current beliefs, expectations, and assumptions regarding future business developments, future plans and strategies, projections, anticipated events and trends, the economy, and other future conditions. Forward-looking statements are subject to inherent uncertainties, risks, and changes in circumstances that are difficult to predict and many of which are outside of Vincerx's control.

Actual results, conditions, and events may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause actual results, conditions, and events to differ materially from those indicated in the forward-looking statements include, but are not limited to: general economic, financial, legal, political, and business conditions; risks associated with preclinical or clinical development and trials, including those conducted prior to Vincerx's in-licensing; failure to realize the benefits of Vincerx's license agreement with Bayer; risks related to the rollout of Vincerx's business and the timing of expected business and product development milestones; changes in the assumptions underlying Vincerx's expectations regarding its future business or business model; Vincerx's ability to successfully develop and commercialize product candidates; Vincerx's capital requirements and availability and uses of capital; and the risks and uncertainties set forth in Form 10-Q for the quarter ended September 30, 2023 and other reports filed with the Securities and Exchange Commission by Vincerx. Forward-looking statements speak only as of the date hereof, and Vincerx disclaims any obligation to update any forward-looking statements.

Vincerx, the Vincerx logo, CellTrapper, and VersAptx are our trademarks. This press release also contains trademarks and trade names that are the property of their respective owners.

Contacts

Gabriela Jairala

Vincerx Pharma, Inc.

[email protected]

Joyce Lonergan

LifeSci Advisors, LLC

781-528-5276

[email protected]