Vincerx Pharma Presents Preclinical Data on VIP236, its Lead Small Molecule Drug Conjugate, at the American Association for Cancer Research Annual Meeting 2021

Rhea-AI Summary

Vincerx Pharma presented promising preclinical data for VIP236, a novel small molecule drug conjugate, at the AACR Annual Meeting 2021. This drug targets the αvβ3 integrin linked to a cytotoxic camptothecin derivative, showcasing enhanced tumor targeting and significant anti-tumor activity across various xenograft models. Specifically, complete tumor regression was observed in 100% of cases in a triple-negative breast cancer model. With first-in-human studies expected in the first half of 2022, VIP236 may address critical needs in aggressive cancer treatment.

Positive

• VIP236 demonstrates enhanced tumor targeting and significant antitumor activity.
• Complete tumor responses observed in 100% of mice in the triple-negative breast cancer model.
• Favorable tolerability with less than 5% mean body weight loss in treated mice.
• Expected to advance to first-in-human studies in H1 2022.

Negative

• None.

VIP236 shows enhanced tumor targeting with robust antitumor activity across multiple xenograft models

First-in-human studies on track for 1H 2022

PALO ALTO, Calif., April 10, 2021 (GLOBE NEWSWIRE) -- Vincerx Pharma, Inc. (Nasdaq: VINC) is a biopharmaceutical company aspiring to address the unmet medical needs of cancer patients through paradigm-shifting therapeutics. Today, Vincerx presented preclinical data characterizing VIP236, a novel small molecule drug conjugate (SMDC) at the American Association for Cancer Research (AACR) Annual Meeting 2021. The SMDC is comprised of an α_vβ₃ integrin antagonist linked to a cytotoxic camptothecin (CPT) derivative, designed to selectively release its payload via neutrophil elastase in the tumor microenvironment (TME).

“These preclinical data demonstrate that VIP236 has enhanced tumor specificity via tumor specific binding through α_vβ₃ integrin and targeted drug release in the TME with our neutrophil elastase cleavable linker,” said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx. “The payload is a modified camptothecin derivative which has been optimized for high cell permeability and a low efflux ratio. When VIP236 is administered to tumor bearing mice, an over 10-fold higher tumor-to-plasma ratio of the CPT payload was observed, when compared to delivery of the payload alone. Importantly, these properties translate into potent antitumor activity across multiple xenograft models, with tumor regression in all models tested and complete tumor responses in 100% across all dose levels of mice in a triple negative breast cancer model. These compelling data, combined with a favorable tolerability profile, suggest that VIP236 has the potential to provide potent, highly targeted antitumor activity to address the needs of patients with advanced and aggressive cancers. We look forward to continued progress as we advance VIP236 towards the clinic, with first-in-human studies expected in the first half of 2022.”

Key Presentation Highlights:

Poster presentation, titled, “A novel small molecule drug conjugate - α_vβ₃ integrin antagonist linked to a cytotoxic camptothecin derivative – for the treatment of multiple cancer types” presented by Hans-Georg Lerchen, Ph.D., Chief Scientific Officer of Vincerx.

• VIP236 is a novel SMDC targeted by an α_vβ₃ integrin antagonist with a neutrophil elastase cleavable linker linked to a modified CPT payload derived from SN38, a well-known cytotoxic drug and active metabolite of irinotecan.
• Efficient anti-tumor targeting and greater cytotoxicity is achieved by multiple mechanisms associated with aggressive tumor cells and its microenvironment.
  • VIP236 targets α_vβ₃ integrin which is overexpressed by invasive cancer and stromal cells in the TME such as endothelial cells undergoing neovascularization. Efficient tumor homing with the α_vβ₃ integrin antagonist is demonstrated by the imaging studies.
  • Neutrophil elastase (NE) is overexpressed in the invasive TME associated with advanced cancers. The abundance of NE in the TME promotes linker cleavage, release of the active modified CPT payload and enhances VIP236 cytotoxicity.
  • Drug resistant cancer cells often have greater drug efflux capabilities. The CPT payload is modified to improve cellular permeability and lower cell efflux properties resulting in better cytotoxicity in cancer cells overexpressing drug efflux pumps when compared to SN38.
  • The combination of these properties results in a 10.8-fold higher tumor-to-plasma ratio of the targeted and modified CPT payload compared to administration of the payload alone.
• In vivo, VIP236 demonstrates higher antitumor efficacy in comparison to reference chemotherapy drugs across multiple mouse xenograft models.
  • Complete tumor responses were observed in 100% of mice across all dose levels in the MX-1 triple negative breast cancer model.
  • Partial responses were observed in 100% of mice in both the NCI-H69 small cell lung cancer and SW480 colorectal cancer mouse models at a VIP236 dose of 40mg/kg.
  • Across mouse models, VIP236 showed good tolerability as evidenced by less than 5% mean body weight loss.

The poster can be accessed on the presentations section of the Vincerx website.

About Vincerx Pharma, Inc.
Vincerx Pharma, Inc. (Vincerx) is a recently formed clinical-stage life sciences company focused on leveraging its extensive development and oncology expertise to advance new therapies intended to address unmet medical needs for the treatment of cancer. Vincerx’s executive team has assembled a management team of biopharmaceutical experts with extensive experience in building and operating organizations that develop and deliver innovative medicines to patients. Vincerx’s current pipeline is derived from an exclusive license agreement with Bayer and includes a clinical-stage and follow-on small molecule drug program and a preclinical stage bioconjugation/next-generation antibody-drug conjugate platform. For more information, please visit www.vincerx.com.

Cautionary 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,” “seek,” “intend,” “plan,” “goal,” “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, preclinical and clinical data and results and product candidates. 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 our 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 and changes in domestic and foreign markets; the potential effects of the COVID-19 pandemic; risks associated with preclinical or clinical development conducted prior to Vincerx’s in-licensing; failure to realize the anticipated benefits of the business combination with LifeSci Acquisition Corp.; 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 milestones; changes in the assumptions underlying Vincerx’s expectations regarding its future business or business model; Vincerx’s ability to develop and commercialize product candidates; the availability and uses of capital; the effects of competition on Vincerx’s future business; and the risks and uncertainties set forth in Forms 10-K, 10-Q and 8-K filed with or furnished to the SEC from time to time by Vincerx. Forward -looking statements speak only as of the date hereof, and Vincerx disclaims any obligation to update any forward-looking statements.

Contacts
Bruce Mackle
LifeSci Advisors, LLC
646-889-1200
bmackle@lifesciadvisors.com

FAQ

What is VIP236 and how does it work?

VIP236 is a novel small molecule drug conjugate targeting the αvβ3 integrin, designed to release a cytotoxic camptothecin derivative specifically in the tumor microenvironment.

What were the results of the preclinical studies for VIP236?

The studies showed robust antitumor activity, with complete responses in 100% of mice in triple-negative breast cancer models and significant efficacy in other cancer types.

When are the first-in-human studies for VIP236 expected to begin?

The first-in-human studies for VIP236 are expected to start in the first half of 2022.

What is the significance of the αvβ3 integrin in the context of VIP236?

The αvβ3 integrin is overexpressed in aggressive cancer cells, making it a critical target for VIP236 to enhance tumor specificity and efficacy.

What implications do the results of VIP236 have for cancer treatment?

The promising results may lead to a new targeted therapy option for patients with advanced and aggressive cancers, addressing unmet medical needs.