On April 10, 2021 Vincerx Pharma, Inc. (Nasdaq: VINC) is a biopharmaceutical company reported that aspiring to address the unmet medical needs of cancer patients through paradigm-shifting therapeutics (Press release, Vincerx Pharma, APR 10, 2021, View Source [SID1234577836]). Today, Vincerx presented preclinical data characterizing VIP236, a novel small molecule drug conjugate (SMDC) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 . The SMDC is comprised of an αvβ3 integrin antagonist linked to a cytotoxic camptothecin (CPT) derivative, designed to selectively release its payload via neutrophil elastase in the tumor microenvironment (TME).
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"These preclinical data demonstrate that VIP236 has enhanced tumor specificity via tumor specific binding through αvβ3 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 – αvβ3 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 αvβ3 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 αvβ3 integrin which is overexpressed by invasive cancer and stromal cells in the TME such as endothelial cells undergoing neovascularization. Efficient tumor homing with the αvβ3 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.