On February 3, 2022 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported the publication of a peer-reviewed article titled, "A Small Molecule–Drug Conjugate (SMDC) Consisting of a Modified Camptothecin Payload Linked to an αVß3 Binder for the Treatment of Multiple Cancer Types" in the special issue "The Role of Tumor Microenvironment in Solid Tumors: The New Frontier of Cancer Research" of the journal Cancers (Press release, Vincerx Pharma, FEB 3, 2022, View Source [SID1234607677]). The preclinical data in the paper highlight the potential of VIP236, a small molecule-drug conjugate (SMDC), to directly target cancer cells, while reducing the harmful effects of chemotherapy to normal tissue.

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"These preclinical data provide compelling proof-of-concept that our novel SMDC, VIP236, can direct a potent cancer chemotherapy drug to tumors while sparing healthy tissues," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. "We have a diverse, modular platform of linkers and payloads that can be conjugated with typical antibodies or small molecules, creating the potential for novel drugs with greater efficacy and lower toxicities than current antibody-drug conjugates; VIP236 is an example of the strength of this platform."

VIP236 tumor homing is guided by an αVß3 integrin ligand, which targets mechanisms that drive aggressive and invasive cancers. The published results provide preclinical validation of this targeting strategy and demonstrate how this approach can deliver 40 times more drug to the cancer than the surrounding tissues or normal organs. VIP236 is further activated by another component prevalent in the tumor microenvironment of invasive cancers, neutrophil elastase, which cleaves the linker, releasing a potent payload directly in the tumor microenvironment. The payload is a differentiated camptothecin (CPT) optimized to be more cell permeable and to overcome drug resistance observed with traditional CPTs.

Dr. Hamdy continued, "Our promising in vivo mouse data across various tumor types highlight the potential of our rationally designed SMDC to transform the treatment paradigm for advanced solid tumors. We look forward to advancing VIP236 into the clinic in the second half of 2022."

Key Article Highlights Include:

The αVß3 integrin targeting strategy in VIP236 increases tumor homing by 42-fold as measured by a fluorescent dye conjugated to the integrin targeting moiety and demonstrated in a human renal cell carcinoma (786-O) xenografted mouse model.
The cytotoxic payload of VIP236, VIP126, is an optimized CPT which shows improvement in permeability, efflux ratio and cytotoxicity in drug transporter overexpressing cancer cells compared with SN38, a clinically validated CPT. Unlike SN38, VIP126 is a very poor substrate for P-gp- or BCRP-mediated efflux transport, which translated into greater efficacy.
VIP236 in vitro cytotoxic activity against tumor cell lines is neutrophil elastase (NE) dependent.
Neutrophil elastase, prevalent in the tumor microenvironment, cleaves the linker, to release the anticancer payload within the tumor.
VIP236 results in a ten-fold higher tumor-to-plasma ratio of the payload, VIP126, when compared to direct administration of VIP126 in vivo, highlighting a potential therapeutic advantage of the conjugate delivery system.
Compared with commonly used chemotherapeutics, VIP236 shows very effective tumor targeting, better tumor regression, and better tolerability in mouse models of triple negative breast cancer, small cell lung cancer and colorectal cancer.