Vincerx Pharma Presents Preclinical Data on VIP943 in Models of Acute Myeloid Leukemia at the 2022 American Society of Hematology 64th Annual Meeting.

  • Vincerx’s proprietary carrier and linker technology and VIP943, a novel anti-CD123 antibody drug conjugate (ADC), demonstrated superiority with significantly improved safety in non-human primates (NHPs) compared to Mylotarg™ (gemtuzumab ozogamicin).
  • VIP943 demonstrated monotherapy activity in ex vivo AML models and in vivo activity with significant tumor regression in combination with venetoclax and azacitidine in mouse model of acute myeloid leukemia (AML).
  • Studies enabling the VIP943 IND continue to progress, with an IND submission expected in mid-2023

PALO ALTO, Calif., Dec. 11, 2022 (GLOBE NEWSWIRE) — Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company striving to address the unmet medical needs of cancer patients through paradigm-shifting therapies, today announced a poster presentation of preclinical data on Vincerx’s proprietary cargo and linker technology and VIP943, the company’s internalized ADC targeting CD123 , at 64th American Society of Hematology (ASH) 2022 Annual Meeting.

VIP943 is a new ADC, which binds to the alpha chain of the IL3-receptor (CD123). VIP943 combines a unique payload class of kinesin spindle protein inhibitor (KSPi) with a proprietary linker that is cleavable from legumain. Vincerx’s CellTrapper™ modification of KSPi prevents diffusion outside the cell, allowing intracellular accumulation. The impermeability of the payload prevents off-target toxicity, leading to favorable efficacy and safety profiles.

“I am truly excited about the preclinical results for VIP943 and our proprietary utility and linker technology presented at ASH,” said Ahmed Hamdy, MD, Chief Executive Officer of Vincerx. “We demonstrated for the first time a significant improvement in safety over an approved ADC, demonstrating in non-human primates the benefit of our KSPi payload and CellTrapper technology specifically designed to address some of the well-known challenges of ADCs on the market. Results from an in vivo AML mouse model also demonstrated improved efficacy and survival for VIP943 in combination with venetoclax and azacitidine. This triple combination resulted in significant tumor regression as demonstrated by five complete responses and significantly prolonged survival time without increased toxicity,” added Dr. Hamdy.

dr. Anthony Tolcher, MD, CEO, founder and director of clinical research at NEXT Oncology, added, “This ADC is innovative and exciting. The target is well known, and the new payload that targets myeloid cells suggests that this could be a valuable tool for patients with AML.”

“The current standard of care for patients with AML is combination therapy with venetoclax and azacitidine, but most patients eventually relapse with progressive disease. The efficacy and safety data for VIP943 seen in our studies suggest that it may be a promising option for the treatment of AML as monotherapy in relapsed/refractory elderly, unfit and high-risk patients, as well as in combination with venetoclax and azacitidine. Our results also provide compelling evidence that VIP943 represents a significant advance and potential paradigm shift in ADC technology. We look forward to continuing to advance the IND-enabling studies for VIP943 and expect to submit our IND in mid-2023,” concluded Dr. Hamdy.

Key highlights of the presentation:

A poster presentation titled “VIP943 is a novel anti-CD123 antibody drug conjugate with in vitro and in vivo efficacy in acute myeloid leukemia (AML) models” was presented by Beatrix Stelte-Ludwig, Ph.D., Vincerx Pharma GmbH, Monheim, Germany, includes:

  • Bone marrow samples obtained from patients with AML were used to evaluate VIP943 monotherapy at various concentrations (0.1 pM to 1 µM) in a depletion assay (without the addition of cytokines) and a proliferation assay. A combination treatment of VIP943 (using 8 different doses) and venetoclax (one fixed dose of 16.5 nM) was evaluated. All patient samples were analyzed by flow cytometry and were positive for CD123 cell surface expression. In the depletion assay, only samples that showed spontaneous proliferation were sensitive to VIP943 treatment consistent with the mode of action of the KSPi payload.
  • In a patient-derived AML xenograft model, the triple combination of VIP943 with venetoclax and azacitidine increased the number of complete responses (56% vs. 22%) and overall survival (>107 vs. 83 days) compared with venetoclax and azacitidine.
  • VIP943 did not induce cytokine release in the human cytokine release assay compared to positive controls. A single dose of VIP943 in an immunophenotyping study in NHP resulted in a reversible reduction of CD123+ basophils.
  • In a NHP safety study, a newly generated ADC using biosimilar gemtuzumab as a target antibody conjugated to our effector chemistry consisting of a proprietary linker and payload (Gem-KSPi ADC) and VIP943 (anti-CD123-KSPi ADC) was directly compared with Mylotargus.

    • CD33+/CD123+ basophils showed the expected decrease during treatment; however, the VIP943 and Gem-KSPi ADC groups showed complete recovery during the observation period, while Mylotarg showed increased severity. Over time, a significant adverse effect was observed with a single dose of Mylotarg on platelets, leukocyte count, reticulocyte count, hemoglobin, hematocrit and lymphocytes. In contrast, a single dose of Gem-KSPi ADC and VIP943 showed no effects on hematological parameters other than the above-mentioned transient decrease in CD123+ basophils.
    • Serum chemistry assessment showed an increase in liver function enzymes, bilirubin and urea nitrogen in the Mylotarg group. A female monkey treated with Mylotarga died before the end of the observation period, and the male had to be euthanized. All monkeys from the Gem-KSPi ADC and VIP943 groups were healthy and returned to the colony without significant changes in serum chemistry.

  • Overall, these results demonstrate a significant advance in ADC technology with the development of VIP943. Further IND enabling studies are underway, and the Company expects to submit an IND in mid-2023.

A copy of this presentation can now be accessed on the investor section of the Company’s website at www.vincerx.com. Vincerx’s other presentations related to enitociclib will be available on the company’s website on Monday, December 12 at 9:00 a.m. CST.

ABOUT VINCERX PHARMA, INC.
Vincerx Pharma, Inc. (Vincerx) is a clinical-stage life sciences company focused on leveraging its extensive development and oncology expertise to advance novel therapies designed to address unmet medical needs for the treatment of cancer. Vincerx has assembled a management team of biopharmaceutical experts with extensive experience in building and managing organizations that develop and deliver innovative medicines to patients. Vincerx’s current pipeline stems from an exclusive license agreement with Bayer and includes a clinical stage and continuation small molecule drug program and a preclinical modular bioconjugation platform, which includes next-generation antibody-drug conjugates and innovative small molecule drug conjugates. For more information visit www.vincerx.com.

PRECAUTIONARY 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. supplements, which are intended to be covered by the “safe harbor” created by those parts. 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 expressions such as “believe”, “expect”, “may”, “will” ,” “should,” “would,” “could,” “suggest,” “seek,” “intend,” “plan,” “goal,” “potential,” “on target,” “on the way, ” “ project”, “estimate”, “anticipate” or other comparable terms. All statements other than statements of historical fact included in this press release are forward-looking statements. Forward-looking statements include, but are not limited to: Vincerx’s business model, planning, strategy, timeline, product candidates and attributes, and preclinical and clinical development and results. Forward-looking statements are neither historical facts nor guarantees of future performance or events. Rather, they are based only on current beliefs, expectations and assumptions regarding future business developments, future plans and strategies, projections, expected events and trends, the economy and other future conditions. Forward-looking statements are subject to uncertainties, risks and changes in circumstances that are difficult to predict and many of which are beyond our control.

Actual results, conditions and events may differ materially from those expressed in forward-looking statements. Therefore, you should not place undue reliance on any of these forward-looking statements. Important factors that could cause actual results, conditions and events to differ materially from those stated in 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 possible effects of health epidemics and pandemics, including COVID-19; risks associated with preclinical or clinical development and trials, including those conducted prior to the licensing of Vincerx; failure to take advantage of Vincerx’s license agreement with Bayer; the risks associated with the initiation of the Vincerx business and the timing of expected business milestones; changes in the assumptions underlying Vincerx’s expectations regarding its future operations or business model; Vincerx’s ability to develop and commercialize product candidates; Vincerx’s capital requirements and the availability and use of capital; the effects of competition on Vincerx’s future business; the impact of Vincerx’s workforce and cost reductions; and the risks and uncertainties set forth in Forms 10-K, 10-Q and 8-K recently filed or furnished with the SEC 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
[email protected]



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