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

Rhea-AI Summary

Vincerx Pharma (Nasdaq: VINC) reported preclinical results for VIP943, its novel anti-CD123 antibody drug conjugate, at the 64th American Society of Hematology Annual Meeting. VIP943 showed significant safety improvements in non-human primates compared to Mylotarg. The drug demonstrated effective monotherapy activity in AML models and significant tumor regression when used with venetoclax and azacitidine in mouse models. The company is advancing IND-enabling studies with an IND filing anticipated by mid-2023, indicating potential benefits for AML patients.

Positive

• VIP943 demonstrated superior safety profile compared to Mylotarg in non-human primate studies.
• Significant tumor regression was observed with VIP943 in combination with venetoclax and azacitidine.
• VIP943 showed promising monotherapy activity in acute myeloid leukemia (AML) models.
• Anticipated IND filing for VIP943 by mid-2023, progressing the clinical development of the drug.

Negative

• None.

Vincerx’s proprietary payload and linker technology and VIP943, a novel anti-CD123 antibody drug conjugate (ADC), demonstrated superiority with significant improved safety in non-human primates (NHP) when compared with 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 an acute myeloid leukemia (AML) mouse model

VIP943 IND-enabling studies continue to advance, with IND filing expected mid-2023

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

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

“I am truly excited about the preclinical results for VIP943 and our proprietary payload and linker technology presented at ASH,” said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx. “For the first time, we showed 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. The in vivo AML mouse model results also showed 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, M.D., Chief Executive Officer, Founder and Director of Clinical Research at NEXT Oncology, added, “This ADC is innovative and exciting. The target is well understood and the novel payload that targets myeloid cells suggests this could be a valuable agent for patients with AML.”

“Current standard of care for AML patients is combination therapy with venetoclax and azacitidine, yet most patients eventually relapse with progressive disease. The efficacy and safety data for VIP943 we see in our studies suggest it may be a promising option for treating AML as a monotherapy in relapse/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 substantial advancement and potential paradigm-shift in ADC technology. We look forward to continuing to advance the IND-enabling studies for VIP943 and expect to file our IND in mid-2023,” concluded Dr. Hamdy.

Key Presentation Highlights:

Poster presentation titled, “VIP943 is a Novel CD123 Antibody Drug Conjugate with In Vitro and In Vivo Efficacy in Acute Myeloid Leukemia (AML) Models”, presented by Beatrix Stelte-Ludwig, Ph.D., Vincerx Pharma GmbH, Monheim, Germany, includes:

• Bone marrow samples derived from patients with AML were used to evaluate VIP943 monotherapy at different concentrations (0.1 pM to 1µM) in a depletion (without cytokine addition) and a proliferation assay. 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 the samples which showed spontaneous proliferation were sensitive to VIP943 treatment in accordance 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 the overall survival (>107 vs 83 days) compared with venetoclax and azacitidine.
• VIP943 did not induce cytokine release in a human cytokine release assay when compared with positive controls. One dose of VIP943 in an immunophenotyping study in NHP resulted in a reversible reduction in CD123+ basophils.
• In a NHP safety study, a newly generated ADC using a gemtuzumab biosimilar as the targeting antibody conjugated to our effector chemistry comprised of a proprietary linker and payload (Gem-KSPi ADC) and VIP943 (anti-CD123-KSPi ADC) were directly compared with Mylotarg.
  • CD33+/CD123+ basophils showed an expected decrease across treatments; however, the VIP943 and Gem-KSPi ADC groups demonstrated a full recovery over the observation period, whereas Mylotarg showed an increased severity. Over time, a significant deleterious effect was seen with a single dose of Mylotarg on platelets, WBC count, reticulocytes, hemoglobin, hematocrit and lymphocytes. In contrast, a single dose of Gem-KSPi ADC and VIP943 showed no effects on hematology parameters other than the aforementioned transient reduction of CD123+ basophils.
  • Evaluation of serum chemistry showed increases in liver function enzymes, bilirubin and urea nitrogen in the Mylotarg group. The female monkey treated with Mylotarg died before the end of the observation period and the male monkey had to be euthanized. All monkeys from the Gem-KSPi ADC and VIP943 groups were healthy and returned to the colony with no remarkable changes in serum chemistry.
• Overall, these results demonstrate the substantial advancement in ADC technology with the development of VIP943. Further IND-enabling studies are ongoing, and the Company expects to file an IND in mid-2023.
  

A copy of this presentation can now be accessed on the Investors section of the Company’s website at www.vincerx.com. Other Vincerx presentations related to enitociclib will be available on the company website on Monday, December 12 at 9:00AM 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 new therapies intended 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 operating organizations that develop and deliver innovative medicines to patients. Vincerx’s current pipeline derives from an exclusive license agreement with Bayer and includes a clinical-stage and follow-on small molecule drug program and a preclinical stage modular bioconjugation platform, which includes next-generation antibody-drug conjugates and innovative small molecule drug conjugates. 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,” “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 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 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 health epidemics and pandemics, including COVID-19; 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 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; Vincerx’s capital requirements and availability and uses 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 most recently filed with or furnished to 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
bmackle@lifesciadvisors.com

FAQ

What are the results of the VIP943 preclinical studies?

VIP943 showed improved safety over Mylotarg and significant tumor regression in AML models, demonstrating potential effectiveness as a treatment.

When is Vincerx planning to file the IND for VIP943?

Vincerx expects to file the IND for VIP943 by mid-2023.

How does VIP943 compare to existing therapies for AML?

VIP943 demonstrated a better safety profile and promising efficacy in combination with venetoclax and azacitidine compared to current standard treatments.

What is the significance of the ASH Annual Meeting presentation?

The presentation showcased VIP943's safety and effectiveness in AML models, highlighting its potential as a paradigm-shifting therapy in the ADC landscape.