On October 7, 2024 Equillium Inc. (Nasdaq: EQ), a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders, reported that an abstract was accepted for poster presentation at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Equillium, OCT 7, 2024, View Source [SID1234647076]). The conference will take place at the George R. Brown Convention Center in Houston, Texas from November 6 to 10, 2024.

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Title: Interleukin (IL)-15 and IL-21 synergistically enhance NK and CD8+ T cell responses
Presenting Author: Phoi Tiet, Senior Research Associate, Equillium, Inc.
Abstract Number: 908
Location: Exhibit Halls A & B
Date: Saturday, November 9, 2024

The abstract highlights that cytokines are a focus of anti-cancer therapeutic development due to their central role in regulating anti-tumoral immune responses, and that data demonstrates that IL-15 and IL-21 synergistically augment NK and CD8 T cells activities, which further enhanced their proliferation and cytolytic function. With the ability to rescue T cell dysfunction, this cytokine combination could be a promising treatment approach to stimulating anti-tumor immune responses.

About Multi-Cytokine Platform and Multi-Cytokine Inhibitors EQ101 & EQ302

Our proprietary multi-cytokine platform generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. This approach is expected to avoid the broad immuno-suppression and off-target safety liabilities that may be associated with other therapeutic classes, such as Janus kinase inhibitors. Many immune-mediated diseases are driven by the same combination of dysregulated cytokines, and we believe identifying the key cytokines for these diseases will allow us to target and develop customized treatment strategies for multiple autoimmune and inflammatory diseases.

Current platform assets include EQ101, a clinical stage, first-in-class, selective, tri-specific inhibitor of IL-2, IL-9, and IL-15 for intravenous and subcutaneous delivery and EQ302, a preclinical stage, first-in-class, selective, bi-specific inhibitor of IL-15 and IL-21 for oral delivery.

On October 7, 2024 BPGbio, Inc., a leading biology-first, AI-powered, clinical stage biopharma focused on mitochondrial biology and protein homeostasis, and the University of Oxford’s Centre for Medicines Discovery, reported a five-year research collaboration focused on advancing novel protein degradation technologies, particularly in oncology and central nervous system (CNS) diseases, with the goal of unlocking new therapeutic pathways for conditions with limited treatment options (Press release, BPGbio, OCT 7, 2024, View Source [SID1234647077]). The organizations will work in phases, starting with the validation of BPGbio’s novel E2 TPD technology, and expanding into future study of the degradable target space, to identify novel targets and generate high quality publications.

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This collaboration builds on BPGbio’s first-in-class E2-based protein degradation program, which features a proprietary library of more than 1,000 Ro3 fragments discovered by BPGbio that are potential ligands and seed compounds to a variety of E2 targets. The collaboration will also utilize BPGbio’s proprietary ternary structures, its computational toolkit for E2 ligand design, and assays for rapidly attaining selectivity and specificity.

The partnership will leverage the Centre for Medicines Discovery’s expertise in translational research, including their groundbreaking efforts in neurological diseases such as Parkinson’s Disease. The team will utilize BPGbio’s proprietary NAi Interrogative Biology Platform, which integrates patient biology with AI-driven analysis, to accelerate biomarker discovery and therapeutics development.

"This collaboration represents a powerful alliance of biology-first science and cutting-edge translational research," said Niven R. Narain, Ph.D., President and CEO of BPGbio. "By harnessing our NAi Interrogative Biology Platform alongside the University of Oxford’s expertise, we aim to push the boundaries of protein degradation science and deliver transformative therapies for diseases like cancer and CNS disorders, where unmet medical needs remain significant."

"By partnering with BPGbio, we’re combining our world-class translational research expertise with their pioneering approach to protein degradation," said Prof. Paul Brennan, Ph.D., FRSC, Director of the Centre for Medicines Discovery at University of Oxford. "This collaboration has the potential to unlock new therapeutic strategies for diseases that have long resisted treatment, including challenging cancers and CNS disorders. We are excited to explore novel targets and bring forward breakthrough therapies that could make a profound difference for patients."

On October 7, 2024 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, reported seven oral and poster presentations will be featured at the 2024 AACR (Free AACR Whitepaper)-NCI-EORTC Symposium on Molecular Targets and Cancer Therapeutics ("Triple Meeting"). The conference is being held October 23-25, 2024 in Barcelona, Spain (Press release, Revolution Medicines, OCT 7, 2024, View Source [SID1234647062]).

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Two late-breaking presentations will feature new clinical data from patients treated for PDAC, including updated safety and efficacy data from the ongoing RMC-6236 monotherapy study and initial safety and antitumor activity data from the first-in-human monotherapy study of RMC-9805.

Details of the presentations are listed below:

Revolution Medicines Late Breaking Presentations:

Title: Updated safety and efficacy from a Phase 1 study of RMC-6236, a RAS(ON) multi-selective, tri-complex inhibitor, in patients with RAS mutant pancreatic ductal adenocarcinoma (PDAC)
Presenter: Brian Wolpin, M.D., M.P.H., Dana-Farber Cancer Institute
Abstract Number: 514LBA
Session: Late Breaking Posters
Date/Time: 12:00 p.m. – 7:00 p.m. CEST on October 23, 2024
9:00 a.m. – 5:30 p.m. CEST on October 24, 2024
9:00 a.m. – 3:00 p.m. CEST on October 25, 2024

Title: Preliminary safety, pharmacokinetics, and antitumor activity of RMC-9805, an oral, RAS(ON) G12D-selective, tri-complex inhibitor in patients with KRAS G12D pancreatic ductal
adenocarcinoma (PDAC) from a Phase 1 study in advanced solid tumors
Presenter: David S. Hong, M.D., MD Anderson Cancer Center
Abstract Number: 502LBA
Session: Late Breaking Abstracts and Proffered Papers: Novel discoveries in drug development
Date/Time 4:12 – 4:24 p.m. CEST on October 25, 2024

Additional Revolution Medicines Presentations:

Title: Selective Inhibition of Active KRAS G13C with RMC-8839 Reveals an Increased Dependence of Codon-13 KRAS-Mutant Cancers on Wild-Type RAS Isoforms
Presenter: Kyle Seamon, Ph.D.
Abstract Number: 92
Session: Molecular Targeted Agents
Date/Time: 12:00 p.m. – 7:00 p.m. CEST on Wednesday, October 23

Title: The RAS(ON) Multi-Selective Inhibitor RMC-6236 Synergizes with T Cell-Directed Immunotherapies to Extend Durability of Antitumor Activity in Preclinical RAS-Driven Cancer Models
Presenter: Elsa Quintana, Pharm.D., Ph.D.
Abstract Number: 307
Session: Translational Studies
Date/Time 9:00 a.m. – 5:30 p.m. CEST on Thursday, October 24

Title: Combination of RAS(ON) Multi-Selective and G12D-Selective Inhibitors Improves Antitumor Activity and Enhances Antitumor Immunity in Preclinical Models of KRAS G12D-Driven Cancers
Presenter: Mallika Singh, Ph.D.
Abstract Number: 300
Session: Translational Studies
Date/Time: 9:00 a.m. – 5:30 p.m. CEST on Thursday, October 24

Collaborator Presentations:

Title: Preclinical Evaluation of RMC-7977, a Multi-Selective RAS(ON) Inhibitor, as a Therapeutic Strategy for KRAS-Mutant Cholangiocarcinoma
Presenter: Rodrigo Entrialgo-Cadierno, M.D., Universidad de Navarra
Abstract Number: 297
Session: Translational Studies
Date/Time 9:00 a.m. – 5:30 p.m. CEST on Thursday, October 24, 2024

Title: Targeting KRAS codon 13 mutations using direct combination approaches in non-small cell lung cancer
Presenter: Dr. Helen Adderley, The University of Manchester and The Christie NHS Foundation Trust
Abstract Number: 113
Session: New Drugs
Date/Time: 12:00 p.m. – 7:00 p.m. CEST on October 23, 2024

Investor Webcast
Revolution Medicines will host an investor webcast focused on PDAC data from the RMC-6236 and RMC-9805 monotherapy studies on Friday, October 25, 2024, following the AACR (Free AACR Whitepaper)-NCI-EORTC Symposium’s Late-Breaking Session. Details for the webcast will be forthcoming and available on the Investors section of the Revolution Medicines website at View Source

Additional updates on the company’s three RAS(ON) inhibitor clinical development programs will be provided later in the quarter.

On October 7, 2024 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported that two of its lead investigators are presenting findings from recent additional, supportive trials with HyBryte (synthetic hypericin) in the treatment of cutaneous T-cell lymphoma (CTCL) (Press release, Soligenix, OCT 7, 2024, View Source [SID1234647063]). The presentations will occur at the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Tumour Group Annual Meeting in Lausanne, Switzerland on October 9-11, 2024. Dr. Ellen Kim, Director, Penn Cutaneous Lymphoma Program, Vice Chair of Clinical Operations, Dermatology Department, and Professor of Dermatology at the Hospital of the University of Pennsylvania, will present a poster with expanded preliminary results from the investigator-initiated study (RW-HPN-MF-01) she is leading at the University of Pennsylvania. Dr. Brian Poligone, Director of the Rochester Skin Lymphoma Medical Group, will give an oral presentation on recent results from two expanded treatment studies (HPN-CTCL-02 and HPN-CTCL-04) conducted at the Rochester Skin Lymphoma Medical Group.

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Oral Presentation:

Session Title: ORAL PRESENTATIONS – CLINICAL STUDIES 1. The official conference program can be found here.

Oral Presentation Title: Phase 2a Study of Topical 0.25% Hypericin in Mycosis Fungoides:
Results and Review of the FLASH Study presented by Brian Poligone, MD, PhD, Director of the Rochester Skin Lymphoma Medical Group on October 9, 2024 at 5:54 pm.

Poster Presentation:

Topical hypericin ointment photodynamic therapy for early stage mycosis fungoides/CTCL – a Phase 2 real world investigator-initiated study presented on October 9th, 2024 by Ellen Kim, MD, Director, Penn Cutaneous Lymphoma Program, Vice Chair of Clinical Operations, Dermatology Department, and Professor of Dermatology at the Hospital of the University of Pennsylvania.

These presentations further elaborate on the Company’s findings in these supportive studies which have demonstrated the utility of longer treatment times (Study RW-HPN-MF-01; investigator-initiated study), the lack of significant systemic exposure to hypericin after topical application (Study HPN-CTCL-02) and its relative efficacy and tolerability compared to Valchlor (Study HPN-CTCL-04).

About the EORTC CLTG Meeting

An annual meeting of the cutaneous lymphoma tumour group (CLTG), a division of the European Organisation for Research and Treatment of Cancer (EORTC), focuses this year on facilitating the convergence of experts, delegates, and sponsors from Europe and around the globe, all convened to deliberate upon the latest advancements in skin lymphoma as well as the common ground between malignant and benign skin inflammation’s research, diagnostics and treatment. The meeting website is available here.

About HyBryte

HyBryte (research name SGX301) is a novel, first-in-class, photodynamic therapy utilizing safe, visible light for activation. The active ingredient in HyBryte is synthetic hypericin, a potent photosensitizer that is topically applied to skin lesions that is taken up by the malignant T-cells, and then activated by safe, visible light approximately 24 hours later. The use of visible light in the red-yellow spectrum has the advantage of penetrating more deeply into the skin (much more so than ultraviolet light) and therefore potentially treating deeper skin disease and thicker plaques and lesions. This treatment approach avoids the risk of secondary malignancies (including melanoma) inherent with the frequently employed DNA-damaging drugs and other phototherapy that are dependent on ultraviolet exposure. Combined with photoactivation, hypericin has demonstrated significant anti-proliferative effects on activated normal human lymphoid cells and inhibited growth of malignant T-cells isolated from CTCL patients. In a published Phase 2 clinical study in CTCL, patients experienced a statistically significant (p=0.04) improvement with topical hypericin treatment whereas the placebo was ineffective. HyBryte has received orphan drug and fast track designations from the U.S. Food and Drug Administration (FDA), as well as orphan designation from the European Medicines Agency (EMA).

The published Phase 3 FLASH trial enrolled a total of 169 patients (166 evaluable) with Stage IA, IB or IIA CTCL. The trial consisted of three treatment cycles. Treatments were administered twice weekly for the first 6 weeks and treatment response was determined at the end of the 8th week of each cycle. In the first double-blind treatment cycle (Cycle 1), 116 patients received HyBryte treatment (0.25% synthetic hypericin) and 50 received placebo treatment of their index lesions. A total of 16% of the patients receiving HyBryte achieved at least a 50% reduction in their lesions (graded using a standard measurement of dermatologic lesions, the CAILS score) compared to only 4% of patients in the placebo group at 8 weeks (p=0.04) during the first treatment cycle (primary endpoint). HyBryte treatment in this cycle was safe and well tolerated.

In the second open-label treatment cycle (Cycle 2), all patients received HyBryte treatment of their index lesions. Evaluation of 155 patients in this cycle (110 receiving 12 weeks of HyBryte treatment and 45 receiving 6 weeks of placebo treatment followed by 6 weeks of HyBryte treatment), demonstrated that the response rate among the 12-week treatment group was 40% (p<0.0001 vs the placebo treatment rate in Cycle 1). Comparison of the 12-week and 6-week treatment responses also revealed a statistically significant improvement (p<0.0001) between the two timepoints, indicating that continued treatment results in better outcomes. HyBryte continued to be safe and well tolerated. Additional analyses also indicated that HyBryte is equally effective in treating both plaque (response 42%, p<0.0001 relative to placebo treatment in Cycle 1) and patch (response 37%, p=0.0009 relative to placebo treatment in Cycle 1) lesions of CTCL, a particularly relevant finding given the historical difficulty in treating plaque lesions in particular.

The third (optional) treatment cycle (Cycle 3) was focused on safety and all patients could elect to receive HyBryte treatment of all their lesions. Of note, 66% of patients elected to continue with this optional compassionate use / safety cycle of the study. Of the subset of patients that received HyBryte throughout all 3 cycles of treatment, 49% of them demonstrated a positive treatment response (p<0.0001 vs patients receiving placebo in Cycle 1). Moreover, in a subset of patients evaluated in this cycle, it was demonstrated that HyBryte is not systemically available, consistent with the general safety of this topical product observed to date. At the end of Cycle 3, HyBryte continued to be well tolerated despite extended and increased use of the product to treat multiple lesions.

Overall safety of HyBryte is a critical attribute of this treatment and was monitored throughout the three treatment cycles (Cycles 1, 2 and 3) and the 6-month follow-up period. HyBryte’s mechanism of action is not associated with DNA damage, making it a safer alternative than currently available therapies, all of which are associated with significant, and sometimes fatal, side effects. Predominantly these include the risk of melanoma and other malignancies, as well as the risk of significant skin damage and premature skin aging. Currently available treatments are only approved in the context of previous treatment failure with other modalities and there is no approved front-line therapy available. Within this landscape, treatment of CTCL is strongly motivated by the safety risk of each product. HyBryte potentially represents the safest available efficacious treatment for CTCL. With very limited systemic absorption, a compound that is not mutagenic and a light source that is not carcinogenic, there is no evidence to date of any potential safety issues.

Following the first Phase 3 study of HyBryte for the treatment of CTCL, the FDA and the EMA indicated that they would require a second successful Phase 3 trial to support marketing approval. With agreement from the EMA on the key design components, the second, confirmatory study, called FLASH2, is expected to be initiated before the end of 2024. This study is a randomized, double-blind, placebo-controlled, multicenter study that will enroll approximately 80 subjects with early-stage CTCL. The FLASH2 study replicates the double-blind, placebo-controlled design used in the first successful Phase 3 FLASH study that consisted of three 6-week treatment cycles (18 weeks total), with the primary efficacy assessment occurring at the end of the initial 6-week double-blind, placebo-controlled treatment cycle (Cycle 1). However, this second study extends the double-blind, placebo-controlled assessment to 18 weeks of continuous treatment (no "between-Cycle" treatment breaks) with the primary endpoint assessment occurring at the end of the 18-week timepoint. In the first Phase 3 study, a treatment response of 49% (p<0.0001 vs patients receiving placebo in Cycle 1) was observed in patients completing 18 weeks (3 cycles) of therapy. In this second study, all important clinical study design components remain the same as in the first FLASH study, including the primary endpoint and key inclusion-exclusion criteria. The extended treatment for a continuous 18 weeks in a single cycle is expected to statistically demonstrate HyBryte’s increased effect over a more prolonged, "real world" treatment course. Given the extensive engagement with the CTCL community, the esteemed Medical Advisory Board and the previous trial experience with this disease, accelerated enrollment in support of this study is anticipated, including the potential to enroll previously identified and treated HyBryte patients from the FLASH study. Discussions with the FDA on an appropriate study design remain ongoing. While collaborative, the agency has expressed a preference for a longer duration comparative study over a placebo-controlled trial. Given the shorter time to potential commercial revenue and the similar trial design to the first FLASH study afforded by the EMA accepted protocol, this study is being initiated. At the same time, discussions with the FDA will continue on potential modifications to the development path to adequately address their feedback.

In addition, the FDA awarded an Orphan Products Development grant to support the evaluation of HyBryte for expanded treatment in patients with early-stage CTCL, including in the home use setting. The grant, totaling $2.6 million over 4 years, was awarded to the University of Pennsylvania that was a leading enroller in the Phase 3 FLASH study. Additional supportive studies have demonstrated the utility of longer treatment times (Study RW-HPN-MF-01), the lack of significant systemic exposure to hypericin after topical application (Study HPN-CTCL-02) and its relative efficacy and tolerability compared to Valchlor (Study HPN-CTCL-04).

About Cutaneous T-Cell Lymphoma (CTCL)

CTCL is a class of non-Hodgkin’s lymphoma (NHL), a type of cancer of the white blood cells that are an integral part of the immune system. Unlike most NHLs which generally involve B-cell lymphocytes (involved in producing antibodies), CTCL is caused by an expansion of malignant T-cell lymphocytes (involved in cell-mediated immunity) normally programmed to migrate to the skin. These malignant cells migrate to the skin where they form various lesions, typically beginning as patches and may progress to raised plaques and tumors. Mortality is related to the stage of CTCL, with median survival generally ranging from about 12 years in the early stages to only 2.5 years when the disease has advanced. There is currently no cure for CTCL. Typically, CTCL lesions are treated and regress but usually return either in the same part of the body or in new areas.

CTCL constitutes a rare group of NHLs, occurring in about 4% of the more than 1.7 million individuals living with the disease in the United States and Europe (European Union and United Kingdom). It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of CTCL that it affects approximately 31,000 individuals in the U.S. (based on SEER data, with approximately 3,200 new cases seen annually) and approximately 38,000 individuals in Europe (based on ECIS prevalence estimates, with approximately 3,800 new cases annually).

On October 7, 2024 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported two complete responses in the ongoing first-in-human, Phase 1 dose-escalation study of VIP943, the Company’s next-generation antibody-drug conjugate (ADC) being evaluated in relapsed/refractory acute myeloid leukemia (AML), higher-risk myelodysplastic syndrome (HR-MDS), and B-cell acute lymphoblastic leukemia (B-ALL) (Press release, Vincerx Pharma, OCT 7, 2024, View Source [SID1234647064]). The Company also provided pipeline and corporate updates.

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VIP943 Data Highlights

The ongoing Phase 1 dose-escalation study of VIP943 has enrolled 22 patients to date across several escalating dose cohorts (0.2 to 1.3 mg/kg once weekly). These 22 patients represent a ‘hard-to-treat’ salvage population, which rarely responds to monotherapy. Nine patients (six AML; three HR-MDS) have received at least three doses of an efficacious dose of VIP943 (i.e., ≥1.0 mg/kg). Of these nine patients, four (44%) remain on study. So far, one patient with relapsed AML has achieved complete remission with incomplete hematologic improvement (CRi) and one patient with HR-MDS has achieved complete remission with limited count recovery (CRL) based on international consensus response criteria. These response criteria are widely recognized as an approvable benchmark in AML and MDS studies, further underscoring the significance of these early results.

"We are excited by the emerging data from our Phase 1 study of VIP943, showing clinical responses in difficult-to-treat patients," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx. "We believe these promising clinical responses highlight the potential of VIP943 as a best-in-class therapy for CD123+ hematologic malignancies and validate our VersAptx platform’s ability to create safer, more effective bioconjugates by overcoming the challenges of historical ADCs."

As of August 2024, VIP943 has shown favorable safety and tolerability, with no dose-limiting toxicities reported in 22 patients. Serious adverse events (SAEs) have been consistent with expectations for this patient population. The most common SAEs included pneumonia (three patients, 14%), and cellulitis and febrile neutropenia (two patients each, 9%). Only one patient (5%) experienced a drug-related SAE (Grade 3 diarrhea).

Target engagement (i.e., receptor occupancy) has been demonstrated by binding of VIP943 to CD123+ peripheral blood blasts from patients with AML from the Phase 1 study. Maximal receptor occupancy of 84% was achieved in the highest dose cohort (1.3 mg/kg). Across all the cohorts, receptor occupancy was retained for less than 96 hours. Concurrent decreases in CD123+ peripheral blood blasts were also observed after dosing. These pharmacodynamic (PD) markers show that VIP943 is binding to and eliminating CD123+ malignant cells. Preliminary pharmacokinetic (PK) data continues to show low release of payload (≤1% in plasma). The half-life of VIP943 is less than 96 hours, and no accumulation occurs with repeat dosing. These PK and PD results have prompted evaluation of twice weekly dosing of VIP943 as a potential "induction" regimen. Enrollment in the once weekly and twice weekly dosing cohorts is ongoing.

Dr. Hamdy continued, "Our initial clinical results demonstrate that VersAptx is a next-generation platform that overcomes key challenges associated with traditional ADCs. The PK profile shows that our linker is stable, cleaving exclusively inside cells without extracellular degradation. Our PD results coupled with clinical responses confirm the payload effectively kills cancer cells in peripheral blood and bone marrow without harming nearby healthy tissue. This innovative design with proof-of-concept in Phase 1 reinforces our confidence in VersAptx as a transformative platform for ADC development."

The company anticipates providing another data update on the ongoing Phase 1 VIP943 study by the end of the year.

Dr. M. Yair Levy, Director of Hematologic Malignancies Research at Texas Oncology added, "Although this is still early data, VIP943 is clearly differentiated from other ADCs, particularly with its favorable safety profile. We’re not seeing neutropenia as a dose-limiting toxicity, which is encouraging and may allow the drug to move into earlier lines of therapy in combination. I look forward to the continued development of VIP943 and its potential to improve treatment options for patients with CD123+ malignancies."

VIP236 Update

VIP236 is Vincerx’s first-in-class small molecule drug conjugate (SMDC) being evaluated in an ongoing first-in-human, Phase 1 dose-escalation study as a monotherapy in patients with advanced solid tumors. As of September 2024, 29 patients have been enrolled. Of these patients, 20 were evaluable per-protocol for response from the every 2- or 3-week schedule; nine of 20 patients had stable disease for a disease control rate of 45%. In addition, one of these subjects has been on treatment for over 300 days and four additional patients were on study for more than 120 days, demonstrating promising monotherapy duration of response in patients with advanced cancer. VIP236 continued to show a favorable safety and tolerability profile in these 29 patients, with no instances of the dose-limiting side effects commonly associated with camptothecins, such as life-threatening diarrhea, severe stomatitis/mucositis, or interstitial lung disease. These results support the potential role of VIP236 as a strong combination agent for the treatment of advanced cancers.

Considering the promising VIP236 clinical data, the Company intends to pursue a strategic partner to champion its future development for the benefit of patients.

"We’ve made significant progress in identifying an effective dose and schedule. We believe it is now crucial to study VIP236 in the right patient population, which could include triple-negative breast cancer and gastric cancer, where camptothecins are used, especially in combination with other anticancer agents," added Dr. Hamdy.

By transitioning VIP236 to a partnering asset, the Company plans to streamline its operations and focus its efforts on the continued development of its lead ADC, VIP943.

Enitociclib Update

Enitociclib, a highly selective CDK9 inhibitor, is currently being evaluated in a Phase 1 dose-escalation study in combination with venetoclax and prednisone for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL), in collaboration with the National Institutes of Health (NIH). As of September 2024, the study reported four partial responses (PRs) in seven patients (57% overall response rate), including one patient with double hit lymphoma (DH-DLBCL) and three patients with PTCL. All responses occurred in patients considered refractory by SCHOLAR-1 criteria and included one patient with prior CAR-T therapy. The study is currently enrolling in the third dose level (enitociclib 30 mg [efficacious dose] and venetoclax 600 mg) with two patients enrolled to date.

Additionally, in a separate Phase 1 study of enitociclib as a monotherapy (30 mg), one patient with transformed follicular lymphoma achieved a metabolic PR. As of September 2024, this patient remains on enitociclib monotherapy after more than 26 months. Overall, these clinical results continue to show the promising safety, tolerability, and efficacy of enitociclib for the treatment of relapsed/refractory lymphoma. The Company is actively focused on finding a strategic partner to continue the development of this asset.

Corporate Webcast

Vincerx will host a corporate webcast today at 5:00 PM EDT. The webcast will provide a pipeline and corporate update, including discussing the initial clinical data from the Phase 1 dose-escalation study of VIP943, followed by commentary with key opinion leader, Dr. M. Yair Levy (Texas Oncology), and live Q&A with Vincerx leadership.

The webcast may be accessed through the "Corporate Overview & Events" in the Investors section of the Company’s website, located at investors.vincerx.com. An archived replay will be available shortly following the webcast.

About VIP236
VIP236, the first-in-class SMDC from the VersAptx Platform, consists of an αvβ3 integrin binder, a neutrophil elastase linker cleaved in the tumor microenvironment, and a camptothecin payload optimized for high permeability and low active efflux. VIP236 was designed to deliver its payload to advanced/metastatic solid tumors that express αvβ3. VIP236 is being evaluated in a first-in-human, Phase 1 dose escalation study in patients with advanced malignancies (NCT05712889).

About VIP943
VIP943, the first ADC from the VersAptx platform, consists of an anti-CD123 antibody, a unique linker cleaved intracellularly by legumain, and a novel kinesin spindle protein inhibitor (KSPi) payload enhanced with Vincerx’s CellTrapper technology. Vincerx’s proprietary effector chemistry (linker + payload) was designed to reduce non-specific release of the payload and ensure payload accumulation in cancer cells versus healthy cells. The increased therapeutic index has the potential to address challenges associated with many ADCs by improving efficacy and reducing severe toxicities. VIP943 is being evaluated in a Phase 1 dose-escalation trial in patients with relapsed/refractory AML, HR-MDS, and B-ALL who have exhausted standard therapeutic options (NCT06034275).

About Enitociclib
Enitociclib, a highly selective CDK9 inhibitor, is currently being evaluated in a Phase 1 dose-escalation study (NCT05371054) in combination with venetoclax and prednisone for DLBCL and PTCL, in collaboration with the NIH. Enitociclib has demonstrated favorable safety and PK, with significant clinical benefits across various indications, including durable complete metabolic remissions in patients with double-hit (DH)-DLBCL and stable disease in solid tumors, notably in ovarian cancer, suggesting promising potential for future combination studies.

About VersAptx Platform
VersAptx is a versatile and adaptable next-generation bioconjugation platform. The modular nature of this innovative platform allows the combination of different targeting, linker, and payload technologies to develop bespoke bioconjugates that address different cancer biologies. With this platform, (i) antibodies and small molecules can be used to target different tumor antigens, (ii) linkers can be designed to reduce non-specific release of the payload, cleave intracellularly or extracellularly, and conjugate to single or multiple payloads, and (iii) payloads can be designed with reduced permeability using our CellTrapper technology to ensure accumulation in cancer cells or to be permeable for release in the tumor microenvironment. The VersAptx platform allows the development of bioconjugates designed to address the safety and efficacy challenges of historical ADCs.