Pre B-cell acute lymphoblastic leukemia

VIP943 demonstrates promising safety and tolerability and achieves two complete responses to date in Phase 1 dose-escalation study, reinforcing the program’s potential and validating the VersAptx™ Platform technology Vincerx focusing resources on continued development of VIP943 Expected cash runway into early 2025 PALO ALTO, CA, USA I October 07, 2024 I Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, announced 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). The Company also provided pipeline and corporate updates. 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 ( CR L ) 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 α v β 3 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 α v β 3 . 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. About Vincerx Pharma, Inc. Vincerx Pharma, Inc. is a clinical-stage biopharmaceutical company committed to developing differentiated and novel therapies to address the unmet medical needs of patients with cancer. Vincerx has assembled a seasoned management team with a proven track record of successful oncology drug development, approvals, and value creation. Vincerx’s diverse pipeline consists of the next-generation antibody-drug conjugate, VIP943, in Phase 1; small molecule-drug conjugate, VIP236, in Phase 1; preclinical antibody-drug conjugate, VIP924; CDK9 inhibitor, enitociclib, in an NIH-sponsored Phase 1; and VersAptx, its versatile and adaptable, next-generation bioconjugation platform. Vincerx is based in Palo Alto, California, and has a research facility in Monheim, Germany. For more information, please visit www.vincerx.com and follow Vincerx on LinkedIn . SOURCE: Vincerx Pharma

South San Francisco, CA, USA - May 1, 2022: Exterior view of the Merck Researches Laboratories in South San Francisco, California. Merck & Co., Inc. is a global pharmaceutical company headquartered in Rahway, New Jersey. iStock, hapabapa On the heels of Keytruda’s success in a Phase III perioperative trial for a disease where it had previously failed to improve event-free survival, Merck touts an I&I deal with UK biotech Mestag. After a 2022 failure, Merck’s mega-blockbuster has rallied in head and neck cancer. The company dropped data from a successful Phase III trial as a perioperative treatment for patients with late stage, resected, locally advanced head and neck squamous cell carcinoma. In the KEYNOTE-689 trial, Keytruda was used as a neoadjuvant then continued after surgery in combination with radiotherapy. Compared to radiotherapy alone, the Keytruda regimen offered clinically meaningful improvement in event-free survival (EFS) for patients as well as major pathological response. Overall survival (OS) showed a trend toward improvement but without statistical significance in PD-L1 patients. OS data will be evaluated in the next interim analysis and submitted to regulatory authorities, Merck said in its announcement. If approved, it would add another notch to Keytruda’s indications belt. As of June, Keytruda has 40 FDA-approved indications and is projected to bring in more than $27 billion in sales this year. “These results are substantial, as KEYNOTE-689 marks the first positive trial in two decades for patients with resected, locally advanced head and neck squamous cell carcinoma,” Marjorie Green, SVP and head of oncology at Merck, said in a statement. Keytruda had previously failed to show EFS benefit as a combo treatment with chemoradiation for locally advanced head and neck squamous cell carcinoma. Results from KEYNORE-412 were presented in 2022, with the caveat of a “favorable trend toward improvement” was seen. Meanwhile, Merck has been doubling down on I&I investments in October. A collaboration with Cambridge biotech Mestag Therapeutics announced Tuesday carries a potential value of $1.9 billion for novel therapeutic targets for inflammatory disease. Mestag specializes in harnessing fibroblast immunology, a connective tissue cell that plays an important role in driving the immune system’s response in inflammatory disease and cancers. The biotech’s in-house programs include a bispecific antibody for solid tumors in pre-IND and assets in discovery that it says could be beneficial for rheumatoid arthritis, lupus, Sjogren’s syndrome and more. This week’s deal allows Merck the option to license one or more targets, up to a prespecified number, from Mestag and then to take over discovery, development and commercialization. Mestag will receive an undisclosed upfront payment with the future potential fees and downstream payments totaling $1.9 billion. The Mestag collab is Merck’s second deal in just over a week, having announced the completion of its $750 million acquisition of a clinic-ready bispecific antibody from Curon Biopharmaceutical. CN201 actively depletes B cells, offering therapeutic applications in both B cell malignancies and autoimmune diseases. The asset is in early-stage clinical trials for non-Hodgkin’s lymphoma and B cell acute lymphocytic leukemia.

Study marks the first time these side effects were reported in children PHILADELPHIA, Sept. 26, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) revealed for the first time that children, adolescents and young adults may experience very rare neurological issues of paraparesis and quadriparesis following chimeric antigen receptor T-cell (CAR-T) therapy, a type of immunotherapy used to treat B-cell Acute Lymphoblastic Leukemia (B-ALL). Additionally, these complications occurred without the type of inflammation typically seen in adults. The findings were published today in the journal Blood. Continue Reading Dr. Caroline Diorio Researchers previously reported that CAR-T may lead to complications known as immune effector cell-associated neurotoxicity syndrome (ICANS), which can present with a range of neurological symptoms from mild confusion to severe issues such as brain swelling, seizures and coma. However, as CAR-T therapy becomes a more prevalent cancer treatment, new patterns are emerging, revealing complex side effects in younger patients. "Our findings suggest CAR-T induced neurological side effects, while rare, can impact a spectrum of age ranges, from children to young adults. The causes of these complications in young people could be more complex than the exclusive T-cell activation and excessive cytokine production that typically leads to inflammation in adults," said Caroline Diorio, MD, FRCPC, FAAP, an attending physician with CHOP's Cancer Center. "The lack of inflammation points to a host of other underlying culprits, such as metabolic profiles, that require extensive additional research to understand." In this study, Diorio and her team analyzed two children, two teenagers and one young adult who developed severe muscle weakness, either in all four limbs (quadriparesis) or the lower half of their body (paraparesis) after receiving an infusion of either CD19- or CD22-directed CAR-T therapy to treat B-ALL. All but one of the five patients died during the study due to their cancer. The researchers performed detailed examinations on all five patients, such as tests on spinal fluid, and protein analysis to understand the response. They also later performed full autopsies on two of the deceased patients. Overall, they found chronic damage to white matter in the brain, but without the usual inflammatory responses. The children also had lower levels of certain inflammatory chemicals compared to those who did not have severe symptoms. "I can't emphasize enough that for most patients, immunotherapy, such as CAR-T, is a lifesaver," said Diorio, who is also an Assistant Professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine. "However, these study findings empower us to understand the rare instances when it's not effective and take prompt action to address that." The study was supported by the ACC K12 Award, a CIHR Fellowship Award and a CHOP Cell and Gene Therapy Award. The authors would like to gratefully acknowledge the assistance of the Translational and Correlative Studies Laboratory at the University of Pennsylvania. Diorio et al. "Quadriparesis and paraparesis following chimeric antigen receptor T-cell (CAR-T) therapy in children and adolescents." Online September 26, 2024. Blood. DOI: 10.1182/blood.2024023933. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Jennifer Lee Children's Hospital of Philadelphia (267) 426-6084 [email protected] SOURCE Children's Hospital of Philadelphia WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED