Vincerx Pharma, Inc. presented positive preliminary Phase 1 data for VIP236 and updates on pipeline progress at the American Association for Cancer Research (AACR) Annual Meeting 2024. VIP236 Updates Study VNC-236-101 is an open-label, multicenter, Phase 1 dose-escalation study with monotherapy VIP236 for the treatment of patients with metastatic tumors who have exhausted all standard therapy options. The study's main objective is to determine a safe dose and schedule for VIP236 for further clinical development.

Fifteen patients have been dosed to date on the once every three weeks (Q3W) schedule. Sequential dose-escalation cohorts with the Q3W schedule were 0.2 mg/kg (n=2), 0.4 mg/kg (n=5), 0.6 mg/kg (n=5), and 0.8 mg/kg (n=3). Results of the Q3W schedule (n=15) show: The patient population is typical of a Phase 1 study with heavily pretreated patients and a wide range of tumor types.

The Q3W schedule is well tolerated with no dose-limiting toxicity (DLT) in any patients, and no patients have discontinued VIP236 due to an adverse event. Importantly, no severe or life-threatening diarrhea has been observed, validating the purposeful design of VIP236?s optimized camptothecin payload. First efficacy assessment was at the end of cycle 2 (i.e. after only two doses on the Q3W schedule).

Seven patients have achieved objective stable disease, including tumor reduction. Four patients remain on study with the longest treated patient on study for 168 days. Dose escalation continues on the Q3W schedule.

Vincerx anticipates presenting additional Phase 1 data for VIP236 later this summer. VIP943 Updates. Study VNC-943-101 is an open-label, multicenter, Phase 1 dose-escalation study with monotherapy VIP943 for the treatment of patients with CD123+ acute myeloid leukemia (AML), B-cell acute lymphocytic leukemia (B-ALL) or myelodysplastic syndromes (MDS) who have exhausted standard therapeutic options.

The study's main objective is to determine a safe dose and schedule for VIP943 for further clinica development. VIP943 is administered once per week. Three patients were dosed in Cohort 1 (0.2 mg/kg) and four patients were dosed in Cohort 2 (0.4 mg/kg).

Despite the initial low doses in the study, all seven sequentially enrolled patients completed the 28-day DLT evaluation period. Five out of seven received a cycle 2 dose and two of these patients started cycle 3. One patient with MDS is still on study on cycle 3. No DLTs occurred in Cohort 1 and 2. Four patients have been enrolled in Cohort 3 (0.7 mg/kg) and are undergoing DLT assessment. VIP943 PK data shows very little free payload in circulation, consistent with the favorable safety profile observed preclinically and clinically.

As the study progresses through the dose escalation, Vincerx will present additional Phase 1 data for VIP943 on or around the 2024 European Hematology Association Annual Meeting in June 2024. NewIn Vitro Solid Tumor Data Vincerx also reported preclinical experiments applying the next-generation effector chemistry of its VersAptx platform to the antibodies of approved ADCs, TRODELVY and ENHERTU, demonstrating the potential to improve tumor toxicity of ADCs by orders of magnitude. in vitro tumor models, Vincerx?s sacituzumab-legumain-KSPi ADC had a 20-fold improvement in tumor toxicity compared with TRODELVY (sacituzumab-govitecan).

The company?s trastuzumab-legumain-KSPi ADC demonstrated an 8-fold increase in tumor toxicity compared with ENHERTU (fam-trastuzumab-deruxtecan). These findings further support the versatility of VersAptx to address multiple cancer types, including solid tumors, and increase the efficacy and safety of ADCs. Further studies will be conducted in animal models.

VIP236, the first-in-class small molecule drug conjugate (SMDC) from the VersAptx Platform, consists of an avß3 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 tumors that express avß3. Preclinical data show enhanced efficacy, independent of HER2 status, in patient-derived and cell line-derived gastric cancer models compared with ENHERTU®, an approved ADC. VIP236 is being evaluated in a Phase 1 dose-escalation trial treating patients with advanced or metastatic solid tumors .

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 CellTrapper technology. The next-generation effector chemistry (linker + payload with CellTrapper) 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 in a Phase 1 dose-escalation trial evaluating patients with relapsed/refractory AML, B-ALL, and MDS who have exhausted standard therapeutic options (NCT06034275).