On February 22, 2024 Notable Labs, Ltd. (Nasdaq: NTBL) ("Notable", "Notable Labs"), a clinical-stage therapeutics platform company developing a new class of cancer therapies based on its Predictive Precision Medicine Platform (PPMP), reported the advancement of its volasertib Phase 2 program utilizing PPMP to enrich the study population for clinical responders (Press release, Notable Labs, FEB 22, 2024, View Source [SID1234640394]). Notable is developing its lead drug asset volasertib with its proprietary PPMP for patients with relapsed/refractory acute myelogenous leukemia (r/r AML).

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"PPMP’s recently reported, 100% accurate prediction of fosciclopirox’s clinical trial outcome has allowed us to eliminate an entire 30-patient cohort from the planned volasertib program, and further validated our PPMP-guided development strategy to target responding patients, improve patient outcomes and reduce the risk, time, and cost of drug development," said Thomas Bock, M.D., Chief Executive Officer of Notable Labs.

"We in-licensed volasertib because of its robust clinical experience in Boehringer Ingelheim’s expansive Phases 1-3 program and our PPMP data that distinguished predicted volasertib-responders from predicted non-responders based on samples from patients with AML. We therefore believe that PPMP will focus volasertib’s development on clinically responding patients, boost its clinical response rate and enhance patient outcomes," continued Dr. Bock. "The open label design of our Phase 2 trial will enable us to provide frequent data updates, and initiate a subsequent Phase 3 trial at the earliest possibility."

Joseph Wagner, Ph.D., Chief Scientific Officer of Notable, added, "In our PPMP-guided Phase 2 trial, we are additionally leveraging important learnings from the extensive post-hoc analysis of the original Phase 2 and 3 trials. This analysis suggests that standardizing best supportive care and introducing body surface area-based dosing are likely to enhance patient responses and tolerability. We are going to include and evaluate these refinements in a small all-comers dose optimization prelude, expected to begin in Q2 2024 and be completed in Q4 2024, prior to enrolling PPMP-predicted responders."

Volasertib Phase 2 program: Summary of expected near-term clinical milestones

● Volasertib IND filing: Q1 2024
● Phase 2 program initiation: Q2 2024
● Prelude data on dose optimization: Q4 2024
● Enrollment of first PPMP-selected patient: Q4 2024

About Volasertib

Volasertib is a PLK-1 inhibitor with demonstrated activity in AML and other tumor types, including solid tumors, with significant unmet medical need. Building on the performance of volasertib on PPMP, an important and proprietary step during Notable’s targeted in-licensing strategy and decision making, Notable will utilize PPMP to predict volasertib-responsive patients prior to their treatment, with the goal of selectively enrolling and treating those predicted responders, increasing volasertib’s response rates and overall patient outcomes, and fast-tracking volasertib’s remaining clinical development in this patient population. Volasertib was originally developed and manufactured by Boehringer Ingelheim and previously granted breakthrough therapy designation by the FDA. Notable in-licensed volasertib and obtained exclusive worldwide development and commercialization rights, except for certain rare pediatric cancers.

About the Volasertib Phase 2 trial

Notable’s single-arm, open-label Phase 2 study of volasertib combined with decitabine in r/r AML patients is designed to achieve two objectives: i) to confirm the optimized tolerability profile suggested by volasertib’s Phase 3 post-hoc analysis through the introduction of body-surface area-based volasertib dosing and standardizing best supportive care, and ii) to evaluate the clinical impact of volasertib treatment on selectively enrolled r/r AML patients who are predicted to clinically respond, based on PPMP testing of their blood or bone marrow samples (PPMP-predicted responders). Parallel primary endpoints are i) a positive predicted response rate and ii) a per-protocol response assessment of complete remission and overall survival.

The Phase 2 program is designed to include a non-selective dose optimization prelude expected to enroll a small cohort of all-comers patients with r/r AML. This dose optimization prelude will evaluate the use of standardized best supportive care and body surface area-based dosing prior to beginning the prospective PPMP-based patient selection. Data on patient safety, tolerability, and efficacy, including overall safety, response and duration of response, will be evaluated.