8-K: Notable Labs Presents Design for PPMP-Enabled Phase 2 Trial of Volasertib in AML at AACR 2024

Notable Labs announced the design of its Phase 2 trial for volasertib in relapsed/refractory AML, incorporating its Predictive Precision Medicine Platform (PPMP) to identify likely responders.

Summary

• Notable Labs presented the design of its Phase 2 clinical trial for volasertib in combination with decitabine for patients with relapsed/refractory acute myeloid leukemia (AML) at the AACR 2024 conference.
• The trial will utilize Notable's Predictive Precision Medicine Platform (PPMP) to identify patients likely to respond to volasertib.
• The PPMP is a flow-cytometry-based companion diagnostic test developed using 41 primary AML samples.
• The study aims to optimize volasertib dosing using body surface area-based dosing to improve patient tolerability and response.
• A proof-of-concept study using 41 AML samples suggests a correlation between volasertib resistant fractions and areas under the dose-response curves, which could be used to predict responders.
• Preliminary metrics suggest that 32-33% of de novo AML patients and 25% of relapsed/refractory AML patients would be predicted to be responders to volasertib.

Sentiment

Score: 7

Explanation: The document is positive about the potential of the PPMP and the volasertib trial, but also acknowledges the risks and challenges associated with clinical development. The sentiment is cautiously optimistic.

Positives

• The use of the PPMP aims to improve patient selection for the volasertib trial, potentially increasing response rates.
• The dose optimization plan, including body surface area-based dosing, is expected to reduce toxicity and improve tolerability.
• The company has a targeted in-licensing strategy to deliver medical impact and commercial value faster.
• Volasertib has previously been granted breakthrough therapy designation by the FDA.
• The company is using a companion diagnostic to predict responders.

Negatives

• Prior studies of volasertib were halted due to toxicity issues, which the company is now addressing with a new dosing strategy.
• The company is still in the clinical stage and has not yet brought a product to market.
• The company is reliant on the success of its PPMP and volasertib program.

Risks

• The success of the trial depends on the accuracy of the PPMP in predicting patient response.
• There are risks associated with clinical development and regulatory approval of product candidates, including potential delays.
• The company may face challenges in obtaining sufficient additional capital to advance its programs.
• There are uncertainties in obtaining successful clinical results and unexpected costs may arise.
• The company faces risks related to the failure to realize any value from product candidates.
• The company's future financial and operating results are uncertain, including its ability to become profitable.
• The company's ability to retain key personnel is a risk.
• The company faces risks related to the Israel-Hamas war.
• The company may not obtain orphan drug designation or regulatory approval for its drug candidates.
• Changes in regulations could impact the company.

Future Outlook

The company plans to implement a dosing optimization plan and co-develop a companion diagnostic assay to predict responders, with the goal of improving patient outcomes and fast-tracking clinical development.

Management Comments

• Thomas Bock, M.D., Chief Executive Officer of Notable, stated that the presentation at AACR 2024 highlights the potential for the PPMP to effectively predict responders.
• Joseph Wagner, Ph.D., Chief Scientific Officer of Notable, commented that the abstract highlights technical features of volasertib on Notable's PPMP and the method to develop a companion diagnostic test.

Industry Context

This announcement is relevant to the broader trend of precision medicine in oncology, where treatments are tailored to individual patient characteristics. The use of a companion diagnostic to predict response is a key aspect of this trend.

Comparison to Industry Standards

• The use of a companion diagnostic to predict response is becoming more common in oncology drug development, with companies like Foundation Medicine and Guardant Health leading in this area.
• The 30% complete response rate previously observed with volasertib in combination with cytarabine is comparable to other AML treatments, but the toxicity issues highlight the need for improved dosing strategies.
• Companies like Agios Pharmaceuticals and Jazz Pharmaceuticals are also developing treatments for AML, and Notable's approach of using a predictive platform could differentiate it from competitors.

Stakeholder Impact

• Shareholders may view this announcement positively as it represents progress in the company's clinical development program.
• Patients with relapsed/refractory AML may benefit from the development of a more effective and less toxic treatment option.
• The healthcare community may be interested in the potential of the PPMP to improve patient selection and treatment outcomes.

Next Steps

• The company will proceed with the Phase 2 clinical trial of volasertib in combination with decitabine for relapsed/refractory AML.
• The company will co-develop a companion diagnostic assay to predict responders using its PPMP.
• The company will implement a dose optimization plan using body surface area-based dosing.
• The full poster will be posted to the company's website shortly after the event.

Key Dates

Keywords

volasertib, acute myeloid leukemia, AML, Predictive Precision Medicine Platform, PPMP, companion diagnostic, clinical trial, cancer therapy, precision oncology, AACR 2024