Benzinga | Jul 27, 2021 11:13AM EDT

Kronos Bio Reports FDA Clearance Of Its Investigational New Drug Application For Lanraplenib For Treatment Of Patients With Acute Myeloid Leukemia

Company intends to develop LANRA as a once-daily chronic treatment for genetically-defined AML patients

Two Phase 1/2 clinical trials of LANRA are planned, with first trial to initiate in Q4 2021

SAN MATEO, Calif. and CAMBRIDGE, Mass., July 27, 2021 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (NASDAQ:KRON), a company dedicated to transforming the lives of those affected by cancer, today announced the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug Application (IND) for lanraplenib (LANRA), allowing the company to proceed with a Phase 1/2 clinical trial of LANRA in patients with relapsed or refractory FLT3-mutated acute myeloid leukemia (AML) in combination with gilteritinib. Kronos Bio expects to initiate the trial in the fourth quarter of this year. The company is developing LANRA as a next-generation spleen tyrosine kinase (SYK) inhibitor, with improved pharmacokinetic (PK) and pharmacologic properties compared with entospletinib (ENTO), the company's lead program. ENTO will be evaluated in combination with standard chemotherapy in a planned Phase 3 clinical trial in patients newly diagnosed with NPM1-mutated AML.

"This LANRA IND caps off an outstanding year for our SYK portfolio, which we acquired just over a year ago. Since that time, we have nearly completed the integration of the ENTO and LANRA programs with our systems, built out the requisite clinical, translational, regulatory and manufacturing infrastructure for LANRA and ENTO and had successful interactions with the FDA, both for the ENTO Phase 3 clinical trial, as well as for LANRA in relapsed/refractory FLT3-mututated AML patients. The stage is now set to demonstrate the value of SYK inhibition for patients with this life-threatening disease," said Jorge DiMartino, M.D., Ph.D., chief medical officer and executive vice president, clinical development of Kronos Bio. "Based on the existing clinical data and differentiated pharmacologic properties of ENTO and LANRA, we have designed a complementary development strategy that seeks to maximize the impact of both investigational medicines. ENTO is entering a registrational Phase 3 clinical trial that may support its accelerated approval to treat newly diagnosed NPM1-mutated AML patients in combination with chemotherapy for a defined duration of treatment. LANRA's differentiated pharmacologic properties support its evaluation as a component of more extended combination dosing regimens with gilteritinib or venetoclax/azacitidine, which are dosed to progression. We believe this precision oncology approach will allow us to systematically address patients with genetic mutations present in more than two-thirds of the AML patient population."

This is the first IND for LANRA in an oncology indication. Previously, LANRA demonstrated an acceptable safety profile in clinical trials of more than 250 healthy volunteers and patients with autoimmune diseases. In preclinical studies, LANRA showed anti-leukemic activity equivalent to ENTO in NPM1-mutated and FLT3-mutated AML patient blood and bone marrow samples. The PK profile of LANRA enables once-daily dosing in the fed or fasted state and is compatible with proton pump inhibitors, suggesting that it may be more suitable than ENTO for chronic treatment paradigms.

The first of the two planned Phase 1/2 clinical trials of LANRA will include a dose-escalation and an expansion cohort study design. The first stage will evaluate initial safety, PK and anti-leukemic activity of escalating once-daily doses of LANRA in combination with the standard approved dose of gilteritinib. This stage also will assess FLT3 measurable residual disease negativity (if any) in patients who achieve a complete response (CR) and explore the predictive value of a number of biomarkers that may correlate with clinical outcomes. Initial data from this first stage of the trial are anticipated to be available in the second half of 2022. Once a recommended dose is established, an expansion cohort of approximately 30 patients is planned to further evaluate the safety of LANRA and assess its anti-leukemic activity as measured by composite CR rate and duration of response. These data are anticipated in the second half of 2023.

In the first half of 2022, Kronos Bio plans to initiate a second Phase 1/2 clinical trial, also involving a dose-escalation and expansion cohort study design of LANRA in combination with venetoclax/azacitidine in patients newly diagnosed with NPM1-mutated and/or FLT3-mutated AML who are older than age 75 or not eligible for intensive induction chemotherapy. Kronos Bio anticipates initial data from this trial in the first half of 2023 and proof-of-concept data from an escalation cohort in late 2023 or early 2024.