Hanmi Pharmaceutical unveiled additional treatment options for patients with progressive leukemia at the European School of Haematology (ESH) webcast held in Estoril, Portugal on October 30th. In collaboration with Aptose Biosciences, the company presented compelling cases and information regarding the efficacy and safety of their drug. The announcement was made by Dr. Rafael Bejar, Chief Medical Officer of Aptose, and Dr. Naval G. Daver, a professor in the Department of Leukemia at MD Anderson Cancer Center at the University of Texas.

Tuspetinib, called TUS in short, an orally administered myeloid kinome inhibitor (MKI), targets key kinases involved in hematologic malignancies. Aptose licensed TUS technology for $420 million in 2021, establishing itself as a major player in innovative AML therapies. TUS earned rare disease and Fast Track Development designations from the U.S. FDA in 2018 and 2022, respectively. Hanmi Pharmaceutical recently made a strategic investment in Aptose, strengthening their partnership.

Updated clinical data includes progress in the Phase 1/2 clinical trial, Aptivate, featuring the interim analysis of the TUS/VEN (Venetoclax) combination therapy.

As of the latest update on October 23rd, more than 140 patients have received TUS. Of these, 91 received single therapy, and the rest participated in the TUS/VEN combination therapy within the clinical trial. Notably, the data analysis revealed a favorable safety profile for TUS in both single and combination therapy groups, with no significant adverse events.

In the Phase 2 clinical trial at the recommended Phase 2 dose (RP2D) of 80mg, administered as a single therapy, a complete response (CR/CRh) was observed in 42% of patients who hadn't received VEN (Venetoclax) previously. Among patients with FLT3 mutations, a complete response rate of up to 60% was confirmed. Additionally, for patients without FLT3 mutations and no prior VEN treatment, the complete response rate was 29%. This indicates a potential treatment option for a significant group of AML patients who do not have FLT3 mutations, accounting for 70-75% of AML cases.

The combination therapy of TUS 80mg and VEN 400mg has the potential to introduce a new paradigm in AML treatment. Notably, the APTIVATE clinical trial cohort for the TUS/VEN combination therapy primarily includes American patients who have previously failed VEN monotherapy, highlighting the need for improved salvage therapies post-VEN treatment. TUS has shown promise in inhibiting multiple resistance mechanisms against VEN, leading to the possibility of seeking accelerated approval for VEN-failed patients.

The objective response rate (ORR) for the 31 evaluable patients in the TUS and VEN combination therapy is 48%. Among these patients, 81% exhibited resistance to VEN, with an ORR of 60% for FLT3 mutation patients and 43% for FLT3 wild-type patients.

Aptose's CMO, Rafael Bejar, expressed satisfaction with the evolving safety and efficacy data for TUS, stating, "We expect TUS to make a significant contribution to patients with FLT3 non-mutated AML, which accounts for over 70% of AML cases and lacks effective treatment options, as well as to patients who have failed VEN therapy."

Dr. Dever, the Chief Clinical Officer for TUS, commented, "The safety and efficacy data observed with TUS/VEN combination is highly encouraging, indicating that we can effectively treat the frequently encountered VEN-failed AML patients." He further explained, "The accumulated data for TUS/VEN combination therapy instills confidence in advancing clinical development into three-agent combinations like TUS/VEN/hypomethylating agents (HMA) in the future."