PMV Pharma reports Q1 revenue, cash $165.8 mln, Phase 2 trial on track.

• Enrollment on track in Phase 2 PYNNACLE trial for rezatapopt in TP53 Y220C and KRAS wild-type tumors. • Interim analysis expected mid-2025 with data for approximately 50 patients. • Cash runway extended to end of 2026 with $165.8 million in cash and marketable securities as of March 31, 2025.

Aptose Biosciences has provided an update on its Phase 1/2 TUSCANY trial, which is testing tuspetinib (TUS) in combination with venetoclax and azacitidine (TUS+VEN+AZA) for newly diagnosed acute myeloid leukemia (AML) patients. The trial, which began in 2025, has shown promising early results, achieving complete remissions in 6 out of 7 patients across two dose cohorts (40mg and 80mg) [1].

The 40mg cohort achieved complete remission in 3 out of 4 patients, with two reaching MRD-negative status. The 80mg cohort saw all three patients achieve blast reductions meeting complete remission criteria. Notably, the treatment showed efficacy in patients with challenging mutations, including TP53-mutated/CK and FLT3-wildtype AML. Both dose levels demonstrated favorable safety with no dose-limiting toxicities [1].

The company aims to enroll 18-24 patients by mid-late 2025 across multiple U.S. sites. The early data from Aptose's TUSCANY trial demonstrates promising efficacy signals for their tuspetinib-based triplet therapy. The achievement of complete remissions (CR/CRi) in 6 out of 7 patients across two dose cohorts (40mg and 80mg) is noteworthy, especially considering these are newly diagnosed AML patients ineligible for standard induction chemotherapy. Particularly impressive is the activity observed in patients with TP53 mutations and complex karyotype, historically among the most challenging AML subgroups with dismal prognosis and limited treatment options [1].

The MRD (measurable residual disease) negativity observed in multiple patients is clinically significant. In AML, MRD negativity correlates strongly with reduced relapse risk and improved survival outcomes. The triple combination appears effective across diverse mutation profiles beyond just FLT3-mutated disease, including IDH2 mutations and FLT3-wildtype patients. From a safety perspective, the absence of dose-limiting toxicities at both dose levels is encouraging. AML patients are often elderly with comorbidities, making tolerability a crucial consideration. The 80mg dose showing favorable safety while maintaining efficacy appears to justify the company's designation of this as the "optimal dose" [1].

However, several limitations warrant caution. The sample size remains extremely small (only 7 patients total), and follow-up duration is still short. The durability of responses - a critical factor in AML treatment success - cannot yet be assessed. Additionally, one patient at the 40mg dose did not respond, highlighting that not all patients benefit from this approach. The planned enrollment of 18-24 patients by mid-late 2025 will provide more comprehensive data on efficacy, safety, and durability across diverse AML genetic subtypes [1].

If these early results hold in a larger cohort, tuspetinib could potentially enhance the standard venetoclax/azacitidine regimen, particularly for high-risk genomic subtypes where current options are limited. Aptose is developing TUS+VEN+AZA as a one-of-a-kind safe and mutation agnostic frontline triple drug therapy for newly diagnosed AML patients [1].

References:
[1] https://www.stocktitan.net/news/APTO/aptose-provides-clinical-update-for-the-tuspetinib-based-triple-drug-sc4hdv5haroo.html