A 100% overall response rate in 18 evaluable patients is a number that demands scrutiny, not celebration, because small Phase Ib samples can flatter almost any regimen. What makes Oryzon’s updated ALICE-2 data for iadademstat worth taking seriously is where those responses are landing: in patients with TP53 mutations and RAS pathway alterations, two genomic subgroups that have historically resisted even the best available combinations. Both TP53-mutated patients achieved complete remission and showed measurable reductions in variant allele frequency, and all three patients with RAS pathway mutations hit CR. That is not a numerical artifact of sample size; it is a directional signal about mechanism.
The triplet of iadademstat, azacitidine, and venetoclax produced an 89% composite complete remission rate and a 78% CR rate, with most complete responses arriving in cycle one. After a median follow-up of eight months, neither median overall survival nor event-free survival had been reached, and estimated 12-month OS sat at 79%. Nine patients proceeded to allogeneic hematopoietic cell transplantation, the group that showed an estimated 12-month OS of 88%. Enrollment in ALICE-2, an investigator-initiated study led by OHSU’s Knight Cancer Institute, is at roughly 85% of the 21-patient target. The company is also reporting a 67% CRc rate from the FRIDA trial of iadademstat plus gilteritinib in relapsed or refractory FLT3-mutated AML, compared to CR plus CRi rates around 28% reported for gilteritinib monotherapy in real-world cohorts of heavily pretreated patients, a benchmark the source cites directly.
The clinical story exists alongside a fragile financial one. Cash at June 30 was $16.7 million, a runway that would ordinarily cap ambition. Oryzon has since raised €12 million in a capital increase and locked in a €25 million commitment from COFIDES for future increases tied to mental health programs, which cover vafidemstat’s path toward Phase III in borderline personality disorder aggression and a new Phase II in autism spectrum disorder. The IDEAL Phase II trial in essential thrombocythemia has also enrolled its first patient, extending iadademstat’s reach into myeloproliferative neoplasms. These are parallel bets that require capital discipline to survive alongside the AML program.
The single marker to watch is whether the final ALICE-2 dataset, expected before year-end, confirms the CR rate and the adverse-risk subgroup activity at full enrollment. That data package is what Oryzon intends to bring to an FDA meeting about a registrational design, with a 2027 trial start as the stated objective. If the final numbers hold at or near what EHA showed, the FDA conversation shifts from exploratory to structural, and the question of partnership or financing at the registrational level becomes unavoidable.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
