Oryzon Advances FDA Protocol Resubmission for PORTICO-2 Phase III Trial in BPD Aggression

Oryzon Genomics is in active preparation for a Phase III protocol resubmission to the FDA for PORTICO-2, its vafidemstat trial targeting aggression in borderline personality disorder, following agency feedback that required protocol-level revisions. For regulatory affairs teams managing CNS INDs, the case illustrates the iterative negotiation cycle that characterises late-stage protocol alignment with the agency on psychiatric endpoints and patient population definitions.

The resubmission work runs alongside two additional vafidemstat programs: the EVOLUTION study in schizophrenia and preparatory activities for HOPE-2 in autism spectrum disorder. Managing parallel IND tracks across distinct CNS indications places concurrent demands on regulatory resourcing, particularly where FDA feedback on one protocol may carry implications for endpoint strategy in adjacent programs.

On the oncology side, updated clinical data for iadademstat in first-line acute myeloid leukemia will be presented at the European Hematology Association (EHA) 2026 congress, drawing from 18 patients in the ALICE-2 study. Reported figures at abstract submission cut-off include a 100% overall response rate, 93% complete remission with incomplete count recovery, and 79% strict complete remission. A separate dataset from the FRIDA study in relapsed/refractory FLT3-mutated AML showed a 67% complete remission with incomplete count recovery rate, also accepted at EHA.

Oryzon characterises iadademstat's development scope as expanding across investigator-sponsored studies at U.S. cancer centres, National Cancer Institute-sponsored trials in hematologic malignancies and solid tumors, and emerging non-malignant hematology indications including sickle cell disease and essential thrombocythemia. Each new indication adds a distinct regulatory pathway and associated CMC and process validation considerations for any future commercial manufacturing scale-up.

The company reported a cash position of $25.4 million (€22.1 million) at the quarter ended March 31, 2026, providing the near-term runway against which both the PORTICO-2 resubmission timeline and ongoing clinical enrollment are being managed.

The PORTICO-2 resubmission, once filed, will serve as a measurable checkpoint for how effectively Oryzon has addressed the FDA's protocol-level concerns in a CNS indication where endpoint sensitivity and patient stratification remain areas of regulatory scrutiny.

Source: Oryzon Genomics via company press release, May 14, 2026.