Oryzon secures US patent for LSD1 inhibitor vafidemstat in BPD

Oryzon Genomics (Madrid: ORY), the Barcelona-based epigenetics company, has secured a US Patent (No. 12,673,044) covering methods of treating non-aggressive symptoms of borderline personality disorder using LSD1 inhibitors, including vafidemstat (ORY-2001). The grant, issued by the USPTO, is commercially significant because it fills a gap in Oryzon’s existing BPD patent estate, which previously focused on aggression and social withdrawal. Together, the two patent families now protect vafidemstat across the full clinical presentation of BPD — from impulsivity and emotional dysregulation to overt aggression — through at least 2043 in the US.

Oryzon is preparing to initiate a Phase III registrational trial in BPD, having received FDA written feedback on its submitted PORTICO-2 protocol in October 2025. With no pharmacological treatment approved anywhere in the world for BPD as a primary indication, the company is pursuing first-in-class status in an indication defined by high unmet need and a long history of failed drug development attempts.

BPD is a heterogeneous disorder. Clinically, it encompasses both aggressive and non-aggressive symptom clusters: the former includes overt agitation, hostility, and impulsive violence; the latter encompasses emotional dysregulation, identity disturbance, fear of abandonment, and interpersonal dysfunction. Oryzon’s earlier patent family, which has been granted or allowed in Australia, Canada, Europe, Hong Kong, Israel, Japan, South Korea, Malaysia, the Philippines, and Russia, covers the aggression and social withdrawal dimension. The European Patent Office recently granted a second patent within that family — EP4512473 — with specific claims covering vafidemstat for aggression associated with BPD or autism spectrum disorder, and social withdrawal associated with schizophrenia.

The newly granted US patent addresses the non-aggressive symptom domain. This is not a minor distinction. BPD’s non-aggressive features — including chronic emptiness, dissociation, and unstable self-image — represent a substantial and clinically distinct treatment burden. A patent portfolio that covered only aggression would have left open a meaningful gap, both clinically and commercially, particularly as the field moves toward more nuanced regulatory endpoints. The new patent closes that gap in the US market through March 2043, a date that includes 1,095 days of Patent Term Adjustment awarded by the USPTO to compensate for prosecution delays. The company noted that any potential Patent Term Extension following regulatory approval, if applicable, is not yet included in that estimate.

The patent’s commercial value rests on the clinical evidence accumulated through Oryzon’s Phase II program. The completed Phase IIb PORTICO trial enrolled 211 patients in a global, double-blind, randomized, placebo-controlled design. While primary endpoints were not met with statistical significance — the trial was adaptive and powered for signal detection rather than registration — secondary endpoints showed nominal statistical significance: the BEST Total Score, measuring overall BPD severity, reached p=0.0260 with the full dataset, and the STAXI-2 Trait Anger measure reached p=0.026 at weeks 8 through 12. All efficacy endpoints favored vafidemstat over placebo.

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Following an End-of-Phase II meeting with the FDA in October 2024, at which the agency indicated that agitation-aggression in BPD has the potential to be an acceptable target indication, Oryzon submitted the PORTICO-2 Phase III protocol in June 2025. The FDA’s written feedback, received in October 2025, was characterized by the company as constructive; the full content has not been publicly disclosed. Phase III initiation remains pending as Oryzon incorporates that feedback.

The mechanism underlying the vafidemstat borderline personality disorder program is distinct from all existing psychiatric pharmacology. Vafidemstat inhibits LSD1 (KDM1A), a histone demethylase that regulates gene expression in neurons by removing methyl marks from histone H3 at lysine 4. Inhibiting LSD1 shifts chromatin toward a transcription-permissive state, de-repressing activity-dependent genes involved in synaptic plasticity and emotional circuit consolidation. The drug also inhibits MAO-B, adding a monoaminergic dimension to its epigenetic mechanism. This dual profile — operating upstream of neurotransmitter receptor pharmacology at the level of chromatin regulation — is the basis for Oryzon’s argument that vafidemstat addresses the epigenetic underpinnings of maladaptive neural circuit encoding in BPD, rather than modulating receptor-level signaling as existing psychiatric drugs do. Notably, vafidemstat remains the only LSD1 inhibitor in clinical development for a psychiatric indication, distinguishing it from other LSD1 programs that remain focused on oncology.

The patent grant arrives as Oryzon is also actively financing its clinical programs. The company completed a EUR 12 million capital increase in July 2026 and signed a financing agreement with COFIDES, moves that support continued advancement of the Phase III program. A patent estate extending to 2043 and covering both the aggressive and non-aggressive symptom domains of BPD strengthens the asset’s intellectual property position ahead of what is expected to be a capital-intensive Phase III development program and any future partnering discussions.


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