2024 has been a decisive year for Oryzon Genomics. If we have to highlight our last major milestone, it is undoubtedly the favorable results of the End-of-Phase II meeting with the US Food and Drug Administration (FDA), which allows us to begin preparations for a Phase III PORTICO study. 2 for our drug vafidemstat in Borderline Personality Disorder (BPD). Vafidemstat is an LSD1 inhibitor in clinical development for the treatment of psychiatric disorders such as BPD and schizophrenia.
This clarification of the regulatory path forward came following the presentation of the final results of the Phase IIb PORTICO study at the 37th ECNP congress in Milan, with a significant overall improvement compared to the preliminary topline data presented. Vafidemstat has demonstrated a significant and clinically relevant reduction in agitation and aggression as well as an overall improvement in illness compared to placebo in patients with BPD, a disorder for which there are currently no approved drugs. Vafidemstat was safe and well tolerated by BPD patients, in line with the safety observed in previous clinical studies.
We are currently fully focused on preparations for the Phase III program, including preparing a full protocol for the PORTICO-2 trial for submission to the FDA in Q1 2025.
During 2024 we have also substantially strengthened our patent portfolio for vafidemstat with grants or notifications of intent to grant for patents covering its use for the treatment of aggression, social withdrawal, and BPD in important markets such as Europe, Japan, Korea and others. These patents will not expire until at least 2038-2040, not counting potential patent extensions that could provide years of additional protection, significantly extending the commercial life of vafidemstat.
For its part, iadademstat, our LSD1 inhibitor for oncology, has also made progress in 2024. In June we presented promising initial data from the Phase Ib FRIDA trial, evaluating iadademstat in combination with gilteritinib in Acute Myeloid Leukemia (AML) with FLT3 mutation in relapse/refractory. Data from the first two cohorts showed that the combination was safe and showed strong antileukemic activity, with encouraging response rates and a shorter response time compared to historical data for gilteritinib alone.
During this year we have expanded efforts to evaluate the therapeutic efficacy of iadademstat via new clinical trials, which will be carried out through our Cooperation Research and Development Agreement (CRADA) with the US National Cancer Institute (NCI). or via “researcher-initiated studies” in collaboration with prestigious institutions in the US. Among them, it is worth highlighting two clinical studies that will evaluate the combination of iadademstat with venetoclax and azacitidine in AML in the first line. These trials are the natural continuation of our ALICE trial, which explored the combination with azacitidine in this same population with very favorable results and, if positive, could open additional options for our clinical development strategy. ALICE-2 is one of these studies that explores the combination with Ven-Aza and is having very promising results in the first patients. A new Phase I/II trial, already authorized by the FDA, in combination with an immune checkpoint inhibitor in patients with metastatic small cell lung cancer in the first line, sponsored by the NCI, will also begin recruitment soon , in which prestigious American cancer centers will participate.
With all the clinical studies underway or that we plan to start, by 2025 we hope to take the development of both vafidemstat and iadademstat one step further, in addition to continuing to promote other programs such as ORY-4001, nominated as a candidate for clinical development for the treatment of neurological diseases such as Charcot Marie-Tooth disease and ALS.
In an international context marked by uncertainty, which has affected specialized investors who finance biotechnology in the last three years, we hope that 2025 will also certify the change in trends in international markets and that the investment interest that the sector so badly needs will recover. biotechnology sector. For our part, at Oryzon, our commitment to the development of innovative drugs will remain firm in its purpose: improving the quality of life of patients, our first priority.