Basma Radwan Ibrahim

Basma Radwan from Leerink Partners inquired about the clinical differences between Type I and Type II bipolar depression, whether Ezetucalner is expected to have differential efficacy, and if mania is being assessed as an endpoint in the trial.

Answer

Chief Medical Officer Christopher Kenney explained that Type I involves manic episodes while Type II involves hypomania, and the trial includes both populations with stratification to ensure balance. He stated that while they expect efficacy in both, it is unknown. Mania is being monitored as a safety outcome to ensure the drug does not exacerbate the condition, rather than as an efficacy endpoint.

Basma Radwan Ibrahim, on for Marc Goodman, asked about the plan to assess efficacy for the Nav1.1 asset in Dravet syndrome given the competitive landscape, and whether the trial would also assess behavior and cognition.

Answer

President and CEO Ian Mortimer explained that their Nav1.1 program is differentiated as an oral small molecule targeting the underlying genetic cause of Dravet syndrome. He confirmed that the clinical development plan aims to assess not only seizure reduction but also disease-modifying endpoints related to cognition and behavior, which he believes is critical for treating genetically defined epilepsies.

Basma Radwan Ibrahim of Oppenheimer & Co. Inc. asked for an update on the PHOENIX trial's discontinuation rates and enrollment progress, and inquired about recent regulatory meetings concerning trial requirements for Stargardt disease.

Answer

Chairman and CEO Dr. Tom Lin stated the PHOENIX trial's dropout rate is approximately 20%, which he noted is well below rates seen in comparable studies. Chief Medical Officer Dr. Hendrik Scholl added that higher dropout rates are common for injectables and other visual cycle modulators. Regarding regulatory discussions for Stargardt disease, Dr. Lin confirmed that meetings are being scheduled but there were no updates to report at this time.

Basma Radwan Ibrahim, on behalf of Marc Goodman at Leerink Partners, asked if Belite Bio could get confirmation on a broad label for Stargardt disease beyond the adolescent study population when meeting with regulators. She also requested an update on the current discontinuation rates in the PHOENIX trial for Geographic Atrophy (GA).

Answer

Chairman and CEO Dr. Tom Lin stated the dropout rate for the PHOENIX trial is approximately 20%, which he noted is favorable compared to competitor studies. Chief Medical Officer Dr. Hendrik Scholl addressed the label question, explaining that since the disease is typically more severe in younger patients, demonstrating efficacy in adolescents should support a straightforward path to approval for adults as well. Chief Scientific Officer Dr. Nathan Mata added that a competitor's trial had a dropout rate over 40%.

Basma Radwan Ibrahim inquired about market research on the tolerance of geographic atrophy (GA) patients to ocular adverse events (AEs) and whether these AEs could affect the drug's market uptake.

Answer

Chief Scientific Officer Nathan L. Mata explained that while a slightly higher incidence of AEs might be expected in the more diseased GA population compared to Stargardt's patients, these events are manageable. He noted that in the ongoing PHOENIX trial with over 280 subjects, such AEs are observed in a minority of patients, indicating good overall tolerance.

Basma Radwan Ibrahim from Leerink Partners, on for Marc Goodman, sought clarification on the 160,000 prevalent patient population for post-bariatric hypoglycemia (PBH). She asked how many are actively seeking treatment and about the new incidence rate, questioning if the 8% rate of development post-surgery is still a valid assumption.

Answer

Co-CEO Justin Klee explained that the 160,000 figure represents patients with persistent hypoglycemia despite initial management, a subset of a much larger group who experience some form of hypoglycemia post-surgery. He affirmed that these patients are actively seeking medical attention due to the debilitating nature of the condition. Both Justin Klee and Co-CEO Joshua Cohen confirmed the 8% incidence rate remains a reasonable assumption based on recent surgery data, noting that PBH typically manifests 1-3 years post-procedure.

Basma Radwan Ibrahim of Leerink Partners, on for Marc Goodman, asked if the ORION study in PSP will use tau PET imaging in addition to CSF biomarkers for its decision-making. She also questioned if the Phase III avexitide trial will include an active standard-of-care comparator arm.

Answer

Dr. Camille Bedrosian, Chief Medical Officer, responded that the PSP study will primarily look at CSF biomarkers compared to baseline, referencing the strong signal seen in the prior Alzheimer's study. For the avexitide trial, she explained that since there are no approved therapies for PBH, the trial will be placebo-controlled, with all participants continuing their medical nutrition therapy.

Basma Radwan Ibrahim of Leerink Partners inquired about ZURZUVAE's current market penetration among OB/GYNs and asked about the safety thresholds, specifically somnolence rates, for advancing SAGE-319 in DEEs.

Answer

CEO Barry Greene addressed the pipeline question by clarifying that SAGE-324, not SAGE-319, is being evaluated for DEEs. The decision for SAGE-324 will be based on a combination of factors including appropriate dosing for chronic use, the regulatory pathway, and overall portfolio strategy, with an update expected mid-year. He did not provide a specific answer on OB/GYN penetration, indicating the topic had been covered.

Basma Radwan Ibrahim, on behalf of Marc Goodman at Leerink Partners, inquired about the safety profile of sepranolone and the potential of Prader-Willi Syndrome as a second indication, given the competitive landscape.

Answer

Executive Sergio Traversa detailed that sepranolone has a well-known and favorable safety profile from over 350 patients, with the primary side effect being minor, temporary injection site irritation. Regarding Prader-Willi Syndrome, he stated that there is ample room for new therapies and that sepranolone's unique mechanism, which targets compulsivity via the GABAA pathway, is complementary to existing and developing treatments rather than purely competitive.

Basma Radwan Ibrahim of Leerink Partners asked if Relmada would have access to additional unblinded data, such as patient baseline characteristics, from the interim analysis beyond the DMC's primary recommendation.

Answer

CEO Sergio Traversa stated that to maintain the integrity of the data, the company will not receive any additional color or details. Relmada will only be informed of one of the three potential outcomes: continue as planned, add patients to increase power, or that the study is futile.

Basma Radwan Ibrahim, on for Marc Goodman, asked about the lifecycle strategy for ACP-204, including the potential for a broad dementia-related psychosis indication, and inquired about the awareness goals for the NUPLAZID campaign.

Answer

EVP of R&D Elizabeth Thompson stated that the company will pursue separate indications for Alzheimer's disease psychosis and Lewy body dementia psychosis for ACP-204, as the FDA prefers disease-specific data. CCO Tom Garner and CEO Catherine Owen Adams noted the NUPLAZID campaigns are successfully driving patient-doctor conversations, evidenced by increased website traffic and a rise in NBRx market share from 20% to 25%.