Madison Wynne El-Saadi

Madison El-Saadi inquired about any informal communications with the FDA following the CRL and whether Capricor expects a decision on the proposed primary endpoint change for HOPE-three during the Type A meeting.

Answer

CEO Linda Marbán confirmed a brief, informal meeting occurred with the FDA primarily to align on timelines, but it did not involve clinical or statistical reviewers. She affirmed that getting clarity on the LVEF primary endpoint for HOPE-three is a key objective for the upcoming formal Type A meeting.

Madison Wynne El-Saadi asked about the ideal baseline ejection fraction where deramiocel's impact is highest and whether the estimated eligible patient population of 7,500 would be based on a strict ejection fraction threshold.

Answer

CEO Linda Marbán explained that while the greatest long-term benefit is seen when treating patients early (e.g., ejection fraction >45%), the therapy also shows stabilization in patients with lower ejection fractions. She emphasized that early treatment is better to preserve healthy heart tissue. The decision to treat will ultimately be made by care providers, not a hard threshold, and Capricor is actively educating both cardiologists and neurologists on using deramiocel as part of the DMD treatment paradigm.

Madison El-Saadi of B.Riley Securities asked if subsequent dosing cohorts for WVE-006 (AATD) have been initiated and what triggers might be for further dosing or expansion. For the DMD program, she inquired about enrollment in the open-label extension and the treatment duration needed before the NDA submission.

Answer

President & CEO Paul Bolno explained that decisions on subsequent WVE-006 cohorts will be informed by the upcoming 200 mg multi-dose and 400 mg single-dose data, which will clarify the PK/PD relationship and dosing needs. For the DMD program, he confirmed patients remain on study in the extension and that there is no change to the planned 2026 NDA filing timeline, indicating progress is on track.

Madison Wynne El-Saadi of B. Riley Securities asked if upcoming AATD cohorts could push M-protein conversion over 80%, inquired about the delivery method for a potential Rett syndrome program, and sought details on the expanded DMD trial enrollment.

Answer

President and CEO Dr. Paul Bolno noted strong AATD enrollment and highlighted that the 200mg multi-dose cohort will be highly informative for determining the upper limits of editing efficiency. For CNS delivery, he indicated that Wave is exploring alternative approaches to cross the blood-brain barrier, with more details to come at a future R&D Day. For DMD, he reiterated that the expanded trial's patient numbers would align with previous exon 53 filings, with the next major milestone being the NDA submission in 2026.

Madison El-Saadi of B. Riley Securities inquired about plans for the upcoming MDA conference, asked for a characterization of previously reported NfL data for WVE-003, and sought a comparison of WVE-003's profile against emerging exon 1-targeted candidates for Huntington's disease.

Answer

President and CEO Paul Bolno stated the full DMD data and regulatory update will be released by month-end, not timed for the MDA conference. Regarding Huntington's, he reiterated that NfL has not correlated with clinical outcomes in past studies and was not a focus of FDA discussions. He also questioned the specificity of the exon 1 target, noting that some supportive data for that approach was actually generated using Wave's own allele-specific oligonucleotides.

Madison Wynne El-Saadi from B. Riley Securities asked about the schedule of GSK milestone payments, whether biomarker data for the FDA's Huntington's discussion would come from existing SELECT patients, and if securing a partner is necessary to initiate the WVE-003 trial.

Answer

CEO Paul Bolno declined to disclose specific GSK milestone details but confirmed they are expected in 2025 and beyond. Chief Development Officer Anne-Marie Li-Kwai-Cheung clarified that the FDA discussion was based on a new, prospective registrational study, not on further follow-up of the stopped SELECT-HD trial. Dr. Bolno added that while partnership discussions are ongoing, the company has ample time and options before initiating the trial and is focused on advancing the program design.

Madison Wynne El-Saadi from B. Riley Securities asked for an update on Increlex prescription trends, the expected timing for initial ET-400 revenue post-approval, and the company's potential exposure to the White House's 'most favored nation' drug pricing policy.

Answer

CEO Sean Brynjelsen stated that while the rate of new Increlex patients may slow as they near the total addressable market, the launch is currently 'firing on all cylinders' and he expects to exceed goals. For ET-400, he anticipates a June launch but noted that meaningful revenue would likely begin in Q3 due to prescription lag. He also clarified that he does not believe the 'most favored nation' policy would have a meaningful impact, as Eton only sells in the U.S., is less reliant on Medicare, and focuses on ultra-rare diseases.

Madison El-Saadi from B. Riley Securities asked about the gating factors for initiating the PH80 hot flash study and the Phase IIb MDD study. She also inquired about the recent increase in headcount and which programs it supports.

Answer

CEO Shawn Singh explained that the PH80 program is gated by the completion of U.S. IND-enabling nonclinical and CMC studies, with an IND submission targeted for the second quarter of the following year. The MDD study is primarily gated by the finalization of the protocol. He stated the headcount is now around 50, with the increase being mostly R&D-related to enhance internal capabilities for clinical trial surveillance and training, particularly for the PALISADE program.

Madison El-Saadi of B. Riley Securities asked if PALISADE-4 will use the same clinical sites as PALISADE-3, whether PALISADE-3 data will be released before PALISADE-4 begins, and about the gating steps and dose selection for the MDD Phase IIb trial.

Answer

Chief Executive Officer Shawn Singh clarified that PALISADE-3 and PALISADE-4 will use distinct clinical sites and that PALISADE-4 will begin before PALISADE-3 data is released, with both studies reading out in 2025. For the MDD trial, he indicated the 6.4-microgram dose is the likely choice for a 6-week, placebo-controlled study, with the protocol currently being finalized.

Madison Wynne El-Saadi of B. Riley Financial asked about expectations for survival and durability in the next data cut, assuming the ORR remains around 20%. She also sought confirmation on the status of two patients who had not yet had confirmatory scans and inquired about the potential control arm for the Phase III trial.

Answer

CEO Garo Armen confirmed that all reported Overall Response Rates (ORR) are confirmed, implying no downside risk to the reported figures. He emphasized that the trends in the Phase II trial are nearly identical to those in the Phase I trial, expressing confidence that the deep and durable responses from the IO-IO combination will translate to a survival benefit. He noted this is a point they need to better educate the FDA on. The questions regarding the two specific patients and the control arm were not directly addressed.