Pete Stavropoulos

Pete Stavropoulos from Cantor Fitzgerald inquired about Definium's potential filing strategy for DT120 ODT, specifically whether positive results from two GAD Phase III studies and the Emerge MDD study would lead to an sNDA filing before completing a second MDD study. He also asked for details on key scales and functional biomarkers being used to assess clinical effect for the earlier-stage asset, DT-402, in autism spectrum disorder.

Answer

Robert Barrow, CEO, stated it is premature to comment on specific filing strategies without data, but strong data would enable more compelling arguments for an efficient pathway. Daniel Karlin, CMO, explained that for DT-402, Definium is employing high-granularity, high-sensitivity measures, including established and novel approaches for social interaction and communication, with a focus on measurement techniques that can track through all development phases.

Pete Stavropoulos asked about Definium's potential filing strategy if both GAD Phase 3s and the first MDD Phase 3 (Emerge) are positive, specifically whether they would wait for the second MDD study. He also requested more color on assessing the clinical effect of DT-402 in ASD, including key scales and elaboration on 'functional biomarkers.'

Answer

Robert Barrow, CEO, stated it would be premature to comment on specific filing strategy without data, but emphasized that stronger data would enable more compelling arguments for efficient pathways. Dr. Daniel Karlin, Chief Medical Officer, discussed the challenges of ASD measurement, noting the use of high-granularity, sensitive measures, components of established scales, and novel approaches to social interaction/communication in the DT-402 Phase 2a study.

Pete Stavropoulos (question asked by Sarah) asked about the assumptions for Nuvaxovid's 2026 uptake under Sanofi's control, specifically the balance between contracting wins and physician/patient pull-through, and also requested the current number of Material Transfer Agreements (MTAs) in place.

Answer

President and CEO John Jacobs and Chief Strategy Officer Elaine O'Hara explained that contracting with retail pharmacies is crucial for U.S. uptake, and Sanofi initiated its first full-cycle negotiation for 2026 with the BLA in hand, making the outlook optimistic. They did not disclose the exact number of MTAs but highlighted significant and growing interest, with companies frequently expanding their MTAs after initial experiments, including a recent new MTA with an oncology company and an amendment for a large pharma.

Pete Stavropoulos inquired about the baseline seizure rates and anti-seizure medication use for EPX-100 in Dravet syndrome, comparing them to real-world patients and other clinical trials. He also asked for the emerging benefit-risk profile, competitiveness, and market fit. Additionally, he sought details on the orexin 2 receptor agonist's Phase 1 PK, PD, and safety bar for advancing to later stages, and its positioning in the competitive landscape.

Answer

Jeffrey M. Dayno, President and CEO, deferred to Kumar Budur. Kumar Budur, Chief Medical and Scientific Officer, explained that Dravet patients had treatment-resistant seizures (approx. 4 anti-seizure methods) with comparable baseline seizure rates to other studies. He highlighted EPX-100's efficacy (approx. 50% median seizure reduction, 50% reduction in half of patients) alongside a favorable safety profile (minimal GI AEs, normal liver function, no special monitoring). For the orexin 2 receptor agonist, Dr. Budur stated Phase 1 PK, safety, and tolerability data are expected mid-2026, not anticipating significant differences from other agonists, and plans to accelerate development by leveraging learnings, acknowledging Takeda's lead.

Peter Stavropoulos inquired about the baseline seizure rates and anti-seizure medication use for EPX-100 in Dravet syndrome, comparing it to real-world patients and other clinical trials. He also asked about the emerging benefit-risk profile and competitive positioning of EPX-100, and the PK, PD, and safety bar for the orexin 2 receptor agonist in Phase 1, along with its fit in the competitive landscape.

Answer

Dr. Kumar Budur, Chief Medical and Scientific Officer, stated that baseline seizure rates for EPX-100 patients were comparable to other studies, highlighting approximately 50% median seizure reduction and a favorable safety profile with minimal GI adverse events and no special monitoring. He emphasized the ease of use with a liquid, BID dosing formulation. Regarding the orexin 2 receptor agonist, Dr. Budur noted that Phase 1 PK, safety, and tolerability data are expected mid-2026, with a sleep-deprived healthy volunteer study planned for H2 2026. He acknowledged Takeda's lead in the competitive landscape and the company's goal to accelerate development by leveraging learnings from other programs.

Pete Stavropoulos of Cantor Fitzgerald asked about the RECONNECT study's primary endpoint, including potential variability, placebo mitigation measures, and key differences from the prior CONNECT study. He also asked the CCO about new levers to accelerate Wakix growth.

Answer

Chief Medical & Scientific Officer Dr. Kumar Budur detailed enhancements in the RECONNECT study, such as focusing on complete methylation patients and optimizing dosing, to increase the probability of success. EVP & CCO Adam Zaeske outlined his focus on improving top-line demand by increasing daily referrals, optimizing the conversion of referrals to dispenses, and enhancing patient retention through superior service.

Pete Stavropoulos asked about the drivers behind Sunosi's double-digit year-over-year growth, specifically whether it was volume-driven, from improved access or persistence, or share gains, and if growth differed between narcolepsy and OSA segments.

Answer

Ari Maizel, Chief Commercial Officer, confirmed Sunosi's steady growth in both OSA (70% of prescriptions) and narcolepsy (30%) markets. He attributed growth to new patient starts, total active writers, and total prescriptions, driven by efforts to deepen engagement with existing writers and expansion across various prescriber segments including PCPs, pulmonologists, sleep specialists, and neurologists.

Pete Stavropoulos asked about the drivers of Sunosi's double-digit year-over-year growth, specifically whether it was volume-driven, from improved access, persistence, or share gain, and if growth was more from narcolepsy or OSA, noting any differences in prescriber behavior.

Answer

Ari Maizel (Chief Commercial Officer, Axsome Therapeutics) explained that Sunosi continues to deliver steady growth in both OSA (70% of prescriptions) and narcolepsy (30%), driven by positive growth in new patient starts, total active writers, and total prescriptions. He noted growth from both OSA and narcolepsy segments, across PCPs, pulmonologists, sleep specialists, and neurologists.

Pete Stavropoulos asked about adoption expectations for AXS-05 in Alzheimer's agitation, given Rexulti's uptake, and the planned strategy to drive adoption in various channels.

Answer

Chief Commercial Officer Ari Maizel stated that while they are watching the Rexulti launch, the key differentiator for AXS-05 is its combination of strong efficacy with a favorable safety and tolerability profile. He mentioned plans to leverage the Auvelity sales force and expand into geriatric psychiatry and long-term care facilities.

Pete Stavropoulos asked about the number of U.S. patients in the Open Label Extension (OLE) and the expected timeline for their transition to commercially reimbursed scripts. He also inquired about the outcomes of non-access patient outreach and educational programs, and the proportion of start forms resulting from these efforts.

Answer

Benjamin Palleiko, CEO, clarified that U.S. OLE patients numbered in the dozens, not hundreds, and their transition was subsumed by broader demand. Nicole Sweeny, Chief Commercial Officer, discussed patient outreach efforts, including the HAEA patient summit and local education programs, noting early adopters clustered around key physicians.

Pete Stavropoulos asked for the number of U.S.-based patients in the open-label extension (OLE) and the expected timeline for their transition to commercially reimbursed scripts. He also inquired about the outcomes of non-access patient outreach and educational programs, and if a proportion of the 460 start forms could be attributed to these efforts.

Answer

Ben Palleiko, CEO, clarified that the U.S. OLE population was several dozen patients, not hundreds, and their transition to commercial scripts is subsumed by the broader demand uptake rather than being a distinct burst. Nicole Sweeny, Chief Commercial Officer, discussed early patient adopters being clustered around tier one and tier two physicians, engagement at the HAEA Patient Advocacy Summit, and local education programs for patients and families, but did not provide a specific proportion of start forms from these efforts.

Pete Stavropoulos asked for clarification on the number of U.S.-based patients in the open-label extension (OLE) and the expected timeline for their transition to commercially reimbursed scripts. He also inquired about the outcomes of non-access patient outreach and educational programs, and if the company had a sense of the proportion of the 460 start forms that resulted from these efforts.

Answer

Ben Palleiko, CEO, stated that the U.S. OLE involved several dozen patients, not hundreds, and their transition to commercial scripts is subsumed by general demand rather than a dramatic burst. Nicole Sweeny, Chief Commercial Officer, explained that early patient adopters are clustered around tier one and tier two physicians, linking to marketing efforts. She highlighted the HAEA patient summit (1,400 attendees) as a key engagement opportunity and mentioned ongoing local education programs for families and non-personal marketing efforts.

Pete Stavropoulos of Cantor Fitzgerald asked about any observed trends between seizure reduction and neurodevelopmental benefits, whether younger patients were driving improvements, and if the Phase 3 trial had enrollment caps based on age.

Answer

Interim CEO Ian Smith highlighted the trend of continued seizure reduction in lower-dose patients on the 45mg maintenance dose. SVP & Head of Neurology Kimberly Parkerson noted that correlating seizure and Vineland scores is difficult with the current sample size. She confirmed that benefits are seen across the 2-18 year age range, which is why the trial enrolls this spectrum without specific caps, though Ian Smith mentioned a slight loading towards ages 7-10.

Pete Stavropoulos inquired about how new biomarker data informs Acumen's clinical strategy, whether they are monitoring blinded ARIA rates in the ALPITUDE study, and asked for details on the design of the blood-brain barrier candidate.

Answer

Chief Medical Officer Dr. Eric Siemers stated that while they monitor new biomarkers, their current panel (pTau217, Tau181, GFAP) is robust. On ARIA rates, he commented that blinded data has not been inconsistent with Phase 1 results. President & CDO Jim Doherty added that for the EBD technology, they are exploring various combinations of antibody cargo and JCR's carrier technology to optimize pharmacokinetics, brain penetration, and safety, with findings to be confirmed in preclinical studies, including a primate study.

Pete Stavropoulos inquired how recent biomarker disclosures in the Alzheimer's field are shaping Acumen's clinical strategy, which key biomarkers might be emphasized in the ALTITUDE-AD data readout, and what to expect in the top-line results scheduled for late 2026.

Answer

Dr. James Doherty, President and Chief Development Officer, explained that the company is closely monitoring the rapid advancements in biomarkers, particularly P-tau217, and is biobanking samples for future analysis. Dr. Eric Siemers, Chief Medical Officer, reiterated that the primary endpoint is the clinical IADRS measure. CEO Daniel O'Connell clarified that top-line results will feature clinical endpoints, with biomarker data to be released subsequently.

Pete Stavropoulos questioned the prescriber profile for AvmapKefaxin Jakobak, asking about the mix between targeted physicians, academic centers, and community settings, and how early traction compares to internal expectations. He also inquired about the company's experience with payers.

Answer

President and CEO Dan Paterson noted that traction has exceeded expectations, with prescriptions coming from a mix of Gyn-oncs and Med-oncs. Chief Commercial & Strategy Officer Michael Crowther added that uptake is balanced between top-tier customers and broader community physicians. Regarding payers, Paterson explained there has been no significant pushback, with reimbursement occurring for both on-label and off-label use, and the company's co-pay assistance program has been highly effective.

Pete Stavropoulos from Cantor Fitzgerald asked for details on the powering assumptions and dropout rates for the VOYAGE and PANORAMA studies, and how the trial design, including the open-label extension (OLE), aims to generate data on real-world treatment patterns.

Answer

CEO Robert Barrow stated the trials are powered at 90% to detect a five-point difference on the HAM-A scale, assuming a 15% dropout rate. Chief Medical Officer Dr. Daniel Karlin added that the open-label extension (OLE) is a key feature to encourage retention and will help establish real-world treatment patterns by observing redosing needs over a full year.

Pete Stavropoulos from Cantor Fitzgerald inquired about the statistical powering assumptions and dropout rates for the VOYAGE and PANORAMA studies, and also asked how the trial design aims to generate data on real-world treatment patterns.

Answer

CEO Robert Barrow stated the trials have 90% power to detect a five-point difference on the HAM-A scale, assuming a 15% dropout rate. CMO Dr. Daniel Karlin added that the open-label extension (OLE) is a key feature to improve retention and is designed to capture real-world retreatment patterns by allowing up to four doses per year, which they believe will establish the range of anticipated usage.

Pete Stavropoulos asked about the key differences between tau silencing gene therapy and anti-tau antibodies, the potential for a combination approach, and how Voyager plans to establish human proof-of-concept for its capsid technology following the pause of the SOD1 program.

Answer

CMO Dr. Toby Ferguson explained that the IV-delivered tau silencing therapy aims for broad knockdown to remove existing tau, while antibodies aim to impede spread, suggesting they could be sequenced. He stated that human proof-of-concept for the capsid will now likely come from partnered programs with Neurocrine for Friedreich's ataxia and GBA, which have clear biomarker endpoints like frataxin and GCase levels.

Pete Stavropoulos asked about the safety monitoring protocols for the ARCT-032 study, the patient characteristics in the ARCT-810 OTC deficiency trial, and what to expect from the interim data for the H5N1 vaccine study.

Answer

President and CEO Joseph Payne noted that the ARCT-032 study has a Data and Safety Monitoring Committee staffed by the CF Foundation's network, though specific safety thresholds were not disclosed. For ARCT-810, he confirmed the trial is enrolling younger and more advanced disease patients. For the H5N1 vaccine, he stated that interim data in H2 2025 will be a robust dataset covering immunogenicity across multiple doses and regimens in ~200 participants.

Samantha, on behalf of Pete Stavropoulos, asked for an update on the H5N1 pandemic flu program, including key details and what to expect next.

Answer

CEO Joseph Payne confirmed that the company remains on track to initiate the clinical trial for its H5N1 pandemic flu vaccine this year. He noted the program's importance to its partner, BARDA, and mentioned that the relationship with the agency is being elevated.

Asked about expectations for the upcoming TREM2 data, the bar for advancing the program, safety monitoring for ARIA, and details about the ABC technology's CD98 target.

Answer

The TREM2 data release will include clinical outcomes, safety, and key biomarker data. The bar for advancement is a combination of consistent clinical and biomarker signals, not just a p-value. ARIA incidence and severity have come down, and the LTE is exploring mitigation strategies. The CD98 target is expressed in various tissues, including endocrine glands and specific brain cells, which will be monitored for safety.

Samantha, on behalf of Pete Stavropoulos from Cantor Fitzgerald, asked about expectations for the upcoming TREM2 data release, the bar for advancing the program, the status of ARIA-like safety observations, and details on the ABC technology's CD98 target.

Answer

Dr. Gary Romano, Chief Medical Officer, stated the data release will include top-line clinical, safety, and key biomarker data, with the bar for advancement being a consistent signal of slowing disease progression across these measures. He noted ARIA incidence has decreased and the LTE is exploring mitigation strategies. Dr. Arnon Rosenthal, CEO, and Dr. Sara Kenkare-Mitra, President, added that the CD98 target is expressed in various tissues, including the brain, and will be monitored for safety.

Pete Stavropoulos of Cantor Fitzgerald inquired about the strategic rationale behind Sanofi's investment, the management of BK viremia in the upcoming BESTOW study, and the clinical benefits and measurement of steroid tapering in the trial.

Answer

CEO David-Alexandre Gros explained that Sanofi's investment was a standard financial one without any special rights, viewing Eledon as a good opportunity. President and Chief Scientific Officer Steve Perrin detailed that BK viremia is common and managed at the investigator's discretion by weaning immunosuppressants, with some flexibility for delaying Tegoprubart infusions. Perrin and Gros both highlighted that steroid tapering reduces significant side effects, improving patient quality of life, and will be compared across both arms of the study.

Pete Stavropoulos of Cantor Fitzgerald inquired about the specifics of the upcoming data presentation for tegoprubart, asking about efficacy measures beyond eGFR, KOL feedback, the biological mechanism for creating a tolerogenic environment, the cause of new-onset diabetes post-transplant, and the steroid tapering protocol in the BESTOW study.

Answer

President and Chief Scientific Officer Steven Perrin explained the presentation will focus on eGFR data, as it is a highly predictable biomarker. He noted that while blocking CD40 ligand can induce regulatory T-cells, these changes are typically observed in tissue (via biopsy), not in circulation. He also clarified that new-onset diabetes is driven by CNI toxicity to pancreatic beta cells. CEO David-Alexandre Gros added that the BESTOW trial will aim to taper patients off steroids within a few months.

Pete Stavropoulos of Cantor Fitzgerald inquired about the clinical significance of the IgA reduction observed in the ALS study for IgAN patients, the ideal target patient population for tegoprubart in IgAN, and the anticipated number of patients for whom data will be presented in the Q1 2023 updates.

Answer

President and Chief Scientific Officer Steve Perrin explained that while the double-digit IgA reductions in the ALS study were rapid and meaningful, their direct translation to IgAN is currently unknown. He and Chief Medical Officer Jeff Bornstein concurred that earlier intervention in IgAN is likely better to prevent irreversible kidney damage, though tegoprubart's dual upstream and downstream mechanism could benefit patients with significant inflammation. CEO David-Alexandre Gros added that the number of patients in the Q1 2023 data release will be comparable to initial Phase 2 readouts from other companies.