Benjamin Burnett

Benjamin Burnett asked about the expected biodistribution of WVE-007, specifically if any would reach muscles, and how WVE-007's impact on liver fat would coexist with WVE-008 over longer periods.

Answer

President and CEO Paul B. Bolno clarified that WVE-007 is a GalNAc conjugated siRNA, designed for active receptor-mediated uptake in the liver, which is its target organ for delivery. Chief Scientific Officer Erik Ingelsson and Paul B. Bolno explained that WVE-008 targets the PNPLA3 I148M genetic mutation, addressing overall liver disease beyond just MASH. WVE-008 aims to correct the disease-driving variant, restoring enzyme functionality to repair cells and prevent fibrosis, which is distinct from WVE-007's focus on fat reduction and its impact on liver fat as a comorbidity of obesity.

Benjamin Burnett inquired about the progress of Axsome's direct-to-consumer (DTC) campaign for Auvelity, asking where the script growth was originating given a flat MDD market, and if adoption was increasing in earlier lines of care.

Answer

Ari Maizel, Chief Commercial Officer, reported that the national TV campaign, launched in September/October, generated an inflection in new patient starts, with optimized spend for 2026. Growth is driven by expanding use in primary care, which was the fastest-growing segment for new patient starts and writers in Q4, alongside continued growth in psychiatry practices.

Benjamin Burnett inquired about the progress of the DTC campaign for Auvelity, asking where the growth was coming from given a flat MDD market, and if adoption was seen in earlier lines of care.

Answer

Ari Maizel (Chief Commercial Officer, Axsome Therapeutics) stated that the national TV campaign launched in late 2025 generated an inflection in new patient starts, with optimized spend for 2026. He noted that growth is coming from both primary care (fastest-growing segment in Q4 for new patient starts and writers) and psychiatry practices, with efforts expanding in primary care.

Benjamin Burnett asked for more details on the alternative titration protocol for ulixacaltamide, specifically if it involves a lower starting dose, and whether the choice of standard review was influenced by the need to iron out titration protocols.

Answer

President and CEO Marcio Souza clarified that the alternative titration protocol for ulixacaltamide involves staying at 20mg for a longer duration, not a lower starting dose, to allow side effects to subside. He stated that ironing out titration protocols was not an important consideration for choosing standard review, as robust discussions with the FDA indicated it was not a major concern.

Benjamin Burnett followed up on ulixacaltamide's titration, asking for more color on the alternative protocol (specifically if it involves a lower starting dose) and whether the standard review decision was partly to allow time to iron out a titration protocol.

Answer

CEO Marcio Souza clarified that the alternative titration protocol for ulixacaltamide does not involve a lower starting dose but rather staying at 20 milligrams for a longer period to allow side effects to subside. He reiterated that the standard review decision was not primarily driven by the need to iron out a titration protocol, as robust discussions with the FDA had already occurred, and it was not considered a major concern.

Benjamin Burnett asked for physician feedback on the evolving competitive landscape in advanced melanoma, particularly regarding a potential new entrant expected later in the year.

Answer

Interim CEO and President Frederick Vogt stated that Iovance views the potential new entrant as very similar to the currently marketed T-VEC, with clinical data from a much earlier-line patient population that is not comparable to Amtagvi's. He concluded that they do not anticipate a significant impact on the Amtagvi launch.

Benjamin Burnett of Stifel asked about Iovance's path to achieving its 70% gross margin goal and the specific operational levers that will be utilized to reach that target.

Answer

Interim CEO Frederick Vogt and CFO Jean-Marc Bellemin responded. They explained that increased capacity utilization at the company's ICTC facility is a primary driver. They also cited ongoing operational excellence initiatives, process improvements, automation, and better raw material cost management as key levers to improve margins over time.

Benjamin Burnett of Stifel requested more details on the planned Q2 data update for zoldonrasib and asked about overlapping toxicities and the perceived debate around combining daraxonrasib with chemotherapy.

Answer

CEO Dr. Mark Goldsmith declined to provide more color on the upcoming zoldonrasib data. He clarified there is no 'debate' on combinability, but rather a fundamental challenge that standard-of-care chemotherapy alone is often poorly tolerated by PDAC patients. The focus is on managing the chemo backbone's toxicity to ensure continuous, effective dosing of daraxonrasib.

On behalf of Benjamin Burnett, Carolina Ibanez-Ventoso asked about the key factors for the PRGN-2012 rolling BLA submission and the likelihood of an AdCom meeting, given a competitor's recent filing delay.

Answer

President and CEO Dr. Helen Sabzevari confirmed that Precigen remains on track for a BLA submission by the end of 2024. She emphasized the drug's differentiation, including its subcutaneous delivery and strong safety profile. Regarding a potential AdCom meeting, Dr. Sabzevari noted that while it is at the FDA's discretion, the remarkable consistency in complete response rates between the Phase I (50%) and Phase II (52%) trials suggests the data is robust and may not require such a review.

On behalf of Ben Burnett, Carolina Ibanez-Ventoso asked about the key factors for commencing the PRGN-2012 rolling BLA submission and the potential for an AdCom meeting with the FDA.

Answer

President and CEO Dr. Helen Sabzevari confirmed that the company is on track for a year-end 2024 BLA submission. She stated that while an AdCom is at the FDA's discretion, she believes the strong consistency between the Phase I (50% complete response) and Phase II (52% complete response) pivotal trial data may obviate the need for one.

Carolina Ibanez-Ventoso, on behalf of Benjamin Burnett, asked about the key factors for initiating the rolling BLA submission for PRGN-2012 and the potential for an AdCom meeting with the FDA.

Answer

President and CEO Dr. Helen Sabzevari confirmed that the company is on track for a BLA submission by the end of 2024. She emphasized the drug's differentiators, such as subcutaneous delivery and strong efficacy. Regarding a potential AdCom, Dr. Sabzevari noted that while it is at the FDA's discretion, the remarkable consistency between the Phase I (50% complete response) and Phase II (52% complete response) pivotal trials may obviate the need for one.