David Dai

David Dai inquired about the reasonable steady-state percentage for Revuforj post-transplantation maintenance use and how axatilimab could differentiate itself in the competitive IPF landscape against inhaled therapies like Tyvaso and Insmed's TPIP.

Answer

Michael Metzger, CEO, projected that 70-80% of KMT2A patients could eventually go back on maintenance, acknowledging fewer NPM1 patients receive transplants. Nick Botwood, Head of R&D and Chief Medical Officer, highlighted IPF's high unmet need, axatilimab's unique macrophage-targeting mechanism (vs. fibroblast-targeting), potential for disease modification, and the planned convenient sub-Q regimen (Q2 or Q4) as key differentiators against onerous inhaled competitors.

David Dai asked what would be a reasonable percentage for post-transplantation maintenance use at steady state, given the current 40%-45%. He also inquired about the competitive landscape for axatilimab in IPF, particularly against Tyvaso and Insmas TPIP, and how axatilimab could differentiate itself.

Answer

Michael Metzger, Chief Executive Officer, expects 70%-80% of patients could eventually go back on maintenance post-transplant, representing a significant change. Nick Botwood, Head of R&D and Chief Medical Officer, emphasized IPF's high unmet need and axatilimab's potential for disease modification. He highlighted its unique mechanism targeting macrophages (versus fibroblasts for other agents) and the planned subcutaneous regimen (Q2 or Q4) as key differentiators against existing, often onerous, treatments.

David Dai asked for details on Revuforge's Q2 revenue, specifically the contribution from inventory versus new and refill patients. He also questioned if the stem cell transplant rate is expected to rise from the current one-third.

Answer

CFO Keith Goldan clarified that revenue growth was driven by patient demand, as inventory levels remained stable at two to three weeks. CEO Michael Metzger confirmed that they expect the transplant rate to 'materially change over time and get better' than the current one-third, driven by the trend of treating patients in earlier lines of therapy, which improves their eligibility for transplant.

David Dai asked about the Q4 Proleukin sales uptick, distinguishing between restocking and actual AMTAGVI demand, and whether Proleukin sales are expected to stabilize. He also requested clarification on how Iovance plans to achieve the $1 billion peak sales opportunity for AMTAGVI, specifically detailing the contributions from melanoma, non-squamous non-small cell lung cancer, and soft tissue sarcoma.

Answer

Dan Kirby, Chief Commercial Officer, clarified that the Q4 Proleukin uptick was primarily driven by AMTAGVI demand, with a small amount of buy-in due to a February 1st price increase. He expects Proleukin sales to stabilize, driven by AMTAGVI demand. Frederick Vogt, Interim CEO and President, and Dan Kirby reiterated that the $1 billion peak sales opportunity is for AMTAGVI in U.S. melanoma alone, with non-small cell lung cancer representing a 7x larger market ($10 billion opportunity) and sarcoma being equivalent to melanoma, projecting total potential well over $10-$12 billion.

David Dai asked about the Proleukin sales uptick in Q4, distinguishing between restocking and Amtagvi demand, and whether Proleukin sales would stabilize. He also sought clarification on the $1 billion peak sales opportunity for Amtagvi, specifically the contribution from melanoma, non-squamous non-small cell lung cancer, and soft tissue sarcoma.

Answer

Dan Kirby, Chief Commercial Officer, explained the Q4 Proleukin uptick was primarily driven by Amtagvi demand, with a small amount of buy-in due to a February 1st price increase, expecting sales to level out. Frederick Vogt, Interim CEO and President, clarified the $1 billion peak sales potential is for Amtagvi in U.S. melanoma alone, with NSCLC (7x larger market, $10B opportunity) and sarcoma (equivalent to melanoma) representing additional significant opportunities, potentially leading to over $10-12 billion in total U.S. sales.

David Dai of UBS sought confirmation that the patient ramp for Amtagvi was on track to meet the midpoint of guidance, and asked for an update on the number of newly activated ATCs versus those still in the activation process.

Answer

Chief Commercial Officer Dan Kirby clarified that the full-year guidance of $250M-$300M includes both Amtagvi and Proleukin revenue, making the required quarterly patient growth lower than the analyst's calculation. He expressed confidence in meeting the guidance, citing strong Amtagvi demand and normalizing Proleukin orders. He noted new ATCs have been activated but emphasized the focus is on the quality of centers, not just the quantity.

David Dai asked if there was any spillover impact from the holiday season on patient start forms or tumor resections.

Answer

Interim CEO Frederick Vogt stated they did not observe a general slowdown, as cancer centers typically operate through the holidays. Chief Commercial Officer Dan Kirby added that as this was the first full year of launch, they are still establishing commercial patterns and will monitor for seasonality, but none is apparent in the current data.

David Dai from UBS inquired about the specific activities Iovance undertook to improve the patient dropout rate this quarter compared to the last.

Answer

Interim CEO Frederick Vogt clarified that the improvement was not due to a single new initiative but rather the result of ongoing launch optimization. This includes educating ATCs on better patient selection and surgical resection quality. He expects this trend to continue as centers gain experience.

David Dai asked for additional color on FDA interactions leading to the HARMONi BLA submission and any changes in the FDA's stance on overall survival (OS). He also inquired about the initial indication for the GSK B7-H3 ADC + Ivonescimab collaboration, specifically if non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) would be explored.

Answer

Allen Yang, Chief R&D Strategy Officer, reiterated that the HARMONi study was positive on PFS but missed OS due to enrollment delays, and that Summit submitted the full data package for review despite the FDA's desire for OS. Dave Gancarz, Chief Business and Strategy Officer, confirmed that small cell lung cancer (SCLC) is a specific focus for the GSK collaboration, noting the potential of both assets in multiple solid tumor settings.

David Dai asked for additional color on FDA interactions leading to the HARMONi BLA submission for second-line EGFR mutant NSCLC, specifically regarding the FDA's stance on OS. He also inquired about the initial indication for the collaboration with GSK involving their B7-H3 ADC and ivonesimab.

Answer

Allen Yang, Chief R&D Strategy Officer, explained that despite missing statistical significance for OS due to enrollment delays, Summit submitted the full HARMONi package, which was accepted, believing it addresses an unmet need. Dave Gancarz, Chief Business and Strategy Officer, confirmed that small cell lung cancer is an initial area of exploration for the GSK collaboration, among other solid tumor settings where both B7-H3 and ivonesimab have shown promise.

David Dai sought clarification on the HARMONi-3 phase III trial update, specifically if the regulatory de-risking means Summit Therapeutics can file each histology separately, even if one cohort fails. He also asked for Summit Therapeutics' thoughts on combination strategies for non-small cell lung cancer, particularly with ADCs and chemo combos.

Answer

Dave Gancarz, Chief Business and Strategy Officer, confirmed that the separate histology analyses in HARMONi-3 are independent Intent-to-Treat (ICTs), allowing for separate filings. He expressed excitement about collaborations, including with Rev Med for RAS inhibitors and plans for additional combinations, likely with ADCs. He highlighted Summit Therapeutics' strategic advantage of not having internal ADCs, enabling them to pursue the best data-driven combinations.

David Dai questioned the gross margin performance of the RLS business, its impact on the overall company gross margin, and the key drivers for RLS gross margin improvement moving forward.

Answer

Christian Behrenbruch, CEO and Managing Director of Telix Pharmaceuticals, clarified that the RLS segment reports third-party generic products with lower margins, effectively subsidizing manufacturing infrastructure. He emphasized that Telix's own products, when run through the RLS network, are reported under Precision Medicine, and that increased volume through Telix's in-house pharmacy network could improve overall gross margin towards 70%.

David Dai asked about the gross margin for the RLS business moving forward, specifically inquiring about the key drivers and its impact on the overall gross margin.

Answer

CEO Christian Behrenbruch clarified that the RLS segment reports on third-party, generic nuclear medicine products with inherently lower margins, effectively subsidizing manufacturing infrastructure. Telix's product margins (mid-60%) are reported under Precision Medicine. He expects overall gross margin to trend towards 70% as a larger share of Telix's product volume goes through the in-house pharmacy network.

David Dai of UBS Group AG inquired about the company's launch readiness for ZERKAIX and the expected performance in the initial quarters following its potential approval.

Answer

Group CEO Christian Behrenbruch affirmed that the commercial team is fully prepared for the ZERKAIX launch, as it targets the same urology and nuclear medicine customer base as Elucix, creating a straightforward path to market. Kevin Richardson, CEO of Telix Precision Medicine, noted that the successful expanded access program has already demonstrated the product's value, indicating strong market readiness.

David Dai of UBS Group asked what is driving the long 13-month real-world duration of therapy for Chemtrac, specifically about treatment beyond progression, and inquired about the expected patient breakdown in the PRISMEL trial's control arm.

Answer

Ralph Torbay, EVP of Commercial, attributed the long duration to patients feeling good due to the favorable safety profile, and confirmed that treatment beyond progression is common in the real world. David Berman, EVP of R&D, stated that a minority of patients in the PRISMEL control arm will receive Opdualag, with the majority receiving nivolumab, but expressed confidence in beating both based on prior data.

David Dai from UBS sought clarification on the data cut for the upcoming ASCO presentation and asked about the baseline characteristics of patients in the pivotal trial. He also inquired about Kyowa Kirin's potential contribution to expediting the KOMET-017 trial.

Answer

CEO Troy Wilson clarified it is effectively the same data cut being submitted to the FDA, not a later one. CMO Dr. Mollie Leoni added that patient characteristics are similar to Phase I, with most having prior venetoclax treatment. She also confirmed the hope is that Kyowa Kirin's regional presence and expertise will help accelerate trial start-up and execution.