Paul Jeng

Paul Jeng asked about KIMMTRAK's positioning in the evolving second-line cutaneous melanoma landscape 2-3 years out, considering other emerging therapies, and factors like patient characteristics or sites of care that could drive its utilization.

Answer

Ralph Torbay, EVP of Commercial, highlighted that current approved therapies like TILs are highly selective, while KIMMTRAK would offer an OS endpoint, be off-the-shelf, have long-term safety data, and benefit from existing physician experience. Mohammed Dar, EVP of Clinical Development and Chief Medical Officer, added that data from the randomized Phase III trial will ultimately drive physician choices.

Paul Jeng, on for Michael Schmidt at Guggenheim Partners, asked if there are meaningful differences in ChemTrak's real-world duration of therapy between academic and community settings and about the potential competitive positioning against a developing oral regimen for uveal melanoma.

Answer

Ralph Torbay, EVP of Commercial, stated that duration of therapy is very similar in both academic and community settings, driven by the drug's favorable long-term safety profile. He positioned Chemtrac as the established standard of care for HLA-A2 positive patients, with a high bar for overall survival that any competitor would need to meet.

Paul Jeng of Guggenheim Partners inquired about the rationale for adding a second dose to the KT-621 Phase 1b study and which data sets informed the dose selection for the upcoming Phase 2 trials.

Answer

CEO Nello Mainolfi explained that rapid trial enrollment enabled the addition of a second dose, providing a richer data set to inform Phase 2b dose selection. He clarified that while the healthy volunteer data was the primary driver for dose choice, confirmatory data from the Japanese study and long-term toxicology studies supported their initial decisions without altering them.

Paul Jeng from Guggenheim Partners inquired about the current understanding of KT-621's bioavailability in disease-relevant tissues like skin and lungs, and whether the Phase II atopic dermatitis study design would resemble the ongoing IRAK4 study.

Answer

CEO Nello Mainolfi cited extensive preclinical data showing KT-621 is orally bioavailable and distributes evenly across key tissues, expressing confidence in its translation to humans. Regarding the Phase II design, Mainolfi declined to comment on specifics, stating that details would be shared at a more appropriate time.

Paul Jeng, on for Michael Schmidt, asked about the extent of off-label use of AvmapKefaxin Jakobak in the wild-type LGSOC population, associated reimbursement trends, and the expected scope of the Q4 update for the VS7375 KRAS program.

Answer

COO Matthew Ros confirmed that while not promoted, off-label use has been observed in the wild-type population with no reimbursement issues to date. President and CEO Dan Paterson added that the Q4 update for the U.S. VS7375 study would be similar in magnitude to the ASCO data from their partner Genfleet, who is also expected to present two additional updates later in the year.

Paul Jeng from Guggenheim Partners inquired about the qualitative trends in patient referrals and screening, given the accelerated onboarding of treatment centers. He also asked about the average time from a positive test to apheresis and the potential to expedite this process.

Answer

CEO Adrian Rawcliffe and Cintia Piccina confirmed expectations for incremental quarter-over-quarter growth, driven by rising awareness and new centers, without anticipating major seasonality. Piccina noted that the time to apheresis is primarily driven by patient schedules, as about 40% of patients travel for treatment, and Adaptimmune itself has no capacity constraints that would cause delays.

Paul Jeng of Guggenheim Securities asked for an update on the 15 double-positive patients identified in November 2024, questioning what portion underwent apheresis and why others may not have. He also inquired about the typical line of therapy for patients undergoing testing.

Answer

Executive Cintia Piccina explained that the majority of the previously identified double-positive patients have either undergone apheresis or are still progressing through the treatment journey, with minimal dropouts observed. She added that the vast majority of patients being tested are in later lines of therapy and eligible for immediate treatment with TECELRA upon qualification.

Paul Jeng, on for Michael Schmidt, asked about the five active Authorized Treatment Centers (ATCs), the patient volume they represent, the timeline for onboarding more centers, and the company's visibility into real-time patient testing metrics.

Answer

Executive Cintia Piccina explained the long-term plan is to onboard approximately 30 ATCs, which represent about 80% of patients seen at sarcoma centers of excellence. She noted that since testing is conducted by independent labs, Adaptimmune does not have full visibility into all testing metrics and will not report them, relying instead on anecdotal information from treatment sites.

Paul Jeng of Leerink Partners inquired about expectations for the upcoming Phase III trial of Opzelura in prurigo nodularis (PN), specifically the clinical bar for success, and asked for an update on the CDK2 inhibitor program, including plans for further clinical data and the factors determining the pivotal study dose.

Answer

Pablo Cagnoni, President, Head of R&D, stated that for the CDK2 inhibitor, pivotal trials in platinum-resistant ovarian cancer are planned to start in 2025, with an update to come later in the year. For ruxolitinib cream in PN, he explained that if the Phase III results are anywhere near the Phase II data, it would be a very important therapy, given its strong safety profile and the unmet need for a topical treatment.

Asked about the impact of summer seasonality on Q3 AYVAKIT sales, the general view on seasonality, and for BLU-808, the expectations for biomarker responses (like tryptase) and their correlation to clinical endpoints.

Answer

The company stated that while short-term quarterly dynamics exist, their team managed them well in Q3, and the focus remains on strong year-over-year growth. For BLU-808, early 2025 data will include biomarkers like tryptase, which is considered a supportive marker whose relevance varies depending on the specific disease being targeted.