David Nierengarten

David Nierengarten asked about the design of the KPL-387 transition arm study, specifically whether it biases patient enrollment towards certain prior therapies, such as steroids, or aims for an even split.

Answer

John Paolini (CMO, Kiniksa Pharmaceuticals) clarified that the KPL-387 transition to monotherapy study is a supplemental, global study designed to inform clinicians on moving patients from various prior therapies, including NSAIDs, colchicine, corticosteroids, and other IL-1 inhibitors. He stated that the study aims to capture necessary information for each transition type to advise clinicians and regulatory authorities, without a pre-specified hypothesis or specific population balance.

David Nierengarten of Wedbush Securities asked about the specific efficacy bar for the KPL-387 (March) study, questioning if it needs to match Arcalis's near-100% recurrence reduction or if a lower bar is acceptable due to dosing convenience. He also asked for thoughts on emerging oral competition.

Answer

EVP & CCO Ross Moat stated it was too early to define a precise efficacy expectation for KPL-387 but noted the study is designed to optimize and demonstrate the drug's strength. On competition, he reinforced KNSA's leadership position, emphasizing their understanding that complete disease control requires inhibiting both IL-1 alpha and IL-1 beta, a key differentiator from other potential mechanisms.

David Nierengarten of Wedbush Securities inquired if the upcoming clinical trial for KPL-387 will mirror the design of the pivotal ARCALYST study and whether it will incorporate a component for patients switching from ARCALYST.

Answer

Chief Medical Officer Dr. John Paolini stated that while the Phase II/III study for KPL-387 will start mid-year, specific details of the trial design are not being shared at this time. He noted the plan is based on regulatory interactions and directed investors to clinicaltrials.gov for future updates.

David Nierengarten followed up on the topic of first-recurrence patients, asking if there are any observable trends indicating that more experienced or repeat prescribers are the ones using ARCALYST earlier in the disease course.

Answer

Chief Commercial Officer Ross Moat responded that prescribing for first-recurrence patients appears to be scattered across the board, with no specific correlation to prescriber experience or repeat status observed yet. He emphasized that the company's strategic initiatives, like the partnership with the American Heart Association, are focused on shortening the overall patient journey to an accurate diagnosis for all patient types.

David Nierengarten of Wedbush Securities asked about the PROSTACT Global study, specifically what the company is looking for from the initial dosimetry and safety data and whether all three combination arms will proceed to Part 2.

Answer

Group CEO Christian Behrenbruch confirmed the plan is to advance all three combination arms. He clarified that Part 1 was designed to confirm the safety profile with different combination therapies, which required a demanding patient protocol. He expects the larger Part 2 of the study, which is more patient-friendly, to accrue much faster and demonstrate a consistent safety profile across the different combinations.

David Nierengarten asked about the sacrocitinib program, specifically whether the FDA had recommended adding a maintenance evaluation arm to the study and what the company's current thinking is on the design for a registrational trial, such as using PFS as the primary endpoint.

Answer

CEO Dr. David Hung clarified that the decision to add the maintenance arm was made by Nuvation Bio, not at the FDA's recommendation. He stated that discussions with the FDA regarding the pivotal trial design are ongoing and that the final study design will be made public on clinicaltrials.gov once those discussions are concluded.

David Nierengarten asked about the development of sacrocitinib, specifically whether the FDA had recommended adding a maintenance evaluation arm to the study and what kind of primary endpoint, such as PFS, was being considered for the registrational trial design.

Answer

David Hung, Founder, President & CEO, clarified that the decision to add a maintenance arm was the company's, not an FDA recommendation. He stated that discussions with the FDA regarding the pivotal trial design and endpoints are ongoing, and details will be made public on clinicaltrials.gov upon their conclusion.

David Nierengarten of Wedbush Securities asked about the status of labeling discussions with the FDA and whether a potential PDUFA date delay could jeopardize the Priority Review Voucher (PRV).

Answer

CEO David Hallal stated that a potential delay would have "no impact" on the PRV. President of R&D Akshay Vaishnaw confirmed that labeling was part of the constructive late-cycle meeting, but could not share specifics, only reiterating that the FDA is working towards the September 22 PDUFA date.

David Nierengarten asked about plans for expanding apitegromab into additional indications like Duchenne muscular dystrophy (DMD) and whether any new developments have made certain neuromuscular disorders particularly attractive for pursuit.

Answer

President of R&D Akshay Vaishnaw confirmed a significant opportunity exists beyond SMA in disorders like DMD and FSHD, referencing strong preclinical data. He also mentioned ALS as a potential area of interest and stated that the company is working through details for new studies, with more information to be shared later in the year.

David Nierengarten questioned the rationale for starting the CD38-SADA study with the original linker if the company was already planning to swap it out for an improved version in the GD2-SADA program.

Answer

CEO Michael Rossi clarified that the primary goal of the initial studies (1001 and 1201) is to establish the safety of the SADA protein itself, which remains constant. By using the existing linker, they minimize variables. Once the protein's safety is confirmed, the new, improved linker-chelator can be introduced via a bridging study or amendment for the treatment phase of development.

David Nierengarten asked for the rationale behind adjusting the GD2-SADA dose back to 1 mg/kg, questioning whether it was driven by differences in tumor types, tumor burden, or simply pharmacokinetics (PK).

Answer

President and CEO Michael Rossi clarified the decision was driven purely by PK data, not tumor type or burden. The human PK profile at 0.3, 1, and 3 mg/kg closely matched preclinical models, which had pointed to 1 mg/kg as the optimal dose to 'paint the tumor' without prolonging clearance time. The adjustment back to 1 mg/kg was a logical step to fine-tune the dosing window based on this data, and was not related to any toxicity concerns.

David Nierengarten asked if the treatment dynamics for ocular MG differ from generalized MG and how this might affect commercialization plans and treatment duration.

Answer

Chief Executive Officer Tim Van Hauwermeiren described ocular MG as a debilitating condition with high unmet need and a very limited treatment toolbox, typically consisting of mestinon and high-dose corticosteroids. He positioned VYVGART as a disruptive alternative with a strong benefit-risk profile, highlighting the opportunity to offer these patients a real alternative to chronic high-dose steroids.

Asked for details on the profile of patients starting OGSIVEO (e.g., active progressors, switching, from watch-and-wait) and whether this mix has been changing.

Answer

Patients are coming from across the entire treatment continuum, including newly diagnosed, those who were on 'watch and wait', and patients switching from other therapies like TKIs or chemotherapy. There isn't one specific group that is dominant. The company believes it's a matter of 'when, not if' patients get treated, and with greater awareness, they expect more patients to receive OGSIVEO earlier in their treatment journey.

David Nierengarten from Wedbush Securities asked if the EOS-448/dostarlimab combination trial is dependent on data from the pembrolizumab study, and inquired about plans to use the adenosine biomarker assay in future combination trials.

Answer

CMO Joe Lager confirmed that the dostarlimab combination trial is not gated by the pembrolizumab study results and is proceeding at full speed. He also stated that the adenosine biomarker assay will be incorporated into future studies, including dedicated cohorts for biomarker-high patients and its inclusion in the melanoma and upcoming randomized trials.

David Nierengarten of Wedbush Securities questioned the proprietary nature of the A2A receptor expression assay and how it could be protected. He also asked if the assay provides a true competitive advantage if a majority of tumors express the receptor, potentially allowing competitors to target tumor types without the assay.

Answer

President and CEO Michel Detheux stated that the company has taken steps to protect the novel biomarker through patent applications. Chief Medical Officer Dr. Joe Lager added that the assay's competitive advantage lies in its novelty and the difficulty of its development, giving iTeos a head-start in understanding A2A receptor expression as a continuous variable across different tumors, which is not widely known.