Alexander Thompson

Alexander Thompson asked about the CAH Phase III trial design, specifically regarding investigator discretion in glucocorticoid reduction and whether guidelines are in place to manage potential variability.

Answer

Dr. R. Struthers, CEO, explained that the trial is designed to reflect real-world clinical practice. He clarified that while investigators have discretion in the pace of glucocorticoid tapering for individual patients, the protocol provides general guidance on reduction increments to ensure a careful and judicious process.

Alexander Thompson asked how the net price of VYVGART should be expected to evolve over time, given the introduction of the pre-filled syringe (PFS) and three available formulations.

Answer

Chief Operating Officer Karen Massey highlighted the positive reception and optimal label for the PFS, positioning it as a growth driver. Chief Financial Officer Karl Gubitz explained that the PFS, as a pharmacy benefit product, will have a lower net price per patient due to manufacturer payments in the catastrophic phase. He reiterated the annual net price guidance of $225,000 for gMG and $450,000 for CIDP, noting it will evolve over time.

Alexander Thompson asked for more detail on the potential magnitude and rate of the net price impact from the prefilled syringe (PFS) launch.

Answer

Chief Financial Officer Karl Gubitz explained that the shift to self-administration will move patients to the pharmacy benefit (Medicare Part D), which will increase the gross-to-net percentage due to higher rebates and the IRA redesign. However, he expects this impact to be offset by increased patient volumes. He also noted that value-based agreements (VBAs) would likely phase out over time.

Alexander Thompson asked about the expectation for self-administration for CIDP at launch and whether the prefilled syringe (PFS) is the primary route to achieving that on the label.

Answer

COO Karen Massey clarified that the initial VYVGART Hytrulo label for CIDP, if approved, would be for healthcare provider (HCP) administration. She confirmed that the PFS is the intended path forward to seek a self-administration label for both gMG and CIDP, subject to FDA review and approval.

Alexander Thompson asked for an update on the progress toward restarting the Phase III HARMONY study for pegtibatinase and when more specific timelines might be provided.

Answer

SVP of R&D, Dr. Bill Rote, reported that the company is making good progress with its CDMO partners on the necessary process improvements for manufacturing scale-up. He reiterated the expectation to restart enrollment for the HARMONY study in 2026, noting that a more precise timeline is data-driven and depends on the outcomes of the ongoing scale-up experiments.

Alexander Thompson inquired about the commercial supply readiness for YORVIPATH's U.S. launch and whether the company still plans to run a broader basket study for TransCon CNP.

Answer

Jan Mikkelsen, President and CEO, asserted that Ascendis has 'unlimited supply' for YORVIPATH, with a robust manufacturing and supply chain in place. He also confirmed the company is planning a basket trial for CNP-related diseases, in addition to a trial in hypochondroplasia, as part of its broader strategy to be a leader in treating various growth disorders.

Alexander Thompson asked what specific data the FDA needs to see to approve the use of current YORVIPATH material for a potential Q4 U.S. launch.

Answer

President and CEO Jan Mikkelsen stated his belief that the FDA already has all the necessary data to make a decision. He clarified that current discussions are focused less on data and more on logistical aspects, such as ensuring sufficient supply to manage the expected high demand upon launch, rather than on any outstanding data requests from the agency.

Alexander Thompson of Stifel asked what the company wants to see from the upcoming Myasthenia Gravis (MG) and CIDP data to validate the best-in-class profile for IMVT-1402. He also questioned if there were any scenarios where the older asset, batoclimab, would be moved forward for registration.

Answer

Executive Peter Salzmann responded that the fundamental thesis is that deeper IgG reduction correlates with better clinical response, a trend seen in the Graves' and nipocalimab data. He stated the goal for the MG and CIDP readouts is to demonstrate this same correlation across multiple clinical parameters over time. The question about batoclimab was not directly answered, with the focus remaining on IMVT-1402.

Alexander Thompson asked what Immunovant needs to see in the upcoming Myasthenia Gravis (MG) and CIDP data to validate the best-in-class profile for IMVT-1402, and if there was any scenario for batoclimab to move forward.

Answer

Executive Peter Salzmann responded that the key goal is to demonstrate a strong correlation between deeper IgG reduction and clinical improvement across multiple endpoints, reinforcing the company's core thesis. He emphasized that seeing this correlation over time in MG and CIDP, similar to the Graves' data, would provide high confidence in the asset's profile. The response focused exclusively on the path forward for IMVT-1402.

Alexander Thompson from Stifel questioned the human dose equivalents being tested in the VTX3232 mouse obesity study and what results would build confidence for the human trial. He also asked about the potential for VTX2735 in hidradenitis suppurativa (HS) following recent data from competitors.

Answer

CEO Raju Mohan clarified that mouse studies are for proof-of-concept and not for determining human dosage, which is calibrated from Phase I human data. He stated the goal is to assess weight loss and other metabolic parameters, and to see if the combination with semaglutide is additive. Regarding HS, he acknowledged the potential for an NLRP3 inhibitor but cautioned that there isn't a direct one-to-one correspondence with the IL-1 alpha/beta antibody mechanism shown by competitors.

Alexander Thompson of Stifel inquired about the appropriate safety benchmark for TEPEZZA, asking if the chronic TED study is more representative than the original Phase III trials due to more focused hearing measurement. He also asked if the VRDN-001 Phase III top-line data release would include information beyond the 15-week endpoint.

Answer

President and CEO Stephen Mahoney confirmed the top-line data release will be limited to the 15-week primary endpoint. Chief Medical Officer Thomas Ciulla added that Veridian is recording adverse events using standard MedDRA terms and is also assessing audiometry at baseline and prespecified points, which aligns with the evolving clinical practice and FDA guidance.

Asked about the key differences between ATI-2138 and Pfizer's ritlecitinib, and whether there is a potential for differentiation on the black box warning or if one is expected.

Answer

The key differentiation is that ATI-2138 has similar high potency against both ITK and JAK3, whereas ritlecitinib is primarily a JAK3-biased drug with little impact on ITK at its clinical dose. Regarding the black box warning, they assume one will be required for any JAK inhibitor but note that the specifics are data-driven and can differ between drugs.

Alexander Thompson asked for more detail on the differentiation between ATI-2138 and Pfizer's ritlecitinib, and whether Aclaris anticipates a black box warning for its drug.

Answer

Interim CEO Neal Walker stated that for any JAK-targeting drug, a black box warning should be anticipated, but the final label is data-driven and varies between products. Chief Scientific Officer Joseph Monahan elaborated on the key differentiation, explaining that while both are covalent inhibitors, ATI-2138 has similar high potency against both ITK and JAK3. In contrast, ritlecitinib is a JAK3-biased drug with little impact on ITK at its clinical dose, meaning ATI-2138 is expected to provide significant blockade of both pathways.

Alexander Thompson asked how ATI-2138 differs from Pfizer's ritlecitinib and whether the drug could potentially differentiate itself regarding the class-wide black box warning.

Answer

Interim CEO Neal Walker noted that while a black box warning should be anticipated for any JAK-targeting drug, the final label is data-driven and can vary. Chief Scientific Officer Joseph Monahan detailed the key differentiation: while both are covalent inhibitors, ATI-2138 has similar high potency on both ITK and JAK3, whereas ritlecitinib is a JAK3-biased drug with little impact on ITK at its clinical dose. This allows ATI-2138 to meaningfully block both pathways.