Whitney Ijem

Whitney Ijem asked for expectations regarding the upcoming WVE-007 data (240mg 6-month, 400mg 3-month) on body composition and fat reduction, and for WVE-006 (400mg multi-dose) on AAT levels.

Answer

President and CEO Paul B. Bolno outlined expectations for WVE-007, noting that the 240mg cohort already shows fat loss similar to GLP-1s, with higher visceral fat reduction and lean mass preservation. He anticipates continued fat reduction and lean mass stabilization, driving overall weight loss, and expects to see the impact of both time and dose on fat reduction. For WVE-006, Bolno reiterated that the goal is to achieve a therapeutic threshold for an MZ phenotype, demonstrated by 20 micromolar AAT levels at the lowest single dose during an acute inflammatory event. He emphasized that the focus for the 400mg multi-dose data will be on durability and the potential for increased M protein production over time, as well as sustained editing efficiency, to support less frequent dosing.

Whitney Ijem asked for clarification on why the POMC, PCSK1, and SH2B1 substudies within EMANATE were considered higher probability for success, inquiring if this was due to enrollment/powering or genetic/biological factors. She also asked if a 5% weight loss remained the benchmark for success in these studies.

Answer

David Meeker, Chairman, CEO, and President, explained that POMC was most likely due to an assay identifying pathogenic variants and full enrollment. He noted the leptin receptor cohort was under-enrolled, and SRC1 had many Variants of Unknown Significance. For SH2B1, he highlighted the 16p11.2 deletion group as having clear loss of function. Dr. Meeker confirmed that 5% weight loss is the minimal threshold for success, particularly in challenging diseases, but emphasized the importance of clinical meaningfulness beyond just the percentage.

Whitney Ijem asked for clarification on why POMC PCSK1 and SH2B1 substudies in EMANATE are considered higher probability, inquiring if this is due to enrollment/powering or genetic/biological factors, and also asked if a 5% weight loss remains the success benchmark.

Answer

David Meeker, Chairman, CEO, and President, explained that the higher probability for POMC is due to an assay identifying pathogenic variants and full enrollment, while SH2B1 is hopeful due to deletions. He noted that leptin receptor was under-enrolled and SRC1 had many Variants of Unknown Significance. Meeker confirmed that 5% weight loss is the minimal threshold for success, especially in challenging diseases like Prader-Willi, but acknowledged that expectations for weight loss drugs in other indications might be higher.

Whitney Ijem from Canaccord Genuity asked about the potential launch trajectory for hypothalamic obesity (HO) in Europe compared to BBS and inquired about expectations for the HO drug label, including any potential restrictions.

Answer

David Meeker, CEO, explained that while Europe has advantages like centers of excellence, the HO launch dynamic will be similar to the U.S. due to the high concentration of patients with endocrinologists. He does not expect a BMI requirement in the label, anticipates an age restriction of 4 years and older based on the trial, and noted the company will again try to get hunger included in the indication statement.

Whitney Ijem requested an update on the ongoing work to define the prevalence of hypothalamic obesity (HO) from causes other than craniopharyngioma, including congenital forms.

Answer

CEO David Meeker explained it is a work in progress but confidence in their initial estimates is growing. He noted that other tumors contribute significantly, the 20-year post-injury survival model may be conservative, and a large pool of patients with HO from other injuries likely remains undiagnosed.

Whitney Ijem sought clarification on the basis for the regulatory filing in Japan, asking if it requires the full Japanese cohort to complete one year of follow-up or if an interim analysis is possible.

Answer

Chairman, CEO and President David Meeker confirmed that the Japanese filing is contingent on the full 12-patient Japanese cohort completing the one-year follow-up period. The filing will occur after the last Japanese patient finishes the trial at the one-year mark.

Whitney Ijem of Canaccord Genuity Inc. asked about the dosing differences for cutaneous venous malformations (CVM) versus microcystic lymphatic malformations (MLM), the relative lesion sizes, and the key criteria used to select new pipeline indications, particularly regarding patient population size.

Answer

Chief Scientific Officer Jeff Martini explained that the dosing is standardized, with one pump actuation covering about 200 cm², up to a maximum of 400 cm² for both indications. President and CEO Wes Kaupinen outlined the selection criteria for new indications, which include a high unmet need (no FDA-approved therapies), a serious impact on quality of life, and an orphan, but not ultra-orphan, patient population.

Whitney Ijem of Canaccord Genuity Inc. asked about long-term follow-up plans for the REMAIN-one midpoint cohort and sought expectations for the six-month DEXA scan data regarding body composition.

Answer

Harith Rajagopalan, Co-Founder, CEO & Director, confirmed that patients in the cohort will be followed for a year with incremental data updates, and the company intends to follow them longer to demonstrate durability. Regarding DEXA scans, he noted a lack of historical data on body composition changes after tirzepatide withdrawal, stating he is excited to see what the randomized, controlled data will reveal.

Whitney Ijem from Canaccord Genuity asked for quantification of how far ahead schedule REMAIN-1 enrollment was, details on the sham procedure, patient stratification methods, and the timeline for dosing patients in the Rejuva study.

Answer

CEO Harith Rajagopalan reported that REMAIN-1 enrollment finished about three months ahead of schedule due to high demand at individual sites. He described a rigorous sham procedure involving a catheter introduction for all patients, with strict blinding protocols. For the midpoint cohort, randomization is stratified by baseline BMI and gender. He reiterated guidance for first Rejuva patient dosing and data in 2026.

Whitney Ijem of Canaccord Genuity asked for an update on the potential Astellas opt-in, questioning if the timeline was accelerated by recent progress and seeking details on current conversations.

Answer

CFO Kamran Alam confirmed that the agreement has specific data-based triggers, and the required pediatric data package is forthcoming. He declined to comment on any specific ongoing discussions with Astellas, stating only that Taysha will execute the agreement as it is written.

Whitney Ijem inquired about the level of patient demand for the TSHA-102 trials, especially among adults, to gauge market opportunity. She also requested details on the patient treatment experience, including the immunomodulatory regimen and administration day logistics.

Answer

CEO Sean Nolan confirmed significant patient demand for trial slots across both adult and pediatric cohorts. President and Head of R&D Sukumar Nagendran detailed the immunosuppression regimen, noting its duration has been shortened with experience. He contrasted the simple, 10-20 minute intrathecal lumbar puncture with more invasive procedures, highlighting its potential for outpatient administration.

Whitney Ijem of Canaccord Genuity asked for specifics on the FEV measurement time points in the CF study, the duration of follow-up data to expect in the interim analysis, and sought clarification on the KOSTAIVE U.S. milestone payment.

Answer

President and CEO Joseph Payne explained that FEV is measured approximately seven times throughout the CF study, and the interim data will cover the full 28-day treatment course, though perhaps not the entire multi-month follow-up period. CFO Andrew Sassine clarified that there is no milestone payment for U.S. approval of KOSTAIVE, but there is one for first commercial sales, which is not included in the cash runway guidance as it's not expected before 2028.

Whitney Ijem asked if the switch to domestic manufacturing at ARCALIS in Japan would lead to an acceleration in KOSTAIVE sales. She also questioned the reason for the shift in the OTC interim Phase II data timeline from Q4 2024 to the first half of 2025.

Answer

CFO Andrew Sassine confirmed that a more aggressive commercial launch for KOSTAIVE could be anticipated in the December-January timeframe once domestic production begins, with revenue likely recognized in the first half of 2025. CEO Joseph Payne explained the OTC data timeline shifted because the company decided it was prudent to combine data from the completed European dosing phase with the newly initiated U.S. study for a more comprehensive interim update.

A representative for Whitney Ijem asked for the rationale behind obtaining a U.S. IND for the NTLA-2001 polyneuropathy study, given that the Phase III trial will be conducted entirely ex-U.S.

Answer

CMO David Lebwohl explained that obtaining the IND was a strategic step to secure agreement with the U.S. FDA on the trial's design. This ensures the study, although conducted abroad, will be suitable for a future BLA submission in the United States.

Whitney Ijem of Canaccord asked about the upcoming FTD data, questioning which biomarkers will be reported, what the target levels are for CSF progranulin, and whether the update will include data from a complete cohort.

Answer

CEO Will Chou clarified that the initial data will focus on safety and CSF progranulin levels, with an expectation to see at least physiologic levels based on preclinical data. He stated they will report data on multiple patients from the first cohort in the second half of the year and will provide more specific guidance on numbers later.

Whitney Ijem of Canaccord Genuity asked about the upcoming FTD program data, seeking details on which biomarkers will be reported, the target levels for CSF progranulin, and whether the data update will represent a complete patient cohort.

Answer

CEO Will Chou clarified that the initial data from Cohort 1 will focus on safety and CSF progranulin levels at baseline and 30 days post-treatment. He noted that based on preclinical data, the expectation is to see at least physiologic levels of CSF progranulin. He also confirmed that data from multiple patients in the first cohort would be provided in the second half of the year.

Whitney Ijem from Guggenheim asked about the data read-through from the initial NCH-treated DMD patients to Audentes' own program and inquired about the financial benefits of in-house plasmid manufacturing.

Answer

Chairman and CEO Matt Patterson explained that data from the 1-2 NCH patients will be of limited value and the key data will come from Audentes' improved product. He also emphasized that in-house plasmid manufacturing offers significant benefits in quality control, cost savings that will rapidly pay for the investment, and more reliable development timelines.

Whitney Ijem of Guggenheim Securities requested more detail on the XLMTM data from ASGCT, specifically asking for mean protein expression numbers from Cohort 1 biopsies and an explanation for the variability in protein expression across muscles and over time.

Answer

Matt Patterson, Chairman and CEO, responded that he would follow up with specific mean protein expression numbers. He addressed variability by explaining that biopsies are inherently variable due to being taken from different muscle sites at different times. He emphasized that after a blinded review by external muscle pathology experts, the consensus was that there were no meaningful differences or drops in expression, and the data received universally positive feedback on its correlation with clinical outcomes.