Michael Ulz

Michael Ulz requested clarification on the specific pharmacodynamic (PD) data expected to be shared for the DM1 and FSHD programs later this quarter, particularly whether splice correction or vHOT data should be anticipated.

Answer

Louise Rodino-Klapac, Executive VP, Chief Scientific Officer, and Head of Research and Development, clarified that for DM1, early DMPK knockdown data will be available. For FSHD, the preliminary readout will include DUX4 targeted gene correction data.

Michael Ulz asked if there has been a recent shift in the age or ambulatory status of patients being treated with ELEVIDYS.

Answer

President and CEO Douglas Ingram responded that while it's too early to identify a precise trend, the company continues to see start forms coming in for both ambulatory and non-ambulatory patients. He reiterated that there is no data suggesting a differential safety risk based on ambulatory status, so there should be no reason for a significant difference in uptake between the groups once education is complete.

Michael Ulz from Morgan Stanley asked for the timeframe and key considerations regarding the company's $500 million share repurchase program.

Answer

CFO Ian Estepan stated the program has an 18-month timeframe. He explained that after funding the Arrowhead transaction, the company projects its cash reserves will return to year-end 2024 levels by the end of 2025 due to the strong ELEVIDYS launch. The company will look to be opportunistic in deploying capital for buybacks as cash reserves build, but will not telegraph the specific timing.

Michael Ulz followed up on PMO cannibalization, asking about the company's expectations for this trend longer-term, beyond 2025.

Answer

CEO Douglas Ingram acknowledged that while the company has always modeled eventual robust cannibalization, what they have observed so far and are modeling for 2025 is very modest. He suggested that cannibalization might become more significant in the years after 2025, but also noted that their internal models may have been too aggressive on this front.

Michael Ulz inquired about recent FDA interactions regarding the sHTG filing for Olezarsen and whether Ionis's confidence in receiving priority review has changed, given the current guidance assumes standard review.

Answer

CEO Brett Monia stated that Ionis believes Olezarsen deserves priority review based on unmet medical need and product profile, noting the ongoing FDA evaluation period and breakthrough therapy designation. Chief Clinical Development Officer Eugene Schneider confirmed that regulatory interactions have been on track.

Michael Ulz asked for an update on any recent FDA interactions regarding the sHTG filing for olezarsen and whether Ionis's thinking on the potential for priority review has changed recently.

Answer

Brett Monia, CEO, stated that Ionis believes olezarsen deserves priority review due to the unmet medical need and compelling product profile, noting its breakthrough therapy designation. He confirmed that the company is within the FDA's evaluation window for priority review. Eugene Schneider, Chief Clinical Development and Operations Officer, added that regulatory interactions have been on track.

Michael Ulz from Morgan Stanley questioned the rationale for narrowing the SHTG data timeline to September and asked for clarity on what level of acute pancreatitis (AP) data would be included in the top-line press release.

Answer

CEO Brett Monia explained that refining the timeline to September was simply due to operational progress in completing the studies and cleaning the data. He confirmed the top-line release will include a statement on AP findings, with the full dataset to be presented at a medical congress later in the year.

Michael Ulz asked for the reason behind narrowing the olezarsen CORE/CORE2 data readout timing to Q3 and whether the initial top-line results will include the 12-month acute pancreatitis (AP) data.

Answer

CEO Brett Monia explained the more precise Q3 timing reflects increased clarity as the readout approaches. He confirmed the top-line data release for the CORE and CORE2 studies will focus on the primary endpoint of triglyceride reduction and safety. He stated that the company is still determining if the AP data analysis will be complete in time for the initial announcement but will share it if available.

Michael Ulz of Oppenheimer & Co. Inc. inquired about the potential read-through from the olezarsen ESSENCE safety study to the pivotal CORE studies in severe hypertriglyceridemia (sHTG), given the different patient populations.

Answer

CEO Brett Monia explained that the ESSENCE study, while conducted in a lower-risk population, will provide important read-throughs on safety and target engagement (APOCIII reductions). He noted that while triglyceride reduction data will be an indicator, it is a less direct predictor for the sHTG population, with the primary focus being on validating the drug's safety profile.

Michael Ulz asked about Vir Biotechnology's confidence in the durability of VIR-5500's strong early data and whether the data presented today is identical to what will be shared at the ASCO GU meeting.

Answer

Mark Eisner, EVP and Chief Medical Officer, expressed encouragement regarding durability, citing RECIST responses up to 27 weeks, concordance with PSMA PET and deep PSA responses, and case studies showing up to one year of durability. He noted that radiographic PFS data is still maturing. Marianne De Backer, CEO and Director, clarified that the ASCO GU oral presentation will be a subset of today's data, with no additional updates.

Michael Ulz asked about the level of confidence in the durability of the strong early VIR-5500 data over the longer term. He also asked if the data shared today is the same as what will be presented at ASCO GU.

Answer

Mark Eisner, EVP and Chief Medical Officer, expressed encouragement regarding RECIST responses up to 27 weeks, confirmed responses, and concordance with PSMA PET and deep PSA responses, noting Dr. Debono's case studies showing up to 1 year of durability. Marianne De Backer, CEO and Director, clarified that the ASCO GU oral presentation will be a subset of the data shared today, with no additional new data.

Michael Ulz followed up on the Phase III trial design for hepatitis delta (HDV), asking if Vir has received any unexpected feedback from the FDA during their recent interactions or if the program is progressing as anticipated.

Answer

Dr. Mark Eisner, Chief Medical Officer, described the meeting with the FDA as "very productive" and stated that Vir aligned closely with the agency on the clinical development plan. He confirmed that the final details will be revealed at the upcoming investor event.

Michael Ulz asked about the potential next steps for Arrowhead's obesity programs, assuming the upcoming data readouts are positive.

Answer

CEO Christopher Anzalone emphasized that the company is in the 'truth-seeking business' and does not pre-plan next steps before seeing the data. Interim Chief Medical Scientist Bruce Given added that because these are novel mechanisms, unlike another GLP-1 agonist, it is difficult to predict the development path without initial human data.

Michael Ulz of Morgan Stanley requested a reminder of the U.S. patient population size for Familial Chylomicronemia Syndrome (FCS) and asked about the company's progress in identifying these patients.

Answer

An executive stated the FCS prevalence is estimated at 1 to 13 per million, translating to a few hundred to mid-single-digit thousands of patients in the U.S. He confirmed that internal analytics and marketing teams are using advanced technologies for patient-finding, which is critical for an ultra-rare condition.

Michael Ulz of Morgan Stanley inquired about the progress with the FDA on the Fragile X syndrome trial design and whether any further regulatory feedback was needed before initiation.

Answer

Chief Medical Officer Joanne Quan confirmed that the company is "good to go" with the trial, having received a "study may proceed" letter from the FDA after clearing the IND. She added that feedback from patient and physician communities has been incorporated, keeping the trial on track to enroll its first patient by year-end.

Michael Ulz asked about chenodiol for CTX, requesting a reminder of the potential market opportunity and the likely impact on sales if the indication is added to the label, given the upcoming PDUFA date.

Answer

President and COO Peter Radovich stated that literature estimates suggest 1,000 to 2,000 prevalent CTX patients in the U.S., with only about 10% currently diagnosed. He explained that an on-label approval would allow for active promotion aimed at increasing the diagnosis rate, which could have a meaningful impact on the product's current sales trajectory.

Michael Ulz of Morgan Stanley followed up on the Prader-Willi trial, asking about the expected duration of patient follow-up and whether next-generation MC4Rs like Bivomelagon would be considered for this indication if the data is positive.

Answer

David Meeker, Chairman, President & CEO, stated that patients will be evaluated at six months but will continue on treatment indefinitely if they are benefiting, as long-term data is valuable. He confirmed that while next-generation molecules are the future, a compelling result could lead to rapidly advancing setmelanotide for Prader-Willi, with next-gen compounds certainly following.

Selina on behalf of Michael Ulz of Morgan Stanley asked for a description of the patient mix being seen in the congenital hypothalamic obesity (HO) substudy and any learnings on reliable diagnosis.

Answer

David Meeker, CEO, responded that it is too early to provide a meaningful breakdown of the patient mix across different pituitary deficiency disorders. He mentioned that conditions like septo-optic dysplasia (SOD) and pituitary stalk interruption syndrome are among those being seen, but the study is in its very early stages.

Michael Ulz of Morgan Stanley asked if the company has observed any combination use of Amvuttra with a stabilizer therapy early in the cardiomyopathy launch.

Answer

CCO Tolga Tanguler confirmed that they have seen a 'very small portion' of patients receiving combination therapy where access is permissible. He suggested this trend could become more prominent in the future as tafamidis becomes generic but noted it is currently difficult to quantify precisely.

Michael Ulz inquired about the rate of diagnosis for ATTR cardiomyopathy and whether it has accelerated with new market entrants. He also asked for an outlook on what the diagnosed patient percentage, currently around 20%, could reach by year-end.

Answer

Chief Commercial Officer Tolga Tanguler stated that there is empirical evidence that more market participants accelerate category growth, pointing to the polyneuropathy market and the recent record growth of the stabilizer class. While he declined to predict a specific diagnosis rate for year-end, he expressed confidence that more voices in the space will help accelerate diagnosis.

Michael Ulz from Morgan Stanley requested more details on the upcoming maintenance study, specifically asking about the number of cohorts being considered and the planned duration of treatment in that trial.

Answer

President & CEO Brian Lian described the maintenance study as complex and sizable, likely with more arms than the VENTURE oral study, as it will test monthly injections, daily orals, and a weekly oral. He indicated the post-transition evaluation period would be around three months but would provide more detail upon study initiation.

Michael Ulz asked about the specific weight loss targets for the upcoming Phase II VENTURE oral data readout and how the company thinks about the potential efficacy levels at both lower and higher doses.

Answer

Brian Lian, President and CEO, stated that it is difficult to project specific outcomes but suggested that achieving around 8% weight loss after 13 weeks would establish a competitive profile. He noted it was hard to predict the performance of lower doses but remained hopeful they would show good efficacy over the extended treatment period.

Michael Ulz asked for the rationale behind narrowing the start time for the Phase III obesity study to Q2 2025 from the previous guidance of H1 2025, and what steps remain before initiation.

Answer

CEO Brian Lian attributed the more precise timing to improved visibility on the logistical timeline for manufacturing the clinical drug product. He reassured that the program is proceeding according to plan without any issues.

Michael Ulz asked for clarification on the Q2 revenue guidance for DANYELZA, which implies a sequential decline from Q1, and questioned the underlying trends.

Answer

CEO Michael Rossi attributed the guidance to product seasonality and a particularly strong Q1 for ex-U.S. sales. CFO Peter Pfreundschuh elaborated that Q2 2024 included nearly $5 million in ex-U.S. stocking orders not expected in Q2 2025. He stressed the guidance is realistic and reiterated confidence in the full-year forecast of $75M-$90M, anticipating a U.S. rebound in the second half of the year.

Michael Ulz of Morgan Stanley requested a breakdown of the 2025 operating expense guidance between R&D and SG&A and asked how R&D spending is expected to evolve as the SADA program ramps up in future years.

Answer

CEO Michael Rossi explained that while SADA R&D costs will increase with new targets, this is factored into the cash runway. He mentioned cost savings from the completion of the DANYELZA 201 study and a new, more efficient process for advancing SADA targets. CFO Peter Pfreundschuh clarified the OpEx guidance, suggesting analysts start with the 2024 SG&A figure of ~$55M, subtract ~$9M in one-time charges, and assume the rest of the guided OpEx is for R&D.

Michael Ulz from Morgan Stanley followed up on the GD2 SADA trial, asking for the specific dose being tested in Cohort 5 and whether there are plans to proceed to a higher-dose Cohort 6.

Answer

Chief Medical Officer Dr. Vignesh Rajah confirmed that Cohort 5 is testing a dose of 1 milligram per kilogram with a 4-day interval. He explained that the decision to proceed to a Cohort 6 will depend entirely on the dosimetry results from the current cohort, and no immediate decision has been made.

Michael Ulz of Morgan Stanley followed up on the REVEAL-1 study, seeking confirmation on the number of patients to be included in the late-month data release. He also requested an update on the development status and next steps for the Rejuva-002 program.

Answer

CEO Harith Rajagopalan confirmed the company still plans to share data from approximately 10 patients in the upcoming REVEAL-1 update. Regarding Rejuva-002, he explained it is a preclinical GIP/GLP-1 dual incretin program and that clinical timeline guidance will be provided after gathering key learnings from the more advanced RJVA-001 program.

Michael Ulz of Morgan Stanley asked about the expected weight change for a control arm at the 4-week mark in the REVEAL-1 study and sought to understand the primary rationale behind the 'controlled' commercial expansion in Germany.

Answer

Executive Harith Rajagopalan explained that based on prior GLP-1 discontinuation studies like SURMOUNT-4, a control group would be expected to regain approximately 3% of body weight at 4 weeks. Regarding Germany, he stated the controlled expansion serves a dual purpose: to carefully manage spending while also proving out the commercial model in new centers, which will generate both revenue and additional real-world data.

Michael Ulz inquired about the status of partnership discussions for zerlasiran, the importance of the delayed HORIZON data to these talks, and the types of partnership structures being considered.

Answer

Craig Tooman, President and CEO, stated that while he could not comment on specific ongoing discussions, the company remains actively engaged. He noted that the HORIZON data delay has spurred more funding interest in the Lp(a) space. Tooman emphasized that Silence is a portfolio company and the decision to wait for a partner before starting the Phase III trial allows for prudent resource management and focus on maximizing returns across all assets, including divesiran.

Michael Ulz inquired about the status of partnership discussions for zerlasiran, the importance of the HORIZON data readout for these talks, and the types of partnership structures being considered.

Answer

Craig Tooman, President and CEO, stated that while he could not comment on specific discussions, the company is actively engaged in partnering talks for zerlasiran. He noted that the decision to require a partner before initiating the Phase III study strengthens the company's cash position and provides flexibility. He emphasized the company's strong belief in zerlasiran's potential and its highly differentiated Phase III program design.

Michael Ulz inquired about the status of partnership discussions for zerlasiran, the importance of the delayed HORIZON data to these talks, and the types of partnership structures Silence Therapeutics is considering.

Answer

Craig Tooman, President and CEO, stated that while he could not comment on specific discussions, the company remains actively engaged in partnering talks for zerlasiran. He noted that the decision to secure a partner before initiating the Phase III trial strengthens the company's cash position and reflects shareholder feedback. Tooman emphasized that Silence is a multi-asset company and this move allows for better resource management while they continue to pursue the right partner for the high-potential zerlasiran program.

On behalf of Michael Ulz of Morgan Stanley, an analyst asked about the observations and safety profile of the first lupus patient treated with FT819 compared to autologous therapies, and which other autoimmune diseases Fate might consider for expansion.

Answer

CEO Scott Wolchko reported that the first lupus patient had an uneventful 3-day hospitalization with no notable adverse events, though the patient is still in the DLT assessment period. Regarding expansion, he stated the company is evaluating opportunities based on clinical precedent from other cell therapies but is not disclosing a specific strategy at this time.