David Lebowitz of Citigroup asked if the company's thinking on the ultimate market size for Yorvipath has evolved.
President & CEO Jan Møller Mikkelsen reaffirmed his bullish outlook, stating he has "no doubt" that hypoparathyroidism will become a "$5,000,000,000 $8,000,000,000 market segment."
David Lebowitz inquired about the expected timeline to transition the remaining NATPARA patient population to new therapies and asked how patient interest in YORVIPATH compares to what was observed with NATPARA.
President and CEO Jan Mikkelsen projected that the last of the NATPARA patients would likely switch over by the end of Q2 or during Q3 2025, based on Takeda's supply communications. He drew a sharp distinction between the two drugs, stating they are not comparable. He positioned YORVIPATH as a superior therapy that normalizes PTH levels, unlike NATPARA, which was labeled as an adjunct therapy and lacked demonstrated benefits on kidney function or quality of life.
David Lebowitz asked about the potential challenges of titrating a long-acting GLP-1 agonist and how SKYTROFA's net price has evolved as the company has added new payers.
Jan Mikkelsen, President and CEO, explained that the TransCon technology's profile, with a very long time to maximum concentration (Tmax), is expected to improve tolerability and mitigate titration issues. Regarding pricing, he reiterated the consistent strategy of maintaining SKYTROFA's net value at approximately 3x that of daily growth hormone.
David Lebowitz sought clarification on the SKYTROFA revenue adjustment, confirming it was a true-up for prior sales due to new payer agreements, and asked what accelerated the TransCon CNP data timeline.
President and CEO Jan Mikkelsen and CFO Scott Smith confirmed the SKYTROFA adjustment was a true-up for sales in Q1 2024 and 2023, which should be added back to reported Q2 revenue to reflect the quarter's actual performance. Regarding TransCon CNP, Mikkelsen attributed the accelerated timeline to highly efficient clinical operations and strong dedication from physicians and trial sites, leading to faster-than-expected data collection.
An analyst on behalf of David Lebowitz from Citigroup asked why a TSH antagonist for Graves' disease hasn't been successfully developed before, given its obvious disease-modifying mechanism, and what Crinetics is doing differently.
CEO R. Scott Struthers positioned this as a core strength, noting these are very difficult targets. Chief Scientific Officer Stephen Betz elaborated that Crinetics focuses on directly blocking the primary receptor (like the TSH receptor for Graves' or ACTH receptor for CAH) rather than finding workarounds. He credited the company's 17 years of expertise in medicinal chemistry, biology, and receptor pharmacology for enabling them to create the right molecules for these challenging targets.
David Lebowitz noted that the new primary endpoint for the CAH trial appears to be a higher bar and asked if Crinetics could fall back on an endpoint similar to that used by crinecerfont if necessary for FDA approval.
Dr. R. Struthers, CEO, and Dr. Dana Pizzuti, CMDO, addressed this. Struthers agreed it is an intentionally high bar designed for atumelnant. Pizzuti explained that because their trial enrolls a broader patient population, a different endpoint is necessary. While secondary endpoints will capture other measures, the primary endpoint cannot be changed post-hoc for regulatory approval.
An analyst on behalf of David Lebowitz asked for the current thinking on the lack of an observed dose response in 17-OHP reduction in the atumelnant Phase II CAH data.
Chief Endocrinologist Dr. Alan Krasner explained that 17-OHP is a highly variable biomarker and that the observed clinical benefits are more significant. CEO R. Struthers added that he disagreed with the premise, stating that the company's exposure-response modeling does show a clear response for both 17-OHP and A4.
David Lebowitz of Citi inquired about potential learnings from the launch of another Kallikrein knockdown therapy that could inform Intellia's future launch of LONVOZIE for HAE.
President and CEO John Leonard acknowledged they monitor all new entrants but stressed that LONVOZIE's profile is unique. He highlighted its potential as a permanent, one-time therapy that offers freedom from both attacks and chronic treatment. He believes this unique value proposition for patients and the reduced administrative burden for physicians will make it a formidable competitor, regardless of other market entries.
David Lebowitz asked about the financial implications if events in the MAGNITUDE trial accrue slower than expected and how the FDA might view the primary endpoint's wide 18-to-48-month timing range.
CEO John Leonard assured that the company's financial runway guidance takes a conservative view, accounting for potential trial extensions. He clarified that unlike time-based trials, the MAGNITUDE study is an event-driven trial by design, meaning it concludes when a pre-specified number of events is reached, which mitigates issues with endpoint timing. The financial bridge is solid through the anticipated launch of NTLA-2002.
David Lebowitz asked what Intellia views as the bar for success in HAE, suggesting that achieving a 'functional cure' might not be the only measure.
CEO John Leonard reiterated that the 'functional cure' concept is the key commercial driver, as market research shows patients and physicians want a transformative therapy, not marginal improvements. He noted the large majority of patients have already achieved this. He also added that on traditional metrics like attack rate reduction, their data is competitive with all other agents.
David Lebowitz of Citi questioned the dramatic shift in LIVMARLI's peak sales potential from a prior $500 million figure to the new $1 billion+ target, asking for the key drivers.
Co-Founder & CEO Chris Peetz clarified the $500M figure was an old market size estimate for Alagille in the U.S. only, not a peak sales forecast. The new $1B+ global target reflects stronger-than-expected uptake across Alagille, PFIC, and international markets, plus future potential from the EXPAND study.
David Lebowitz asked for clarification on the international inventory build, questioning if it represents a new steady state. He also inquired about the nature of one-time operating expenses and what to expect for the remainder of the year.
President and Chief Operating Officer Peter Radovich explained the Q1 international inventory was a new dynamic from partners stocking product, unlike prior patient-specific orders, and should be viewed as a Q1 event. CFO Eric Bjerkholt noted that milestone payments are tied to progress and, while not providing specific guidance, expects more as the business advances.
David Lebowitz asked how the recent FDA approval of CTEXLI for CTX is expected to impact its sales trajectory, considering the existing use of chenodiol in this population.
CEO Chris Peetz explained that the strategy is to convert existing patients to the branded CTEXLI and, more importantly, to drive growth by improving diagnosis rates. He expects this to create a gradual 'bending of the curve' by getting newly diagnosed patients onto treatment earlier.
David Lebowitz asked for a comparison between the strategic decisions to in-license the Travere assets versus the new MRM-3379 asset, and how these deals reflect Mirum's general business development strategy going forward.
CEO Christopher Peetz framed both transactions as part of a consistent strategy to find 'overlooked value' that Mirum's rare disease expertise can grow. President and COO Peter Radovich elaborated that the Travere deal leveraged their pediatric liver disease insights, while the experience with Chenodiol's neurologist prescribers provided insight into the underappreciated opportunity in rare neurology with MRM-3379.
Ike Lee, on for David Lebowitz at Citigroup, asked about the number of clients using the predictive toxicology beta, its pricing model, and the timeline for a full rollout and its subsequent impact on gross margins.
CEO Ramy Farid stated that while the number of beta clients is not disclosed, all collaborators have access, and the feature will be a separately priced add-on. CFO Richie Jain clarified the current gross margin impact is tied to the two-year Gates Foundation grant that began in Q3 2024, not the beta rollout timeline.
Ike Lee, on behalf of David Lebowitz, asked about the long-term outlook for software gross margins, which have declined from the low 80s. He also asked if Schrödinger has had direct conversations with regulators about the practical implications of the FDA's guidance on reducing animal testing.
CFO Geoffrey Porges explained the margin compression is temporary and due to the Gates-funded predictive tox project, expecting margins to revert to their prior range or slightly better after its completion. CEO Ramy Farid confirmed that the company is engaged with the FDA at multiple levels and expects that engagement to increase as their predictive tox solution advances.
David Lebowitz from Citigroup inquired about the company's strategy for managing the inevitable price change for olazarsen when it gains approval for the broad SHTG indication, following its launch in the ultra-rare FCS market.
CGO Kyle Jenne acknowledged that pricing work is ongoing. He mentioned that while a typical price for a large population is in the $10-20k range, they are conducting more payer research based on olazarsen's potential value. He stated that regardless of the timing of the price adjustment, the SHTG patient population is substantial enough to maintain revenue momentum post-approval.
David Lebowitz requested details on how the acute pancreatitis (AP) analysis will be conducted in the olezarsen CORE trials and what the FDA might consider acceptable for potential labeling.
Chief Clinical Development Officer Eugene Schneider explained the prespecified analysis will assess all AP events over 12 months, comparing the olezarsen arm to placebo, and will include subgroup analyses. CEO Brett Monia added that any label inclusion for AP is data-driven, but emphasized that the primary market opportunity is based on triglyceride lowering, which is a significant unmet need. Chief Global Product Strategy Officer Kyle Jenne noted the existing AP data in the TRYNGOLZA label is beneficial.
David Lebowitz asked for details on how Ionis is building its sales operation for the independent launches of donidalorsen and olezarsen, including the structure of the sales teams and the strategy for competing in the crowded HAE market.
Chief Commercial Officer Jonathan Birchall stated that the company is fully prepared for the olezarsen FCS launch, with all commercial functions and the field force hired and in place. He noted significant synergies for the subsequent donidalorsen launch, with hiring for its sales leadership underway. He expressed confidence that donidalorsen's strong data package will allow it to compete effectively in the HAE market, which remains underserved despite being competitive.
David Lebowitz from Citi asked for the specific indication drivers for Jakafi's growth in the quarter and inquired about any impact from the Inflation Reduction Act (IRA) on out-of-pocket costs.
CEO Bill Meury confirmed growth across all three indications, highlighting polycythemia vera (PV) as a double-digit grower, with MF and GVHD growing in the mid-single digits. EVP Mohamed Issa stated the IRA had no impact on Q2 performance, clarifying that a favorable gross-to-net impact in Q1 was a one-time effect and that Q2 growth was driven by demand.
David Lebowitz of Citi inquired about the practical implementation of the IRA's out-of-pocket cap, asking about the process patients must follow to ensure the cap is applied and how long it might take for the benefits of this change to become visible in sales figures.
Christiana Stamoulis, CFO, clarified that the 2025 out-of-pocket cap is $2,000 and patients have an option to spread these payments throughout the year. She noted that it will likely take some time for patients to navigate this new process, so the benefit may not be immediate, but it is expected to provide a continued positive impact as seen in 2024.
David Lebowitz from Citigroup Inc. asked if the reduction in Medicare Part D out-of-pocket costs played a role in Jakafi's recent growth and inquired about the type of data that might be presented at the upcoming ASH conference.
An unnamed executive stated that while lower out-of-pocket costs are beneficial for patients, Jakafi's growth is primarily driven by strong demand, particularly in polycythemia vera, where physicians are initiating treatment earlier based on the MAGIC-PV study results. Steven Stein, an executive, added that it was premature to comment on specific ASH presentations until acceptances are confirmed.
David Lebowitz of Citi asked for key takeaways from the discontinuation of the STELLAR-305 head and neck cancer trial and whether any learnings could be extrapolated to future studies.
Amy Peterson, EVP of Product Development & Chief Medical Officer, explained that zanzalutinib is a franchise molecule with numerous development paths. She emphasized that rigorous drug development requires continuous assessment of emerging data and that the company will share the specific trial data at a future point.
David Lebowitz asked how to interpret the various patient subgroups from the recent cabozantinib NET data presented at ASCO GI in the context of potential clinical use and the final label.
Chief Medical Officer Amy Peterson explained that while she couldn't comment on the final label, the CABINET trial enrolled a very broad patient population across various tumor origins and types. She noted that clinical benefit was observed across all subgroups, and the data for the GI-origin subgroup was consistent with the overall population, suggesting broad applicability of the drug.
Jonathan, on behalf of David Lebowitz, asked about the commercial preparations for a potential CABOMETYX launch in neuroendocrine tumors (NET) and the expected cadence of the initial rollout.
EVP of Commercial P.J. Haley confirmed the team will be ready for launch on day one. He anticipates a very strong and rapid uptake, driven by strong data, an expanded sales force, significant prescriber overlap with current CABOMETYX users, and a lack of direct competition from other branded oral therapies.
David Lebowitz of Citi inquired about the market opportunity presented by the MAPLE-HCM trial, given that beta-blockers are inexpensive and widely used.
Robert I. Blum, President and CEO, characterized a positive MAPLE result as an incremental, not transformative, opportunity that would enhance category penetration, particularly with community cardiologists. Andrew Callos, EVP and CCO, added that a second positive dataset would boost physician confidence in the CMI class and could increase aficamten's market share.
David Lebowitz asked if the FDA provided a specific framework for the clinical endpoints and analysis they want to see from the Huntington's disease trial data.
CEO Dr. Matthew Klein clarified that the FDA was not prescriptive about specific endpoints or statistical values. Instead, the agency asked PTC to demonstrate associations between the changes in huntingtin (HTT) protein levels and clinical effects in the PIVOT-HD dataset to support the biomarker's use for potential accelerated approval.
David Lebowitz from Citigroup questioned how the potential approval and reimbursement of GLP-1s for MASH could affect Rezdiffra's usage, both in combination therapy and in discussions with payers.
CEO William Sibold stated that about 25% of Rezdiffra patients are already on a GLP-1 for comorbidities and that GLP-1s will likely expand the overall market. He emphasized that Rezdiffra's strong profile and value proposition in preventing downstream costs will maintain its status as the product of choice and ensure productive payer conversations, regardless of GLP-1 entry.
David Lebowitz inquired about the early feedback Arrowhead is receiving from physicians regarding APOC3 targeting and the current commercial launches in the space.
An executive, likely Andy Davis, Head of Global Cardiometabolic Franchise, stated that feedback on plozasiran continues to be highly enthusiastic. Physicians and patient societies reportedly view the drug as highly differentiating based on its clinical attributes.
David Lebowitz questioned the market impact of a second competitor in polyneuropathy and whether cardiologists are increasingly asking about the ATTR cardiomyopathy data ahead of approval.
Chief Commercial Officer Tolga Tanguler cited strong U.S. TTR growth (37% YoY) as evidence of successful competition, attributing it to AMVUTTRA's quarterly dosing and rapid knockdown. He confirmed that clear guardrails are in place to ensure compliant promotion, with any questions on the HELIOS-B data being triaged to medical affairs.