Andy Chen

Andy Chen inquired about Crinetics' perspective on competitors' recent revenue trajectory and growth in CAH, asking if this indicates a greater or lesser opportunity for Atumelnant, and if certain patient segments are tougher to capture.

Answer

Dr. Scott Struthers, Founder and CEO, declined to comment on competitors' CAH revenue but highlighted the transferability of Crinetics' commercial capabilities from acromegaly to CAH, emphasizing the company's long-term commitment to endocrinology. Isabel Kalofonos, Chief Commercial Officer, added that PALSONIFY's highly differentiated profile sets a high standard for future molecules.

Andy Chen inquired about the growth and revenue trajectory of Crinetics' competition in CAH, asking if this indicates a greater or lesser opportunity for Crinetics and if certain patient segments are harder to capture.

Answer

CEO Scott Struthers declined to comment on competitors' CAH revenue, emphasizing that learnings and capabilities from the PALSONIFY launch are directly transferable to the CAH patient population. Chief Commercial Officer Isabel Kalofonos highlighted PALSONIFY's highly differentiated profile and published superiority data, indicating a strong foundation for future molecules.

An analyst on behalf of Andy Chen of Wolfe Research, LLC questioned if the paltusotine approval would draw acromegaly patients to see their doctors sooner than the typical 2-4 times per year, potentially accelerating the launch, and asked when patients are expected to start flowing in.

Answer

CEO R. Scott Struthers noted the real-world delays in seeing specialists. Chief Commercial Officer Isabel Kalofonos added that while the company is actively working on patient activation to encourage proactive appointments, they remain cautious, expecting the initial uptake to follow the regular rhythm of patient visits, which will be a barrier early on.

Andy Chen sought clarification on the Phase III CAH trial design, asking if glucocorticoid reduction is mandatory or optional, and if optionality could skew the primary endpoint.

Answer

Dr. R. Struthers, CEO, and Dr. Alan Krasner, Chief Endocrinologist, clarified the design. Struthers noted some patients may not need GC reduction. Krasner then stated that for patients on high GC doses, reduction is mandatory per the protocol at specific visits. The investigator individualizes the reduction based on patient safety and toleration, but it is not optional.

Andy Chen asked which features of paltusotine are most exciting to payers, particularly with generic versions of older injectable therapies becoming available.

Answer

CEO R. Struthers positioned paltusotine as a next-generation therapy, not an incremental improvement. CCO Isabel Kalofonos added that payers are receptive to paltusotine's value proposition, as they see current injectables as having high discontinuation rates and breakthrough symptoms, leading to 'wastage'. Payers are positive about paltusotine's sustained effect and potential to improve the standard of care.

Andy Chen from Wolfe Research asked if there was any reason to doubt that the preclinical data for the IRF5 degrader would translate to humans as successfully as the STAT6 program did, and what the top safety signals would be.

Answer

CEO Nello Mainolfi expressed high confidence in the IRF5 program's translation, citing the company's strong track record. He highlighted that the IRF5 degrader, KT-579, has shown no adverse events in non-GLP toxicology studies at very high exposures. He confirmed the team is already planning patient studies under the assumption of a successful and clean translation from preclinical models.

Andy Chen of Wolfe Research asked about the single-arm design of the KT-621 Phase Ib trial and whether the Th2 biomarker data would be convincing enough without showing a dose-response relationship to assess efficacy.

Answer

CEO Nello Mainolfi explained that the trial will use a dose already shown to achieve at least 90% degradation in healthy volunteers, which is expected to produce a dupilumab-like effect based on preclinical data. Chief Medical Officer Jared Gollob added that the subsequent Phase IIb trial is designed as the dose-ranging study to establish a dose-response on both biomarkers and clinical endpoints.

An analyst from Wolfe Research, on behalf of Andy Chen, asked for the rationale behind Sanofi adding another dose to the IRAK4 trials, questioning if it was due to the safety profile of the existing doses.

Answer

CEO Nello Mainolfi clarified the decision was driven by regulatory requirements to conduct a formal dose-ranging study to support Phase 3 dose selection. He stressed that the move followed a positive interim analysis that supported accelerating the program, framing it as a strategic step to shorten the overall development timeline rather than a reaction to a specific safety or efficacy signal.

Andy Chen asked if the IRF5 degrader is conceptually equivalent to a combination of multiple biologics (like Humira and anifrolumab) and if in vivo data supports this, questioning if a combo of existing drugs in mice could replicate the effect.

Answer

President and CEO Nello Mainolfi and CMO Jared Gollob responded. Nello Mainolfi agreed it acts like a multi-asset combo but highlighted its context-specific action as a key safety advantage over broadly blocking cytokines. Jared Gollob added that while substantial single-agent activity is expected, the favorable safety profile creates future optionality for combining it with other oral drugs, either from Kymera's pipeline or other standard-of-care agents.

Andy Chen asked about the underlying biology of chronic rhinosinusitis (CRS) without nasal polyps, questioning if the patient population is heterogeneous with distinct eosinophilic and neutrophilic endotypes.

Answer

CEO William Lewis referenced data from the Aspen study, which showed brensocatib was effective regardless of eosinophil levels, suggesting efficacy in mixed-profile patients. CMO Martina Flammer elaborated that while different endotypes exist, neutrophils play a role in all of them, and the largest proportion of CRS patients have either a mixed or a strongly neutrophil-driven endotype, supporting the drug's mechanism.

An analyst on behalf of Andy Chen at Wolfe Research asked for commentary on the competitive landscape in both PAH and PH-ILD, considering existing products and upcoming pipeline assets.

Answer

CEO Will Lewis positioned TPIP as a potential cornerstone therapy in PH-ILD, offering a superior profile with once-daily, 24-hour coverage at higher doses. In PAH, he views TPIP as a perfect complement to sotatercept, suggesting the combination could be a breakthrough. Regarding brensocatib's DPP1 competitors, he stated their data validates the mechanism while expressing confidence in the relative strength of Insmed's own data.

An analyst on for Andy Chen asked for commentary on the competitive landscape in both PAH and PH-ILD for existing and pipeline products.

Answer

CEO Will Lewis positioned TPIP as a potential cornerstone therapy in PH-ILD, offering a superior profile to the current standard of care. In PAH, he described TPIP as a perfect complement to sotatercept, with the combination holding breakthrough potential. He also addressed DPP1 competition by noting that rival programs validate the mechanism while expressing confidence in the relative strength of Insmed's data.

Andy Chen of Wolfe Research sought more clarity on the 20-30% gross-to-net guidance, asking if this figure is an educated prediction or a known fact based on existing payer contracts and negotiations.

Answer

CEO Bill Sibold asserted that the 20-30% range is not a guess but is based on decades of team experience and the company's ongoing conversations with the payer community. CFO Mardi Dier reinforced this, stating they have good visibility for the rest of the year and that the range is consistent with typical specialty medicine launches and their messaging since launch.

Andy Chen of Wolfe Research asked about the strategy for the upcoming European launch, focusing on potential pricing challenges compared to the U.S. and the plan to achieve success in that market.

Answer

CEO William Sibold outlined a disciplined, country-by-country approach with a goal for each market to achieve a positive contribution within 2-3 years. He expressed confidence that Rezdiffra's innovative profile and strong value data would support favorable pricing discussions with Health Technology Assessment (HTA) bodies, but noted they would only launch where that value is recognized.

An analyst on behalf of Andy Chen asked for a breakdown of free drug utilization between the Bridge and Patient Assistance Programs (PAP), and whether the recent patient campaign could translate into revenue in Q4 or Q1.

Answer

CEO William Sibold clarified that the Bridge program for commercially insured patients has some utilization but is not yet broad. He reiterated that PAP (free goods) usage is very low, indicating strong coverage. Regarding the patient campaign, he described it as a critical component of building awareness but noted it is one part of a larger effort that also depends on practice readiness.

Speaking for Andy Chen from Wolfe Research, an analyst asked for the specific indicators that lead management to state they are still in the 'early stages' of the MG and CIDP launches, questioning if it relates to prescriber coverage, new prescription growth, or distance from the total addressable market (TAM).

Answer

COO Karen Massey confirmed it is all of those factors. For MG, she cited continued quarter-over-quarter growth, market expansion from biologics, and a 60,000-patient TAM including future label expansions. For CIDP, she noted they are only one year into the launch with a 12,000-patient initial TAM and long-term potential for market growth. She concluded that with six Phase 3 readouts in 18 months, the company is on the early side of its growth trajectory.

Andy Chen asked if the 'narrow band' for global list prices is within the 20% discount paid for Part D, and questioned if the company could strategically push patients to Part D to minimize potential MFN exposure.

Answer

Chief Financial Officer Karl Gubitz clarified that the MFN discussion pertains to list prices, which are kept in a narrow band, and declined to speculate further. CEO Tim Van Hauwermeiren stated that the company is not in the business of pushing patients in certain directions. Instead, he asserted that the Q1 acceleration in Part D uptake reflects strong patient demand for at-home administration, which is a positive signal for future market growth, especially with the PFS launch.

An analyst on behalf of Andy Chen asked about early CIDP launch metrics, specifically whether there are signs of physicians preferring VYVGART over IVIg and transforming the standard of care, given most patients are IVIg-experienced.

Answer

Chief Operating Officer Karen Massey expressed pleasure with the early launch, noting a clear unmet need. She believes argenx will transform the market over time but stated that two quarters in, the dynamic of 85% of patients switching from IVIg is exactly in line with the company's initial expectations.

Andy Chen of Wolfe Research, with Brandon on the line, asked about the source of patients for WAYNUA in polyneuropathy, specifically whether they are new to brand or being switched from competitors like Alnylam.

Answer

CGO Kyle Jenne responded that the polyneuropathy market is a growth market and WAYNUA's success is driven predominantly by newly identified, new-to-brand patients. He noted that while some switching occurs, the primary focus of their partner AstraZeneca is on market expansion and educating HCPs to identify untreated patients.

Andy Chen asked about the opportunity for donidalorsen to capture HAE patients who are on older therapies or currently untreated. He also questioned whether payers might start to favor certain drugs in the increasingly crowded HAE market.

Answer

CEO Brett Monia and CCO Jonathan Birchall affirmed their belief that donidalorsen's strong profile creates an opportunity to capture new patients, switchers, and the untreated population. Birchall added that despite the competition, they are comfortable that payers will continue to support the full range of HAE treatments at current prices, given the well-established nature of the market.

Andy Chen from Wolfe Research asked for Roivant's estimate of the observable dermatomyositis (DM) patient population in the U.S. and inquired about physician feedback comparing the off-label use of Xeljanz to the approved therapy, Octagam.

Answer

CEO & Director Matt Gline estimated the DM market to be between 40,000 and 70,000 patients, noting about 34,000 are currently treated, and agreed it may be underdiagnosed. Regarding physician feedback, he stated there is significant excitement for an on-label oral option like brepocitinib, driven by experience with off-label JAKs and the complexity of IVIG administration. He highlighted brepocitinib's dual mechanism as a key differentiator from Xeljanz.

Andy Chen of Wolfe Research asked about the statistical assumptions for the brepocitinib Phase III uveitis trial, specifically questioning the expected placebo response rate given its more stringent steroid taper compared to the pivotal HUMIRA trial.

Answer

Priovant CEO Ben Zimmer responded that the base case assumes a placebo rate similar to what was seen in the HUMIRA VISUAL I study, though he acknowledged the faster taper could potentially lower it. He emphasized that the study is deliberately overpowered to ensure it can detect a difference even if the placebo rate is higher than expected, providing a conservative design.

An analyst on behalf of Andy Chen compared Intellia's projected enrollment rate for the MAGNITUDE study to Alnylam's HELIOS-B, asking if the ratio is a fair gauge of enthusiasm and if other quantitative metrics exist.

Answer

CEO John Leonard described such a ratio as a 'very, very blunt instrument' and reiterated high confidence in meeting their enrollment target of over 550 patients by year-end. CMO David Lebwohl added that they are observing a 'very high level of enthusiasm' from both physicians and patients for the trial.

A representative for Andy Chen asked to compare physician excitement for Intellia's ATTR therapy versus stabilizers and silencers, and inquired about any safety concerns with using gene editing in an elderly population.

Answer

CMO David Lebwohl reported high physician excitement based on the hypothesis that deeper, more rapid TTR reduction will yield better results. He noted no safety concerns have been raised in the elderly. CEO John Leonard added that they have over three years of follow-up data showing an excellent safety profile and clarified that ATTR-CM is primarily a disease of aging.

Andy Chen of Wolfe Research asked about the povorcitinib HS trial, inquiring about specific protocol differences compared to competitor trials and what was done to amplify efficacy. He also asked if the base case assumption is for only the high dose or both doses to be approved.

Answer

Pablo Cagnoni, President, Head of R&D, explained that their Phase III trial was designed with a higher percentage of more severe (Hurley III) patients to reduce placebo effect and that extensive site training was conducted to ensure consistency with Phase II. He noted that if both doses are positive, they will discuss a broad label with the FDA, but a decision will be made after seeing the data.

Andy Chen of Wolfe Research, LLC inquired about the size of Incyte's sales force, its distribution across hematology and dermatology, and whether SG&A expenses would trend up with upcoming launches for Opzelura and povorcitinib.

Answer

Herve Hoppenot, CEO, stated that the company has established dermatology teams in the U.S., Europe, and Canada that are sized to handle the new indication launches for Opzelura. Matteo Trotta, an executive, added that the U.S. footprint is around a couple of hundred people, and for povorcitinib, the approach will be a mix of capturing synergies with the current footprint and some additional staffing.

Andy Chen of Wolfe Research asked Dr. Taylor if autoantibodies are the primary driver of disease pathogenesis in ACPA-positive RA patients compared to other pathways. He also asked the Immunovant team if the 70,000 U.S. prevalence figure for difficult-to-treat RA represents a diagnosed or estimated population.

Answer

Dr. Peter Taylor explained that while the exact contribution is unknown, FcRn is a validated target in a subgroup, and studies with optimal autoantibody-reducing drugs will provide more clarity. Executive Peter Salzmann clarified that the 70,000 prevalence figure represents the current population of diagnosed patients in clinics who meet the difficult-to-treat criteria, noting this number may grow over time.

Brandon, on behalf of Andy Chen at Wolfe Research, asked about the specific challenges encountered in developing the STAT6 degrader and how difficult it would be for a competitor to replicate their success.

Answer

CEO Nello Manalfi described STAT6 as a high-priority industry target for years. He emphasized Chimera's extensive, multi-year effort resulted in one of the company's best-ever molecules. He expressed confidence that it would be difficult for competitors to match Chimera on both development timing and the quality of the asset, noting no other company is as clinically advanced.