Andrea Newkirk

Andrea Newkirk asked about the anticipated data for ARO-DimerPA, specifically inquiring about the target product profile (TPP) and the desired levels of LDL-C and triglyceride reduction. She also asked how these reductions would influence a go/no-go decision and confidence in MACE benefit.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, indicated that ARO-DimerPA might not need to achieve the same level of APOC3 and triglyceride reduction as volanesorsen. He referenced preclinical monkey data showing 40%-50% reductions in both LDL and triglycerides, suggesting similar human results would be encouraging.

Andrea Newkirk asked about the target product profile for ARO-DimerPA, specifically the desired level of LDL-C and triglyceride reduction for a go/no-go decision, and how that reduction might translate to confidence in MACE benefit.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, responded that the level of APOC3 and triglyceride reduction might not need to reach that seen with vosaraben. He suggested that reductions of around 40-50% in both LDL and triglycerides, as observed in dyslipidemic monkey data, would be encouraging.

Andrea Newkirk inquired about Arrowhead's expectations for the initial cadence of the Redemplo launch in FCS, and how it might compare to the Trilipix launch, particularly given the significant pricing differential.

Answer

Andy Davis, SVP and Head of Global Cardiometabolic Franchise, expressed high ambitions for the Redemplo launch, expecting it to be best in class. He attributed this to Redemplo's differentiating attributes, including significant and sustained triglyceride reduction, reduced incidence of acute pancreatitis, a favorable safety and tolerability profile with no contraindications, warnings, or precautions, and a convenient once-every-three-month dosing regimen.

Andrea Newkirk from Goldman Sachs asked about Arrowhead's expectations for the initial cadence of the Redemplo launch in FCS, and how it might compare to the Trilipix launch, particularly considering the significant pricing differential.

Answer

Andy Davis, Senior Vice President and Head of Global Cardiometabolic Franchise for Arrowhead Pharmaceuticals, expressed high ambitions for Redemplo's launch, expecting it to be "best in class" due to its significant and sustained triglyceride reduction, reduced incidence of acute pancreatitis, favorable safety profile (no contraindications, warnings, or precautions), and convenient once-every-three-month dosing regimen. He did not directly compare it to Trilipix.

Andrea Newkirk's representative, Morgan Lamberti, asked about the ARO-ALK7 program, inquiring about the method of siRNA delivery to adipocytes, the basis for safety confidence, and the existence of human loss-of-function data.

Answer

Management explained that ARO-ALK7 uses a ligand-targeted approach to deliver siRNA to adipocytes. Confidence in its safety is supported by human genetic data from ALK7 loss-of-function carriers and comprehensive non-clinical toxicology studies in animals, which showed no dose-limiting toxicities.

Andrea Newkirk asked for the rationale behind restarting development of zodasiran and requested management to quantify the commercial opportunity they see in homozygous familial hypercholesterolemia (HoFH).

Answer

An executive, likely CEO Dr. Christopher Anzalone, described the decision as a 'no-brainer' following the capital infusion from the Sarepta deal. He noted the Phase III study is relatively small and inexpensive, and the incremental commercial cost is minimal because it can be handled by the same sales force being built for plozasiran.

Andrea Newkirk inquired about AbCellera's data disclosure strategy for the Phase I ABCL 635 study, including SAD, MAD, and efficacy cohorts, and what profile would be deemed supportive for advancing to Phase II. She also asked about the platform validation and read-through to the pipeline if the desired target profile is achieved.

Answer

Carl Hansen, AbCellera's President and CEO, stated that a single disclosure is expected after the proof-of-concept part of the study, likely in the early to mid-new year. He indicated that a supportive profile would include a safety signal and efficacy competitive with existing products. Mr. Hansen added that success would strongly validate the platform's capabilities, particularly for ion channel and GPCR targets, with intent to replicate this success across the pipeline.

Telani, on behalf of Andrea Newkirk from Goldman Sachs, asked about potential regulatory risks for ABCL635 following a competitor's PDUFA delay and inquired about the key focus areas for regulators during the drug's development.

Answer

CEO Carl Hansen stated that the competitor's delay was due to an information request and he still expects approval. For ABCL635, he said regulators will focus on efficacy and safety, noting that as an antibody, it is not metabolized in the liver, potentially avoiding liver toxicity seen in small molecule competitors, and is designed to avoid somnolence by not targeting NK1R.

Andrea Newkirk asked if Madrigal has observed any signs of Novo's marketing campaign broadening the addressable patient pool and if the 315,000 patient target for Rezdiffra remains accurate. She also inquired about the company's path to profitability given the successful launch.

Answer

Bill Sibold, Chief Executive Officer, noted it's early (first quarter with Novo in market) but Madrigal continued to add patients. He mentioned anecdotal reports of increased referrals, suggesting Novo's efforts to drive diagnosis could ultimately benefit Madrigal by expanding the overall market beyond the initial 315,000 diagnosed patients. Mardi Dier, Chief Financial Officer, stated that the current focus is on driving top-line growth and pipeline development, with profitability expected at a later point.

Andrea Newkirk asked if Madrigal has observed any signs of Novo's marketing campaign broadening the pool of addressable patients to date, if the 315,000 target population is still accurate, and about the path to profitability.

Answer

CEO Bill Sibold noted it's early (first quarter with Novo in market) but anecdotally hearing more referrals, suggesting Novo's PCP education might be driving diagnosis. He reiterated the 315,000 target is for *diagnosed* patients among targeted prescribers, acknowledging more prevalent patients exist and Novo's efforts could help increase overall diagnosis, benefiting Rezdiffra. CFO Mardi Dier stated the focus for now and into 2026 is driving top-line growth and pipeline expansion, not immediate profitability, though it will happen eventually.

Andrea Newkirk of Goldman Sachs asked about the anticipated launch in Europe, specifically how the launch curve might differ from the U.S. and when the company expects to begin recognizing revenue from the region.

Answer

CEO Bill Sibold explained that they are applying learnings from the U.S. launch but noted that Europe has had more time to prepare, with clinical guidelines already including ResDiffera. He specified the initial launch will be focused on Germany. He stated that any revenue from Europe in 2025 would be minimal, positioning it as a growth driver for 2026 and beyond.

Andrea Newkirk from Goldman Sachs asked about the clinical significance of the 6.7 kilopascal reduction in the F4 cirrhosis data, whether the same outcome-related VCTE thresholds from F2/F3 patients apply, and how this new data affects the company's confidence in the MAESTRO-NASH OUTCOMES trial.

Answer

CEO William Sibold stated the new data provides even greater confidence in the MAESTRO-NASH OUTCOMES trial. Dr. Michael Charlton, Head of Clinical Development, explained that the 6.7 kPa reduction from a high baseline of 25 kPa is highly predictive of decreased risk for clinical outcomes, as predictivity increases with higher baseline liver stiffness.

Andrea Newkirk asked for more specifics on the specialty drug analogs Madrigal is using for benchmarking its launch and requested an update on the adoption of Rezdiffra among hepatologists versus gastroenterologists.

Answer

CEO William Sibold described the analogs as approximately 10 first-in-class, blockbuster specialty medicines but did not name them. Regarding prescribers, he noted that hepatologists were faster to adopt due to their specialty. However, he emphasized that gastroenterologists, who represent the majority of prescribers, are now rapidly establishing pathways to treat NASH, showing a significant increase in engagement.

Andrea Newkirk asked about the investment needed for BRINSUPRI's EU commercial launch, particularly salesforce infrastructure, and inquired about the gross-to-net adjustment for BRINSUPRI in the quarter.

Answer

Will Lewis, Chairman and CEO of Insmed, stated a cautious strategy for Europe, awaiting reimbursement clarity before significant additional investment, but noted Japan's expanded salesforce for ARIKAYCE prepares for BRINSUPRI. Sara Bonstein, Chief Financial Officer, did not provide quarter-specific gross-to-net but referred to launch analogs of 25-35%, with half attributed to IRA impact.

Andrea Newkirk asked about the investment needed for Brensupri's European launch, particularly regarding salesforce infrastructure, and inquired about the gross-to-net adjustment for Brensupri in the current quarter.

Answer

Will Lewis, Chairman and CEO, stated that the European strategy is to ensure reimbursement is favorable before significant additional investments, though some preparatory work has been done. Sara Bonstein, Chief Financial Officer, clarified that quarter-to-quarter Brensupri gross-to-net figures are not being provided, but noted that initial launches often have flexibility and lumpiness. She reiterated previous analogs of 25% to 35% at launch, with half attributed to IRA impact.

Andrea Newkirk asked about TPIP's potential in idiopathic pulmonary fibrosis (IPF), inquiring about the read-through from a competitor's upcoming trial and how quickly Insmed could advance TPIP into an IPF study if that trial were positive.

Answer

Chief Medical Officer Martina Flammer stated that Insmed is watching the competitor's TETON study with great interest. She conveyed that if the study shows positive results, Insmed believes TPIP's profile could yield even stronger effects and the company would be positioned to initiate a Phase 3 study in IPF on very short notice.

Andrea Newkirk asked what would be considered a clinically and commercially meaningful PVR reduction for TPIP and inquired about the status of the Phase III trial initiation in PH-ILD.

Answer

CEO Will Lewis stated that a PVR reduction exceeding the low-20% range seen with other prostacyclins would position TPIP as best-in-class. He noted the last remaining step for the Phase III PH-ILD trial is finalizing a single-capsule administration for all dose strengths, with the study on track to start in the second half of the year.

An analyst on for Andrea Newkirk asked for a reminder of the specific activities the newly deployed expanded sales force is undertaking for both ARIKAYCE and pre-launch brensocatib.

Answer

CEO Will Lewis explained that the full 184-rep sales force is actively detailing ARIKAYCE to pulmonologists while simultaneously conducting disease state awareness for bronchiectasis. He stressed this dual-role strategy builds key physician relationships and educates the community on the disease burden ahead of the potential brensocatib launch, leveraging the successful model from the original ARIKAYCE launch.

An analyst on behalf of Andrea Newkirk at Goldman Sachs asked for a reminder of the activities currently being undertaken by the newly expanded sales force for both ARIKAYCE and in preparation for the brensocatib launch.

Answer

CEO Will Lewis explained that the 184-person U.S. sales force, deployed on October 1, is engaged in a dual role: actively detailing ARIKAYCE to pulmonologists while also conducting disease state awareness for bronchiectasis. He emphasized this strategy builds crucial physician relationships and educates the community on the disease burden ahead of a potential launch, leveraging the successful model used for ARIKAYCE. The overlap in treating physicians makes this a natural and efficient approach.

Andrea Newkirk of Goldman Sachs questioned the company's expectations for clinical efficacy measures like EASI and NRS in the Phase 1b data and inquired about the potential safety risks of complete STAT6 degradation.

Answer

CMO Jared Gollob noted that while biomarkers are the primary objective, they expect clinical endpoints like EASI and pruritus to be in the ballpark of dupilumab's 28-day data. He highlighted the clean safety profile in all toxicology and healthy volunteer studies, consistent with STAT6's specific role. CEO Nello Mainolfi added that their expectation is for KT-621 to be a very active drug, on par with dupilumab.

Andrea Newkirk from Goldman Sachs asked for insights into the launch cadence of Xtendi two years post-approval and sought clarification on the factors driving the newly increased peak sales potential.

Answer

CCO Aziz Mottiwala projected continued steady growth driven by prescriber education, DTC, and strong payer access, noting they've only 'scratched the surface' of the 25 million patient TAM. CFO Jeff Farrow added that early signals suggest a higher peak potential as the addressable market appears larger than initial estimates, but declined to provide a new figure. CEO Bobak Azamian highlighted that 80% of ECPs now prescribe across all patient segments, supporting future growth.

Andrea Newkirk followed up on the DTC campaign, asking about its anticipated duration and whether the $60-70 million annual expense should be modeled as an ongoing cost.

Answer

Chief Commercial Officer Aziz Mottiwala explained the campaign's duration will depend on its continued positive ROI, noting that sustained education is necessary to build the new market. Chief Financial Officer Jeff Farrow advised that for modeling purposes, the $60-70 million should be included annually, but the investment would be re-evaluated if it does not generate a positive return.

Andrea Newkirk from Goldman Sachs questioned whether the company's current strategy for MGD patients with Demodex blepharitis (DB) rules out pursuing a broader MGD indication later. She also asked for the basis of the long-term gross-to-net discount guidance.

Answer

Chief Operating Officer Sesha Neervannan clarified that the current focus is on educating physicians about treating DB in MGD patients, which is covered by the existing label, and there are no current plans to expand the label. Chief Commercial Officer Aziz Mottiwala added that physician enthusiasm for this data is high. CFO Jeff Farrow explained the long-term gross-to-net estimate is based on eye care analogs and the now-secured broad Medicare and commercial contracts, expecting to reach the low 40s by mid-2025.

Andrea Newkirk from Goldman Sachs asked about the extent of Revolution Medicines' pre-commercial activities for doraxonrasib, given the reiterated timelines. She also inquired about any learnings from the launches of other RAS inhibitors like Lumakras or Krazati that could be applied to the upcoming PDAC launch.

Answer

CEO Mark Goldsmith clarified that the company has not guided to a specific commercial launch date. Chief Global Commercialization Officer Anthony Mancini confirmed that launch readiness plans are progressing well, with an experienced team engaged in market shaping, such as the 'Expect RAS' educational campaign. He noted the company is building its US field teams and learning from other launches to ensure readiness.

Andrea Newkirk of Goldman Sachs inquired about the observed patient durability and persistence for Ogenda one year post-launch, physician intent for treatment duration, and the potential impact of upcoming three-year data.

Answer

CEO Jeremy Bender stated that real-world persistence is consistent with the FIREFLY-1 trial and that the median duration of treatment for commercially launched patients has not yet been reached. CCO Lauren Merendino noted that physicians often intend to treat for two years and that the upcoming three-year data will provide valuable insights into outcomes for patients who stop or continue therapy beyond that point.

Andrea Newkirk asked about the specific actions being taken to increase the depth of OJEMDA prescribing and how the sales team prioritizes efforts between reaching new Priority 3 accounts versus deeper penetration in Priority 1 accounts.

Answer

Chief Commercial Officer Lauren Merendino explained that driving depth involves helping physicians gain experience with OJEMDA and educating them on the full range of eligible patients beyond initial later-line use. She noted the sales team has always focused on all priority tiers, but the approach is tailored; for some lower-volume accounts, it's a matter of waiting for an appropriate patient to present for treatment.

Andrea Newkirk of Goldman Sachs requested an update on the total number of patients on OJEMDA, the EAP versus de novo split, and the continuation rate for the Q2 patient cohort.

Answer

CCO Lauren Merendino stated the company will no longer disclose specific patient counts but confirmed EAP transitions are complete and discontinuations are in the low single digits. CEO Jeremy Bender added this real-world persistence aligns with FIREFLY-1 trial data.

Andrea Newkirk of Goldman Sachs asked about the potential regulatory path for elixorexant, including whether the VIBRANCE studies could serve as registrational trials and if one or two pivotal trials would be required per indication.

Answer

Richard Pops, Chairman & CEO, explained the plan is to await data from the narcolepsy type 2 (NT2) study before a formal end-of-phase-2 meeting with the FDA, aiming for a broad narcolepsy label. He stated the current assumption is that the Phase 3 program will require one three-month study in NT1 and a similar one in NT2, subject to FDA confirmation.

Andrea Newkirk of Goldman Sachs sought clarification on whether the guidance implies 500 infusions for 2025 and the resulting assumption for Proleukin sales. She also asked for the drivers behind the Q1 increase in patient drop-offs and lower manufacturing success rates.

Answer

Interim CEO Frederick Vogt described the guidance as conservative, suggesting that 500 infusions could lead to revenue above the high end of the range. Chief Operating Officer Igor Bilinsky attributed the Q1 manufacturing issues to patient selection and tumor procurement techniques at newer ATCs, noting the rates have already rebounded in Q2.

Andrea Newkirk asked for an intra-quarter update on patient infusions and for the rationale behind maintaining confidence in the full-year 2025 revenue guidance.

Answer

Interim CEO and President Frederick Vogt stated that Iovance will no longer provide intra-quarter infusion metrics, as they can be prone to overinterpretation. He affirmed confidence in the 2025 guidance, pointing to significant growth potential within the existing Authorized Treatment Center (ATC) network, where only 13% of centers have infused more than 10 patients, indicating substantial room for acceleration.

Andrea Newkirk of Goldman Sachs asked for more detail on ATCs initiating patient preconditioning before Amtagvi arrives, questioning its frequency and if it signals improving manufacturing success rates.

Answer

Interim CEO Frederick Vogt confirmed this practice reflects growing ATC confidence in Iovance's manufacturing process and out-of-spec rates. He noted it is more common at larger, experienced ATCs and expects the trend to grow as more centers gain confidence and seek to expedite treatment.

An analyst on for Andrea Newkirk of Goldman Sachs asked about the strategic rationale for the Chimerix acquisition, the most compelling aspects of the Dordaviprone opportunity, and the company's forward-looking business development plans.

Answer

Bruce Cozadd, Chairman and CEO, explained that the acquisition was a perfect strategic fit, targeting a serious unmet need with an efficient commercial call point and long durability. Rob Iannone, Head of R&D, highlighted Dordaviprone's potential as a breakthrough therapy for a rare and aggressive brain tumor with no currently approved drug therapies, noting its impressive efficacy and safety profile.

Andrea Newkirk of Goldman Sachs requested an update on the ongoing CEO search, including the desired background for the new leader, and asked how the leadership transition might affect the company's M&A strategy and timing for potential transactions this year.

Answer

Bruce Cozadd, Chairman and CEO, stated that the board is taking its time to find the right candidate and that the position is viewed as highly attractive. He emphasized that the company is operationally and financially well-positioned for M&A and that strategic corporate development activities are not on hold during the transition period.

Andrea Newkirk from Goldman Sachs requested an update on the CEO search, the desired candidate profile, and how the ongoing transition affects the M&A strategy and potential timing of a deal.

Answer

CEO Bruce Cozadd stated the board is taking its time to find the right leader and is receiving positive feedback on the attractiveness of the role. He emphasized that the company is operationally and financially well-positioned for M&A, and the transition does not slow down these activities.

An analyst on behalf of Andrea Newkirk at Goldman Sachs asked for more detail on the company's pipeline prioritization and how it affects the appetite for business development in oncology versus neuroscience.

Answer

CEO Bruce Cozadd noted that zanidatamab is the clear top priority in the pipeline. CFO Phil Johnson added that under their capital allocation strategy, after investing in commercial products and the internal pipeline, the company is actively pursuing business development. They are looking at opportunities in oncology, neuroscience, and select rare diseases, supported by strong cash flow and access to capital.

Andrea Newkirk asked for more color on the pipeline prioritization mentioned in the prepared remarks and how these strategic shifts impact the company's appetite for business development in neuroscience versus oncology.

Answer

CEO Bruce Cozadd and CFO Philip Johnson responded. Cozadd affirmed that zanidatamab is the top priority. Johnson outlined their capital allocation strategy: investing in commercial products, prosecuting the internal pipeline, and then bolstering future growth via BD. He noted they are actively looking for opportunities in oncology, neuroscience, and rare diseases, supported by strong cash flow.

Andrea Newkirk asked what is needed to reaccelerate new patient starts for VYJUVEK to reach the two-year, 60% penetration goal. She also requested more granularity on the geographic breakdown of the $1 billion+ global peak sales opportunity.

Answer

Jennifer McDonough, SVP of Patient Access, noted that after a holiday slowdown, the patient start trajectory has already increased and they remain on track. Krish Krishnan, Chairman and CEO, explained the peak sales breakdown is a function of pricing, as patient prevalence is similar across the U.S., EU, and rest of world. He anticipates European prices at 50-70% of the U.S. price, reflecting the drug's strong value proposition.

An analyst from Goldman Sachs inquired about the preparations for the European launch, asking what activities are underway for Germany and what infrastructure will be required to support the launch across Europe next year, including onboarding timelines.

Answer

Chairman and CEO Krish Krishnan detailed that the company is preparing pricing dossiers and hiring commercial teams in Germany and France. He estimated a lean infrastructure of fewer than 10 employees per country. The German team is expected to be onboarded by year-end, with France following shortly after. The Japan team is also being built out in anticipation of a 2025 launch.

An analyst on for Andrea Newkirk at Goldman Sachs asked for confirmation that the interim analysis does not incur a statistical penalty and requested an update on screen failure rates in Reliance II compared to prior studies.

Answer

CEO Sergio Traversa confirmed there is no alpha penalty paid for the interim analysis because it is not designed for an early efficacy stop. He also shared that the dropout rate is low, in the mid-single digits, which is lower than in the previous trial, but cautioned against interpreting this as an indicator of efficacy.