Marc Frahm

Marc Frahm inquired about Scholar Rock's disclosure plans regarding Novo Nordisk's reinspection of the Bloomington facility, specifically what information would be shared and on what timeline, given it's a partner's facility. He also asked if there's value in filing the BLA ahead of the reinspection to potentially accelerate the inspection timeline.

Answer

CEO David Hallal stated that Scholar Rock will disclose material information, such as the reinspection timeline and outcome, maintaining open communication. He explained that while a BLA submission can create urgency, the Type A meeting highlighted the shared urgency for apitegromab, and there are other pending applications at the site that also contribute to inspection urgency. President of R&D Akshay Vaishnaw emphasized a collaborative approach with the FDA rather than a 'forcing function' by premature resubmission.

Marc Frahm inquired about Scholar Rock's disclosure plans regarding Novo Nordisk's reinspection timeline and outcome, including any Form 483 observations. He also asked if filing the BLA ahead of the reinspection could serve as a 'forcing mechanism' to expedite the inspection, or if other products at the facility would naturally drive the timeline.

Answer

David Hallal, Chairman and Chief Executive Officer, stated that Scholar Rock will disclose material information, including the reinspection timeline and outcome, maintaining open communication. He acknowledged that pending applications create urgency but emphasized the strong foundation for collaboration built with the FDA. Akshay Vaishnaw, President of R&D, advised against a 'forcing function' resubmission, preferring to work collaboratively and be guided by the FDA.

Marc Frahm of TD Cowen asked for more detail on payer discussions regarding the budget impact of two concurrent SMA drugs and whether the planned new indication is a single pilot or the start of a broader pipeline expansion.

Answer

COO Keith Woods noted that payers already cover two concurrent SMA therapies for some patients, setting a precedent. President of R&D Akshay Vaishnaw confirmed the new indication is the first of many, stating the company sees "enormous opportunity" for its myostatin platform and will add more indications "in quick succession."

Marc Frahm asked for perspective on the apitegromab launch trajectory, comparing it to prior SMA launches by weighing tailwinds like established screening and treatment centers against headwinds like a less acute initial unmet need.

Answer

CEO David Hallal focused on the persistent unmet need, noting that even treated patients can experience motor function loss. COO Keith Woods added that while patient identification is an advantage, the launch dynamic will differ from prior SMA launches because patients are already on therapy and have less frequent physician visits, suggesting a steady, consistent launch.

An analyst on behalf of Marc Frahm asked about the potential implications of the FDA's recent draft guidance on obesity clinical trials for the SRK-439 program, noting the agency's continued focus on BMI and overall weight loss rather than body composition.

Answer

Executive Jay Backstrom responded that they were not surprised by the FDA's approach but noted the guidance now asks sponsors to assess lean mass loss, reinforcing the importance of their strategy. He highlighted that the FDA guidance invites discussion on body composition, which he sees as 'foreshadowing.' He reiterated that a clear path for approval would be to show additional benefit on endpoints like HbA1c or functional measures.

Mark Frahm asked about the evaluation criteria for the ALISCA-Breast1 interim analysis, specifically regarding the willingness to continue investment in the indication while maintaining profitability, and later inquired about funding a potential pivotal Phase 3 program without compromising profitability or requiring a partner.

Answer

CEO Alan Auerbach explained that the ALISCA-Breast1 trial's efficacy would be compared to the previous TBCRC41 trial and standard of care in the third-line HER2-negative, hormone receptor-positive metastatic breast cancer 'white space.' He emphasized the importance of identifying a predictive biomarker and reiterated the commitment to staggering indications to control burn and remain profitable. Regarding a pivotal Phase 3, Mr. Auerbach noted that debt repayment by mid-next year would free up cash flow, and he anticipates a manageable trial size with expenses spaced out, allowing funding from Nerlynx cash flow while remaining net income positive.

Mark Frahm asked about the evaluation criteria for the ALISCA-Breast1 interim analysis, specifically regarding the efficacy bar and the company's willingness to continue spending on the indication while maintaining profitability, and if a pivotal program would require a partner or impact profitability.

Answer

Alan Auerbach, CEO, President, and Chairman of the Board, explained that the company would compare efficacy to the previous TBCRC41 trial of alisertib with endocrine therapy, focusing on the third-line endocrine white space for HER2-negative breast cancer. He noted that finding a predictive biomarker would be compelling and reiterated the commitment to staggering indications to control burn and remain profitable. He also clarified that debt payments cease mid-next year, improving cash flow, and anticipated a pivotal Phase 3 trial would be manageable within Nerlynx's cash flow without necessarily requiring a partner or leading to losses, as expenses would be spaced out.

Marc Frahm from TD Cowen inquired about the upcoming alisertib data disclosures, asking about the venue, the clinical bar for further development in both lung and breast cancer, and how the trial outcomes would influence the company's strategy for in-licensing additional assets.

Answer

Chairman, President & CEO Alan Auerbach stated the data would likely be a corporate update around November. He detailed that for small cell lung cancer, the bar is a Progression-Free Survival (PFS) and Overall Survival (OS) benefit comparable to a prior combination study. For breast cancer, a significant PFS benefit over endocrine therapy alone is required. Auerbach emphasized that regardless of the outcome, the company is committed to maintaining profitability and would be highly selective with any potential in-licensing, ensuring it would not jeopardize their positive net income status.

Marc Frahm questioned the rationale behind pursuing only combination therapies for Zoledronrasib in first-line PDAC, asking if it implied less durability than Diraxonrasib monotherapy. He also inquired about the event rate trending in Resolute 302 and the disclosure strategy for interim analyses.

Answer

Mark Goldsmith, Chairman and CEO, clarified that the decision for Zoledronrasib combinations does not imply anything about monotherapy durability, but rather leverages its favorable safety profile as an ideal combination agent to maximize patient impact. He declined to comment on the event rate or disclosure strategy for Resolute 302 at this time.

Marc Frahm questioned if pursuing only combinations for the Zoledronrasib first-line trial implies monotherapy is less durable than Diraxonrasib monotherapy. He also asked about the event rate trending for Resolute 302 and the disclosure strategy for interim analyses.

Answer

Mark Goldsmith, Chairman and CEO, clarified that the company never committed to Zoledronrasib monotherapy in first-line, emphasizing its ideal profile as a combination agent due to its safety. He stated they are seeking the best ways to deliver patient impact. He declined to comment on Resolute 302 event rates or interim disclosure strategy.

Marc Frahm from TD Cowen asked for characterization of the chemotherapy regimens being considered for the first-line pancreatic cancer trial, specifically how much they might be dose-adjusted from standard of care. He also sought clarification on whether the guided 2026 data readout for the second-line trial refers to the final analysis or includes interim analyses.

Answer

CEO Mark Goldsmith stated that the chemotherapy dosing being studied is well within standard practice and that the 2026 data readout refers to the first analysis, which could be either an interim or final analysis as it is event-driven. He noted that the first analysis cannot be skipped and the company is optimistic about delivering a report in 2026 based on robust enrollment.

Marc Frahm of TD Cowen asked about the average follow-up in the combination cohorts to gauge durability and questioned what specific data (e.g., safety, robust PFS) is needed before the company formally declares Phase III intent for these combinations.

Answer

Dr. Mark Goldsmith, CEO, directed the question on follow-up to previously released December data. Dr. Stephen Kelsey, President of R&D, explained that the non-G12C program is operationally ready, while the G12C program is gated by dose optimization of the RAS(ON) doublet for the first-line setting. Both executives clarified that achieving mature PFS data is not a gating factor, as the high response rates observed in lung cancer are considered a reasonable correlate for PFS.

Marc Frahm of TD Cowen questioned the design of the adjuvant PDAC trial regarding patient inclusion criteria and the use of hierarchical analysis for RAS mutations. He also asked about the strategic balance between moving quickly versus ensuring optimal trial design for long-term success.

Answer

Chief Medical Officer Dr. Wei Lin indicated the goal is to include the broadest possible patient population in the adjuvant trial, potentially an 'all-comer' approach for RAS-mutant PDAC. CEO Dr. Mark Goldsmith addressed the strategic question by emphasizing the urgency to serve patients and the competitive need to 'create the bar' rather than chase others. He described the situation as an 'embarrassment of riches' that necessitates swift, real-time decision-making.

Marc Frahm questioned why the timelines for the pancreatic and lung cancer Phase III trials have diverged since the parallel decision to pursue them a year ago. He also asked about the company's broader strategy for novel-novel combinations.

Answer

Dr. Mark Goldsmith, Chairman and CEO, responded that while the steps to start trials are similar, practical realities like enrollment can cause timelines to diverge and are difficult to predict a year in advance. Regarding combinations, he stated the Tango collaboration is not a one-off and they expect more, but internal priorities remain combinations of RMC-6236 with other RAS(ON) inhibitors, pembrolizumab, and chemotherapy.

Marc Frahm from TD Cowen asked about the status of the thalassemia regulatory review, including whether labeling discussions have begun and what to expect for the safety information. He also questioned if the current SG&A spending level represents a run-rate or if further increases are expected for the launch.

Answer

CMO Dr. Sarah Gheuens noted the review is ongoing and the final label will be known at the PDUFA date, but at a minimum, the label will be updated for the thalassemia indication and dose. CFO Cecilia Jones stated that some additional growth in SG&A is expected for launch-related expenses post-approval.

Marc Frahm of Cowen sought clarification on whether the mutant CALR program requires convincing monotherapy activity in MF to advance and if the G12D program needs to be best-in-class to justify further investment.

Answer

President and Head of R&D Pablo Cagnoni confirmed they 'absolutely have to have single agent activity in MF' for the CALR program. Regarding G12D, CEO Bill Meury stated the hurdle is high and the position must be defensible. Pablo Cagnoni added that their G12D inhibitor's potential for better combinability could be a key differentiator, particularly in pancreatic cancer.

Marc Frahm asked if Incyte would discuss the pivotal path for Klar upon its data release and questioned if the povorcitinib HS data could help prospectively identify patients who would respond better to a JAK inhibitor versus an IL-17.

Answer

Executive Pablo Cagnoni confirmed that next steps for Klar will be discussed with the data release. Regarding povorcitinib in HS, he explained that it is difficult to prospectively identify patient responders but noted that the company has a clear view of where the drug will fit into the treatment paradigm initially.

Marc Frahm from TD Cowen asked for clarification on the povorcitinib HS trial protocol regarding antibiotic use and how it compares between Phase II and Phase III. He also requested a breakdown of the U.S. versus ex-U.S. growth assumptions within the 2025 Opzelura guidance.

Answer

Pablo Cagnoni, President, Head of R&D, confirmed that antibiotic use is treated identically in Phase III as it was in Phase II, where starting systemic antibiotics for a flare is considered a non-response. Christiana Stamoulis, CFO, stated that while the global Opzelura guidance includes increased contribution from Europe (Germany, France, Italy, Spain), the company will not be providing a regional breakdown.

Marc Frahm of TD Cowen questioned the rationale for adding a 25 mg dose to the INCB00262 trial and asked what minimum efficacy bar would be needed to justify its use after antihistamines in chronic spontaneous urticaria (CSU).

Answer

An unnamed executive reiterated that the 25 mg cohort was a separate study initiated early to be ready for Phase III as soon as possible. Regarding the efficacy bar, he stated that since all trial patients are refractory to antihistamines, demonstrating efficacy over placebo combined with an expected excellent safety profile would be sufficient for INCB00262 to become a first option after antihistamines for some patients.

Marc Frahm from TD Cowen asked for clarification on the timing between patient apheresis, treatment, and invoicing, and questioned if the Q2 apheresis and invoice numbers were overlapping. He also inquired about the expected trend for apheresis patient volume in Q2.

Answer

Cintia Piccina explained that the 21 year-to-date apheresed patients include some who were already invoiced in March and April, with the majority to be invoiced shortly. CEO Adrian Rawcliffe declined to provide quarterly apheresis guidance but expressed strong confidence in the full-year revenue forecast of $35 million to $45 million, based on current momentum.

Marc Frahm inquired about the timeline for the Tecelra launch, from initial physician interest to patient treatment, and the rationale behind discontinuing the SURPASS-3 trial for uza-cel in ovarian cancer.

Answer

CEO Adrian Rawcliffe explained that the process from initial testing to treatment could take 3-4 months, with the first significant revenues expected in 2025 as the initial 15 double-positive patients progress. He clarified that the decision to halt the uza-cel trial was based on capital allocation and portfolio prioritization, favoring the high-return sarcoma franchise and early-stage assets like PRAME and CD70, rather than being driven by specific data from the trial.

Marc Frahm inquired about the initial patient flow for Tecelra, asking if patients are being identified through the company's website and what new sources of patient referrals have emerged since the launch.

Answer

CEO Adrian Rawcliffe deferred to Cintia Piccina, an executive leading commercial efforts. Piccina confirmed significant enthusiasm from treatment centers and awareness of patients beginning the biomarker testing process. She noted that the majority of new interest and potential referrals are coming from other sarcoma centers of excellence across the U.S.

Marc Frahm asked about the current manufacturing and intellectual property locations for ampreloxetine, given potential tariff policy changes. He also inquired about specific refinements being made to improve the conversion rate of YUPELRI hospital prescriptions to chronic use in the community.

Answer

An executive, Rick Winningham, stated that ampreloxetine's IP resides in Ireland and its API is manufactured in Taiwan, emphasizing the company has flexibility to adapt. Chief Business Officer Rhonda Farnum addressed the YUPELRI question, highlighting the close partnership with Viatris at a local level, the sharing of best practices from successful territories, and the critical role of the transition of care voucher program in ensuring patients move smoothly to maintenance therapy.

Marc Frahm from TD Cowen asked about Phase Ib enrollment criteria regarding prior therapies, whether the Phase IIb trials would be sufficient to inform dosing for all indications, and the acceptable efficacy bar for success relative to DUPIXENT.

Answer

CMO Jared Gollob confirmed prior-treated patients could enroll if they had responded previously. CEO Nello Mainolfi expressed high confidence the two Phase IIb studies would be sufficient for broader Phase III dose selection. He stated Kymera's internal bar is to be 'dupi-like' and they do not expect a lesser effect.

Marc Frahm of TD Cowen asked about the reliability of Th2 biomarker changes in healthy volunteers for KT-621 compared to historical dupilumab data, and whether cost savings from deprioritizing oncology would be reinvested into the immunology pipeline.

Answer

CEO Nello Mainolfi explained that the primary endpoint is STAT6 protein degradation, the most direct biomarker, noting that downstream markers like IgE and TARC are variable in healthy volunteers but should be in line with precedents. CFO Bruce Jacobs confirmed that savings from the oncology shift will be meaningfully reinvested into the immunology pipeline, maintaining the company's cash runway guidance into mid-2027.

Marc Frahm asked about the newly disclosed IRF5 program, questioning the minimum target degradation level required for efficacy and the importance of demonstrating superior efficacy in diseases like lupus, where there is significant room for improvement, versus simply matching existing therapies with oral convenience.

Answer

President and CEO Nello Mainolfi, CMO Jared Gollob, and Senior Director of Immunology Veronica Campbell all contributed. Nello Mainolfi stated that preclinically, over 80% degradation provides a best-in-class profile and that superiority is a key goal in lupus due to high unmet need. Jared Gollob added that over 90% knockdown is achievable and safe in NHP models. Veronica Campbell emphasized that they expect superior efficacy by targeting multiple disease biologies simultaneously.

Marc Frahm inquired about the enrollment trends for the CRDF-004 trial and the rationale for aggressively adopting the newer, more intensive NALIRIFOX regimen for the investigator-initiated pancreatic cancer trial.

Answer

Mark Erlander, an executive at Cardiff Oncology, confirmed that CRDF-004 enrollment is on track for an initial data readout later in the year, aided by their partnership with Pfizer Ignite and a lack of competing trials. Regarding the pancreatic cancer trial, Erlander explained that onvansertib has already been successfully combined with three of the four agents in NALIRIFOX, shows good tolerability, and the remaining agent (oxaliplatin) lacks overlapping toxicities, making it a confident choice to pair with a superior efficacy regimen.

Marc Frahm of TD Cowen inquired about the reasons for the revised timeline for the CRDF-004 trial's initial data readout and asked about potential scenarios, such as early termination for futility or accelerated development plans based on the interim results.

Answer

Mark Erlander, an executive at Cardiff Oncology, clarified that the updated Q3/Q4 2024 timeline for the initial data readout is based on the actual pace of enrollment now that the trial is active, rather than site activation delays. He expressed high confidence in meeting this timeline by leveraging the resources of their partner, Pfizer Ignite. Erlander also noted that since the CRDF-004 trial is a dose confirmation study under the FDA's Project Optimus, the primary goal is to identify the optimal dose as quickly as possible to advance to a registrational trial.

Questioned the implied slowdown in AYVAKIT's quarterly growth in the guidance despite strong commentary, asking if there were other dynamics like inventory stocking. Also asked what would be needed to increase the peak sales forecast beyond $2 billion.

Answer

The company confirmed no inventory stocking occurred. The guidance reflects various factors including seasonality, but year-over-year growth remains substantial. To raise the peak sales forecast, the company will continue to monitor key dynamics like the broadening of patient eligibility and growth in the diagnosed population, and will update the forecast when it is meaningful to do so.

Asked for clarification on the discrepancy between the safety and efficacy patient numbers, whether efficacy was concentrated in patients with prior PARP experience, and about the expected dataset size for the upcoming mirvetuximab (MIRV) combo data.

Answer

The company clarified that the five patients not yet evaluable for efficacy are all still on study awaiting their first scan. It is too early to determine if efficacy correlates with prior PARP inhibitor use. For the MIRV combo trial, they expect to enroll up to 70 patients across high, medium, and low folate expression levels and are working with ImmunoGen to establish response benchmarks for each subgroup.