Faisal Khurshid

Faisal Khurshid asked about the benefits Revolution Medicines is seeing or expects to receive from the Commissioner's Priority Review Voucher (CNPV), beyond what is already provided by programs like Breakthrough Designation and real-time oncology review.

Answer

Chairman and CEO Mark A. Goldsmith stated that the company does not disclose details about its interactions with the FDA but noted a constructive dialogue with the review team. He explained that the main described advantage of the CNPV is a faster review process, which is ultimately a question for the FDA once a submission is accepted. He emphasized that the company's role is to provide the requested data as quickly as possible.

Faisal Khurshid asked about the specific benefits Revolution Medicines expects to receive from the Commissioner's Priority Review Voucher (CNPV), beyond those offered by Breakthrough Designation and real-time oncology review.

Answer

Mark Goldsmith, Chairman and CEO, stated that Revolution Medicines does not typically disclose details of FDA interactions but confirmed a constructive dialogue. He noted that the main advantage described for the CNPV is a faster review process, but this is ultimately a question for the FDA, as their clock starts ticking once they accept an adequate submission.

Faisal Khurshid inquired about the company's perspective on the upcoming competitor readout from IDEAYA in frontline uveal melanoma and its potential impact on KIMMTRAK's position in frontline HLA-positive uveal melanoma.

Answer

Ralph Torbay, EVP of Commercial, stated that the company awaits randomized Phase III data from the competitor, focusing on hazard ratio and safety given the evolving standard of care and potential tolerability challenges of small molecules. Bahija Jallal, CEO, expressed confidence in KIMMTRAK's robust data, real-world evidence, and upcoming five-year survival data.

Faisal Khurshid asked for Ascendis Pharma's latest thoughts on the TransCon CNP competitive landscape, including upcoming FGFR data from BridgeBio and the earlier-stage long-acting CNP from BioMarin.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, acknowledged the safety and tolerability of CNP therapy. Regarding BioMarin's long-acting CNP, he stated that he would need to see PK data to assess its viability. For BridgeBio's non-specific FGFR inhibitor, he anticipated linear growth improvement but expressed significant concern about the non-specific inhibition of FGFR1, FGFR2, and FGFR3, particularly regarding potential long-term impacts on CNS development that may not be evident in short-term clinical trials.

Faisal Khurshid asked for Ascendis Pharma's latest thoughts on the TransCon CNP competitive landscape, including upcoming FGFR data from BridgeBio and the earlier-stage long-acting CNP from BioMarin.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, acknowledged BioMarin's attempt to develop a long-acting CNP, but expressed skepticism without seeing PK data. He highlighted TransCon CNP's superior safety and tolerability profile compared to VOXZOGO. Regarding BridgeBio's FGFR inhibitor, he expects linear growth improvement but questioned its ability to deliver benefits beyond linear growth (e.g., muscle strength, leg bowing, quality of life). He expressed 'extreme worry' about the nonspecific inhibition of FGFR1 and FGFR2, and potential long-term CNS development impacts that may not be evident in short-term trials.

Faisal Khurshid inquired about a specific benchmark for testosterone reduction in healthy male volunteers for ABCL 635 and discussed the potential risks of engaging a CNS target like NK3R with a monoclonal antibody (MAB).

Answer

Carl Hansen, AbCellera's President and CEO, stated that while no specific level would be disclosed, the company would look for engagement at least as good as that seen with small molecules like fezolinetant. Regarding the CNS target, Mr. Hansen explained that the NK3R pathway is well-validated, and given its expression in KNDy neurons and connections to the endocrine and thermoregulatory systems, engagement in the arcuate nucleus is expected to be efficacious for VMS, pending proof-of-concept study results.

Faisal Khurshid from Leerink Partners asked whether the higher-than-usual partnership and licensing revenue recorded in the quarter should be considered a new baseline for future quarters.

Answer

CFO Andrew Booth clarified that the $10 million in licensing revenue was a one-off payment related to an earn-out from the Trianni acquisition. He explicitly stated that this level of revenue is not expected to be recurring.

Faisal Khurshid from Leerink Partners sought clarification on whether the second dose added to the Phase 1b study was higher or lower than the first, if these doses would be used in Phase 2b, the patient count, and if a dose-response was expected.

Answer

CEO Nello Mainolfi declined to specify if the added dose was higher or lower to avoid speculation, but confirmed both were tested in healthy volunteers. He also withheld the Phase 2b doses for competitive reasons. He affirmed the trial size remains approximately 20 patients and deferred comment on observing a dose-response until the full data is presented.

Faisal Khurshid of Leerink Partners questioned the sufficiency of the 28-day dosing period in the KT-621 Phase Ib trial for atopic dermatitis to show robust biomarker activity, and asked about the rationale for the study's inclusion criteria and lack of a placebo arm.

Answer

Chief Medical Officer Jared Gollob stated that 28 days is sufficient based on prior dupilumab trial data showing clear impacts at 4 weeks. He also highlighted the importance of stringent eligibility criteria. CEO Nello Mainolfi added that the study is designed to expedite the move to a pivotal Phase IIb trial and that a placebo arm is unnecessary for the primary biomarker endpoints.

Faisal Khurshid of Leerink Partners asked about Kymera's strategy regarding potential partnerships for the KT-621 program and the ideal timing for such a transaction.

Answer

CEO Nello Mainolfi described any near-term partnership for KT-621 as 'exceptionally premature.' He stated that Kymera is best positioned to develop the asset through key inflection points, likely Phase 2b studies. While a deal might be considered closer to commercialization, he emphasized the bar for partnering would be 'extremely high.'

Faisal Khurshid noted another disclosed IRF5 program using an allosteric modulator and asked about the potential benefits of Kymera's degrader approach over such a mechanism.

Answer

President and CEO Nello Mainolfi responded that while there is no public data from the competitor, he believes the key challenges for any IRF5 drug are achieving selectivity and blocking all protein functions, including splicing variants. He argued that a degrader is uniquely suited to accomplish this, which is extremely difficult for a traditional inhibitor, and also offers a PK/PD advantage for maintaining continuous target suppression.

Faisal Khurshid asked for more specific details on what is driving the significant inflection and expansion of the overall ACTH drug class. He also inquired about the economics of the new Cortrophin prefilled syringe and whether they differ from the traditional vial and syringe format.

Answer

President, Director & CEO Nikhil Lalwani attributed the strong growth to multiple factors: the faster-than-expected impact of the expanded sales force, acceleration in newer indications like gout and ophthalmology, the rapid uptake of the new prefilled syringe (accounting for 70% of new cases initiated), and the addition of new prescribers who were previously naive to ACTH therapy. He noted a modest upward pricing advantage for the prefilled syringe but declined to provide further economic details.

Faisal Khurshid requested more detail on the commercial and market access challenges for ILUVIEN, specifically asking how the company plans to work around them using specialty pharmacy and Medicare Part D. He also asked about opportunities to replicate Cortrophin Gel's success in acute gouty arthritis in other indications.

Answer

President and CEO Nikhil Lalwani clarified that the ILUVIEN challenge stems from a lack of foundation co-pay support for Medicare Part B patients. He explained the strategy to mitigate this involves exploring access for patients with a Part D pharmacy benefit, which offers co-pay caps, via a specialty pharmacy channel. Regarding Cortrophin, he confirmed that opportunities exist to apply focused commercial efforts to other therapeutic areas, citing the fact that 40% of its prescribers were new to the ACTH category as evidence of their ability to expand the market.

Faisal Khurshid of Leerink Partners requested more clarification on the Medicare reimbursement changes, asking if it was related to the Part D redesign and whether the impact was specific to ILUVIEN and YUTIQ or if it also affected Cortrophin.

Answer

Executive Nikhil Lalwani explained the issue is not a redesign but rather a lack of 2025 funding for certain third-party programs that assist Medicare patients with co-pays. He confirmed this dynamic does not impact Cortrophin, which is primarily a Part B drug and sees some tailwinds in Part D from IRA changes. He noted the funding issue could affect other products beyond ANI's portfolio.

Faisal Khurshid of Leerink Partners inquired about the progress and potential risks of the ongoing respiratory depression study (TITLE) and the rationale for conducting a drug-drug interaction (DDI) study given prior background use of anti-fibrotics.

Answer

James Cassella, Chief Development Officer, explained the respiratory safety study is an FDA-requested assessment to characterize Haduvio's effects in IPF patients and is on track for the end-of-Phase 2 meeting. He described the DDI study as a standard, pre-Phase 3 "check the box" activity to formally characterize any potential pharmacokinetic interactions with common anti-fibrotics, thereby de-risking the Phase 3 program.

Faisal Khurshid inquired about the criteria for a positive readout from the CORAL trial for both efficacy and safety, and asked about the company's next major catalysts following the CORAL data release.

Answer

Executive Jennifer Good stated that for the CORAL trial, a statistically significant positive result is the primary bar for success to continue development, especially given the high unmet need in IPF chronic cough. She confirmed the safety profile has shown no unusual adverse events and that the company will provide a clearer catalyst path after the CORAL data is analyzed.

Faisal Khurshid of Leerink Partners asked about the patient characteristics in the CORAL study, inquiring if there were differences between the first and second halves of enrollment, and also requested an update on the study's discontinuation rate.

Answer

Executive Jennifer Good stated that no changes were made to the CORAL study protocol, sites, or enrollment criteria following the sample size reestimation, ensuring population consistency. She also confirmed that the blinded discontinuation rate remained low and consistent in the single digits throughout the entire study.

Faisal Khurshid from Leerink Partners inquired about the expected drug liking results for the comparator butorphanol in the Human Abuse Potential (HAP) study and what specific outcomes for nalbuphine would support an unscheduled designation.

Answer

Dr. James Cassella, Chief Development Officer, explained that butorphanol is a scheduled drug and is expected to show a clear differentiation from placebo to validate the study. For nalbuphine to support an unscheduled label, it would need to show no significant difference from placebo within a prespecified equivalence margin of 11 points on the drug liking scale. This is one of several factors in the overall scheduling decision.

Faisal Khurshid from Leerink Partners asked about the company's confidence in the safety and efficacy of using inhaled nintedanib (MANNKIND-201) on top of background pirfenidone therapy, and questioned what would be required to bring the development program into the U.S.

Answer

SVP, Therapeutic Area Head - Rare Lung Diseases, Wassim Fares stated that due to the low systemic exposure of inhaled nintedanib, drug-drug interaction with pirfenidone is expected to be minimal, and the future of IPF is combination therapy. CEO Michael Castagna added that while the Phase 2 trial is ex-US due to enrollment challenges with a placebo arm in the US, a successful outcome would lead to a global Phase 3 trial that includes the U.S.

Faisal Khurshid from Leerink Partners asked about the balance between maintaining operational profitability and funding the Afrezza pediatric launch, and also questioned the priority of pipeline expansion.

Answer

Executive Michael Castagna explained that after prioritizing debt reduction, the company's focus is now on deploying capital for growth drivers, including the Afrezza pediatric launch and advancing the clofazimine and nintedanib trials. He also confirmed that pipeline expansion is a key priority, with several non-public product opportunities and life cycle management programs for existing assets currently in development.

Faisal Khurshid of Leerink Partners requested more information on the adverse event profile from the MNKD-201 Phase I study, specifically asking about the cause and time course of FEV1 drop and cough events.

Answer

Executive Michael Castagna clarified that there were no significant concerns regarding the FEV1 drop, as it was not progressive and led to no discontinuations. He hypothesized the events were likely caused by lung irritation from the frequent, protocol-mandated FEV1 tests rather than the drug itself, noting similar occurrences in the placebo (excipient-only) arm.

Faisal Khurshid asked management to identify the primary issues that hindered the Rytello launch in late 2024 and Q1 2025, which new strategies had the most significant impact in Q2, and for an update on therapy duration.

Answer

Dawn Bir, Interim President & CEO, pointed to the strategic pivot in March focusing on brand awareness, prescribing clarity, and KOL support. Jim Ziegler, EVP & CCO, added that educating physicians on the product profile is key and noted that duration of therapy should improve as use shifts from third-line plus to earlier lines, where duration is naturally longer.

Faisal Khurshid of Leerink Partners questioned the sustainability of the 10% demand growth for RYTELO seen in April and asked how reliably this demand would translate into revenue.

Answer

Dr. Joseph Eid, EVP of R&D, characterized the 10% growth as a single but promising data point. He expressed confidence that the company's strategy of targeted physician education is proving successful, as evidenced by changing perceptions. Dr. Eid stated the team's expectation is to build on this momentum and return to sustained growth through strong commercial execution.

Faisal Khurshid of Leerink Partners questioned whether the flat revenue trend was driven by a slowdown in new patient starts or by discontinuations. He also asked for management's confidence level in the new sales strategy creating a growth inflection and the expected timing for such a change.

Answer

Jim Ziegler, Chief Commercial Officer, clarified that the primary issue is a softness in new patient starts, not treatment duration, which appears consistent with clinical trial data. He explained that initial uptake came from early adopters, and the focus is now on broader physician outreach. He characterized the goal as achieving 'steady growth' rather than a sharp 'inflection,' as driving adoption across all treatment lines is an ongoing execution-based effort.

Faisal Khurshid from Leerink Partners asked for clarification on the royalty percentage rates and cap multiplier, and for an update on the company's cash runway expectations following the new financing.

Answer

EVP & CFO Michelle Robertson emphasized that the deal is capped at 1.65 times the initial payment, a level she is confident Geron can reach before peak sales based on internal projections. She clarified that the financing allows Geron to maintain over 12 months of cash going forward and could potentially fund the company to breakeven without additional equity.

Faisal Khurshid asked for expectations on the upcoming MCL data update, including patient numbers and follow-up, and inquired about the target product profile needed to differentiate from the two currently approved CAR-T therapies in MCL.

Answer

Clinical Program Head Omotayo Fasan stated that patient numbers have increased since the last update and follow-up will be at least a year longer, with the goal of matching the best-in-class efficacy and safety of existing therapies. CEO Paulus Stoffels emphasized the 7-day vein-to-vein time as a key differentiator, especially for patients with short life expectancies.

Faisal Khurshid of SVB Securities asked for the evidence supporting the three-month PFS assumption for the MANTRA trial's control arm and questioned the company's confidence in the MDM2 copy number cutoff used for the MANTRA-2 trial.

Answer

CSO Robert Doebele explained the control arm's PFS assumption was based on the 2.2-month PFS from the trabectedin registrational trial, with a conservative cushion added. Regarding the MANTRA-2 cutoff, he cited observed activity below the prior threshold of 12 and supporting mutual exclusivity analysis with p53 mutations.