Cory Kasimov

Cory Kasimov followed up on ACACIA-HCM, asking if US investigators view one of the primary endpoints (KCCQ or peak VO2) as more important, and what constitutes a clinically meaningful change from a physician's perspective for this patient population.

Answer

President and CEO Robert Blum and EVP of R&D Fady Malik explained that co-primary endpoints were chosen for regulatory harmonization, not physician preference, and physicians will consider the totality of evidence. Robert Blum emphasized that for non-obstructive HCM, with no approved therapies, the study will help define what is clinically meaningful.

Cory Kasimov asked about the ACACIA-HCM primary endpoints, specifically if U.S. investigators view KCCQ or peak VO2 as more important, and what is considered a clinically meaningful change from a physician's perspective for non-obstructive HCM.

Answer

Robert Blum, President and CEO, and Fady Malik, EVP of R&D, explained that co-primary endpoints were chosen for regulatory harmonization, and physicians will likely consider the totality of evidence. Given no approved therapies for nHCM, the study itself is intended to define what constitutes a clinically meaningful benefit.

Cory Kasimov of Evercore ISI asked for a comparison of the drug interruption and discontinuation protocols in the ACACIA trial versus the competitor's ODYSSEY trial, especially concerning LVEF drops.

Answer

Fady Malik, EVP of R&D, detailed significant differences. In ACACIA, patients can down-titrate without interruption if LVEF is above 40%, and only interrupt for one week if it drops below 40%. This contrasts with the competitor's four-week interruption protocol. He also noted differences in dose ranges and patient selection.

Cory Kasimov of Evercore inquired whether a REMS was submitted as part of the European Medicines Agency (EMA) filing and if it was raised in the day 120 questions.

Answer

Robert I. Blum, President and CEO, and Fady Malik, EVP of R&D, clarified that the EMA uses a Risk Management Plan (RMP), not a REMS. An RMP was submitted as a standard part of the MAA filing, and they do not anticipate any issues or additional submissions related to it based on the day 120 questions received.

Cory Kasimov of Evercore ISI inquired about the potential for market expansion in hypertrophic cardiomyopathy (HCM), asking for expectations on how diagnosis rates might increase over the next 3-5 years with two companies actively educating the market.

Answer

EVP & CCO Andrew Callos estimated the current HCM diagnosis rate is about 30% and could reach 50% in the next 3-5 years, noting that nonobstructive HCM is growing at a double-digit rate. President & CEO Robert I. Blum added that the amyloidosis and pulmonary arterial hypertension markets serve as good proxies for how a next-in-class drug can increase diagnosis and category penetration.

Cory Kasimov asked about the expected safety profile of BMN 333, based on preclinical data and initial thoughts, and whether it would largely mirror Voxzogo or show any meaningful differentiating factors.

Answer

Greg Friberg, Chief R&D Officer, stated that preclinical models (cynomolgus monkey) for BMN 333 have not shown additional safety concerns compared to Voxzogo as a free drug. He noted that the profile of free CNP allows for much higher exposures with BMN 333 (3-7x higher AUC) compared to daily Voxzogo, opening a therapeutic window that is hoped to recapitulate efficacy seen in animal models for a 'best-in-disease' profile.

Cory Kasimov requested qualitative commentary on BioMarin's prior long-term mid-2030s guidance, specifically regarding the Voxzogo opportunity and the anticipated CAGR for the enzyme therapies business. He also asked about the company's capital deployment strategy, particularly the consideration of share buybacks given the significant cash balance and operating cash flow.

Answer

Brian Mueller, Chief Financial Officer, indicated continued sustainable growth for enzyme therapies, targeting a high single-digit CAGR, and ongoing Voxzogo growth through patient penetration and indication expansion, but noted uncertainty due to potential competition. Alexander Hardy, President and CEO, stated that business development is the priority for capital allocation, believing it offers the greatest opportunity for top-line growth and stock appreciation, leveraging BioMarin's rare disease expertise. Share buybacks are regularly reviewed but not the current priority.

Cory Kasimov requested qualitative commentary on BioMarin's prior long-term mid-2030s guidance, specifically regarding the opportunity for VOXZOGO and the anticipated CAGR for the enzyme therapies business. He also asked about the consideration of share buybacks given the substantial cash balance and operating cash flow.

Answer

Brian Mueller (CFO, BioMarin Pharmaceutical) stated that BioMarin still targets a high single-digit sustainable growth rate for enzyme therapies and plans to grow VOXZOGO, but noted uncertainties from potential competition. Alexander Hardy (President and CEO, BioMarin Pharmaceutical) emphasized business development as the priority for capital allocation to drive top-line growth, believing assets are worth more in BioMarin's hands. He confirmed share buybacks are reviewed but not the current priority.

Cory Kasimov from Evercore inquired about BioMarin's perspective on the evolving competitive landscape for achondroplasia, particularly concerning recent data on long-acting CNP combined with growth hormone.

Answer

Gregory Friberg, EVP and Chief R&D Officer, responded that while short-term growth with a growth hormone combination is unsurprising, the long-term persistence of this effect is questionable since achondroplasia is not a growth hormone-deficient condition. He noted that long-term data for growth hormone has shown only modest final height benefits and less evidence of improving other health aspects, such as facial morphology, compared to CNP therapy.

Cory Kasimov from Evercore inquired about BioMarin's perspective on the evolving competitive landscape for achondroplasia, specifically regarding recent data on combining long-acting CNP with growth hormone.

Answer

Gregory Friberg, EVP and Chief R&D Officer, explained that while short-term growth increases with such combinations are not surprising, the long-term persistence of this effect is unproven in achondroplasia, which is not a growth hormone-deficient condition. He noted that long-term follow-up on growth hormone alone has shown minimal final height benefit and lacks the broader health improvements, like facial morphology changes, seen with CNP therapy.

An analyst on behalf of Cory Kasimov of Evercore ISI asked for details on the evolution of U.S. versus ex-U.S. sales for VOXZOGO in Q1 and the expected trend for the remainder of the year.

Answer

Cristin Hubbard, Chief Commercial Officer, explained that the revenue split fluctuates quarterly but is currently around 75% ex-U.S. and 25% U.S. She stated that in the long term, the split is expected to normalize and mirror BioMarin's overall portfolio, which is approximately two-thirds of revenue from outside the U.S. and one-third from the U.S.

Cory Kasimov sought clarification on the BMN 351 DMD program, asking if the 10% dystrophin level target is the expectation for the 25-week biopsy data, or if that level is only expected at the one-year steady-state mark.

Answer

Chief R&D Officer Gregory Friberg explained that the 25-week data will provide a 'clear line of sight' on whether the 10% target is achievable at steady state, based on their predictive models. He emphasized this time point will be a very solid read on their trajectory and noted that they are also advancing a higher 9 mg/kg dose cohort, providing another path to achieving their goal.

Cory Kasimov asked for the number of patients from the original Voxzogo Phase III trial who have reached full adult height. He also sought clarification on whether the in-house data for the DMD program, expected in Q2, would be publicly disclosed at that time.

Answer

EVP, Worldwide R&D Greg Freiberg explained that while the company is tracking final adult height data as part of its post-marketing commitment, it will not release specific numbers yet. Regarding the DMD program, he stated that the company will have dystrophin data from the first six patients in-house mid-year and will decide on public release based on the quality and meaningfulness of the data.

Cory Kasimov asked about the potential risk of hypogammaglobulinemia adverse events associated with povetacicept and its possible impact on the drug's label.

Answer

Reshma Kewalramani (CEO and President, Vertex Pharmaceuticals) explained that while a decrease in IgG is an expected mechanism of action for BAFF/APRIL inhibitors, the RUBY-3 80 mg cohort data showed no serious adverse events of infection, and average IgG levels remained within the normal range, suggesting a favorable overall benefit-risk profile.

Cory Kasimov inquired about the potential risk of hypogammaglobulinemia adverse events associated with povetacicept (pove) and its possible impact on the drug's label.

Answer

Reshma Kewalramani, CEO and President of Vertex Pharmaceuticals, explained that while a decrease in IgG levels is an expected mechanism of action for BAFF/APRIL inhibitors, the RUBY-3 data showed no serious adverse events (SAEs) related to infection. She noted only one patient had IgG levels below 300 mg, which was not associated with serious infection, and the average IgG levels remained within the normal range, indicating a favorable overall benefit-risk profile.

Cory Kasimov asked for Alnylam's latest views on the potential for competitive silencer data, expected this year, to achieve a differentiated label and its possible commercial impact on AMVUTTRA.

Answer

Tolga Tanguler, Chief Commercial Officer, noted it's difficult to assess impact without seeing competitor data but believes additional entrants will expand the large, underserved category. He emphasized Alnylam's strong position with a head start, robust clinical data, and convenient quarterly dosing. Pushkal Garg, Chief Research and Development Officer, expects the competitor study to be positive but doesn't foresee a materially different treatment effect size than HELIOS-B or a significantly differentiated label, given AMVUTTRA's broad label covering use with and without stabilizers.

Cory Kasimov inquired about the strategic use of the recently presented receptor occupancy data comparing INGREZZA and Austedo XR, and its potential implications for Neurocrine's next-generation VMAT2 inhibitors.

Answer

Chief Medical Officer Sanjay Keswani highlighted that INGREZZA demonstrated nearly double the VMAT2 target occupancy compared to Austedo XR, reinforcing INGREZZA's superior efficacy. He noted that this experience in matching receptor occupancy with clinical efficacy is being applied to the development of their two VMAT2 follow-on compounds, including the recently initiated Phase II study for NBI-890.

Cory Kasimov inquired about the implications of the recent receptor occupancy poster comparing INGREZZA and Austedo XR, and how this information might be used for Neurocrine's next-generation VMAT2 inhibitors.

Answer

Sanjay Keswani, Chief Medical Officer, expressed excitement about the head-to-head PET study, which showed nearly double the VMAT2 target occupancy for INGREZZA compared to Austedo XR. He believes higher VMAT2 occupancy correlates with greater efficacy and confirmed this relationship is being utilized in the development of Neurocrine's two VMAT2 follow-on compounds, with a Phase 2 study recently initiated for the first follow-on.

Cory Kasimov inquired about the progress of CRENESSITY adoption at Centers of Excellence (COEs) versus the community setting, asking if all COEs are now adopting and about the opportunity in community practices.

Answer

Eric Benevich, Chief Commercial Officer, stated that all 20 estimated COEs, which care for about 15% of classic CAH patients, have started adopting CRENESSITY, albeit at varying paces. He noted pleasant surprise at the adoption rate among community endocrinologists, who typically treat fewer patients, and highlighted this as a rationale for expanding the sales team to reach a wider pool of HCPs.

Cory Kasimov inquired about CRENESSITY's adoption progress at Centers of Excellence (COEs) and in the community setting, asking if the company has reached every COE and the extent of the opportunity at the community level.

Answer

Eric Benevich, Chief Commercial Officer, confirmed that all 20 estimated COEs have started adopting CRENESSITY, albeit at different paces. He noted pleasant surprise at the adoption rate among community endocrinologists, who typically treat fewer patients, and highlighted this as a rationale for expanding the sales team to reach a wider pool of HCPs.

Cory Kasimov of Evercore requested more detail on the adult patients from the Crinesity open-label extension (OLE) study transitioning to commercial product, including the number of patients and any nuances in the process.

Answer

CEO Kyle Gano clarified that the number of patients transitioning from the adult OLE is very small, totaling less than 40 patients. He explained that these transitions are split between Q2 and Q3, making their impact 'de minimis' relative to the more than 600 new patient starts in the quarter.

Cory Kasimov asked if there was any material inventory stocking for CRENESSITY in Q1 and when to expect long-term data from the drug's open-label extension study.

Answer

Chief Financial Officer Matthew Abernethy confirmed there was very little inventory stocking for CRENESSITY in the quarter. Chief Medical Officer Dr. Eiry Roberts stated that one-year data from the open-label extension, covering androgen control, glucocorticoid levels, and other clinical endpoints, will be presented at upcoming medical meetings.

Cory Kasimov requested additional details on payer traction for CRENESSITY and the expected duration of the free drug program for new patients.

Answer

Chief Commercial Officer Eric Benevich explained that CRENESSITY is initially non-formulary, so a 'Fast Start' program provides free product while reimbursement is secured, a process expected to take one to two months for most patients early in the launch. Chief Financial Officer Matthew Abernethy added that early signs from payers are positive, citing a recent favorable coverage policy from a major plan.

Cory Kasimov of Evercore ISI asked about the Crinecerfont launch, specifically the number of prescribers at CAH Centers of Excellence, the patient portion they serve, and which patient segments they are most eager to treat.

Answer

CCO Eric Benevich estimated that the dozen or so CAH Centers of Excellence manage about 10-15% of the total patient population, with the majority being cared for in community and pediatric endocrinology practices. CMO Eiry Roberts added there is significant interest in the pediatric setting, where managing androgen levels is critical for normal growth and development.

Cory Kasimov asked about the primary drivers behind Attruby's impressive growth in both unique prescribers and prescriptions per prescriber, specifically whether it's due to greater penetration within existing accounts, expansion into new centers, or improved conversion rates.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, explained that the momentum is driven equivalently by both greater penetration within existing accounts and expansion into new centers. He noted that many new prescribing HCPs are affiliated with or refer to centers of excellence. BridgeBio has actively expanded its reach to previously uncovered practices, including using IT techniques to identify prescribing patterns.

Cory Kasimov asked about the primary drivers behind Atrobi's impressive growth in both unique prescribers and prescriptions per prescriber, specifically whether it's due to greater penetration within existing accounts, expansion into new centers, or an improved conversion rate.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, indicated that the momentum is driven equivalently by both greater penetration within existing accounts and expansion into new centers. He noted that many new prescribing HCPs are capitated parts of or referrers into centers of excellence. He also mentioned efforts to reach previously uncovered practices, including using IT techniques for alerts.

Cory Kasimov from Evercore ISI asked what the company's market research indicates would be considered a meaningful win in the upcoming Phase 3 CALIBRATE trial for incaleret in ADH1.

Answer

COO Ananth Sridhar explained that given the limited efficacy of the current standard of care, any successful study would be a 'home run.' He defined a clinically meaningful result as a majority of patients achieving concomitant normalization of both blood and urine calcium, noting that 69% of patients in the Phase 2 study achieved this endpoint versus zero on standard of care.

Cory Kasimov of Evercore ISI asked for an updated perspective on the growth of new patient starts in the ATTR-CM category, suggesting that previous estimates now appear conservative.

Answer

CEO Neil Kumar agreed that the market is ramping faster than historically, attributing the acceleration to a higher share of voice from multiple companies launching products, which enhances physician education and screening. He stated the market could easily become a $20 billion opportunity and expects the high rate of new diagnoses to continue. VP of Strategic Finance Chinmay Shukla added that many new diagnoses are coming from high-volume heart failure clinics.

Cory Kasimov with Evercore inquired about the evolving commercial opportunity for cimdisiren in generalized myasthenia gravis (GMG) and Regeneron's plans for the asset in Europe.

Answer

Regeneron President and CEO, Leonard Schleifer, initiated the discussion by asking for a review of current GMG therapies. President and CSO, George Yancopoulos, detailed cimdisiren's potential as a best-in-class treatment due to its convenient subcutaneous once-every-three-months dosing, stable and deep efficacy in cross-trial comparisons, and potential safety benefits from partial complement pathway inhibition. Executive Vice President of Commercial, Marion McCourt, added that the launch strategy is based on this encouraging clinical profile, positioning it as a highly differentiated product for patients with unmet needs.

Cory Kasimov inquired about the commercial opportunity for cemdisiran in Generalized Myasthenia Gravis (GMG) following positive Phase III data, and Regeneron's plans for the asset in Europe.

Answer

President and CSO George Yancopoulos detailed cemdisiran's potential advantages: subcutaneous once-every-three-months dosing (most convenient), seemingly best-in-class and stable efficacy in cross-trial comparisons, and potential safety benefits due to partial complement pathway inhibition. EVP of Commercial Marion McCourt added that the launch strategy is based on this encouraging clinical profile, and they are excited about bringing a highly differentiated product to market for patients with unmet needs.

Cory Kasimov from Evercore ISI asked for Regeneron's perspective on competitive data for OX40 Ligand inhibitors and how they might compete with Dupixent's overall profile.

Answer

President & CSO Dr. George Yancopoulos argued that current OX40 data offers no clear advantages and emphasized Dupixent's superior and extensive safety profile, which targets a specific pathway unlike broader immunomodulators. President & CEO Dr. Leonard Schleifer added that Dupixent's ability to treat multiple common co-morbidities provides a significant commercial advantage.

Cory Kasimov from Evercore ISI asked for Regeneron's perspective on recent competitive data for OX40 Ligand inhibitors and how they might compete with Dupixent's overall profile.

Answer

President & Chief Scientific Officer Dr. George Yancopoulos argued that the competitor data does not suggest an advantage and it will be a long time before any competitor can match Dupixent's extensive safety profile, which targets a largely non-essential immune pathway. CEO Dr. Leonard Schleifer added that Dupixent's ability to treat multiple comorbidities is a key commercial advantage.

Cory Kasimov of Evercore ISI asked about the adjuvant CSCC Libtayo data, questioning the necessity of showing an overall survival benefit and the scale of the commercial opportunity.

Answer

President and CSO, Dr. George Yancopoulos, stated that an overall survival benefit is not critical as a primary endpoint due to few events in this early-stage population, though the FDA will review the trend. EVP of Commercial, Marion McCourt, estimated the U.S. market opportunity at approximately 10,000 patients.

Cory Kasimov of Evercore ISI followed up on capital allocation, asking about the potential for an Accelerated Share Repurchase (ASR) and the company's evolving views on initiating a dividend, given its large cash position.

Answer

President and CEO Dr. Leonard Schleifer reiterated that the company does not comment on the specific mechanics or timing of share repurchases. Regarding a dividend, he repeated prior commentary that the most opportune time to consider it would be after the Sanofi development balance is paid off, which is anticipated around the end of 2026.

Cory Kasimov of Evercore asked about the potential read-through from Biohaven's upcoming MDD data to Xenon's program and the key differences between the two assets. He also asked new Chief Commercial Officer Darren Cline about the primary headwinds and market nuances for the Ezetucalner launch in epilepsy.

Answer

President and CEO Ian Mortimer stated that while they are confident in the Kv7 mechanism for MDD, the Biohaven data will be the first placebo-controlled results for that specific molecule. Chief Commercial Officer Darren Cline identified the main commercial headwind as overcoming the inertia of physicians accustomed to existing therapies, despite the significant opportunity for a novel mechanism after a long period without new branded launches.

Cory Kasimov asked how R&D spending is expected to evolve following the Bristol Myers Squibb deal, and whether the cost-sharing benefits would be reallocated to other programs or result in lower overall spend.

Answer

CFO Ramón Zapata clarified that while the BMS collaboration is beneficial, overall R&D investments are set to increase in the second half of the year. He stated that spending will be focused on priority late-stage programs, including mRNA cancer immunotherapies and ADCs, while spending on non-priority areas will decrease.

Cory Kasimov asked for BioNTech's perspective on competitor Akeso's preliminary overall survival data for its bispecific and whether this data impacts the trial design for BNT327 in NSCLC.

Answer

Chief Medical Officer Özlem Türeci called the competitor's data encouraging as it validates the VEGF/PD-L1 bispecific concept. However, she stated it has no direct impact on their Rosetta Lung-02 trial, which evaluates BNT327 in combination with chemotherapy in a different population, but viewed the news as a positive signal for the drug class overall.

Cory Kasimov of Evercore ISI followed up on the upcoming BNT327 data at ELCC, asking for specifics on the duration of follow-up and the relevant clinical trial comparator.

Answer

CMO Özlem Türeci confirmed the data would include Progression-Free Survival (PFS) and emerging Overall Survival (OS) data, though not median OS. Both she and CSO Ryan Richardson identified the benchmark comparator as the Tecentriq plus chemotherapy regimen from the IMpower133 trial.

Cory Kasimov asked about the combination strategy of the Trop-2 ADC (BNT325) with BNT327, focusing on the dosing strategies being evaluated and the confidence level that combining the three mechanisms will not compromise safety.

Answer

CEO Dr. Ugur Sahin explained that the current combination trial is designed to explore the safety profile, particularly whether there is additive toxicity, as the Trop-2 ADC is associated with stomatitis. He noted they do not expect other overlapping toxicities due to BNT327's favorable safety profile and will use a dose escalation approach to find a safe and effective dose.

Cory Kasimov asked whether the strong Progression-Free Survival (PFS) benefits seen in the HARMONi-2 trial are expected to translate to Overall Survival (OS) and if the safety trends observed in China are anticipated to be consistent in the global patient population.

Answer

Executive Dave Gancarz deferred commentary on HARMONi-2 OS subgroup data until their partner Akeso releases it. Chief Medical Officer Dr. Allen Yang addressed safety, stating they are pleased with the profile from randomized trials and do not expect significant differences between China and the U.S., aside from minor cultural variations in reporting lab abnormalities. Dr. Jack West, VP and Thoracic Oncology TA Head, added that the most concerning adverse events are not subject to nuanced interpretation and the data seen to date is very reassuring to clinicians.

Cory Kasimov asked if the profound PFS benefits in HARMONi-2 are expected to hold for overall survival across subgroups and whether safety trends in the global population are expected to match data from China.

Answer

Executive Dave Gancarz deferred comment on HARMONi-2 OS subgroups to their partner, Akeso. Chief Medical Officer Dr. Allen Yang stated he does not expect significant safety differences between China and global populations, noting only minor cultural differences in reporting non-impactful lab abnormalities. Dr. H. Jack West, VP, added that serious adverse events are not subject to nuanced interpretation and the data seen so far is reassuring.

Cory Kasimov sought clarity on the updated timeline for the flu/COVID combination vaccine, asking if Moderna expects to refile or submit the new flu data as a major amendment, which could impact the approval date.

Answer

President Stephen Hoge stated that the exact procedural path is not yet determined and will depend on consultations with the FDA after the flu data is finalized. He noted that while an amendment to the existing BLA is a pragmatic option, a resubmission is also possible. The review of other components of the file is already progressing.

On behalf of Cory Kasimov, an analyst asked about the reason for a perceived 'bump' in expense guidance and requested more color on the propionic acidemia (PA) program's endpoint related to metabolic decompensation events (MDEs).

Answer

CFO Jamey Mock clarified there was no change to expense guidance, explaining the potential confusion between GAAP costs and the company's defined 'cash costs.' President Stephen Hoge confirmed that a reduction in MDEs is the pivotal endpoint for the PA program, as agreed with regulators, and the trial will compare MDE rates before and after treatment.