Tazeen Ahmad

Tazeen Ahmad inquired about the impact of the $400 million OMERS financing on Ultragenyx's future financing needs, particularly concerning the renewal of priority review vouchers (PRVs) in September 2026. She also asked about the company's strategy if one of the Orbit or Cosmic studies for OI were positive while the other was not, and its potential effect on approval chances.

Answer

Howard Horn, Chief Financial Officer, stated that the financing strengthens the balance sheet, supporting the company's path to profitability in 2027, which relies on continued double-digit revenue growth, expense management, and the monetization of three PRVs (UX111, DTX401, UX143). Erik Harris, Chief Commercial Officer, expressed confidence that both Orbit and Cosmic studies are powered to succeed. He noted that even if one study missed, the safety and bone mineral density data would likely support a broad age indication, and the drug's mechanism of action should be consistent across age groups.

Tazeen Ahmad asked how the $400 million OMERS financing addresses potential 2026 financing needs, particularly concerning Priority Review Voucher (PRV) renewals, and about the company's strategy if one of the Orbit or Cosmic studies is positive while the other is not.

Answer

Howard Horn, Chief Financial Officer, stated that the financing, combined with continued double-digit revenue growth, managed expenses, and planned PRV monetizations (UX111, DTX401, UX143), supports the path to profitability in 2027. Erik Harris, Chief Commercial Officer, expressed confidence in both Orbit and Cosmic succeeding, but noted that even if one missed, the safety and bone density data would likely support a broad label, and adoption would be driven by the overall clinical picture.

Tazeen Ahmad from Bank of America questioned whether the magnitude of clinical benefit in the ORBIT trial's final 18-month readout would be more critical than just statistical significance, given the time taken to show separation from the control group.

Answer

Emil Kakkis, Founder, President & CEO, responded that the treatment effect size could be consistent, with variation merely extending the time to statistical separation. He argued that any fracture reduction in the 40-60% range is a substantial benefit. He emphasized that, similar to Crysvita, the key driver for adoption will be the drug's impact on functional ability and overall patient health, not just the primary endpoint percentage.

Tazeen Ahmad asked about the osteogenesis imperfecta (OI) study, questioning the likelihood of success and potential reasons for concern if the trial proceeds to its final analysis instead of stopping at the second interim.

Answer

CEO and President Emil Kakkis clarified that the next step after the second interim is the final analysis, not a third interim. He expressed high confidence that the study would succeed at one of these two points, noting the final analysis has a much easier p-value threshold of 0.04. He identified patient variability as the main risk in rare disease trials but stated that the study's large size (159 patients) and the drug's profound effect on bone mineral density provide a strong basis for success.

Tazeen Ahmad inquired about Ultragenyx's confidence in the second interim analysis of the Orbit study for osteogenesis imperfecta (OI) being sufficient to stop the trial early.

Answer

CEO Emil Kakkis expressed high confidence that the trial will succeed this year, either at the second interim analysis or the final readout. He noted the second interim has a greater chance of success than the first due to a stringent 0.01 p-value threshold and patients having at least 12 months of treatment, allowing for better separation between study groups.

Tazeen Ahmad asked about the setrusumab trial for Osteogenesis Imperfecta (OI), questioning if missing the first interim analysis would impact the overall likelihood of success and how the commercialization timeline would be affected by the different potential stopping points.

Answer

CEO Emil Kakkis clarified that missing the first interim analysis would not affect the ultimate efficacy determination, as it relates to the speed of event separation, not the drug's power. He emphasized that shortening the timeline by even a few months through an interim success has a substantial positive impact on the program's net present value (NPV), justifying the aggressive approach.

Tazeen Ahmed asked about the anticipated initial label for XPAXLY in Wet AMD, considering data from SOL1, SOLar, and SOLx, inquiring about its competitive attributes and potential future label additions.

Answer

Pravin U. Dugel, Executive Chairman, President and CEO, stated that Ocular Therapeutix expects a superiority label based on SOL1, offering dosing flexibility (6-12 months) and repeat dosing. He also noted that SOLar's comparison against high-dose Eylea will provide competitive numeric data.

Tazeen Ahmed asked about the expected initial label for XPAXLY in Wet AMD, considering data from SOL1, SOLAR, and SOLx, and what competitive attributes might be included or added later.

Answer

Dr. Pravin Dugel (Executive Chairman, President and CEO) stated that Ocular Therapeutix expects a superiority label for XPAXLY in Wet AMD based on SOL1, with dosing flexibility of 6 to 12 months from SOLAR and SOL1. He also noted that the SOLAR trial's masking arm against high-dose Eylea could provide a competitive advantage, even if not explicitly in the label.

Tazeen Ahmad from Bank of America inquired about the potential for a shortened regulatory review timeline using the 505(b)(2) pathway and asked when the company plans to ramp up preparations for a potential commercial launch.

Answer

Pravin Dugel, Executive Chairman, President & CEO, confirmed the company plans to submit its NDA after receiving positive 56-week data from the SOLAR trial. He noted that leveraging the 505(b)(2) pathway, available because the drug is already approved for other indications, could shorten the FDA review timeline by approximately two months. He added that details on the commercial strategy would be provided at the upcoming Investor Day.

Tazeen Ahmad questioned the rationale and timing for amending the SOL-1 and SOL-R trial designs, given the strong blinded data. She also asked why Ocular chose to reduce the size of the SOL-R study rather than maintain a larger patient cohort for a statistical cushion.

Answer

President and CEO Dr. Pravin Dugel explained that the changes create a more efficient, complementary trial program. He stated that the FDA's approval for redosing in SOL-1, combined with excellent patient retention, allowed for the streamlined design. This enhances SOL-1's ability to capture durability data at both 9 and 12 months and increases safety data. This efficiency was then applied to SOL-R, permitting a size reduction from 825 to 555 patients without compromising statistical integrity, ultimately aiming for a faster path to market with a superior label.

Tazeen Ahmad inquired about the operational details of the SOL-1 and SOL-R clinical trials, specifically asking about the number of overlapping sites and whether additional sites would be activated for SOL-R given its accelerated enrollment.

Answer

President and CEO Dr. Pravin Dugel confirmed that many sites overlap by design to ensure a seamless transition and maintain recruitment momentum between the SOL-1 and SOL-R trials. He stated that there is no slowdown and that Ocular is continuing to activate new sites for the larger SOL-R study to execute as quickly as possible.

Tazeen Ahmad inquired about the implications of receiving FDA alignment for the SOL-R study, asking if both the SOL-1 and SOL-R trials would need to be submitted concurrently for approval. She also asked about the expected dosing flexibility for AXPAXLI, questioning the potential variability between 6-month and 9-month intervals in clinical practice.

Answer

Dr. Pravin Dugel, President and CEO, confirmed the company received written validation from the FDA that both SOL-1 and SOL-R are acceptable as registration-enabling studies. He noted that SOL-R is designed to accelerate SOL-1 recruitment, which is already in an 'exponential phase.' Regarding dosing, Dr. Dugel explained that the combined data from both trials is intended to provide physicians with the flexibility to personalize treatment, allowing for dosing as frequently as every 6 months or extending it to 9, 10, or even 12 months depending on the patient.

Tazeen Ahmad asked about the market opportunity for MSS-CRC and first-line gastric cancer, seeking insight into how BioNTech's product could be differentiated from existing treatments.

Answer

Özlem Türeci, Chief Medical Officer and Co-founder, responded that both MSS-CRC and first-line gastric cancer represent high medical need indications. She emphasized the biological rationale for developing the VEGF-A and PD-L1 blocking combination, believing it has the potential to improve clinical benefit for these patient populations.

Tazeen Ahmad asked about the market opportunity for pomitamic in first-line microsatellite stable colorectal cancer (MSS-CRC) and first-line gastric cancer, seeking clarification on how BioNTech's product can be differentiated from current treatments.

Answer

Özlem Türeci, Chief Medical Officer and Co-founder, explained that both MSS-CRC and first-line gastric cancer represent high medical need indications. She highlighted the biological rationale for developing the VEGF-A and PD-L1 blocking combination, believing it has the potential to improve clinical benefit for these patient populations.

Tazeen Ahmad asked for clarity on BioNTech's forward-looking vaccine development strategy, questioning what products could increase vaccination rates and the rationale for continued investment amid declining uptake.

Answer

Chief Strategy Officer Ryan Richardson acknowledged lower vaccination rates but emphasized the substantial high-risk population and the franchise's overall value. CFO Ramón Zapata added that combination vaccines are expected to complement, not replace, standalone COVID-19 vaccines, citing sustained demand from specific patient groups like the immunocompromised.

Tazeen Ahmad inquired about the addressable market size for the upcoming endometrial cancer launch, the manufacturing location for BNT323, and the potential impact of tariffs.

Answer

Chief Strategy Officer Ryan Richardson estimated the second-line endometrial cancer market at approximately 10,000 patients in the U.S. and Europe. He clarified that BNT323 is currently manufactured in China via a CDMO, with plans to diversify the supply chain. Both Richardson and CFO Jens Holstein stated they do not anticipate a significant financial impact from currently announced tariffs but are actively monitoring the situation.

Tazeen Ahmad from Bank of America Securities questioned the required efficacy bar for BNT323 in endometrial cancer to support a BLA filing and asked about commercial launch preparations.

Answer

CEO Ugur Sahin expressed confidence that BNT323's results would meet registration requirements, given its breakthrough therapy designation. CSO Ryan Richardson added that observed response rates of around 50% are significantly higher than the standard of care. The question regarding commercial launch preparations was not fully addressed.

Tazeen Ahmad inquired about the upcoming 2025 data for the BNT323 program in endometrial cancer, asking about the expected level of detail and the criteria for a positive outcome.

Answer

Chief Medical Officer Dr. Özlem Türeci stated that in 2025, the company expects to share efficacy and safety data from its single-arm trial in second-line endometrial cancer across different HER2 positivity populations. Dr. Türeci defined a positive outcome as a strong clinical activity profile and a favorable safety profile, noting the company is already seeing this across various HER2 expression levels.

Tazeen Ahmad at Bank of America inquired about current payer dynamics for AMVUTTRA, including feedback and 2026 negotiation outlook, potential risks of payers preferring stabilizers, and the company's reaction to CMS's proposed 57% cut in PYP scintigraphy reimbursement, questioning if this would remain isolated to diagnostics or extend to therapeutics. She also asked for comment on the U.S. Attorney General subpoena.

Answer

Yvonne Greenstreet, CEO, briefly addressed the subpoena, stating the company's intent to cooperate and address concerns regarding government price reporting, declining further comment on legal matters. Tolga Tanguler, Chief Commercial Officer, reported no payer headwinds for AMVUTTRA, with payers appreciating the product's value in a fatal, progressive disease, leading to favorable 2025 and anticipated 2026 policies without step edits or high co-pays. Regarding PYP scans, Tanguler noted the importance of reimbursement for category growth but stated no current anxiety in health systems, expecting to manage as policy clarifies.

Tazeen Ahmad inquired about current payer dynamics, feedback from payers, ongoing 2026 status negotiations, and any perceived risk of payers preferring stabilizers over silencers.

Answer

Yvonne Greenstreet, Chief Executive Officer, and Tolga Tanguler, Chief Commercial Officer, reported no payer headwinds across Medicare Advantage, fee-for-service, or commercial settings. They noted that payers appreciate the product's value in a fatal, progressive disease, and anticipate similar favorable dynamics for 2026 policies, with no indication of preference for stabilizers.

Tazeen Ahmad of Bank of America inquired about the company's expectations for Amvuttra's net price and gross-to-net adjustments moving forward.

Answer

CFO Jeff Poulton confirmed the expectation for a modest and gradual reduction in net price, forecasting a mid-single-digit decline for the full year 2025 compared to 2024. CCO Tolga Tanguler added that payer dynamics are favorable, with most patients receiving first-line access and paying minimal out-of-pocket costs.

Tazeen Ahmad inquired about the initial prescriber base for AMVUTTRA in ATTR cardiomyopathy, asking whether the early adopters were physicians with prior experience with the drug or a mix including new prescribers.

Answer

Chief Commercial Officer Tolga Tanguler responded that the launch is seeing a "good broad uptick" from both cardiologists familiar with AMVUTTRA and those new to the drug. He highlighted that a key early success was getting AMVUTTRA onto the formulary of over half of the key health systems within just four weeks of approval, which he sees as a significant enabler for future growth.

Tazeen Ahmad inquired about the expected timeline to establish payer policies for AMVUTTRA in ATTR-CM post-approval and how this might affect the initial launch trajectory.

Answer

Chief Commercial Officer Tolga Tanguler explained that while Alnylam is excited about the launch, the formulary uptake will make it a "second half story." He noted that existing value-based agreements will be extended, but the formulary process takes time, so meaningful uptake is expected in the second half of the year.

Tazeen Ahmad asked about the expected time from prescription to dispensation for the AMVUTTRA cardiomyopathy launch and whether experience from the polyneuropathy launch would streamline this process.

Answer

Chief Commercial Officer Tolga Tanguler acknowledged the question's relevance and stated that the company would provide additional color and context on launch metrics, such as script-to-dispense timelines, closer to the actual launch date.

Tazeen Ahmad asked for an update on the CIDP launch, particularly regarding physician excitement to position efgartigimod as a frontline therapy ahead of IVIG. She also requested feedback from the salesforce and details on additional efforts needed to establish efgartigimod as a first-line option for CIDP patients.

Answer

Karen Massey, Chief Operating Officer, reported very positive feedback from prescribers, noting that real-world experience for CIDP patients mirrors clinical trial results in efficacy and safety. She highlighted that while 85% of patients are IVIG switches, naive patients are also starting, indicating the beginning of a growth curve with expanding prescriber base and market penetration.

Tazeen Ahmad from Bank of America asked for insights into the CIDP launch, particularly regarding physician excitement to position efgartigimod as a frontline therapy over IVIg. She inquired about salesforce feedback and additional strategies to establish efgartigimod as a first-line option for patients in CIDP.

Answer

Karen Massey, Chief Operating Officer, reported positive prescriber feedback on the CIDP launch, noting that real-world experience aligns with clinical trial data on efficacy and safety. She highlighted that while 85% of current patients are IVIg switch patients, there's growing penetration among naive patients, indicating early growth curve expansion and increased prescriber base.

Tazeen Ahmad from Bank of America asked about argenx's strategy for handling increasing competition, specifically from UPLIZNA, and inquired about the patient discontinuation or drop-off rates for Vyvgart, particularly in gMG.

Answer

COO Karen Massey stated that argenx welcomes innovation as it expands the overall market. She emphasized that Vyvgart's high bar for efficacy (MSE rate), safety profile, and formulation options position it to remain the leading and fastest-growing biologic. Massey confirmed that discontinuation rates for both MG and CIDP are in line with expectations for a chronic therapy, noting that patients who achieve MSE are motivated to stay on treatment.

Tazeen Ahmad inquired about the current profile of gMG patients starting VYVGART, the company's position on the launch curve, and any observed changes in discontinuation rates or impacts from competitors.

Answer

Chief Operating Officer Karen Massey responded that argenx is still in the early stages of the gMG launch curve, with about 60% of new patients coming from oral therapies, indicating a move into earlier treatment lines. She confirmed that VYVGART maintains the #1 market share among biologics in gMG and that discontinuation rates have remained consistent and strong, with no significant shifts observed.

Tazeen Ahmad inquired about the potential for pent-up patient demand for the upcoming prefilled syringe (PFS), whether to expect a gradual or bolus effect in patient switches upon approval, and the general pricing strategy for the new formulation.

Answer

Chief Operating Officer Karen Massey stated that she does not see significant pent-up demand, but expects the PFS to open up the prescriber and patient base, driving consistent growth rather than a large, immediate switch event. Chief Financial Officer Karl Gubitz added that pricing will be responsible and aim for broad patient access, with specific details to be provided at launch.

Tazeen Ahmad asked about the competitive landscape for VYVGART in generalized myasthenia gravis (gMG) and whether Argenx has experienced any market share loss due to new entrants.

Answer

COO Karen Massey stated that despite increased competition, VYVGART's market share among biologics has continued to grow quarter-over-quarter. She noted that the majority of this growth comes from VYVGART Hytrulo, with new patients switching directly from oral medications, indicating no significant negative impact from competitors due to VYVGART's strong value proposition.

Tazeen Ahmad asked about CRENESSITY, specifically whether payers are requiring a certain level of steroid tapering for continued therapy coverage and the potential for seasonal impact on Q4 sales due to the holiday season.

Answer

Matt Abernethy, Chief Financial Officer, stated that no specific steroid tapering is required for reimbursement, which has been smooth for patients with the underlying disease and hydrocortisone treatment. He also noted that no seasonality is anticipated beyond the pace of patient visits.

Tazeen Ahmad asked if payers are requiring a specific level of steroid tapering for CRENESSITY coverage and about potential seasonal impacts on CRENESSITY sales in Q4 due to the holiday season.

Answer

Matt Abernethy, Chief Financial Officer, stated that seasonality is not anticipated beyond the cadence of patient visits. He clarified that steroid tapering to a specific extent has not been a reimbursement requirement; rather, coverage is based on the underlying disease and hydrocortisone treatment, with smooth reimbursement due to insurers understanding the medicine's benefit.

Tazeen Ahmad from Bank of America asked for the rationale behind narrowing the top end of INGREZZA's full-year sales guidance by $50 million, despite strong volume growth and improved Medicare access.

Answer

CFO Matt Abernethy explained that the guidance adjustment is driven entirely by a change in pricing assumptions, not volume. He noted that Neurocrine successfully accelerated key payer contracts from 2026 into 2025, which shifted the full-year pricing expectation from 'flattish' to a 'negative 5% price decline.' Abernethy reiterated that volume growth remains robust, with record new patient starts and total prescriptions.

Tazeen Ahmad inquired about the market share split for new tardive dyskinesia patients between INGREZZA and its competitor, and asked for the patient demographic split between pediatric and adult users for CRENESSITY.

Answer

Chief Commercial Officer Eric Benevich stated that while Neurocrine does not provide exact market share data, INGREZZA continues to hold the majority of both new and total prescriptions in TD. Regarding CRENESSITY, he explained that uptake is trending towards more pediatric and adolescent patients than adults, which aligns with the company's pre-launch expectations.

Tazeen Ahmad asked for expectations on INGREZZA's Q1 2025 performance, considering typical seasonality and a potential for lower revenue per script, and whether a quarter-over-quarter revenue decline is possible.

Answer

Chief Commercial Officer Eric Benevich acknowledged that Q1 is typically challenging due to prescription reauthorizations and gross-to-net pressures. Chief Financial Officer Matthew Abernethy clarified that while full-year 2025 net revenue per script is expected to be similar to 2024, there is a sequential gross-to-net headwind of about 3% from Q4 into Q1. He also noted potential for ordering pattern noise due to the calendar setup.

Tazeen Ahmad of Bank of America asked for color on INGREZZA's sequential growth expectations for Q4, noting that the updated guidance seems to imply a flattish quarter.

Answer

CFO Matt Abernethy clarified that the guidance implies sequential growth of $10 million to $20 million, which is consistent with historical Q4 trends. He attributed the moderation to the time it takes for the new sales force expansion to become fully productive and a typical sequential increase in the gross-to-net discount in the fourth quarter.

Tazeen Ahmad asked for a breakdown of the 460 patient start forms by quick start versus reimbursed status, whether these numbers would be tracked quarter-to-quarter, and for any early feedback on re-treatment rates and observed side effects like laryngeal attacks or GI discomfort.

Answer

Nicole Sweeny, Chief Commercial Officer, stated that 100% of the 460 start forms received quick start, and noted early paid shipments and refills were already occurring. Ben Palleiko, CEO, mentioned anecdotal positive feedback on re-treatment, with open-label extension data showing a re-dose rate in the low 20s. Ryan Baker, Head of Investor Relations, added that adverse event reports have been minimal and consistent with the open-label extension, with extremely low GI adverse event rates, and Ben Palleiko shared a favorable anecdote regarding a laryngeal attack.

Tazeen Ahmad requested a breakdown of the 460 patient start forms by reimbursement status (quick start, reimbursed, other) and asked about the company's ability to track these numbers quarter-to-quarter. She also inquired about re-treatment rates and any anecdotal feedback on side effects, including laryngeal attacks or GI discomfort.

Answer

Nicole Sweeny, Chief Commercial Officer, confirmed that 100% of the 460 start forms received quick start, with paid shipments and first paid refills already occurring. Ben Palleiko, CEO, noted anecdotal feedback on re-treatment rates was positive, with rates in the low 20s, below the zero rate. Ryan Baker, Head of Investor Relations, added that adverse event reports have been minimal and consistent with the open-label extension, with no GI adverse events and one favorable anecdote regarding a laryngeal attack.

Tazeen Ahmad inquired about the breakdown of the 460 patient start forms between Quick Start and reimbursed prescriptions, early re-treatment rates, and any observed side effects, specifically laryngeal attacks or GI discomfort.

Answer

Nicole Sweeny, Chief Commercial Officer, confirmed that 100% of the 460 start forms received Quick Start, with early paid shipments and refills being encouraging. Benjamin Palleiko, CEO, noted positive anecdotal feedback on re-treatment rates, which were low (low 20s) in the open-label extension. He also reported minimal adverse event reports, no GI-related issues, and a favorable anecdote regarding a laryngeal attack.

Tazeen Ahmad of Bank of America asked for a comparison of Taysha's gene therapy and study design against its competitor, seeking views on what differentiates the two programs.

Answer

CEO Sean Nolan and President & Head of R&D Sukumar Nagendran both responded. Nolan emphasized Taysha's data-driven approach, which establishes a new paradigm by focusing on objective, functional milestone gains that impact daily living. He also highlighted the favorable safety profile attributed to CMC quality and intrathecal delivery. Nagendran added that their comprehensive natural history data clearly shows that gaining skills post-intervention is a strong signal of efficacy, underscoring their commitment to delivering a clinically meaningful and safe therapy.

Tazeen Ahmad from Bank of America asked for confirmation that the year-end data readout for KT-621 would include data on itch reduction (pruritus NRS), highlighting its importance for physicians.

Answer

CEO Nello Mainolfi confirmed that the upcoming data release will include results for pruritus NRS, alongside EASI scores. He acknowledged that itch is a critical factor for patient quality of life and stated the data would be available for all patients enrolled in the study.

Tazeen Ahmad from Bank of America requested color on the types of patients receiving Yorvipath, specifically asking about the split between severe and more moderate cases of hypoparathyroidism.

Answer

President & CEO Jan Møller Mikkelsen explained that there is no formal medical definition to classify hypoparathyroidism by severity, making it impossible to provide such a split. He noted that the commercial strategy targeted high-volume prescribers and that international guidelines suggest approximately 95% of all patients are candidates for PTH replacement therapy, comparing the situation to insulin for type 1 diabetes.

Tazeen Ahmad asked for a breakdown of YORVIPATH's Q1 revenue between U.S. and ex-U.S. markets and inquired about the typical duration from when a prescription is written to when a U.S. patient receives the therapy.

Answer

President and CEO Jan Mikkelsen provided a method to estimate the revenue split, suggesting ex-U.S. growth was steady at around €4-5 million sequentially. By subtracting this from the total quarterly growth, he implied the U.S. launch contributed approximately €26 million in Q1. Earlier commentary indicated the insurance approval process typically takes four to eight weeks.

Tazeen Ahmad asked about the revenue split between the U.S. and ex-U.S. for Yorvipath and the time from script to therapy in the U.S.

Answer

CEO Jan Mikkelsen provided guidance on calculating the U.S. revenue contribution and noted steady ex-U.S. growth.

Tazeen Ahmad asked for an update on the preparation for the TransCon CNP FDA application, questioning if any open items remain and if a rolling submission is a possibility.

Answer

Jan Mikkelsen, President and CEO, stated that Ascendis has the complete data package required for submission to both the FDA and European agencies, with no missing data to be generated. He emphasized the strength of the data in addressing comorbidities beyond linear growth, positioning it as a comprehensive treatment for achondroplasia.

Tazeen Ahmad asked about the competitive dynamics for SKYTROFA following its net price reset, specifically regarding discounts from daily injectors and the impact from Novo Nordisk's competing product.

Answer

President and CEO Jan Mikkelsen stated that SKYTROFA is realizing its best-in-class potential and performing well against competitors, including other long-acting products. He noted that even where competitors have preferred formulary positions, SKYTROFA's differentiated profile drives adoption. He also highlighted that a major supplier of daily growth hormone saw a significant revenue decline, indicating a broader market reset that benefits SKYTROFA.

Tazeen Ahmad from Bank of America Securities asked for clarity on the specific metrics PTC will provide for the Sefiance launch in the upcoming quarters. She also inquired if the company has already started receiving prescriptions and, if so, what the initial patient types are.

Answer

Chief Business Officer Eric Pauwels confirmed that PTC will report on prescriptions, patient start forms, and the number of commercial patients on a quarterly basis, along with color on provider and payer dynamics. He announced that PTC has already received prescriptions and patient start forms in the U.S. and has patients on commercial therapy in Europe. The initial patient types align with expectations, including those poorly controlled on or having failed existing therapies, patients seeking better control, and treatment-naive patients.

Tazeen Ahmad asked for physician feedback on the unmet need for vatiquinone in Friedreich's ataxia and inquired about the FDA's rationale for not planning to hold an AdCom meeting.

Answer

CEO Dr. Matthew Klein stated the FDA communicated at the mid-cycle meeting that an AdCom was not needed, likely due to the agency's familiarity with the disease and endpoints. CBO Eric Pauwels added that physician feedback indicates a high unmet need, especially in pediatrics, and they expect rapid uptake due to vatiquinone's efficacy and strong safety profile.

Tazeen Ahmad asked how PTC's Huntington's disease splicing modulator is differentiated, inquired about the U.S. launch cadence for Translarna, patient identification strategies, and the competitive landscape including gene therapy.

Answer

CEO Dr. Matthew Klein differentiated PTC518 as the only oral, highly selective therapy with full brain biodistribution. CBO Eric Pauwels described a potential U.S. Translarna launch as 'plug-and-play,' leveraging their existing DMD commercial infrastructure, Emflaza patient database, and clinical trial participants for rapid patient identification and uptake.

Tazeen Ahmad asked for confirmation on the start of the ACP204 study in Lewy Body Dementia and sought management's view on the likelihood of that study's success if the upcoming ADP data is positive.

Answer

EVP, Head of R&D, Elizabeth Thompson, confirmed the company still anticipates the Lewy Body study will start in Q3 2025. She expressed that existing NUPLAZID data in Lewy Body is supportive, despite small patient numbers. A positive result in the ADP study would provide further confidence by demonstrating the activity of the ACP204 molecule specifically, reinforcing the potential for success in Lewy Body Dementia.

Tazeen Ahmad of BofA Securities asked how the European launch trajectory for trofinetide might differ from its U.S. launch, considering management's international experience.

Answer

CEO Catherine Owen Adams explained that the European launch will be strategically phased, starting with Germany, which allows for free pricing initially. She emphasized that key learnings from the U.S. launch, especially regarding patient and family engagement on titration, will be applied. The company is building a specialized European team and developing value dossiers for country-by-country reimbursement negotiations.

Tazeen Ahmad asked about the key secondary endpoints for the Prader-Willi syndrome trial (ACP-101) and sought perspective on the competitive landscape and Acadia's potential advantages.

Answer

EVP of R&D Elizabeth Thompson emphasized that while hyperphagia is the primary endpoint, secondary measures like defined responder levels and caregiver assessments are important for context. Both she and CEO Catherine Owen Adams noted that the complexity of Prader-Willi syndrome allows for multiple therapeutic approaches, and Acadia is confident in its distinct mechanism of action.

Tazeen Ahmad from Bank of America Securities asked new CEO Catherine Owen Adams to share insights on the upcoming European launch of Daybue, drawing on her previous experience with ex-U.S. rare disease launches, and to outline the general plan for the region.

Answer

CEO Catherine Owen Adams explained that the European launch process is similar to the U.S. but can be simpler post-approval due to single-payer healthcare systems, which streamline patient access. She outlined the timeline: an MAA submission is planned for early next year, followed by an approximate one-year review, after which reimbursement negotiations will begin with national HTA bodies, starting with Germany. She expressed confidence in the team being built in Europe to manage a successful launch.

Tazeen Ahmad posed commercial questions regarding Vepdeq, asking how the launch preparation and salesforce plans have changed, and whether there could be a gap between potential FDA approval and launch if Pfizer returns the rights and a new partner must be found.

Answer

CEO John Houston explained that the original 50/50 co-commercialization deal with Pfizer is no longer sensible for a second-line monotherapy indication alone. Arvinas is not building out a salesforce and is in active negotiations with Pfizer to either revise the deal for Pfizer to lead the launch or for Arvinas to regain the asset. If the asset is returned, Arvinas would immediately seek a new partner to commercialize it, aiming to avoid any gap between approval and launch.

Tazeen Ahmad asked about the market opportunity for vepdegestrant versus Orserdu, details on remaining Pfizer milestones, including any for the KAT6 collaboration, and whether Arvinas still plans to explore vepdegestrant in first-line metastatic breast cancer.

Answer

CEO John Houston highlighted a significant opportunity, noting a targeted launch to ~6,000 oncologists could be highly effective. CFO Andrew Saik confirmed a milestone is due on first approval but not its amount, and none are specific to the KAT6 combo. Houston reiterated that the first-line trial is not proceeding at this time, with funds being reallocated to other pipeline assets.

Tazeen Ahmad asked what data would be needed to build confidence among Key Opinion Leaders for atirmociclib, given their familiarity with other CDK inhibitors. She also inquired about the differentiation of Arvinas's KRAS G12D degrader in a competitive field.

Answer

Chief Medical Officer Noah Berkowitz suggested that an improvement in median PFS of over 5-6 months would be needed to be viewed as a substantial advance. Chief Scientific Officer Angela Cacace highlighted that their KRAS degrader is significantly more potent than competitors, binds both active and inactive KRAS states, and has a distinct mechanism that could overcome resistance, a point reinforced by Dr. Berkowitz who noted potency could be key to avoiding toxicity issues seen with other agents.

Tazeen Ahmad of Bank of America inquired about the ARV-102 program, asking about the size of the Parkinson's disease population with elevated LRRK2 and how biomarkers will be used for patient segmentation.

Answer

CSO Angela Cacace estimated that about one-third of idiopathic Parkinson's patients have elevated LRRK2 and noted a partnership with the Michael J. Fox Foundation to understand how to use biomarkers for stratification. CMO Noah Berkowitz added that the current healthy volunteer study is in all-comers, and the data will inform the patient selection strategy for future trials.

Tazeen Ahmad of Bank of America asked for clarification on the upcoming Prader-Willi syndrome data, questioning if it's an exploratory or high-conviction study, what would be considered 'good data', and the number of patients expected in the readout.

Answer

David Meeker, Chairman, President & CEO, described the study as exploratory with a 'legitimate fifty-fifty' chance of success. He explained that while there is high conviction in the MC4R pathway's role, the disease is challenging. He noted the goal is to report on 10 to 20 patients by the end of the year to have a meaningful basis for assessment.

Tazeen Ahmad of Bank of America questioned the necessity of continual data updates at conferences given the strength of existing data and asked about expectations for revenue seasonality for the rest of the year.

Answer

David Meeker, Chairman, CEO, and President, explained that early in a launch, every incremental patient data point, like the upcoming 24-patient French HO data, is valuable for building confidence. Jennifer Chien, Head of North America, noted that Q1 sees the biggest seasonal impact from insurance changes, and while Q4 can have some specialty pharmacy ordering variability, significant seasonality is not expected in other quarters.

Tazeen Ahmad asked what level of weight loss physicians want to see in HO patients for immediate adoption and whether the company would consider another capital raise following the HO data readout.

Answer

CEO David Meeker responded that physicians are focused on having an effective therapy where none exists, not a specific weight loss percentage. CFO Hunter Smith added that the recent ATM provides flexibility, so they do not have to raise post-data, but they haven't ruled out future raises to fund pipeline success.

Tazeen Ahmad asked if the H1 2025 guidance for the Phase III hypothalamic obesity (HO) data readout could be narrowed and inquired about physician interest in combining setmelanotide with GLP-1s.

Answer

Chairman, CEO and President David Meeker explained that the H1 2025 timeline is based on the last patient's 60-week follow-up and subsequent data cleanup, making it difficult to refine the guidance further publicly. He confirmed there is physician interest in combination therapies, noting that adding a GLP-1 could provide incremental benefit for patients and that anything improving patient outcomes is a positive.

Tazeen Ahmad of Bank of America inquired if povetacicept (POVY) is planned to launch with an auto-injector for IgAN and asked for the rationale behind prioritizing generalized myasthenia gravis (gMG) in what appears to be a crowded market.

Answer

President and CEO Dr. Reshma Kewalramani confirmed the plan to launch POVY with an auto-injector. She justified prioritizing gMG due to high unmet need, POVY's mechanism targeting the underlying cause, promising class data, an efficient regulatory path, and the drug's best-in-class engineering.

Tazeen Ahmad inquired about the profile of early JOURNAVX patients and the specific treatment settings where scripts are being written. She also asked about the timing of revenue acceleration and whether it would begin in Q2 or be more back-end loaded in 2025.

Answer

CCO Duncan McKechnie stated that JOURNAVX is being used broadly across surgical and non-surgical settings (e.g., joint replacements, ankle sprains) by a wide range of physicians. He confirmed that the company has consistently guided that prescription volume would ramp in the first half of the year, with revenue accelerating in the second half as payer coverage is secured.

Tazeen Ahmad asked if Vertex anticipates cannibalization of TRIKAFTA by ALYFTREK this year and at what rate. She also inquired about expectations for the upcoming data from the Type 1 Diabetes program.

Answer

COO Stuart Arbuckle confirmed that Vertex expects patients to switch from TRIKAFTA to ALYFTREK due to its favorable profile but did not provide guidance on the rate of switching. CEO Reshma Kewalramani detailed the Type 1 Diabetes program, VX-880, noting the initial target population is about 60,000 patients and that the company aims to complete enrollment in the pivotal study this year.

Tazeen Ahmad from Bank of America asked if the upcoming lumbosacral radiculopathy (LSR) data for suzetrigine would have a read-through to other indications and sought commentary on a competitor's discontinuation of a NaV1.8 inhibitor due to a narrow therapeutic window.

Answer

CEO Dr. Reshma Kewalramani stated there is no read-through from LSR to the DPN program, which is already in Phase III. Regarding the competitor, she was not surprised, explaining that achieving high specificity for NaV1.8 is a major challenge that Vertex has overcome with its molecule.

Tazeen Ahmad of Bank of America asked about Orlodeyo's current market penetration, the source of new prescriptions (new vs. existing prescribers), and the expected 'stickiness' of patients with potential new oral competitors on the horizon.

Answer

President & CCO Charlie Gayer stated that with approximately 11,000 diagnosed patients, there is still significant room for growth. He noted a strong influx of 69 new prescribers in Q2. Both Gayer and CEO Jon Stonehouse asserted that patients who do well on Orlodeyo are 'extremely sticky' and unlikely to switch, as they do not see a superior profile among potential future oral therapies compared to the convenience and efficacy of once-daily Orlodeyo.

Tazeen Ahmad inquired about the expected timing for patient data from the Netherton syndrome program, what would constitute a positive outcome, and the potential regulatory path forward for BCX17725.

Answer

Chief R&D Officer Dr. Helen Thackray stated that initial patient data is expected this year, noting that even a small number of patients could validate the mechanism. Positive data would involve suppressing KLK5 activity and observing subsequent skin healing. She suggested the regulatory path could be a single, short pivotal trial. CEO Jon Stonehouse added that the ultimate goal is a "functional cure," and a larger treatment effect could accelerate the development timeline.

Tazeen Ahmad inquired about the specific data investors should expect from the Netherton syndrome program in 2025 and asked for directional guidance on operating expenses for the upcoming year.

Answer

Chief R&D Officer Dr. Helen Thackray outlined a progressive data release for the Netherton program, starting with skin penetration, followed by markers of activity, and then longer-term skin recovery. CEO Jon Stonehouse emphasized the goal is a 'functional cure.' CFO Anthony Doyle indicated that while OpEx will increase in 2025 to support clinical trials, revenue growth will significantly outpace this spending, leading to continued margin accretion.

Tazeen Ahmad from Bank of America inquired about the clinical read-through from the CALR (989) data in essential thrombocythemia (ET) to myelofibrosis (MF) and asked about the minimum activity threshold for monotherapy.

Answer

President and Head of R&D Pablo Cagnoni explained that the drug's mechanism is identical in both diseases, increasing the probability of success in MF. He noted the data release was shifted to later in the year to include combination data with ruxolitinib. For MF, he stated they expect to see improvements in spleen volume, symptoms, and potentially hemoglobin.

Tazeen Ahmad inquired about the data timeline and expected level of detail for Incyte's monoclonal antibody pipeline asset, Klar, anticipated in 2025.

Answer

Pablo Cagnoni, an executive at Incyte, confirmed that a substantive data update for the monoclonal antibody will be presented in 2025. The update will include dose escalation data, results in both ET and myelofibrosis, and information on clinical endpoints and variant allele fraction burden.

Tazeen Ahmad from Bank of America asked for details on how Incyte formulated its 2025 guidance for Opzelura, particularly regarding assumptions on tube usage for atopic dermatitis and vitiligo. She also asked what would be considered clinically meaningful data for povorcitinib in hidradenitis suppurativa (HS), beyond just statistical significance.

Answer

Christiana Stamoulis, CFO, explained that the Opzelura guidance of $630M-$670M reflects 24-32% growth driven by demand in AD/vitiligo, the pediatric AD launch, and EU contribution, with the range accounting for variables in patient adherence. Pablo Cagnoni, President, Head of R&D, added that for povorcitinib, a competitive profile would involve replicating the overall Phase II results, including strong effects on HiSCR levels and pain, coupled with a clean safety profile.

Tazeen Ahmad of Bank of America Corporation asked for clarification on how the hidradenitis suppurativa (HS) opportunity would differ for ruxolitinib cream versus povorcitinib, and inquired about the expected tube usage for the cream in HS.

Answer

Steven Stein, an executive, differentiated the two by patient population: ruxolitinib cream targets the mild-to-moderate HS population (100k-150k patients) with limited abscesses and no draining tunnels, while oral povorcitinib targets the moderate-to-severe population with more extensive disease. He noted that determining tube usage and treatment duration would require data from the Phase III studies but anticipated it would likely be long-term therapy.

Tazeen Ahmad questioned how Apellis calculates its new patient share for SYFOVRE compared to its competitor and asked for the rationale behind not issuing sales guidance when its competitor has.

Answer

Executive David Acheson stated that Apellis uses a highly accurate site-of-care dataset covering 50% of the market, contrasting it with less accurate claims data. Executive Timothy Sullivan explained that the company is holding off on guidance due to recent market dynamics, including a competitor's CRL and co-pay funding issues, as well as the upcoming EMPAVELI launch. Executive Caroline Baumal added that GA market adoption will likely be a steady growth process, similar to the early wet AMD market.

Tazeen Ahmad from Bank of America Securities asked for the Q1 SYFOVRE sales outlook, the potential impact of Medicare Advantage preferred status, and the significance of the competitor's updated label.

Answer

EVP of Commercial David Acheson stated that Q1 net revenue is expected to be lower than Q4 due to temporary factors like sample usage, but noted that underlying injection demand is growing. Regarding the competitor's label, Mr. Acheson and CMO Dr. Caroline Baumal highlighted SYFOVRE's differentiated profile, including its proven efficacy with every-other-month dosing, as a key competitive advantage.

Tazeen Ahmad from Bank of America asked when Apellis might provide formal sales guidance for SYFOVRE and how the company views the growth rate and ultimate size of the geographic atrophy (GA) market.

Answer

CFO Timothy Sullivan responded that providing 2025 guidance is currently under consideration. He explained that the company wants to first observe the impact of its new commercial initiatives and allow market dynamics to settle before committing to a formal sales forecast. The immediate focus remains on solidifying SYFOVRE's market leadership.

Tazeen Ahmad asked which of the three headwinds—site capacity, administrative delays, or the patient death—was the biggest driver of the revised guidance, and whether the situation has worsened in Q2 2025.

Answer

President and CEO Douglas Ingram responded that it was a mix of all three factors, with longer cycle times having the largest mechanical effect on the forecast. He clarified the situation is not worsening and that the company is assuming a steady state for planning purposes, though this may be conservative. He noted the Q2 softness was expected as delays from the late Q1 safety event flowed into the new quarter, but "green shoots" like new start forms are appearing.

Tazeen Ahmad of Bank of America inquired about the patient onboarding cadence for ELEVIDYS in Q1 2025 and the expected trajectory of uptake for the remainder of the year.

Answer

CEO Douglas Ingram reiterated strong confidence in the full-year guidance of $2.9 billion to $3.1 billion, with over two-thirds from ELEVIDYS. He confirmed expectations for sequential quarter-over-quarter growth throughout 2025, attributing the ramp-up pace to the natural cadence of the patient journey, which includes administrative steps, contracts, and infusion scheduling.

Tazeen Ahmad of Bank of America sought clarification on Sarepta's Q4 guidance for ELEVIDYS, asking if the previously guided 100% upside for Q4 would be based on the original Q3 guidance or the newly reported, higher Q3 results.

Answer

President and CEO Doug Ingram confirmed that the company remains comfortable with its prior guidance, which was based on the original Q3 forecast. He also reiterated confidence in the 2025 guidance of approximately $3 billion in revenue and the long-term peak sales forecast of $5 billion or more across its four approved therapies.

Tazeen Ahmad asked for clarification on the primary bottleneck causing the 3-to-5-month patient journey for ELEVIDYS, questioning if this timeline has changed since the initial narrow approval.

Answer

CEO Douglas Ingram responded that there is no fundamental bottleneck, explaining that the 3-to-5-month timeline is a normal process for complex gene therapies, which includes antibody testing. He emphasized that demand, start forms, and payer interactions are all strong, and the company is performing brilliantly. He noted that Q3 will see moderate growth, with a significant ramp in Q4 and into 2025, consistent with prior successful Duchenne therapy launches.

Tazeen Ahmad of Bank of America Securities asked for clarification on the 'onetime' nature of the VPAG rebate, the positioning of Pombiliti/Opfolda in new markets, and if the DMX-200 deal signals a broader strategic move into nephrology.

Answer

President and CEO Bradley Campbell clarified the 'onetime' issue was the unexpectedly large size of the annual VPAG rebate, not the rebate itself. He stated Pombiliti/Opfolda's positioning is based on its strong data, leading to favorable reimbursement. Chief Business Officer Sebastien Martel added that while the deal expands their U.S. presence in rare kidney disease, their strategy remains focused on adjacencies like neuromuscular and rare cardiology.

Tazeen Ahmad questioned the status of the remaining litigants in the Galafold IP case, the potential for a better settlement outcome, and asked for an update on Galafold's patient dropout rates.

Answer

President and CEO Bradley Campbell confirmed two remaining litigants but expressed high confidence in the company's IP position, noting he would not expect a settlement date later than the January 2037 agreement with Teva. He also highlighted that Galafold's patient discontinuation rate has progressively decreased, contributing to sustained growth.

Tazeen Ahmad inquired about the launch cadence for Pombiliti and Opfolda, comparing the dynamics in Europe versus the U.S. given their different labels.

Answer

President and CEO Bradley Campbell explained that both markets are progressing well but have distinct dynamics. The U.S., as the largest single market, will see strong, consistent new patient growth. Europe's growth will be driven by the phased addition of new countries. Campbell noted that in Europe, they see switches from both Myozyme and Nexviazyme plus naive patients, while the U.S. launch primarily involves switches from existing therapies.

Inquired about the ease of identifying Mayo Stage IV patients, the expected ramp-up time for patient onboarding post-launch, and the potential for the drug's label to extend beyond Stage IV patients.

Answer

The quoted patient numbers are for diagnosed and treated patients, so they are not hard to find as they are already in the healthcare system. The company expects a gradual uptake as it will be their first launch, requiring time for contracting and physician education. The current focus is on Mayo Stage IV patients.

Tazeen Ahmad from Bank of America inquired about the commercial launch of birtamimab, including the ease of identifying the ~5,000 U.S. Mayo Stage IV patients, the expected onboarding timeline, and whether the label could extend beyond Stage IV patients.

Answer

COO Brandon Smith stated that since these patients are already diagnosed and treated, they are identifiable, though he acknowledged that building uptake for a first commercial launch will take time. President and CEO Gene G. Kinney added that the current focus of the AFFIRM-AL trial and initial commercial efforts is on the Mayo Stage IV population, where the unmet need is greatest.

Tazeen Ahmad from Bank of America inquired about the ease of identifying the approximately 5,000 Mayo Stage IV AL patients for commercial launch and the expected timeline for patient onboarding. She also asked if the drug's label could potentially expand to less severe patients.

Answer

COO Brandon Smith clarified that the patient numbers represent those already diagnosed and treated, making them identifiable through established channels. He cautioned that while the long-term opportunity is significant, initial commercial uptake will take time to build awareness and secure contracts. President and CEO Gene G. Kinney added that the current focus remains on the Mayo Stage IV population studied in the trial.

Tazeen Ahmad asked about the commercial uptake for birtamimab, specifically how easy it is to find the 5,000 U.S. Mayo Stage IV patients and the expected timeline to onboard them post-launch. She also questioned if the label could expand beyond Stage IV patients.

Answer

Chief Operating Officer Brandon Smith clarified that the quoted patient numbers are already diagnosed and treated, making them identifiable. He noted that while the long-term goal is a multi-billion dollar opportunity, initial uptake will take time as they build awareness and navigate contracting. CEO Gene G. Kinney added that patients are treated upon diagnosis, indicating a high level of physician awareness.

Tazeen Ahmad asked for a repeat explanation of the inventory dynamics for ZURZUVAE and how analysts should incorporate these factors into their models for 2025.

Answer

CEO Barry Greene and COO Chris Benecchi reiterated that patient shipments are the truest measure of demand, showing over 20% quarter-over-quarter growth. They explained that reported revenue is recognized upon shipment to wholesalers and can fluctuate based on inventory management at both wholesalers and specialty pharmacies. They advised focusing on the underlying demand trend rather than short-term inventory shifts.

Tazeen Ahmad asked about the breadth versus depth of Zurzuvae prescribing and sought more detail on the rationale for discontinuing the development of zuranolone for Major Depressive Disorder (MDD).

Answer

CEO Barry Greene explained the MDD decision was a matter of resource prioritization, given the significant time and investment new trials would require. Chief Business Officer Chris Benecchi added that for Zurzuvae, both prescriber breadth and depth are increasing quarter-over-quarter as physicians gain positive real-world experience with the drug.

Tazeen Ahmad asked for guidance on R&D expenses for the remainder of the year, considering the recent decrease and the planned Q4 sales force expansion.

Answer

CEO Barry Greene noted that the Q3 2023 restructuring successfully lowered both R&D and SG&A expenses. CFO Kimi Iguchi reaffirmed that overall operating expenses are expected to decrease in 2024 compared to 2023 and that the company's cash runway guidance remains unchanged, extending into 2026.

Asked about the efficacy bar for FT576 in multiple myeloma, the expected timing for FT522 data, and whether the company would confirm safety before the data release.

Answer

For FT576 to advance, its efficacy profile must be similar to T-cell engagers, with response rates over 60% and complete response rates around 40%. An initial clinical data update for FT522, which will include the no-conditioning arm, is expected in the second half of 2024. The company will provide updates on safety as the study progresses.