Joseph Stringer

Joseph Stringer from Needham and Company followed up on seasonality, asking if the magnitude of the seasonality effect this cycle is in line with expectations and if any nuances of the launch make it more or less sensitive to seasonality.

Answer

Steven Basta, President and CEO, stated that the seasonality pattern observed in January and February is very similar to last year, with an expected meaningful improvement in March. He also noted that IQVIA reported numbers seem to be underreporting compared to internal data, which they believe will resolve.

Joseph Stringer followed up on seasonality, asking if the magnitude of the Q1 2026 seasonality effect is in line with expectations and if the refocused launch effort makes Voquezna more or less sensitive to seasonality.

Answer

Steven Basta, President and CEO, indicated that the seasonality pattern observed is very similar to last year, with January and February being light and March expected to pick up. He noted that typical annual seasonality is the dominant effect, with some noise from plan switching and observed IQVIA underreporting, rather than the refocused effort changing sensitivity.

Joseph Stringer from Needham & Company asked whether the anticipated revenue acceleration from the new focus on GI specialists is already factored into the 2025 revenue guidance of $165-$175 million, or if it could represent potential upside.

Answer

Steven Basta, President, CEO & Director, clarified that while the GI focus is a long-term upside driver, the timing of its impact is uncertain as it takes several months of repeated sales calls to change prescribing habits. The current guidance reflects their expectations, with significant acceleration more likely to materialize in late 2025 or early 2026.

Joseph Stringer of Needham & Company asked about the timing of the C-suite changes ahead of the Citizen's Petition (CP) decision and the potential next steps if the FDA response is delayed.

Answer

President and CEO Steven Basta assured that the management changes would not interrupt the Citizen's Petition activities, as key personnel will remain involved in an advisory capacity. He explained that in a scenario where the FDA needs more time, Phathom would likely need to take proactive steps to formally define its exclusivity period, though the specific actions would depend on the FDA's communication.

Joseph Stringer asked when Phathom expects to have sufficient real-world data to make a go/no-go decision on a Phase III trial for on-demand VOQUEZNA use.

Answer

President and CEO Terrie Curran responded that the company is continuously evaluating real-world utilization data and expects to have enough information to make a decision on whether to proceed with the on-demand study by mid-year 2025.

Joseph Stringer asked for commentary on VOQUEZNA's overall refill rates and how they compare to what is typically seen for prescription proton pump inhibitors (PPIs).

Answer

Chief Commercial Officer Martin Gilligan explained that while a specific rate wasn't provided, the business is healthy with a large increase in new writers. He noted that for physicians who have started prescribing, repeat writing is growing. He added that persistency tracking shows refill rates are healthy and consistent with what is expected in the prescription PPI market.

Joseph Stringer asked about the timing for seeing functional cure rates from the GSK-partnered HBV program (Bepirovirsen) Phase 3 data. He also inquired about Ionis's and GSK's expectations for potential peak sales as a functional cure and the net revenue assumptions baked into Ionis's projected peak royalty revenues from this program.

Answer

Brett Monia, CEO, stated that GSK plans to present the Bepirovirsen Phase 3 data, which shows clinically meaningful and unprecedented functional cure rates, at EASL in May. Beth Hougen, CFO, mentioned GSK's peak sales estimate of approximately $2.5 billion, with Ionis's tiered royalties ranging from 10-12% and anticipated regulatory milestones this year, contributing to several billion dollars in estimated peak royalties.

Joseph Stringer asked about the timing for the presentation of functional cure rates from the GSK-partnered HBV program (Bepirovirsen) Phase 3 data, GSK's and Ionis's expectations for potential peak sales, and the net revenue assumptions for Ionis's projected peak royalty revenues from this program.

Answer

CEO Brett Monia stated that GSK plans to present the Bepirovirsen data, which shows unprecedented and clinically meaningful functional cure rates, at EASL in May. CFO Elizabeth Hougen mentioned GSK's peak sales estimate of approximately $2.5 billion and Ionis's tiered royalties (10-12%) plus regulatory milestones, which are factored into Ionis's multi-billion dollar estimated peak royalties.

Joseph Stringer asked about Vaxcyte's confidence in meeting the FDA's 3,000-patient exposure safety database requirement for VAX-31 and sought additional color on conversations with the FDA regarding this standard.

Answer

Grant Pickering, CEO of Vaxcyte, stated that the 3,000-patient minimum standard has been consistent, and the three OPUS studies were initiated to not only meet this minimum but also to provide robust data for best-in-class claims. Jim Wassil, EVP and COO, and Andrew Guggenhime, President and CFO, confirmed that the protocol was developed in alignment with the FDA and they plan to exceed the minimum exposure.

Joseph Stringer asked about Vaxcyte's conversations with the FDA regarding the 3,000-patient minimum safety database requirement and the company's confidence in meeting it.

Answer

Grant Pickering, CEO of Vaxcyte, stated awareness of the 3,000-patient minimum standard and confirmed no shift in FDA thinking. He noted that the three OPUS studies were initiated to meet this minimum exposure and support best-in-class claims. Jim Wassil, EVP and COO, added that the company is going slightly above 3,000 for a robust label, and Andrew Guggenhime, President and CFO, emphasized that this is part of the protocol developed in alignment with the FDA.

Joseph Stringer from Needham & Company asked about the likelihood of Vaxcyte's candidates not receiving a preferred recommendation from ACIP and whether the company's outlook on this has been affected by the new administration.

Answer

CEO Grant Pickering expressed high confidence in securing a preferred recommendation. He argued that VAX-31's profile in adults (broader coverage, higher immune responses) is what ACIP was looking for, and in infants, their candidates address the specific issue of diminished immune response that prevented a preferred recommendation for PCV20. He emphasized that these decisions are historically based on the scientific merits of a vaccine, making it the primary factor regardless of administration changes.

Inquired about the company's preclinical pipeline, asking which candidate might enter the clinic first, and specifically requested details on the competitive landscape and commercial opportunity for their Group A Strep vaccine.

Answer

The company identified the Group A Strep vaccine as the most advanced preclinical program. They described Group A Strep as an underappreciated disease with a significant global health burden and a large commercial opportunity in children and older adults, similar to PCVs. They noted that the competitive landscape is minimal, with only a few academic centers and one other pharmaceutical company active in the space.

Joseph Stringer inquired about the implications of the Astellas deal for the rest of Vir Biotechnology's oncology pipeline, specifically regarding standalone development versus partnering, and asked about VIR-5500's potential in earlier lines of mCRPC therapy.

Answer

Marianne De Backer, CEO and Director, explained that the Astellas deal was a strategic choice for VIR-5500 due to high unmet need and market dynamics, allowing Vir Biotechnology to retain significant value while accelerating the program. For the rest of the pipeline, Vir Biotechnology will be strategic, considering competitive landscape, commercial opportunity, and financial needs, and will seek partners for some of its seven preclinical masked T-cell engagers. Mark Eisner, EVP and Chief Medical Officer, confirmed potential in earlier lines, with plans for first-line taxane-naive mCRPC and metastatic hormone-sensitive prostate cancer expansion cohorts.

Joseph Stringer asked about the implications of the Astellas deal for the rest of Vir Biotechnology's oncology pipeline, specifically whether programs might be standalone or if the long-term strategy involves seeking partners. He also asked about the outlook for VIR-5500 in earlier lines of mCRPC therapy.

Answer

Marianne De Backer, CEO and Director, explained that the Astellas deal was a strategic choice to accelerate VIR-5500 due to high unmet need and a rapidly evolving landscape, while retaining significant value. For the rest of the pipeline, they will be strategic and thoughtful, considering competitive landscape, commercial opportunity, and financial needs, and will certainly seek partners for some of their seven preclinical masked T-cell engagers. Mark Eisner, EVP and Chief Medical Officer, noted the potential for VIR-5500 across the metastatic prostate cancer landscape, including late-line mCRPC, frontline taxane-naive mCRPC, and metastatic hormone-sensitive prostate cancer.

Joseph Stringer from Needham & Company asked for the rationale behind the 12-week deferred treatment period in the ECLIPSE-1 trial, compared to a competitor's 24-week period, and its potential impact on trial success.

Answer

EVP & Chief Medical Officer Dr. Mark Eisner explained that a 12-week deferred treatment arm is sufficient because spontaneous viral clearance in untreated HDV patients is essentially zero, a point agreed upon by the FDA and EMA. He stated this shorter duration is a more patient-friendly design, as it reduces the waiting time for patients randomized to the deferred arm to receive active treatment. He concluded that from a probability of success standpoint, a 12-week period is equivalent to a 24-week period.

Joseph Stringer asked if there have been any recent changes to U.S. guidelines for HDV diagnosis, such as reflex testing, following VIR's updated patient estimates. He also inquired about the potential impact such changes could have on the addressable patient population.

Answer

Marianne De Backer (Executive) confirmed that there have been no changes to U.S. guidelines for reflex testing yet, but awareness is increasing. Mark Eisner (Executive) added that the current prevalence is likely underestimated due to this lack of testing and that he expects an approved, effective therapy would naturally drive more diagnoses, thereby increasing the identified patient population.

Joseph Stringer of Needham asked for details on the Alnylam collaboration for elebsiran, specifically regarding the cost-profit share, Alnylam's optionality, and whether this is factored into cash burn assumptions. He also questioned how this agreement impacts potential partnership negotiations for the HBV program.

Answer

CEO Dr. Marianne De Backer clarified the Alnylam agreement is a financial arrangement where Alnylam has an option to either co-fund 50% of elebsiran costs for commensurate profit or opt-out for milestones and royalties. She stated this does not preclude a larger partner from taking an operational role in the HBV program. CFO Jason O'Byrne added that the company's cash runway guidance assumes the 'worst case' of Alnylam opting out, meaning an opt-in would be a potential upside.

Joseph Stringer questioned whether a dose-dependent efficacy response is expected in the Phase IIb readout, if that view has changed due to high infection rates, and the importance of observing such a response for data confidence.

Answer

Executive Jeffrey Stein stated that while a dose-dependent response is expected, the company believes it is more important to analyze the 'exposure dependence.' He explained that a subject's drug exposure is a function of both dose and timing of administration within the flu season, and this relationship between exposure and efficacy will be a key focus of the analysis.

Joseph Stringer from Needham & Company asked for the specific number of written and reimbursed prescriptions for IMCIVREE in the U.S. during the first quarter.

Answer

David Meeker, CEO, stated that the company is no longer breaking out those specific numbers. He explained that while they provided them initially to give a sense of the launch, they now rely on reported revenues as a more holistic measure of market performance.

Joseph Stringer asked about the potential impact of including younger (4-6 years) and older (>40 years) patients in the Phase III HO trial on the primary BMI endpoint, compared to the Phase II population.

Answer

CEO David Meeker stated he expects no significant impact from either age group. He noted that the difference between a 4 and 6-year-old is negligible and that French early access data showed older adults respond very well, even years after their initial injury. He also highlighted that BMI change doesn't capture improvements in body composition.

Joseph Stringer asked about the commercial opportunity for hypothalamic obesity (HO) in Japan and whether Rhythm can manage it independently. He also inquired about the profile of new-to-drug Bardet-Biedl syndrome (BBS) patients at this stage of the launch.

Answer

Chairman, CEO and President David Meeker expressed increased optimism for the Japan opportunity, expecting to complete enrollment of the 12-patient cohort by year-end, and affirmed the company's plan to 'go it alone.' EVP, Head of North America Jennifer Chien explained that new BBS patients are a mix, identified through ongoing physician education which makes them more adept at diagnosing patients, leading to growth from both first-time and repeat prescribers.

Joseph Stringer from Needham & Company asked about the switching dynamics between SYFOVRE and its competitor, IZERVAY, and about patient compliance rates.

Answer

EVP of Commercial David Acheson noted that Apellis saw a number of patient switches to SYFOVRE, particularly during the competitor's CRL period, and that the continued growth in injections supports this trend. He reiterated that SYFOVRE's compliance rate is positive and in line with that of anti-VEGF therapies.

Asked about the Phase III trial for sotagliflozin in hypertrophic cardiomyopathy (HCM), specifically regarding FDA alignment on the KCCQ primary endpoint and what the company would consider a successful placebo-adjusted change for that endpoint.

Answer

The company confirmed they are confident in the KCCQ endpoint, having discussed the trial design, endpoint, and statistical plan with the FDA. While they did not specify the exact expected delta, they feel confident in reaching a meaningful result based on prior success with the endpoint in the SOLOIST trial and the symptomatic nature of the enrolled patient population.

Joseph Stringer asked if Lexicon is aligned with the FDA on the KCCQ primary endpoint for the Phase III HCM trial and what would be considered a successful placebo-adjusted change, referencing data from competitors.

Answer

Dr. Craig Granowitz, SVP & Chief Medical Officer, affirmed that Lexicon is confident in the KCCQ endpoint, having discussed the trial design, endpoint, and statistical plan with the FDA. He noted that while the specific expected delta has not been shared, their confidence is based on prior success with this endpoint in the SOLOIST trial and the FDA's acceptance of it in other label-enabling HCM studies.