Alec Stranahan

Alec Stranahan inquired about the opportunity for Zoledronrasib plus chemotherapy versus Diraxonrasib plus chemotherapy in Resolute 303, asking if similar patients would be enrolled or if the frontline opportunity would be subsetted. He also asked about the importance of RAS doublets in the long-term commercial strategy for frontline PDAC.

Answer

Mark Goldsmith, Chairman and CEO, reiterated high conviction in RAS-on inhibitor doublets, citing recent preclinical data for Zoledronrasib plus Diraxonrasib. Wei Lin, CMO, stated that clinically, eligibility for Zoledronrasib versus Diraxonrasib in frontline PDAC is similar, aside from the specific RAS mutation (all RAS vs. KRAS G12D), with eligibility mainly focused on adequate organ function for chemotherapy.

Alec Stranahan asked about the company's strategy for Zoledronrasib plus chemotherapy versus Diraxonrasib plus chemotherapy in Resolute 303, specifically regarding patient enrollment and potential subsetting of the frontline opportunity. He also inquired about the long-term commercial importance of RAS doublets, such as Zoledronrasib and Diraxonrasib, in frontline PDAC.

Answer

Mark Goldsmith, Chairman and CEO, affirmed high conviction in RAS-on inhibitor doublets, citing recent preclinical data for Zoledronrasib plus Diraxonrasib, and indicated that more details on future studies would be shared. Wei Lin, Chief Medical Officer, clarified that clinical eligibility criteria for Zoledronrasib and Diraxonrasib in frontline PDAC are otherwise similar, with the primary difference being the specific RAS mutation targeted (all RAS vs. KRAS G12D).

Alec Stranahan of Bank of America inquired about the specific data points the company is waiting for before advancing zoldonrasib and oleronrasib into additional studies. He also asked about the Iambic collaboration, seeking to understand the synergy between Revolution Medicines' internal data and Iambic's AI platform.

Answer

CEO Mark Goldsmith explained that ongoing studies for zoldonrasib and oleronrasib are being monitored for latent safety signals and expanded to ensure robust data, but declined to detail specific data triggers for future decisions. Regarding the Iambic collaboration, he stated that RevMed's massive proprietary dataset of tri-complex inhibitors will be used to train Iambic's AI models, potentially enhancing the efficiency of lead discovery and optimization for both RAS and non-RAS targets.

Alec Stranahan asked about the upcoming preclinical AML data at ASH, the potential application of the RAS(ON) platform in liquid tumors, and what would be required to advance into clinical studies in this area.

Answer

Dr. Mark Goldsmith, Chairman and CEO, clarified that the hematology program has been almost entirely outsourced to academic collaborators and is not a top internal priority. The company remains focused on pancreatic, non-small cell lung, and colorectal cancers. While acknowledging the unmet need in AML, particularly as a resistance mechanism, he stated it is not a focus for near-term clinical development but could be considered in the future.

Alec Stranahan from Bank of America inquired about the expected speed of payer access for the thalassemia launch and current payer awareness levels. He also asked what additional data to expect from the full ENERGIZE-T readout and if ASH is a likely venue for presentation.

Answer

CCO Tsveta Milanova confirmed the market access team is actively educating payers and aims for strong access similar to their success in PK deficiency. CMO Dr. Sarah Gheuens stated the full ENERGIZE-T data will include key secondary endpoints and safety details, and noted that ASH abstracts would be released on November 5, indicating a potential presentation.

Alec Stranahan from Bank of America asked about Agios' ex-U.S. launch plans for mitapivat, including potential approval timelines and whether the company would partner or self-commercialize. He also questioned if the recent hiring of a Chief Corporate Development Officer signals a shift in strategic priorities or business development focus.

Answer

CCO Tsveta Milanova identified the Gulf (GCC) region as the next priority after the U.S., leveraging a partnership with NewBridge. CFO Cecilia Jones described the NewBridge deal as a capital-efficient revenue-split model and indicated a similar structure is planned for Europe. CEO Brian Goff clarified that the new hire reinforces, rather than shifts, their strategy, which prioritizes successful launches, advancing the internal pipeline, and disciplined business development, all supported by a strong balance sheet.

Alec Stranahan from Bank of America asked about the current level of physician and patient awareness for mitapivat in thalassemia and whether Agios plans to seek approval in both transfusion-dependent and non-transfusion-dependent pediatric PKD populations.

Answer

Chief Commercial Officer Tsveta Milanova reported high awareness among physicians and strong excitement from patient advocacy groups, noting the sales force has been doubled in size for the launch. Chief Medical Officer Dr. Sarah Gheuens confirmed that based on the positive benefit-risk profile across both pediatric studies, Agios intends to seek a broad label covering the full pediatric PKD patient population.

Alec Stranahan of Bank of America asked how adding progranulin as a co-primary endpoint affects the trial's statistical power for the clinical endpoint, the CDR Sum of Boxes. He also inquired if expanded enrollment was discussed with the FDA and if plasma PGRN levels could become part of the drug's label for patient selection.

Answer

CMO Giacomo Salvadore clarified that the two co-primary endpoints are analyzed independently, so the statistical power for the CDR endpoint remains unchanged. He noted they have over 99% power for the progranulin endpoint. He also confirmed that discussions about the drug's label would only occur after the data readout.

Susan, on behalf of Alec Stranahan from Bank of America, asked for insights into the tolerability and efficacy implications of the high patient enrollment rate in the INVOKE-2 long-term extension (LTE) study.

Answer

Dr. Gary Romano, Chief Medical Officer, stated that the company is very pleased with the 95% rollover rate of eligible patients into the LTE. He noted that efficacy remains blinded but that the safety profile has been consistent, with no new significant signals beyond the previously disclosed MRI findings resembling ARIA and minor infusion reactions.

Alec Stranahan asked about the market dynamics for RGX-202 at launch, the potential for a class-effect liver injury warning on its label, and how the two subretinal pivotal studies relate to the separate AbbVie-run ACHIEVE study.

Answer

President & CEO Curran Simpson clarified that the two pivotal studies are sufficient for filing, while ACHIEVE is a post-marketing study. He also stated that over 90% of the prevalent DMD population is expected to be available at launch. CMO Dr. Steve Pakola argued against a class effect label for liver injury, highlighting RGX-202's differentiated product purity and proactive immune regimen, which has resulted in zero liver injury events in the Phase 1/2 study to date.

Alec Stranahan from Bank of America asked about the AFFINITY DUCHENNE trial, inquiring about the timeline for data release after enrollment completion and whether 12-week microdystrophin data would suffice for a top-line update. He also asked for the company's outlook on the DMD commercial market dynamics closer to their potential launch.

Answer

CEO Curran Simpson addressed the commercial outlook, stating they expect at least half of the prevalent DMD market to remain available for their potential launch in early 2027 and that the company is already preparing commercial supply. Chief Medical Officer Dr. Steve Pakola confirmed that the 12-week microdystrophin data is the primary endpoint for accelerated approval and would certainly be released. Mr. Simpson added that at the time of filing, they will also have a 'healthy level' of functional data from both the Phase I/II and pivotal cohorts.

Alec Stranahan from Bank of America requested details on the design, size, and timing of the FDA-requested Post-Marketing Commitment (PMC) study. He also asked how recent shifts in the regulatory landscape, such as reduced funding for mRNA vaccines, might create a tailwind for Novavax.

Answer

EVP, Head of Research & Development Ruxandra Draghia-Akli explained the PMC study will provide additional data in a specific population and is expected to start by year-end. President, CEO & Director John Jacobs noted the $70-$90 million cost reflects its scale. Regarding the regulatory environment, Jacobs and EVP, Chief Corporate Affairs & Advocacy Officer Silvia Taylor suggested that reduced focus on mRNA platforms could create opportunities for Novavax's protein-based technology, particularly for its pandemic influenza candidate and seasonal execution with Sanofi.

Alec Stranahan of Bank of America questioned whether the recognized APA revenue was new cash flow and asked about the key safety metrics from the CIC readout that would be critical for attracting a partner.

Answer

CFO James Kelly clarified that the $603 million in APA revenue recognized was non-cash, relating to the retention of cash received in prior years. Head of R&D Dr. Ruxandra Draghia-Akli explained that the CIC study will supplement the platform's already favorable safety database and that the data, available in the second half of the year, will be key for partnership discussions.

Alec Stranahan sought clarification on the CIC/flu partnering plan, asking if another Phase III trial is expected, and requested details on the new RSV program and how it differs from prior assets.

Answer

President and CEO John Jacobs confirmed the strategy is to find a partner to fund further CIC development. Head of R&D Ruxandra Draghia-Akli and President and COO John Trizzino detailed that the new RSV program is not a 'redo,' but a new approach using AI/machine learning, a modified antigen construct, and the Matrix-M adjuvant to create a superior, differentiated combination product.

Matthew, on behalf of Alec Stranahan at Bank of America, requested color on the net price for Nuvaxovid during the current season and asked for a breakdown of sales channels outside of retail, as well as whether these dynamics are expected to persist.

Answer

President and COO John Trizzino provided guidance on net pricing, stating that while the gross price is around $140 per dose, a reasonable net price assumption would be in the 50% to 75% range of gross, or $70 to $100, subject to fluctuations from returns. The question regarding the non-retail channel split was not directly addressed, though Chief Medical Officer Dr. Robert Walker did provide a clarification on total doses administered based on IQVIA data.

Alec Stranahan asked if the NCCN Category 2A designation was expected and how it compares to competitors, and also inquired about any impact from new appointments at the FDA or CBER.

Answer

CEO Michael Rossi confirmed the 2A designation was expected for an ultra-rare disease and is the same as the competitor, creating a level playing field. Regarding the FDA, he stated that Y-mAbs maintains close working relationships and continues to move forward effectively, expressing a positive outlook on their interactions regardless of administrative changes.

Alec Stranahan of Bank of America inquired about the 2025 revenue trajectory for DANYELZA, asking if it would be flat or have seasonal variations, and also asked which tissues outside the tumor would be most critical for dose selection in the upcoming SADA update.

Answer

CEO Michael Rossi noted that growth plans for DANYELZA will take time to ramp up in 2025. CFO Peter Pfreundschuh elaborated on the guidance, advising analysts to use the midpoint of the wide full-year range and confirming the Q1 guidance is solid. He stated the company intends to provide quarterly guidance updates to account for seasonality and stocking effects. Regarding SADA, Rossi identified the kidney, liver, and bone marrow as key areas for monitoring concentration and potential dose-limiting toxicities, emphasizing that the focus is on actual tissue injury, not just concentration.

Alec Stranahan questioned the company's manufacturing strategy in light of the new headquarters and SADA asset progression, and also asked about the expected commercial rollout and total addressable market (TAM) for DANYELZA in Japan.

Answer

President and CEO Michael Rossi stated that the manufacturing philosophy remains unchanged, utilizing contract manufacturing organizations (CMOs) for both DANYELZA and SADA proteins to invest in drug development rather than infrastructure. Regarding Japan, he explained that a small, 6-patient clinical trial is required, with a potential launch in the second half of 2025 or early 2026. He characterized Japan as an important but smaller market than the U.S., representing an incremental, not massive, expansion of the TAM.

Alec Stranahan of Bank of America asked about the recruitment progress for the GD2 SADA study compared to initial expectations and inquired about any unique logistical considerations for advancing the GD2 or CD38 studies into Parts B and C.

Answer

President and CEO Michael Rossi acknowledged that recruitment was initially slow but has since accelerated for the GD2 trial. He expects a similar pattern for the CD38 trial as physicians gain confidence in the safety data. Chief Medical Officer Dr. Vignesh Rajah highlighted the complexity of Part A, which involves a stepwise process of testing various dose levels and intervals to determine the optimal combination before proceeding to Part B.

Alec Stranahan of Bank of America inquired about the outlook for new patient starts, asking if April's strong trend should be considered the new run rate, and also asked about inventory levels in distribution channels.

Answer

CEO Jeremy Bender reiterated that the company expects a consistent and steady ramp in new patient starts, similar to a rare disease launch rather than a typical oncology product. COO & CFO Charles York added that channel stock remains within the target range of 2-4 weeks of days on hand, with no material impact on the quarter's results beyond the consistent build accompanying sales growth.

Alec Stranahan requested a breakdown of the 1,600 cumulative prescriptions to determine the number from Q4 alone and asked about any seasonal impacts or channel stocking that occurred at year-end.

Answer

Chief Commercial Officer Lauren Merendino confirmed approximately 800 total prescriptions were added in Q4. Chief Operating and Financial Officer Charles York added that while channel stock volume increased in absolute dollars due to growing demand, the company remains within its target of 2-4 weeks of inventory on hand. He also noted the improved gross-to-net as a key factor in Q4 revenue.

Alec Stranahan of Bank of America inquired about the linearity of new patient starts during Q3 and asked how the updated 18-month duration of response data from FIREFLY-1 might impact real-world treatment decisions.

Answer

CEO Jeremy Bender stated that the cadence of new patient starts was very consistent, without seasonal effects. Dr. Samuel Blackman, Head of R&D, explained that the enhanced duration of response data builds prescriber confidence, though clinical decisions on treatment length remain separate from radiographic progression criteria.

Alec Stranahan inquired about the impact of Q1 insurance changes on VYJUVEK sales, the potential for a Q2 rebound, and whether the slowdown in new reimbursement approvals reflects a shrinking addressable market.

Answer

Krish Krishnan, Chairman and CEO, confirmed a minor impact from insurance changes that should be recovered in Q2. He dismissed concerns about the market size, attributing the slower pace of new patient starts to the longer time required for sales reps to educate physicians in community settings. He noted that the company has already begun increasing its commercial team to address this.

Alec Stranahan inquired about potential year-end inventory stocking for VYJUVEK in Q4 and the accounting mechanics of the annual patient price cap as it impacts Q4 and resets for 2025.

Answer

Krish Krishnan, Chairman and CEO, confirmed there were no significant changes in Q4 stocking or inventory levels compared to prior quarters. He explained that the company recalculates the price cap's impact quarterly to smooth out revenue, acknowledging its complexity but stating they have successfully removed volatility from the results.

Alec Stranahan inquired about the number of VYJUVEK patients approaching their annual reimbursement cap and its potential impact on year-end sales, as well as any emerging trends regarding the duration of wound closure and subsequent treatment pauses.

Answer

Chairman and CEO Krish Krishnan explained that the company does not disclose the specific number of patients hitting the annual cap, emphasizing that the goal is to maintain smooth net revenue growth. Regarding wound closure, he stated that while some patients experience extended durability, the company's thesis remains that the average wound is durable for about 90 days based on collagen half-life. An executive added that as patients become more active, they are eager to restart therapy quickly if new wounds appear.

Alex Stranahan of Bank of America asked whether new, more efficient AI models diminish the competitive advantage of Recursion's large-scale data and supercomputer, given the immense complexity of biology.

Answer

CEO Christopher Gibson responded that while models are becoming more efficient, the extraordinary complexity of biology and chemistry ensures that scale will continue to be a critical advantage. He asserted that Recursion's ability to generate massive, multimodal datasets and leverage its compute power remains a key differentiator that cannot be easily bootstrapped.

An analyst on behalf of Alec Stranahan asked about the status of 'incomplete responders' in the HAE Phase I/II study, how they are faring with longer follow-up, and what to expect in the next data update.

Answer

CEO John Leonard clarified that all patients have responded and are better off, suggesting the term 'incomplete responders' is inappropriate. He noted that responses mature over time, as seen in Phase I. CMO David Lebwohl added that patients tend to improve with longer follow-up and that more data on these patients will be presented later in the year.

A representative for Alec Stranahan asked about Intellia's capital allocation priorities, particularly concerning the balance between in vivo and ex vivo programs as the company advances into later-stage clinical trials.

Answer

CFO Ed Dulac stated that with a $945 million cash balance, the company's priority is its three Phase III studies. He also highlighted the importance of the NTLA-3001 gene insertion program and ex vivo opportunities. He noted the current cash runway extends well into the fourth quarter of 2026.

Alec Stranahan from Bank of America inquired if the approach to steroid prophylaxis for VIR-5525 would differ from other assets due to broad EGFR expression. He also asked whether the development of new preclinical targets is driven more by derisked targets or areas of high unmet need.

Answer

CEO Dr. Marianne De Backer explained that Vir is defining a set of high-value next-generation targets and is also engaging with potential partners to understand their interests. Dr. Mika Derynck, EVP of Oncology, stated that based on the confidence built from the other programs, the VIR-5525 study will start without any prophylactic steroids, noting the minimal CRS observed to date.

Alec Stranahan requested more detail on the upcoming Q1 data for T-cell engagers VIR-5818 and VIR-5500, asking if it will focus on safety or include efficacy. He also asked how the dual-masking technology might allow for higher target doses and if reaching MTD is the primary goal.

Answer

Dr. Mark Eisner, Chief Medical Officer, stated that Vir will share preliminary monotherapy data in Q1 but did not specify the exact content. He explained the dual-masking hypothesis is to improve the therapeutic index by enabling higher efficacy with good safety, noting this differentiates their assets from competitors like Janux's PSMA program.

Alec Stranahan inquired about the initial progress of the SERENITY At-Home study, including the enrollment ramp-up, and asked about the use of rescue medications in the trial.

Answer

Executive Vincent O'Neill stated that the study's kickoff is proceeding as expected, with a typical holiday slowdown anticipated before a rebound in January. He expressed confidence in the 9-12 month timeline due to the high number of clinical sites (26). Executive Robert Risinger added that rescue medications are permitted for safety and are being tracked as a surrogate measure of inefficacy, particularly in the placebo arm.

Speaking on behalf of Alec Stranahan, Mary Kate asked about the expected pace of trial execution and enrollment for the Phase III SERENITY At-Home trial upon initiation. She also requested additional details on the potential market opportunity for the at-home patient population.

Answer

Executive Vincent O'Neill explained that while precise timelines are not being given, the SERENITY study is less complex, faster, and less expensive than the TRANQUILITY trial. Executive Matthew Wiley addressed the market opportunity, citing 23 million agitation episodes in the at-home market and market research indicating patients would use BXCL501 in 80% of their episodes.

Alec Stranahan asked for an explanation of how BXCL701 is designed to treat metastatic pancreatic cancer and what the typical results are for KEYTRUDA monotherapy in this patient population.

Answer

Executive Vincent O'Neill explained that KEYTRUDA monotherapy is generally not active in pancreatic cancer, which is considered a 'cold tumor'. He stated that BioXcel's combination approach is supported by strong preclinical data showing BXCL701 can break down the tumor's protective fibrous layer, potentially enabling KEYTRUDA to be effective.

Asked about the low discontinuation rate for OGSIVEO, the profile of patients who stop treatment, the percentage of patients receiving dose reductions, and the potential use of drug holidays.

Answer

Discontinuation rates are low, with fewer than 10% of patients stopping therapy about a year into the launch. Full visibility on dose reductions is not yet available but is improving with the switch to blister packs; so far, a majority of patients remain on the 150mg dose. The DeFi study, where about 40% of patients dose-reduced, is a good reference for the potential future mix, which the new blister pack pricing is designed to capture.

Asked for opinions on PSA50 as a response surrogate for AMG 509 and the rationale behind the recent royalty sale, including the importance of retaining upside potential.

Answer

The company stated that while PSA50 is a positive indicator, RECIST response is more definitive and was outstanding for the drug. The royalty sale was chosen over other financing due to challenging equity markets, and retaining upside on the assets was a critical component of the deal structure.

Alec Stranahan asked about the comparability of historical controls for KEYTRUDA in the broader head and neck cancer population versus the specific HPV16-positive subgroup, and also inquired about capital allocation priorities and the company's cash runway.

Answer

Chief Medical Officer Katia Schlienger stated there are no known differences in KEYTRUDA's performance between HPV-positive and HPV-negative populations based on pivotal trial data. CEO Joern Aldag identified HB-200 and HB-300 as the top spending priorities, noting that partnered programs are funded by collaborators. CFO Reinhard Kandera added that with a cash balance of $113.4 million plus $15 million in recent milestones, the company is well-funded beyond upcoming catalysts, expecting a net loss similar to 2022.

Alec Stranahan from Bank of America Securities asked what additional data from the HB-101 kidney transplant study would be needed to expand into other settings like congenital CMV, and also inquired if there is a specific T-cell generation threshold required to achieve clinical responses with the HB-200 series.

Answer

CEO Joern Aldag stated that confirming the initial proof-of-concept data in a larger patient set for HB-101 would provide a strong signal to move forward. Igor Matushansky, Chief Medical Officer, addressed the T-cell question, explaining there is no 'magical number,' but achieving high single-digit percentages of antigen-specific CD8 T-cells would be a remarkable result that would likely correlate to improved efficacy.

Alec Stranahan of Bank of America asked for a review of the HB-101 Phase 1 safety profile, the rationale for adding a CMV-positive cohort to the Phase 2 trial, contingency plans for data dissemination if conferences are canceled, and whether HOOKIPA has considered developing a coronavirus vaccine.

Answer

CMO Igor Matushansky described the Phase 1 safety profile as very favorable and explained the CMV-positive cohort was added due to investigator interest and to support a broader vaccination strategy. CEO Joern Aldag and Igor Matushansky confirmed they would use press releases for data dissemination if needed. Regarding a coronavirus vaccine, Igor Matushansky stated that while their technology is well-suited, the company is currently 'laser focused' on its core programs.