Gregory Renza

Gregory Renza asked about Fulcrum's strategy for optimizing the strategic value of pociredir globally, particularly in international markets with high unmet need, as they plan for a potential registrational trial. He also asked Dr. Steinberg to contextualize oral scalable HbF options in development, comparing pociredir's EED inhibition with other approaches like degraders.

Answer

Alex C. Sapir, President and CEO, explained that the global Phase III study would include sites in the U.S., Europe, and potentially Sub-Saharan Africa, aiming to provide broader physician experience. He emphasized the market opportunity in the developed world while also committing to ensuring access for patients in the developing world due to the severe unmet need. Dr. Martin Steinberg, Professor of Medicine, Pediatrics, Pathology, and Laboratory Medicine, discussed the limited published data on molecular glue degraders (WIZ and BCL11A), noting their early phase development and profound effects in preclinical studies, but agreed with Alex Sapir that pociredir has a significant head start. He welcomed the development of multiple agents due to the complexity of the disease.

Gregory Renza from Truist Securities inquired about Fulcrum's strategy for optimizing the global strategic value of pociredir, including commercial penetration and addressing high unmet needs in ex-U.S. markets, and asked Dr. Steinberg to contextualize pociredir's mechanism (EED inhibition) against other oral HbF induction approaches like WIZ degraders and molecular glues.

Answer

Alex C. Sapir (President and CEO) outlined plans for a global Phase 3 study including sites in the U.S., Europe, and potentially Sub-Saharan Africa (e.g., Nigeria), aiming to provide broader physician experience. He stressed the organization's commitment to ensuring global access, balancing revenue maximization with addressing the significant unmet need in developing countries. Dr. Martin Steinberg (Professor of Medicine, Boston University) explained that molecular glue degraders targeting WIZ and BCL11A are in very early phase clinical studies, aiming to decrease repressors of fetal hemoglobin gene expression. He agreed with Sapir that Fulcrum has a conservative 2-year head start in this class.

Gregory Renza from RBC Capital Markets asked how the losmapimod experience is informing risk assessment for pociredir and other programs, how the company balances internal discovery with external asset acquisition, and for details on the 2025 spending allocation.

Answer

Executive Alexander Sapir contrasted losmapimod's novel endpoint with pociredir's well-established biomarker (fetal hemoglobin). He stated that while the company has a strong balance sheet for external deals, the focus remains on its promising internal pipeline. CFO Alan Musso confirmed the 2025 spend guidance of $55-$65 million fully funds the advancement of pociredir and preclinical programs, providing a cash runway into at least 2027.

Gregory Renza asked about Fulcrum's payer engagement strategy for losmapimod, including potential tailwinds and challenges, and also inquired about the plan and timing for building out the commercial organization.

Answer

CEO Alexander Sapir stated that early payer research indicates it will be difficult to restrict access due to high unmet need, with payers expecting rare disease pricing. A key factor will be the likely requirement for a confirmed genetic test, which Fulcrum is working to facilitate. Sapir also confirmed the commercial build-out has begun, a Chief Commercial Officer will be appointed in Q3 2024, and the launch is fully funded within the current cash runway.

Gregory Renza inquired about the translation of ACTIVASE prescriptions to treatment initiation and revenue recognition, particularly for the first quarter, and sought expectations for the phase 2 tebapivat data in sickle cell disease, focusing on hemoglobin response and its strategic fit.

Answer

Tsveta Milanova, Chief Commercial Officer, explained that initial prescriptions (44 by Jan 30) are strong, but revenues will lag demand by 10-12 weeks due to conversion time, citing SPARI as a revenue curve analog. Sarah Gheuens, Chief Medical Officer and Head of R&D, noted the tebapivat phase 2 trial is dose-finding, exploring hemoglobin response, and leveraging RISE UP data for clinical benefit modeling, with rapid enrollment reflecting community excitement.

Gregory Renza asked about the translation of ACTIVASE prescriptions to treatment initiation and revenue recognition, specifically seeking color on Q1 and early launch days, and also inquired about expectations for tebapivat's phase II data in sickle cell disease, particularly regarding higher hemoglobin response potential and its fit within the broader portfolio.

Answer

CEO Brian Goff expressed pride in the team's execution. Chief Commercial Officer Tsveta Milanova explained that initial quarters would see prescriptions grow ahead of revenues due to a 10-12 week conversion time, suggesting Filspari as an analog for revenue trajectory. Chief Medical Officer and Head of Research and Development Dr. Sarah Gheuens described the tebapivat phase II trial as a dose-finding study focusing on hemoglobin response, noting that VOCs are safety assessments and that the RISE UP data can be leveraged for modeling clinical benefit.

Gregory Renza of RBC Capital Markets questioned the potential for community mistrust in the sickle cell space following the Oxbryta withdrawal, what Agios is doing to manage this, and if there have been any new communications with regulators about risks at African trial sites.

Answer

CEO Brian Goff highlighted the company's strategy of building trust through high-touch engagement, listening to the patient community, and incorporating their feedback into trial design. CMO Dr. Sarah Gheuens added that the trial is closely monitored and that the high unmet need reinforces their commitment to delivering a meaningful therapy for patients.

Gregory Renza of Mizuho Securities inquired about the FDA review for PYRUKYND in thalassemia, seeking confirmation on the absence of an advisory committee and the status of the mid-cycle review. He also asked how the withdrawal of Oxbryta has impacted the sickle cell disease trial landscape and patient recruitment.

Answer

CEO Brian Goff and CMO Dr. Sarah Gheuens confirmed consistent engagement with the FDA for PYRUKYND in thalassemia, noting the agency has communicated that no advisory committee meeting is planned at this time as the review progresses toward the September 7 PDUFA date. Regarding sickle cell disease, Dr. Gheuens stated they have not observed any impact on their clinical trial conduct from the Oxbryta withdrawal. CCO Tsveta Milanova added that the event reinforces the high unmet medical need in the community.

Gregory Renza of RBC Capital Markets inquired about the company's enthusiasm for the pipeline asset AG-181, its mechanism as a PAH stabilizer, and its potential for non-responders. He also asked about Agios's strategy for external asset acquisition given the active market.

Answer

CEO Brian Goff expressed pride in the entire diversified pipeline, highlighting AG-181 as a Phase I asset addressing a high unmet need in a population of 35,000-40,000 patients. On business development, Goff stated that Agios has scaled up its search and evaluation capabilities and maintains a disciplined approach, leveraging its strong balance sheet to find assets that align with its rare disease expertise.

An analyst on behalf of Gregory Renza asked for clarification on the source of the $100 million revenue guidance increase, specifically the contribution from the new NET indication, and when to expect more clarity on NET's impact.

Answer

President and CEO Michael Morrissey clarified that the guidance raise is driven predominantly by the strength of the base RCC business. He stated that while a small amount for NET is factored in, the company is waiting to gain more clarity and confidence in the launch momentum before providing more specific updates on its contribution.

Gregory Renza asked about the strategy for a potential regulatory submission for cabozantinib in prostate cancer (CONTACT-02), particularly given the absence of an overall survival benefit, and the company's confidence in that process.

Answer

President and CEO Michael Morrissey stated that the company's 'singular focus' from a regulatory perspective is currently on securing approval for the NET indication. He deferred detailed comments on the CONTACT-02 prostate cancer opportunity, indicating that the company will 'circle back' to it after the NET review is complete.

Gregory Renza requested further elaboration on the assumptions behind the long-term peak sales opportunity for zanzalintinib and asked about the optimal portfolio construct for Exelixis moving forward.

Answer

President and CEO Michael Morrissey explained that CABOMETYX provides the foundation for zanzalintinib's future growth. He stated that now is the right time to focus on the future post-ANDA ruling, and while detailed modeling assumptions will be shared over time, the company's goal is to build a multi-product, multi-franchise oncology business.

An associate for Gregory Renza at RBC Capital Markets asked if Inovio would disclose baseline characteristics, particularly HPV genotype, for the confirmatory trial and how genotype might affect results.

Answer

CEO Jacqueline Shea and CCO Michael Sumner explained that the Phase I/II trial population was representative of the real-world RRP patient base (skewing HPV6 and male). They confirmed their goal is to recruit a similarly representative population for the larger 100-patient confirmatory trial to ensure the findings are broadly applicable.

Anish Nikhanj, on for Gregory Renza, asked about the duration and resolution of adverse events like injection site pain from the CELLECTRA device. He also inquired about INOVIO's go-to-market strategy, considering a competitor might launch first.

Answer

CMO Dr. Mike Sumner explained that adverse events were mostly Grade 1 and transient, with injection site pain typically resolving within minutes. CCO Steve Egge outlined the commercial strategy, stating they plan pre-launch activities with MSLs and account managers to engage with health plans. He and CEO Dr. Jacqueline Shea expressed confidence in INO-3107's differentiated product profile to compete effectively, regardless of a competitor's launch timing.

Gregory Renza asked about the strategic positioning of CD388 in relation to flu vaccines, particularly its potential complementarity and role in high-risk populations. He also requested a detailed explanation of the primary endpoint for the NAVIGATE study, including data collection mechanics.

Answer

Executive Jeffrey Stein explained that CD388 is initially focused on high-risk populations underserved by vaccines and is being developed to be used in conjunction with them, noting its different target (neuraminidase vs. hemoglobin). Executive Nicole Davarpanah detailed the primary endpoint as centrally confirmed influenza, requiring a positive PCR test, a fever of 38°C, and at least two respiratory or systemic symptoms.

Gregory Renza asked about the BTK CDAC's positioning, the company's confidence in its head-to-head trial against pirtobrutinib, and potential resistance mechanisms. He also inquired about the strategy for the I&I (Immunology & Inflammation) portfolio, particularly the IRAK4 degrader.

Answer

Wang Lai, Global Head of R&D, stated that confidence in the BTK degrader is increasing daily with new data, leading to the decision to initiate the head-to-head trial. He mentioned they are exploring its use in earlier lines. Regarding the I&I portfolio, Lai expressed excitement about the IRAK4 degrader, highlighting its best-in-class potential and a dozen other preclinical programs, signaling a growing focus on this area.

Gregory Renza questioned the company's confidence in its BTK CDAC being able to beat pirtobrutinib in a head-to-head trial and its views on using degraders in earlier treatment lines. He also asked about the strategy for the I&I (Immunology & Inflammation) portfolio, including the IRAK4 program.

Answer

Lai Wang, Global Head of R&D, expressed growing confidence in the BTK degrader based on emerging data and KOL feedback. He also highlighted the excitement around the I&I portfolio, which includes a dozen preclinical programs and a potentially best-in-class IRAK4 degrader, signaling a key area for future expansion.

Gregory Renza asked about the long-term positioning of the BTK CDAC against traditional BTK inhibitors, the company's confidence in its head-to-head trial against pirtobrutinib, and the potential for resistance mechanisms. He also inquired about the company's strategy for its I&I (Immunology & Inflammation) portfolio, including the IRAK4 degrader.

Answer

Lai Wang, Global Head of R&D, stated that confidence in the BTK degrader is increasing with data showing complete protein degradation, supporting the pirtobrutinib trial. He mentioned they are exploring its use in earlier lines. Regarding I&I, he described it as an exciting area with a dozen preclinical programs, highlighting the IRAK4 degrader's best-in-class potential and expecting more I&I molecules to advance in the coming years.

Gregory Renza of RBC Capital Markets requested more detail on the effectiveness of Xywav's marketing campaigns and the specific impacts driving confidence in the growth of the idiopathic hypersomnia (IH) market.

Answer

Renée Galá, President and COO, reported that the campaigns are successfully increasing disease awareness among physicians and patients. She highlighted strong performance from digital and media initiatives, field team execution, and the nurse educator program. She quantified the success by noting that total net patient adds for Xywav grew 5% year-over-year, while IH patient adds specifically grew 39% over the last 12 months.

On behalf of Gregory Renza, an analyst from RBC Capital Markets asked about the timelines for subsequent overall survival (OS) analyses for the Ziihera GEA trial following the top-line PFS readout. They also inquired about the key levers that can be used to further enhance the uptake of Epidiolex.

Answer

Robert Iannone, EVP and Global Head of R&D, explained that the first interim OS analysis will occur with the PFS readout, and the updated timeline allows for greater maturity in that analysis but does not alter the timing for the second and final OS readouts. Renée Galá, President and COO, identified several growth levers for Epidiolex, including leveraging data on non-seizure benefits, expanding in the adult and long-term care settings, improving market access, and executing targeted commercial programs.

Anish, on behalf of Gregory Renza at RBC Capital Markets, asked about the timeline for subsequent overall survival analyses for the Ziihera GEA trial and what levers could further enhance Epidiolex uptake.

Answer

EVP, Global Head of R&D Rob Iannone explained that the first interim OS analysis will occur with the PFS readout, but the updated timeline for PFS has no direct implication for the second or third OS analyses. President & COO Renée Galá highlighted that Epidiolex growth is driven by data on non-seizure benefits, penetration in adult/long-term care, strong access, and new commercial programs.

An analyst on behalf of Gregory Renza asked for Jazz's current thinking on the peak sales assumption and commercial ramp for zanidatamab in its initial second-line biliary tract cancer (BTC) indication.

Answer

President and COO Renée Galá reiterated that the company does not provide product-specific guidance. She emphasized that BTC is a rare cancer with a very small patient population, leading to low initial revenue expectations. The significant $2B+ peak potential for zanidatamab is expected to come from larger indications like GEA and breast cancer.

An analyst on behalf of Gregory Renza at RBC Capital Markets inquired about the company's current thinking on peak sales assumptions and the commercial ramp for zanidatamab in second-line biliary tract cancer (BTC).

Answer

President and COO Renée Galá stated that while the company does not provide product-specific guidance, the initial BTC indication represents a very small patient population of about 3,000 U.S. patients, leading to modest revenue expectations. She emphasized that the larger $2 billion-plus peak sales opportunity for zanidatamab is expected to come from future indications like GEA, breast cancer, and a potential pan-tumor approval.

Gregory Renza asked for an update on the large dialysis operator (LDO) partnership, including engagement evolution and what the LDO needs to see for a broader rollout, and also inquired about inventory control and potential macro volatility impacts.

Answer

CEO Joseph Todisco expressed optimism for a mid-year 2025 LDO implementation start, citing increased preparatory activities. He clarified that recent order lumpiness was due to a specific customer's price-incentivized early purchase, not macro issues, and affirmed that CorMedix has significant inventory and manufacturing capacity, making supply a non-issue.

Gregory Renza from RBC Capital Markets asked for details on the operational dynamics of DefenCath, including inventory stocking levels at facilities and order frequency. He also inquired about potential macro impacts on the business, such as hurricanes in the Southeast, and requested an update on manufacturing and API supply sufficiency for future demand.

Answer

CEO Joseph Todisco stated that initial customers hold about 10 days of inventory, shipping direct-to-clinic, while the new large dialysis organization (LDO) may stock 15-30 days. He acknowledged minor disruption from hurricanes but noted trends have returned to normal. On manufacturing, Todisco assured that CorMedix has more than sufficient finished dose inventory for a decent part of the next year, has stockpiled key active ingredients, and utilizes two finished dosage manufacturers, ROVI and Siegfried, to ensure supply.

An associate on behalf of Gregory Renza asked for a comparison of CLABSI and CRBSI infection rates, how this distinction affects DefenCath's marketing strategy, and how the product's pass-through status can be leveraged to boost uptake.

Answer

CEO Joseph Todisco and EVP & Chief Clinical Strategy and Operations Officer Elizabeth Masson-Hurlburt clarified the clinical distinctions. Masson-Hurlburt explained that CRBSI is a specific subset of the broader CLABSI category, which is relevant for the TPN study design. Todisco added that pass-through status is meaningful because it allows for buy-and-bill reimbursement when a catheter is first installed, enabling protection of the line from the very beginning.

Gregory Renza of RBC Capital Markets asked for an elaboration on Amgen's KRAS franchise strategy, particularly concerning the AMG 410 asset, and management's confidence in its potential to be a best-in-class molecule in a competitive field.

Answer

James Bradner, EVP of R&D, described AMG 410 as a highly selective, reversible, pan-KRAS inhibitor, which should confer an excellent therapeutic index. While acknowledging the competitive landscape, he emphasized Amgen's leadership in the KRAS field and the positive reception the molecule received from experts at the recent AACR conference.

Gregory Renza inquired about the commercial opportunity in China, especially for oncology drugs through the BeiGene partnership, and how this collaboration fits into Amgen's long-term goals.

Answer

CEO Robert Bradway highlighted that the Japan/Asia Pacific region is Amgen's fastest-growing. Murdo Gordon, EVP of Global Commercial Operations, added that the BeiGene partnership has exceeded expectations, with strong execution for KYPROLIS, BLINCYTO, and XGEVA, complementing the solid growth of Amgen's own affiliate business in China.

Gregory Renza inquired about Amgen's strategy for replenishing its rare disease pipeline and supporting its current portfolio, particularly following a recent discontinuation.

Answer

CEO Robert Bradway noted the current rare disease products are early in their life cycles with significant potential. EVP of R&D James Bradner added that the Horizon acquisition has energized R&D, leading to new projects and a dedicated rare disease initiative. He highlighted a strategy blending internal innovation with the external deal-making Horizon was known for.

Gregory Renza inquired about the relative contributions of EXPAREL, Zilretta, and iovera to the 2025 revenue guidance and any sequential trends to consider beyond the NOPAIN Act ramp. He also asked what assumptions about the competitive landscape are factored into the company's '5/30' plan, which targets a double-digit compound annual growth rate for product revenue.

Answer

CEO Frank Lee and CFO Shawn Cross clarified that while EXPAREL remains the flagship product driving growth, the company is investing to support all three products. They reiterated that the most significant uptake from the NOPAIN Act is expected in the second half of the year. Regarding long-term growth, Lee stated that the '5/30' plan was developed with high confidence, as management does not believe a generic version of EXPAREL will launch in the foreseeable future, supported by a continually strengthening IP estate.

Gregory Renza inquired about Acadia's business development strategy, asking where the current gaps in the pipeline are and what the company considers an optimal pipeline state.

Answer

CEO Catherine Owen Adams stated that Acadia is actively exploring opportunities in its core neuroscience and neuro-rare areas, as well as adjacent rare disease fields like endocrine and immunology. She emphasized the strategy is not stage-specific but focuses on a high bar for scientific evidence, unmet need, and the potential to deliver first-in-class or best-in-class therapies.

Gregory Renza of Mizuho Securities inquired about new CEO Catherine Owen Adams's strategic framework for business development and the early-stage pipeline. He also asked about expected Daybue utilization patterns heading into the Q4 holiday season and the Q1 2025 transition.

Answer

CEO Catherine Owen Adams stated that business development is a key growth driver, with a focus on neuropsychiatry and rare diseases, supported by Acadia's strong cash position. Executive Brendan Teehan addressed the Daybue transition, explaining that a more mature patient mix (over 60% on therapy for 10+ months) and enhanced hub capabilities should create a more dependable Q1 demand base compared to the prior year, although new patient appointments might slow in January.

An analyst on for Gregory Renza asked what the LOTIS-7 data would need to show to be considered a meaningful improvement in the side effect profile, such as CRS. He also asked for expectations for the indolent lymphoma data at ASH, including the data set size needed for a compendia listing and the timeline to acquire that data.

Answer

CEO Ameet Mallik explained that a meaningful improvement in the LOTIS-7 safety profile would be the elimination of high-grade (Grade 3/4) CRS, which would be a significant advantage over bispecific monotherapy. For the ASH update, he said to expect more mature data with additional patients for the indolent lymphoma trials. He noted that for MZL, as few as 36-50 patients have historically been sufficient for guideline inclusion, while the larger 100-patient high-risk FL study could support an accelerated path, though he did not provide a firm timeline as the trials are investigator-initiated.

Inquired about the specific commercial levers being used to accelerate YCANTH growth, the importance of same-day treatment, the contribution from sampling, and the potential timeline for providing long-term revenue guidance.

Answer

The company is focused on removing prior authorizations, simplifying its co-pay program, and leveraging GPO contracts with IPN and Vizient. They noted that the sampling program is tapering down as coverage improves. Regarding financial guidance, the company will consider providing it closer to 2025 but not in the current year.

Gregory Renza of RBC Capital Markets inquired about the current competitive landscape for patient enrollment in clinical trials and asked what strategies Veridian is using to accelerate trial execution and enrollment.

Answer

President and CEO Stephen Mahoney highlighted that the over-enrollment in the THRIVE trial demonstrates strong patient demand. Chief Medical Officer Thomas Ciulla added that promising Phase II results have generated significant investigator excitement. He also noted that for the STRIVE study, the use of an active control arm with no placebo is expected to be a key driver for enrollment.

Inquired about learnings from the xaluritamig adverse event profile and potential mitigation strategies.

Answer

The company views the xaluritamig adverse events as manageable and typical for the drug class, especially given the high efficacy. They noted that standard mitigation strategies like priming doses, step-ups, and premedication are effective and that educating oncologists on managing CRS is key.