Edward Tenthoff

Edward Tenthoff asked for clarification on the full-year fiscal 2026 revenue guidance for Ryoncil.

Answer

CFO James O'Brien reiterated the full-year fiscal 2026 net revenue guidance for Ryoncil to be between $110 million and $120 million.

Edward Tenthoff asked for clarification on the full-year Ryoncil net revenue guidance, as the audio broke up during the initial announcement.

Answer

CFO James O'Brien confirmed that the projected full fiscal year 2026 net revenue for Ryoncil is expected to range between $110 million and $120 million.

Edward Tenthoff of Piper Sandler asked for more details on the delivery mechanism for OPKO Health's in vivo CAR-T platform, specifically how the construct expresses CARs on T-cells or other specific cells. He also inquired about the development strategy for MDX-2004, the immune rejuvenator, given its broad utility.

Answer

Dr. Elias Zerhouni, Vice Chairman and President, explained that the in vivo CAR-T platform uses lipid nanoparticles with covalently conjugated multispecific targeting antibodies to deliver mRNA or DNA to T, B, or NK cells, allowing for multispecific CAR receptors. For MDX-2004, he described it as an immune accelerator, being developed in multi-line treated cancer patients and PD-1 naive/exposed patients to reignite anti-cancer immune responses, with early trials showing good progress.

Edward Tenthoff asked for more details on the in vivo CAR-T opportunity, specifically how OPKO is delivering the construct to express CARs on T-cells or other specific cells. He also inquired about the development vision for MDX-2004, the immune rejuvenator, given its broad utility.

Answer

Elias Zerhouni, Vice Chairman and President, OPKO Health, described the in vivo CAR-T approach as unique, involving covalent conjugation of targeting antibodies on lipid nanoparticles with mRNA or DNA cargo, allowing multispecific targeting of T, B, or NK cells. He highlighted its versatility, preclinical progress, and the potential for multispecific CAR-T receptors. For MDX-2004, he explained it as an immune system rejuvenator, an 'accelerator' for T-cells, being developed in cancer patients with exhausted immune systems (multiple lines of treatment, PD-1 naive, and previously exposed) to reignite anti-cancer effectiveness, with initial progress in 8 patients.

Edward Tenthoff of Piper Sandler Companies asked how OpCo Health's oxymodulin obesity drug will differentiate itself in an increasingly crowded market, considering both its injectable and oral formulations. He also inquired about the clinical trial design planned to demonstrate this differentiation.

Answer

President & Vice Chairman Dr. Elias Zerhouni highlighted the drug's unique biological mechanism, noting its effect on FGF21, which is known to be anti-fibrotic and promising for NASH patients. He added that the oral version offers a convenient maintenance option. Dr. Zerhouni explained the Phase 1 trial will enroll patients with biomarker evidence of NASH and obesity to assess safety and early efficacy signals, avoiding biopsies initially.

Edward Tenthoff of Piper Sandler asked for the next steps and development plans for both the subcutaneous and oral versions of the obesity/MASH program, and how their development would be differentiated.

Answer

Executive Elias Zerhouni stated that both the subcutaneous and oral programs are currently in the pre-IND and CMC manufacturing phase. He clarified that the initial Phase 1 trials for both will focus on safety, dose-ranging, and establishing PK/PD profiles to gather foundational data before advancing to Phase 2.

Edward Tenthoff of Piper Sandler requested clarification on the 2025 product sales guidance and asked about the expected data timeline for the ModeX oncology program (MDX-2001) and the development status of the hematologic cancer program, including its potential application in autoimmune diseases.

Answer

Executive Adam Logal reiterated the full-year 2025 product sales guidance of $165 million to $175 million. Executive Elias Zerhouni stated that safety and tolerability data for MDX-2001 is expected in late 2025, with early efficacy data more likely in the first half of 2026. He confirmed the hematologic program is in the pre-IND stage and is also being considered for autoimmune diseases.

Edward Tenthoff sought details on the ModeX oncology pipeline, asking about the expected timing and format for data releases in the coming year and the strategy for expansion cohorts. He also asked whether the company envisions combining its assets with other standard-of-care agents in the future.

Answer

Executive Elias Zerhouni outlined a timeline with initial MDX2001 safety data expected in mid-2025 and efficacy data around mid-2026. He also noted that news could come from other molecules nearing INDs or new platform collaborations. Zerhouni confirmed that the natural development path, after establishing monotherapy efficacy, would be to explore combinations with other agents like chemotherapy or IO therapies, particularly when moving into earlier lines of treatment.

Edward Tenthoff asked about measures Kymera is implementing in the KT-621 Phase IIb AD trial to mitigate placebo response, such as requiring photographic evidence of moderate to severe disease. He also inquired if Kymera would screen for healthy volunteers with positive antinuclear antibodies in the KT-579 study to provide read-through for the lupus trial.

Answer

CEO Nello Mainolfi stated that for KT-579, Kymera will enroll healthy volunteers without screening for antinuclear antibodies, prioritizing a swift transition to patient studies. CMO Jared Gollob outlined extensive measures for the KT-621 Phase IIb AD trial to mitigate placebo response, including strict eligibility criteria, rigorous screening oversight, selection of board-certified dermatologists as investigators, and a global site strategy with a majority of ex-US sites to enroll more severe patients.

Edward Tenthoff asked about the measures being taken in the KT-621 Phase 2b AD trial to mitigate placebo response, such as requiring photographic evidence of AD at baseline. He also asked if Kymera would screen for healthy volunteers with positive antinuclear antibodies (ANA) in the KT-579 study to provide read-through for the Phase 1b lupus trial.

Answer

Nello Mainolfi, Founder, President, and CEO, quickly dismissed the idea of screening for ANA in healthy volunteers, stating they will enroll truly healthy individuals. Jared Gollob, Chief Medical Officer, detailed measures to mitigate placebo response in the AD Phase 2b trial: strict eligibility criteria, careful oversight of patient screening to ensure moderate-to-severe AD, training board-certified dermatologists as investigators, and global site selection (majority ex-US) where reduced access to biologics may lead to enrollment of more severe patients.

Edward Tenthoff asked about Arrowhead's future revenue recognition and financial reporting, specifically inquiring if the company plans to break out a separate cost of goods sold (COGS) line and if REDEMPLO product sales will be disclosed independently in future reports.

Answer

Dan Apel, CFO, confirmed that initial cost of goods sold for REDEMPLO would largely be expensed to R&D. He stated that specific REDEMPLO product sales and a separate COGS line would not be disclosed until they become a 'meaningful driver' to financials, without providing a specific timeline.

Edward Tenthoff asked about Arrowhead's plans for revenue recognition, specifically if they anticipate breaking out a cost of goods sold (COGS) line and if Redemplo product sales will be disclosed separately in future reports.

Answer

Dan Appel, CFO, explained that COGS would primarily be expensed to R&D in the short term. He stated that specific Redemplo sales numbers would not be disclosed until they become a meaningful driver to the financials, at which point traditional product growth and cost reporting would be implemented.

Edward Tenthoff asked about the first data readout for ArrowDiamond PA next year, other significant data sets expected beyond obesity in the first half of 2026, and an update on the ArrowRage program.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, outlined key 2026 data readouts: obesity data (early January and end of Q2), ArrowDiamond PA dimer data (summer), ArrowMapT data (summer, focusing on CSF tau levels), and SHASTA III and IV readouts (Q3 2026) for an SNDA filing by year-end. For ArrowRage, he noted enticing preclinical data but challenges with clinical benefit biomarkers, stating a challenge study has begun with data not expected until late 2026, aiming to validate the target for potential partnering or franchise development.

Edward Tenthoff asked for clarification on the cash flow from the Viscerna-Sanofi deal and the payment schedule for the annual R&D funding from Sarepta.

Answer

CEO Christopher Anzalone explained that the cash goes to the Viscerna subsidiary, with a large portion to be distributed to its shareholders, including Arrowhead (~56% owner). He also confirmed Sarepta's $50 million annual R&D payment is due in the first quarter of each year, typically February.

Edward Tenthoff from Piper Sandler asked about the likelihood of an FDA Advisory Committee (AdCom) for plozasiran and what other steps the company is taking to prepare for a potential launch.

Answer

An executive confirmed that Arrowhead has not been advised of an AdCom and does not anticipate one. He also noted that medical affairs teams are educating physicians and that a competitor's launch helps increase disease awareness, which ultimately benefits all players in an orphan market by 'priming the pump'.

Edward Tenthoff asked about Arrowhead's plans for commercializing plozasiran in Europe, specifically whether they would seek a partner and if additional studies would be required.

Answer

Andy Davis, SVP and Head of Global Cardiometabolic Franchise, confirmed that Arrowhead is planning for commercialization in European markets with a commercial partner. He stated that more details on this partnership would be shared in the future.

Edward Tenthoff asked about the remaining steps for the plozasiran NDA filing, progress on the CMC side, and whether the year-end filing goal remains. He also inquired about expectations for future data from the muscle programs.

Answer

Dr. Bruce Given, Interim Chief Medical Scientist, confirmed they are actively writing the submission, a pre-NDA meeting is planned, and CMC is progressing, with the year-end filing guidance still in place. Regarding muscle programs, President and CEO Dr. Christopher Anzalone stated no data is expected this year, while Dr. James Hamilton, Chief of Discovery and Translational Medicine, noted readouts would include standard metrics like knockdown and splice correction.

Edward Tenthoff of Piper Sandler Companies inquired about the expected timeline for the RYONCIL label extension into adult graft-versus-host disease (GVHD) and requested an update on the progress of the Phase III chronic lower back pain trial.

Answer

CEO Silviu Itescu explained that the adult GVHD trial is set to begin this quarter in collaboration with the NIH-funded BMT CTN group, positioning RYONCIL as an add-on to existing second-line therapies. Regarding the back pain trial, he confirmed that enrollment is accelerating across nearly 40 U.S. sites, with completion anticipated by the end of the year or in Q1 of the next year, to be followed by a 12-month follow-up period.

Inquired about the size of the adult GVHD trial, its financial impact on the projected 23% cost reduction, the cost and budget for the chronic lower back pain trial, and the company's cash runway.

Answer

The adult trial will be small (60-70 patients per arm) with a mid-single-digit million cost, which will have a very small offset on the 23% cost reduction. The chronic lower back pain trial costs are already covered in the existing budget. Current cash is sufficient through the end of the first calendar quarter of next year, with strategies like partnerships, royalty monetization, and capital markets access to bring in more cash.

Inquired about the potential size of the adult GVHD trial, how its costs would affect the announced 23% budget reduction, the cost and funding for the chronic lower back pain trial, and the company's cash runway.

Answer

The adult trial is expected to be small (60-70 patients per arm) with a mid-single-digit million cost, which will only slightly offset the overall cost reduction. The back pain trial costs are already budgeted. Current cash is sufficient through at least Q1 of calendar 2024, with plans to raise more capital via strategic partnerships, royalty monetization, and capital markets.

Edward Tenthoff of Piper Sandler Companies asked for the expected timing of the iapofacine NDA submission and the associated costs, particularly for initiating the required second-line confirmatory trial.

Answer

CEO James Caruso estimated the total confirmatory trial cost at $40-45 million, with $20-25 million needed to complete enrollment. COO Jarrod Longcor added that the trial must be initiated before NDA submission, requiring about $10-12 million upfront. He projected a submission in late 2025 or early 2026, contingent on funding. Both executives expressed confidence in rapid enrollment due to strong existing data and a larger patient pool in the second-line setting.

Edward Tenthoff of Piper Sandler Companies asked about the anticipated timing for the iapofacine I-131 NDA submission and the estimated cost to get the drug approved, including the confirmatory trial.

Answer

President and CEO James Caruso estimated the total cost for the confirmatory study to be approximately $40-45 million, with $20-25 million required to complete enrollment and obtain initial data. Chief Operating Officer Jarrod Longcor added that the FDA requires the study to be initiated at the time of NDA submission and have enrollment ongoing by the time of regulatory action. He noted that about $10-12 million would be needed to get the study operational. Both executives expressed confidence in rapid enrollment due to strong Phase 2 data, high patient awareness, and moving into an earlier line of therapy.

Edward Tenthoff of Piper Sandler Companies inquired about the likelihood of an FDA advisory committee meeting for INO-3107 and how a competitor's potential approval might influence Inovio's future launch.

Answer

Chief Medical Officer Dr. Michael Sumner stated that based on interactions with the FDA, an advisory committee is not anticipated and the chance is considered low. President and CEO Dr. Jacqueline Shea addressed the competitive landscape, emphasizing key differentiators in trial design, technology (DNA medicine vs. viral vector), and confirmatory trial approaches (placebo-controlled vs. single-arm).

Edward Tenthoff inquired about Capricor's strategy for unblinding the HOPE-three clinical trial and the anticipated timeline for receiving clarity from the FDA on the path forward.

Answer

CEO Linda Marbán explained that the company will not unblind the HOPE-three trial until it receives clear guidance from the FDA following their upcoming Type A meeting. She emphasized the desire to avoid any perception of bias and stated that a public update would follow once they have official written feedback from the agency.

Edward Tenthoff from Piper Sandler inquired about the status of the San Diego manufacturing site inspection and the company's preparations for the upcoming FDA Advisory Committee (AdCom) meeting.

Answer

CEO Linda Marbán confirmed the pre-licensing inspection is scheduled for the current quarter. Regarding the AdCom, she framed it as a positive development, noting the FDA is actively reviewing the file with over 20 information requests and a mid-cycle review that revealed no substantive issues. She added that Capricor has already conducted two successful mock AdComs in preparation.

Edward Tenthoff inquired about the commercial preparations for deramiocel, specifically the division of labor between Capricor and its partner, NS Pharma (Nippon Shinyaku), and the benefits of leveraging NS Pharma's existing commercial infrastructure.

Answer

CEO Linda Marbán explained that the partnership involves daily collaboration, with NS Pharma's 125-person U.S. team, already established in the Duchenne space, handling sales and distribution while Capricor shepherds the product to market. She highlighted joint efforts in market forecasting, physician outreach, and payer meetings, emphasizing NS Pharma's deep engagement and excitement for the launch.

Edward Tenthoff inquired about the joint market preparation activities with Nippon Shinyaku for the deramiocel launch and how Capricor is preparing to scale up manufacturing to meet anticipated commercial demand.

Answer

CEO Linda Marbán explained that Nippon Shinyaku's existing Duchenne muscular dystrophy (DMD) infrastructure provides a 'plug-and-play' model with a 125-person team ready for the deramiocel launch. She detailed that Capricor has kept manufacturing in-house, has a commercial-scale facility in San Diego ready for inspection, and is executing plans for a new, larger facility based on a modular, 'plug-and-play' clean room design to ensure scalability.

Asked about the strategy and decision-making process for moving CX-2051 into earlier lines of colorectal cancer (CRC) therapy and how those trials might be announced.

Answer

The company's primary focus is on the late-line CRC opportunity. Moving to earlier lines is a key long-term goal that will require combination studies, likely starting with bevacizumab. This will happen after the Phase 1 study is complete and the dose for Phase 2 monotherapy is selected. The ultimate vision is to potentially replace irinotecan in second-line therapy.

Edward Tenthoff of Piper Sandler Companies inquired about the strategic decisions and timeline for advancing the CX-2051 program into earlier lines of colorectal cancer (CRC) therapy.

Answer

Sean A. McCarthy, Chairman & CEO, stated that while the immediate priority is the late-line CRC opportunity, moving into earlier lines is a key long-term goal. He explained this would necessitate combination studies, likely starting with bevacizumab, after the Phase 1 dose is selected and the initial monotherapy study is further along.

Edward Tenthoff of Piper Sandler Companies inquired about the Q2 increase in R&D expenses and the Aarecor partnership for a higher concentration Nimazumab formulation.

Answer

President, CEO & Director Punit Dhillon explained the Aarecor partnership is a lifecycle management effort to develop a higher concentration formulation for less frequent dosing, separate from the current clinical track. CFO Kaitlyn Arsenault clarified that the R&D expense increase was primarily driven by $9.1 million in contract manufacturing costs for the Phase 2a extension study resupply and the Phase 2b trial supply.

Edward Tenthoff of Piper Sandler & Co. inquired about the incremental benefit of extending the CBeyond study to 52 weeks and how this extension would impact the timing for initiating a Phase 2b study.

Answer

CEO Punit Dhillon stated the extension maximizes data collection without delaying the overall timeline, slotting in well before the Phase 2b study begins. He emphasized the value of longer-term safety and tolerability data. Dr. Puneet Arora added that the 52-week data will help refine PK/PD models for Phase 2b dose selection and provide invaluable long-term data for the combination arm, as the planned Phase 2b will focus on monotherapy dose-ranging.

Edward Tenthoff asked if over-enrolling in the CBeyond study and removing the interim analysis impacts statistical power, and whether the accelerated timeline for 26-week data would advance the start of the Phase IIb study.

Answer

President and CEO Punit Dhillon clarified that enrolling 136 patients versus the planned 120 evaluable patients enhances the robustness of the data without changing the statistical plan. He stated that while the accelerated 26-week data allows for earlier engagement with regulators, the timeline for the Phase IIb study initiation remains planned for the second quarter of 2026, following the receipt of the full 52-week data.

Edward Tenthoff inquired about the enrollment progress for the CBeyond clinical trial, the level of excitement surrounding it, and expectations for the interim data, particularly for the combination therapy arm which will have a smaller patient count.

Answer

Punit Dhillon, President and CEO, confirmed that enrollment for the CBeyond study is proceeding very well, with 15 of 18 U.S. sites actively recruiting and the company on track to reach 50% enrollment by year-end. He clarified that the study's primary endpoint is an 8% placebo-adjusted weight loss for nimacimab monotherapy. The combination arm with semaglutide is an exploratory endpoint designed to assess for an additive or synergistic effect and improved tolerability. Dhillon emphasized the study's robust design will provide key data for the non-incretin obesity drug class.

Edward Tenthoff asked about the current drivers of XPOVIO utilization in multiple myeloma and the potential marketing synergies for a future launch in myelofibrosis.

Answer

Richard Paulson, President and CEO, highlighted a significant 80% prescriber overlap between multiple myeloma and myelofibrosis, which would enable a rapid launch with minimal additional investment. Sohanya Cheng, EVP and Chief Commercial Officer, detailed that XPOVIO demand is driven by its use as a flexible oral option in community settings and its growing use pre- and post-T-cell therapy in academic centers.

Edward Tenthoff of Piper Sandler inquired about the patient profile being enrolled in the 4WARD clinical trial for chronic neutropenia (CN), asking if it aligns with the population from the earlier Phase II study.

Answer

Executives Paula Ragan, Christophe Arbet-Engels, and Mark Baldry confirmed the enrolled patient demographics are balanced and representative of the target commercial population. They highlighted that the trial is enrolling 'very sick patients' to enrich for success on the infection endpoint, that there is high demand from investigators to enroll more patients, and that market research indicates the CN market is more concentrated than the WHIM syndrome market.

Edward Tenthoff of Piper Sandler inquired about the current number of patients on XOLREMDI and whether the company implemented a price increase for the drug to start 2025.

Answer

Mark Baldry (Executive) responded that the company is not disclosing specific patient numbers while it focuses on building demand. He confirmed that a 7% price increase for XOLREMDI was implemented at the beginning of the year, which is a typical practice.

Edward Tenthoff from Piper Sandler asked if the Phase III trial for chronic neutropenia is designed to capture benefits from G-CSF reduction, such as improved tolerability, and requested more details on the new patient outreach initiatives for XOLREMDI.

Answer

Chief Medical Officer Christophe Arbet-Engels clarified that the Phase III trial is designed for registration per FDA requirements, and benefits from G-CSF reduction would be assessed in follow-on studies. Chief Commercial Officer Mark Baldry described the new patient-directed campaign for XOLREMDI, which uses digital campaigns, websites, and printed materials to educate patients and encourage physician discussions.

Edward Tenthoff asked for more details on the initial patients receiving commercial XOLREMDI, seeking to understand the number of patients on the drug, any backlog, or general characteristics of the patient journey to treatment.

Answer

President and CEO Dr. Paula Ragan stated that the company would not provide specific patient numbers at this time but expressed that they are very pleased with the launch progress. Chief Commercial Officer Mark Baldry added that all U.S. patients from the open-label extension study have been prescribed commercial XOLREMDI and that the company is focused on raising disease awareness to identify new patients.

Edward Tenthoff of Piper Sandler asked what would constitute a 'win' for the upcoming pociredir data release. He sought to understand what the company is looking for to confirm the drug is working in the desired ballpark.

Answer

Executive Alexander Sapir explained that any increase in fetal hemoglobin (HbF) is beneficial, referencing data showing a 1% HbF increase can lead to a 4-8% reduction in vaso-occlusive crises (VOCs). He noted that even single-digit absolute increases in HbF can be clinically meaningful. Iain Fraser, Head of Development, added that they aim to reaffirm the magnitude of induction seen previously and that mid-single-digit percentage increases are expected to be clinically significant.

Edward Tenthoff of Piper Sandler asked if enrollment criteria and the removal of Oxbryta have complicated patient recruitment, inquired about specific DSMB safety assessments, and questioned where pociredir might fit in the future treatment landscape.

Answer

Executive Iain Fraser clarified that the withdrawal of Oxbryta has simplified recruitment, and CEO Alexander Sapir added that a protocol amendment now allows concomitant use of crizanlizumab and L-glutamine. Fraser noted the DSMB has no specific safety signal to monitor but will conduct a broad review. Regarding positioning, Sapir stated it's early but believes pociredir could be broadly used and transformative, and they will engage the FDA on relaxing the hydroxyurea exclusion for future studies.

Edward Tenthoff of Piper Sandler requested more specific guidance on the PIONEER trial data rollout in 2025, asking if the 12mg and 20mg cohort data would be released separately and how quickly the company could transition to a registrational study.

Answer

Executive Alexander Sapir confirmed the 12mg and 20mg cohort data will be released at different times in 2025, with more detailed guidance on timing expected in early 2025. An executive from the clinical team added that post-PIONEER plans, which could range from a combined Phase II/III to separate studies, will be determined after an end-of-Phase I meeting with the FDA. Sapir also noted internal discussions about using fetal hemoglobin as a surrogate endpoint.

Inquired about the areas affected by the layoffs, the remaining clinical team's capacity, and the company's future partnership strategy beyond luvelta.

Answer

The layoffs primarily affect luvelta-related roles and manufacturing, which is being externalized, in order to pivot resources to the early-stage pipeline. While actively seeking a partner for luvelta, the company remains open to partnering its other pipeline assets to secure non-dilutive capital.

Edward Tenthoff from Piper Sandler asked about the composition of the workforce reduction, the company's remaining clinical capabilities, and the future business development strategy for both luvelta and the new pipeline assets.

Answer

Executive Jane Chung clarified that the layoffs primarily affect luvelta-related workstreams and that manufacturing operations are being externalized. She confirmed that while actively seeking a partner for luvelta, Sutro will continue to pursue partnerships for its pipeline candidates as a method to secure non-dilutive capital.

Edward Tenthoff of Piper Sandler questioned the discussions around the required size of the safety database for SER-155. He also asked if the FDA's experience with VOWST's approval might increase the agency's comfort level with microbiome therapeutics in general.

Answer

Eric Shaff, President and CEO, stated that while he cannot speak for the FDA, the precedent with VOWST suggested a safety database of at least 300 patients was a key consideration. Lisa von Moltke, CMO, added that the required database size is not fixed; it evolves based on the emerging safety profile and the specific patient population. She confirmed these conversations with the agency would continue as more data is generated.

Edward Tenthoff asked about the long-term vision for Seres over the next 3-5 years, questioning whether the company aims to be a front-end R&D engine for larger partners or if it aspires to eventually commercialize its own products.

Answer

President and CEO Eric Shaff explained that while Seres' recent value creation has been in innovation and early development, the long-term aspiration is to become a vertically integrated company with commercialization capabilities, similar to legacy biotechs like Genentech. He noted that certain indications could lend themselves to a small, focused commercial team. However, in the short term, the strategy is focused on R&D to drive shareholder value following the VOWST sale.

Edward Tenthoff asked how the second-line treatment paradigm for metastatic breast cancer is evolving with the increased use of SERDs and CDK4/6 inhibitors in the first line, and how this impacts the outlook for vepdegestrant monotherapy.

Answer

Chief Medical Officer Noah Berkowitz acknowledged the changing landscape, including the rise of ribociclib and PI3K pathway drugs. He noted that while many new agents are being combined with fulvestrant, Arvinas aims to conduct studies demonstrating that vepdegestrant can be a preferred oral backbone therapy for various combinations in this setting, offering a potential alternative to injectable fulvestrant.

Edward Tenthoff from Piper Sandler requested an update on the ARV-766 prostate cancer program that was out-licensed to Novartis and how the companies anticipate advancing it.

Answer

CEO John Houston confirmed that the handover of data and materials to Novartis is complete. He reiterated Novartis's commitment to developing ARV-766 in both early and late-stage prostate cancer. He stated that while future significant updates will come from Novartis, Arvinas is pleased with the transition and Novartis's strategic plan.

Edward Tenthoff requested an update on the cystic fibrosis (CF) program being developed in partnership with Vertex Pharmaceuticals.

Answer

President Stephen Hoge confirmed the trial is run by partner Vertex and has completed its single ascending dose portion. The study is now in the multiple ascending dose phase, with a data readout expected sometime in 2025. He noted that Vertex would provide any specific timing updates.

Edward Tenthoff inquired about the path forward for the orphan disease pipeline, specifically the pivotal trial designs, patient numbers, and expected timelines for generating registrational data for the PA and MMA programs.

Answer

President Stephen Hoge explained that the pivotal study for MMA, expected to start in H1 2025, will likely use a biomarker for approval, allowing for a quicker path. The PA program will rely on event rates, which may take more time. He reiterated the goal of launching these products in the 2026+ timeframe, with timing dependent on patient enrollment.

Edward Tenthoff asked for a review of the historical control data for azacitidine (aza) in higher-risk MDS and questioned how the previous AML trial results might inform expectations for the upcoming MDS data.

Answer

Dr. David Roth, Chief Medical Officer, explained that the aza label shows a 17% complete response (CR) rate, with recent trials showing rates in the mid-to-high teens. He clarified that the AML trial tested a different combination (a triplet with venetoclax) and is not predictive of the MDS trial's outcome. However, he noted the AML study did reinforce tamibarotene's favorable safety profile, showing no added myelosuppression.

Edward Tenthoff of Piper Sandler & Co. asked for a reminder on the statistical powering of the SELECT-MDS-1 Phase III trial and the anticipated delta in complete response (CR) rates needed for success.

Answer

Chief Medical Officer Dr. David Roth clarified that the SELECT-MDS-1 trial is powered at over 90% to detect a difference in the primary endpoint of CR rate between the two arms, based on an enrollment of 190 patients. While not disclosing the specific numerical assumptions for each arm, he noted the assumptions were based on standard performance for azacitidine in the control arm and that the final readout will also consider durability and safety.

Edward Tenthoff of Piper Sandler & Co. asked how the safety profile of the Immuno-STAT platform differentiates it from cell therapies for autoimmune diseases and if this is a key focus for investors.

Answer

President and CSO Dr. Anish Suri highlighted three key differentiators: 1) The platform's clinical derisking in over 120 patients with no clinically relevant immunogenicity; 2) Superior safety from selective T-cell engagement, avoiding the high cytokine release seen with pan T-cell engagers; and 3) The ability to harness the body's natural, long-lasting antiviral T-cells. He also noted the significant manufacturing advantages of an antibody-based biologic over autologous cell therapies.

Edward Tenthoff of Piper Jaffray inquired about XOMA's future revenue sources for 2016-2017, the status of the Servier alliance, and whether the company's cash runway guidance through Q1 2017 accounts for debt repayments.

Answer

CFO Tom Burns clarified that declining biodefense and Servier revenues were expense reimbursements, so the net impact is positive, and confirmed that cash projections include all scheduled debt payments. CEO John Varian added that future revenue would be sought from new licensing deals and that the Servier alliance is being terminated, giving XOMA 100% ownership of gevokizumab.