Anupam Rama

Anupam Rama asked about BridgeBio's marketing message for Attruby to physicians regarding patients with mixed phenotype, and a broader strategic question on investments in the early-stage and mid-stage pipeline, including future catalyst timelines.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, stated that mixed phenotype is more of an investor concern, with their focus on cardiomyopathy. He highlighted Attruby's strong data in the variant population, including a 59% hazard reduction in V122i. Regarding the pipeline, Kumar emphasized a laser focus on successfully launching Encalirate, BBP-418, and Infigratinib. He noted the attractive research environment in rare diseases, the 17 assets in Gondola Bio, and the potential to access new growth opportunities from there when appropriate.

Anupam Rama asked about BridgeBio's marketing message for Atrobi to physicians regarding patients with mixed phenotype, and a higher-level strategic question about future investments in the early-stage and mid-stage pipeline, including catalyst timelines.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, stated that mixed phenotype is more of an investor question than a physician concern, with the focus being on cardiomyopathy. He emphasized the variant message, citing a 59% hazard reduction in the V122i variant population and upcoming AHA data. For pipeline diversification, he stressed a laser focus on successfully launching the three upcoming products first. He then highlighted the attractive research environment in rare and orphan diseases, the 17 assets in Gondola Bio, and the potential to access new growth opportunities at the right time.

Anupam Rama of JPMorgan Chase & Co. asked about Atruvy's prescribing metrics, specifically what clinical aspects are resonating with new and repeat prescribers and whether growth is stronger in academic or community centers.

Answer

Chief Commercial Officer Matthew Outten explained that physicians who prescribe Atruvy see its rapid efficacy, which reinforces their decision and leads to more prescriptions. He noted that positive experiences are shared within both physician and patient communities, driving growth in both academic (COE) and community settings, and he expects this trend to continue.

Anupam Rama from JPMorgan Chase & Co. asked about the new data for Encaleret in chronic hypoparathyroidism and what makes this indication an exciting opportunity from a net present value (NPV) perspective.

Answer

CEO Neil Kumar highlighted the indication as a large extension population with a reasonable price point, making it an attractive opportunity, especially as other oral competitors have exited the space. Ananth Sridhar, COO of BridgeBio Cardio Reno, added that early data showed 78% of participants achieved normal calcium levels, positioning it as a potential paradigm-changing treatment in a market 7-8 times larger than the ADH1 market.

Anupam Rama asked for more color and quantification on the sales force expansion for both INGREZZA and CRENESSITY, specifically targeting segments for INGREZZA (psychiatry, neurology, long-term care) and CRENESSITY (general endocrinologists vs. pediatric endocrinologists).

Answer

Eric Benevich, Chief Commercial Officer, characterized the expansion as about a 30% increase in overall sales footprint, with most incremental headcount for INGREZZA. He detailed INGREZZA's restructuring into a combined neuropsych team (psychiatry and neurology) and an expanded long-term care team. For CRENESSITY, he described a smaller expansion to go deeper into community endocrinology practices. Matt Abernethy, Chief Financial Officer, added that this reflects belief in the TD market and aims to accelerate market development and maximize patient numbers.

Anupam Rama requested more color and quantification on the sales force expansion for both INGREZZA and CRENESSITY, specifically targeting segments for INGREZZA (psychiatry, neurology, long-term care) and CRENESSITY (general vs. pediatric endocrinologists).

Answer

Eric Benevich, Chief Commercial Officer, characterized the expansion as about a 30% increase in overall sales footprint, with most incremental headcount for INGREZZA. For INGREZZA, existing psychiatry and neurology teams will be combined and expanded, while the long-term care (LTC) team will remain separate and also expand. For CRENESSITY, the smaller expansion will allow deeper penetration into community endocrinology practices. Matt Abernethy, Chief Financial Officer, added that this investment reflects belief in the TD market and aims to accelerate market development and maximize patient numbers.

Anupam Rama from JPMorgan Chase & Co. asked about the key learnings from the valbenazine study in adjunctive schizophrenia, particularly regarding the VMAT2 mechanism and trial design for next-generation programs.

Answer

CMO Sanjay Keswani and Strategic Advisor Eiry Roberts explained that the study was a valuable learning opportunity. While it missed the primary endpoint, it showed a positive efficacy signal in the PANSS positive symptom scale, which helps inform the target population for future programs. Roberts added that the study confirmed valbenazine's safety profile in this population and provided interesting signals across various sub-scores that will be published and used to guide the next-generation VMAT2 inhibitors.

Anupam Rama asked for the primary drivers behind INGREZZA's record new patient starts, questioning whether it was due to gaining share of voice, overall market expansion, or other factors.

Answer

Chief Commercial Officer Eric Benevich attributed the record starts to two main factors: the tangible benefits from the recently expanded sales force, particularly in psychiatry and long-term care, and enhanced marketing initiatives focused on better differentiating INGREZZA from its competitors.

Speaking for Anupam Rama, Malcolm Kono asked about the primary levers of growth for INGREZZA across its different commercial segments and whether any single segment is expected to show outsized growth.

Answer

CEO Kyle Gano responded that while growth is expected across psychiatry, long-term care (LTC), and neurology, the largest opportunity remains in the psychiatry segment. He mentioned that headwinds like provider turnover and telemedicine in psychiatry are being addressed by the recent sales force expansion, which aims to increase the frequency of interactions with healthcare providers.

Anupam Rama of JPMorgan asked about the timing of the INGREZZA pre-announcement and 2025 guidance, questioning if it would occur at the January healthcare conference or during the Q4 earnings call in February.

Answer

CFO Matt Abernethy confirmed that, consistent with the past two years, the company will not pre-announce revenue at the January conference. He stated that Q4 results and full-year 2025 sales guidance will be provided during the February earnings call.

Anupam Rama inquired about Kiniksa's integration of the recently updated ACC guidelines into their marketing strategies and the initial insights gained from this update.

Answer

John Paolini (CMO, Kiniksa Pharmaceuticals) explained that the concise clinical guidance, released in August, affirms IL-1 pathway inhibition as a second-line treatment after NSAIDs and colchicine, supporting a steroid-sparing approach. Ross Moat (Chief Corporate and Commercial Officer, Kiniksa Pharmaceuticals) confirmed the incorporation of these guidelines into promotional materials, emphasizing their validation of ARCALYST as a targeted immunomodulation approach and a modern standard of care, particularly in reducing corticosteroid use.

Anupam Rama from JPMorgan inquired about the penetration trends for Arcalis in the first recurrence pericarditis setting, referencing the company's data that 20% of total prescriptions originate from this patient group.

Answer

EVP & Chief Commercial Officer Ross Moat explained that while the core focus remains the 15% penetrated 'two-plus recurrence' population, the first recurrence setting represents a significant growth opportunity with 26,000 patients. He attributed the increasing use in this earlier stage to growing physician confidence, familiarity with Arcalis, and a better understanding of recurrent pericarditis as an IL-1 alpha and beta mediated disease.

Anupam Rama of JPMorgan Chase & Co. asked if the increase in new ARCALYST prescribers is primarily from community settings and if this reflects the impact of a sales force expansion.

Answer

Chief Commercial Officer Ross Moat clarified that the company is agnostic to the practice setting (academic vs. office-based) and focuses its sales force on cardiologists with the highest throughput of recurrent pericarditis patients, identified through data analysis. He stated this targeted approach is driving the consistent quarterly growth in the prescriber base.

Anupam Rama of JPMorgan Chase & Co. inquired about market research on patient preference for the monthly subcutaneous KPL-387 versus the weekly ARCALYST and sought confirmation that the presented clinical data represented a subcutaneous dose.

Answer

Ross Moat, Chief Commercial Officer, stated that while ARCALYST acceptance is high, a monthly liquid formulation could be advantageous for patient preference. Dr. John Paolini, Chief Medical Officer, confirmed the data shown was for a subcutaneous dose, supporting a monthly dosing schedule.

Anupam Rama asked if Kiniksa plans to follow its past practice of pre-announcing results and providing forward-year guidance at a healthcare conference in January.

Answer

CEO Sanj K. Patel acknowledged the company's past cadence but stated that no final decision has been made regarding the timing of pre-announcements or guidance for the upcoming year. He indicated they are still evaluating their plans.

Anupam Rama from JPMorgan Chase & Co. asked about the expectations for the preliminary CX-801 monotherapy data in Q4 and any potential risks of overlapping toxicity with the KEYTRUDA combination.

Answer

Sean A. McCarthy, Chairman & CEO, explained that the Q4 update will focus on translational data from paired tumor biopsies in a small number of monotherapy patients, looking for evidence of target engagement and modulation of the tumor microenvironment, such as PD-L1 upregulation. He noted that the combination of interferon and KEYTRUDA has shown powerful activity previously, and CytomX's masking technology aims to mitigate the known toxicity issues.

Anupam Rama inquired about how the serious adverse events (SAEs) were managed and whether CytomX plans to present the CX-2051 data at a medical conference before the next planned update in Q1 2026.

Answer

CEO Sean McCarthy described the safety profile as encouraging and supportive of moving into earlier lines of therapy. He noted that while specific patient-by-patient details on SAEs couldn't be shared, they were consistent with the overall AE profile. McCarthy confirmed the next data update is planned for Q1 2026, which will include data from approximately 70 patients, and the venue for that presentation has not yet been decided.

Anupam Rama asked about the patient selection strategy for the CX-2051 trial, specifically whether future enrollment would be limited to patients with high EpCAM expression or would continue to include all-comers.

Answer

CEO Sean McCarthy explained that for colorectal cancer (CRC), EpCAM expression is high in over 90% of patients, so selection is likely unnecessary. For other cancers with more varied expression, he noted that CytomX has developed an IHC assay that could be used to select patients if needed, highlighting the drug's long-term pan-tumor potential.

Anupam Rama from JPMorgan Chase & Co. asked if outsized growth from the broader commercial franchise, specifically NUZYRA or ZAKDURO, is expected to be a meaningful contributor to achieving the company's guidance and profitability goals in the second half of the year, beyond the contributions from VIVGART and ZEJULA.

Answer

Josh Smiley, President & COO, confirmed that both ZAKDURO and ONCTYRO are expected to show good growth in the second half of the year. He noted that while ZAKDURO's near-term growth might be modestly limited by supply constraints, underlying demand is strong. He also stated that NUZYRA continues to be a strong and consistent driver of growth for the company.

Anupam Rama asked for details on the size, scope, and key data points to focus on in the upcoming ASCO presentation for the DLL3 ADC, ZL-1310.

Answer

Dr. Rafael Amado, President and Head of Global R&D, stated the ASCO update will feature the complete dose escalation dataset and new data from the dose optimization cohort of about 50 patients. He advised focusing on which dose demonstrates the most promising therapeutic benefit to carry forward into the pivotal trial.

Anupam Rama inquired about which products, beyond VYVGART, are expected to contribute significantly to the outsized growth reflected in the 2025 revenue guidance.

Answer

Joshua Smiley, President and Chief Operating Officer, responded that while VYVGART is expected to grow faster than the overall rate, strong growth is also anticipated from the base business, particularly ZEJULA and NUZYRA. He also noted that newly launched products AUGTYRO and XACDURO will contribute to the overall strong performance across the portfolio.

Anupam Rama from JPMorgan Chase & Co. inquired about the progress of VYVGART's hospital formulary listings following its NRDL inclusion, seeking specific metrics on hospital adoption and the expected timeline for completion.

Answer

President and Chief Operating Officer Josh Smiley responded that Zai Lab is targeting 1,000 key hospitals for NRDL pull-through. He stated the goal is to have at least two-thirds of these hospitals complete the listing process by the end of the first half of 2024, confirming they are well on track to meet this objective.

Anupam Rama from JPMorgan Chase & Co. asked about the cadence and level of engagement with the FDA regarding the Filspari REMS update, especially considering the evolving regulatory landscape.

Answer

Dr. William Rote, Chief Research Officer, responded that interactions with the FDA, viewed through the lens of the two ongoing sNDAs (REMS modification and FSGS), have been progressing as expected. He noted the frequency and types of questions have been very similar to the process for the full IgA nephropathy approval, indicating an engaged and active review team.

Anupam Rama from JPMorgan Chase & Co. requested an expansion on the gross-to-net (GTN) commentary, seeking to understand the Q1 impact and if GTN would be a tailwind for the rest of 2025.

Answer

Chief Financial Officer Chris Cline explained that while Q1 typically has the highest discounts, the impact of the Part D redesign will make the GTN discount 'a bit stickier' and more even throughout 2025 compared to 2024. He reiterated guidance for GTN in the low 20s for the year, up from the mid-to-high teens last year.

Anupam Rama of JPMorgan Chase & Co. asked for details on the scope of the data package submitted to the FDA for the FILSPARI liver monitoring REMS modification, confirming if it included all clinical experience from both IgAN and FSGS trials.

Answer

SVP of Research and Development Dr. Bill Rote confirmed that the submission included a substantial body of pooled data from ongoing clinical trials, open-label extensions (DUET, DUPLEX, PROTECT), and commercial real-world experience. He stressed that the safety profile, showing low levels of LFT elevation and no liver injury, remained consistent across this larger dataset.

Representing Anupam Rama of JPMorgan Chase & Co., an analyst asked for details on the additional clinical data required for the UX-111 resubmission, especially since the FDA had already acknowledged the existing neurodevelopmental data as robust.

Answer

Emil Kakkis, Founder, President & CEO, clarified that the FDA requested a routine update of the ongoing clinical endpoint data (Bayley, Vineland) and biomarker data. He explained this was primarily because time has passed since the initial submission, and the agency wants to see the latest information from patients who have continued in the study.

An analyst on behalf of Anupam Rama asked for an update on the enrollment status of the GTX-102 Angelman syndrome program and whether all global clinical trial sites are now active.

Answer

Chief Medical Officer Eric Crombez confirmed that the company is on track to achieve its goal of fully enrolling the 120-patient pivotal study within the year. He stated that global sites in the U.S., Europe, and Japan are active and currently screening patients for the trial.

Priyanka Grover, on behalf of Anupam Rama, asked whether Ultragenyx would file for approval immediately if the Orbit study is successful, or if they would wait for the Cosmic study analysis.

Answer

CEO Emil Kakkis confirmed that if the Orbit study hits its endpoint, the company would proceed to final analysis and file for approval quickly. He indicated this would likely only cause a one-quarter delay compared to a scenario where the interim analysis was the final one.

Anupam Rama asked about Syndax's path to profitability, questioning the top-line assumptions for Revuforge and Nyktymbo and whether profitability can be achieved on the current relapsed/refractory indications alone.

Answer

CFO Keith Goldan confirmed that Syndax expects to reach profitability with its current funds, driven by outperforming launches. He stated that profitability is achievable based solely on the relapsed/refractory indications for Revuforge and Nyktymbo, without relying on future frontline approvals. He also noted that operating expenses are expected to remain stable for the next few years while fully funding strategic priorities.

Anupam Rama of JPMorgan Chase & Co. inquired about the expected Revuforj inventory levels throughout 2025 and asked about early trends regarding repeat prescriptions from key physician accounts.

Answer

CFO Keith Goldan stated that inventory levels are expected to remain stable at 2-3 weeks in the channel, though the absolute dollar value will grow with revenue. CCO Steven Closter noted that while specific repeat prescriber numbers are not yet provided, the majority of ordering accounts have prescribed Revuforj more than once, indicating positive initial experiences and habit formation.

Anupam Rama from JPMorgan Chase & Co. asked for more color on the sampling trends for Cyfovri during the quarter, noting an absolute increase and inquiring about future expectations.

Answer

EVP & Head of Global Commercial David Acheson explained that as the business and injection volume grow, free goods usage will also increase, particularly with the ongoing co-pay foundation funding issues. He anticipates that the impact from free goods, similar to the $13 million seen in Q2, will continue through the rest of the year.

Anupam Rama from JPMorgan Chase & Co. inquired about the sampling trends for Cyfovri during the quarter, noting a slight increase on an absolute basis and asking for the company's forward-looking perspective.

Answer

EVP & Head of Global Commercial David Acheson explained that as the business and total injections grow, free goods usage also increases due to ongoing foundation funding issues. He anticipates that the impact from free goods, which was $13 million in Q2, will remain at similar levels for the rest of 2025.

Anupam Rama from JPMorgan Chase & Co. requested more detail on the sampling and free goods trends for Cyfovri during the quarter, noting what appeared to be a slight increase on an absolute basis.

Answer

EVP of Commercial David Acheson explained that as total injection volume for Cyfovri grows, the absolute number of free goods doses also increases due to the ongoing funding shortage at co-pay assistance foundations. He stated that he expects to see similar trends and levels of free goods usage through the rest of 2025.

Anupam Rama from JPMorgan Chase & Co. inquired about the sampling and free goods trends for Cyfovri during the quarter, noting a slight increase, and asked about expectations moving forward.

Answer

EVP of Commercial, David Acheson, explained that as total injection volume grows, the use of free goods also increases, driven by the ongoing shortage in co-pay foundation funding. He stated that Apellis expects to see similar trends and impact from free goods usage throughout the remainder of 2025.

Anupam Rama asked about the current payer landscape for SYFOVRE following a competitor's label update and inquired about the company's strategies to secure formulary wins.

Answer

Executive David Acheson confirmed that SYFOVRE maintains its preferred positioning on several large Medicare Advantage plans and has not seen significant changes. He emphasized that SYFOVRE's efficacy with every-other-month dosing remains a key differentiator for both physicians and payers, solidifying its competitive position.

Malcolm Kuno, on behalf of Anupam Rama from JPMorgan, questioned how the competitor's updated label might influence payer decisions regarding preferred tiering for SYFOVRE.

Answer

EVP of Commercial David Acheson responded that Apellis is fortunate to already have preferred positions with several sizable payers. He noted that conversations with payers focus on SYFOVRE's strong efficacy data with every-other-month dosing, which is in the label, but he refrained from predicting future payer decisions.

Anupam Rama of JPMorgan Chase & Co. questioned if the current sales team is appropriately sized to reach the next tier of prescribing doctors and asked about trends in product sampling for this physician group.

Answer

COO Adam Townsend affirmed that the field force is believed to be rightsized. He detailed new initiatives to drive referrals, including a dedicated ophthalmology field team and a digital optometry team. He noted that while sampling plays a smaller role in a buy-and-bill model with established reimbursement, it is expected to constitute about 5% of vial demand, particularly for physicians new to prescribing SYFOVRE.

Anupam Rama inquired about Replimune's medical education strategy for RP1 at the upcoming ASCO conference, particularly concerning the data being presented ahead of the potential launch.

Answer

CEO Sushil Patel detailed plans for a significant presence at ASCO, highlighting two key posters. One will present data on RP1's response rates when injecting different types of lesions (superficial, visceral, or a combination), aiming to show a strong rationale for injecting deeper lesions. The second poster will cover biodistribution and safety, demonstrating that RP1 is easily neutralized by common disinfectants and does not lead to infections in patients or their close contacts, reinforcing the therapy's safety profile.

Anupam Rama requested clarification on what was included in the April labeling update submission beyond the patient death information, asking if it contained the 2-year EMBARK safety update or other real-world data.

Answer

Head of R&D Dr. Louise Rodino-Klapac clarified that the update was focused on safety information, specifically to include the case of acute liver failure (ALF) and the patient death. She stated this was the breadth of the update and did not mention the inclusion of other data sets.

Anupam Rama from JPMorgan Chase & Co. asked about the company's strategic focus between internal pipeline development and external business development. He also inquired if Sarepta would pre-announce Q4 results at the January healthcare conference.

Answer

President and CEO Doug Ingram stated that the company's primary focus is on the successful launch of ELEVIDYS, the performance of its PMO franchise, and advancing its internal pipeline, particularly the LGMD programs. Regarding the January conference, he noted that while no commitment was being made, Sarepta would likely be consistent with its history of pre-announcing results.

Anupam Rama inquired about the shape of the revenue growth curve for ELEVIDYS through the 2030-2031 timeframe, asking if it should be modeled as linear growth.

Answer

CEO Douglas Ingram stated that while he would not provide more granular long-term guidance, peak year sales for ELEVIDYS are expected to occur significantly in the back half of the current decade. He reiterated that the company will be treating the prevalent patient population throughout the decade before shifting to the incident population in the 2030s.

Anupam Rama of JPMorgan Chase & Co. inquired about the specific reasons for the higher-than-anticipated Voluntary Scheme for Branded Medicines Pricing and Access (VPAG) rebates in the U.K. for both Galafold and Pombiliti/Opfolda.

Answer

President and CEO Bradley Campbell explained that the U.K.'s industry association negotiated a 22% rebate rate, significantly above the 15% maximum the company had conservatively planned for. Campbell described it as a frustrating, onetime reset for the year's forecast, noting that strong patient growth for Galafold should offset the impact, while Pombiliti/Opfolda's guidance was revised to account for it.

Anupam Rama asked for details on the trends observed among previously untreated patients who are now starting Galafold, seeking a comparison between core legacy regions and emerging markets.

Answer

President and CEO Bradley Campbell stated that in established markets like the U.S., Europe, and Japan, growth is driven by penetrating the diagnosed-but-untreated population and new diagnoses from screening initiatives. In newer markets, such as Latin America and Southeast Asia, there remains a significant opportunity to switch patients from existing therapies in addition to finding new patients.

Anupam Rama questioned whether the increase in Galafold's annual guidance was driven by specific regional performance.

Answer

President and CEO Bradley Campbell confirmed strong growth across all key markets. Chief Business Officer Sebastien Martel added detail, highlighting robust demand from naive patients in the U.S., with new patient starts near a five-year high. Martel also pointed to strong performance in Europe, particularly the U.K., and significant growth potential in Japan.

Anupam Rama inquired about the potential for first-quarter seasonality to create headwinds for ZURZUVAE's growth, given typical industry patterns related to payer dynamics.

Answer

CEO Barry Greene stated that Sage anticipates continued quarter-over-quarter growth for ZURZUVAE in Q1. He explained that since reimbursement is primarily from commercial and Medicaid payers, the company does not expect the classic Medicare 'donut hole' issue that affects other drugs. COO Chris Benecchi added that Q1 has more selling days than the holiday-impacted Q4, which should also support growth.

Anupam Rama inquired about the early script trends and impact observed since the recent expansion of the Zurzuvae sales force.

Answer

CEO Barry Greene stated that while it's too early to provide specific data, the company is confident in seeing an uptick in scripts given the market's promotional sensitivity. He confirmed the expanded sales force was active in the field for the fourth quarter and operating effectively.

Anupam Rama asked how ZURZUVAE's adoption is tracking relative to initial expectations across different physician segments, noting that OB/GYNs appear to be leading.

Answer

CEO Barry Greene confirmed that the prescriber dynamics are aligned with their expectations. He emphasized that OB/GYNs are the frontline caregivers, and ZURZUVAE is enabling a crucial shift from a 'suspect and refer' model to a 'screen, diagnose, and treat' paradigm. He also expressed encouragement at seeing prescriptions from psychiatrists and PCPs, which reflects different patient journeys.

Anupam Rama of JPMorgan Chase & Co. asked for clarification on OJEMDA's channel inventory levels in Q3 2024 and how investors should think about them going forward.

Answer

Chief Operating and Financial Officer Charles York explained that while the company disclosed stocking inventory in Q2, going forward it will guide to a standard 2-4 weeks of channel stock and will not provide a specific dollar value unless it deviates materially from that range.

Anupam Rama inquired about the logistical timeline for GSK's opt-in decision for IDE397 after the data package delivery and whether IDEAYA will announce the package submission or only the final decision.

Answer

Yujiro Hata, CEO & President, explained that while the specific review period is not disclosed, close communication with GSK and early data room population are expected to facilitate an efficient decision. He indicated that IDEAYA hopes the package delivery and GSK's decision will occur in close proximity, suggesting a single announcement of the decision is likely.

Anupam Rama posed a broad strategic question, asking why Solid Biosciences is choosing to advance both SGT-001 and SGT-003 in parallel, rather than prioritizing one program to potentially extend its cash runway further.

Answer

CEO Ilan Ganot responded that the company believes SGT-001 has generated strong data that warrants continued development. Simultaneously, the preclinical data for SGT-003 is so promising that it represents a potentially significant scientific advancement for muscle diseases. He concluded that at this stage, the company is confident that both programs deserve to be advanced and have their 'day in the sun.'

Anupam Rama from JPMorgan Chase & Co. asked for clarification on whether the details of the serious adverse event and clinical profile for Patient 8 had been shared with the FDA and the Data Safety Monitoring Board (DSMB), and inquired about the expected timelines for feedback from these groups.

Answer

President and CEO Ilan Ganot confirmed that all information regarding the patient's SAE had been shared with both the FDA and the DSMB. He stated that dialogues with both bodies are ongoing but that the company could not project specific timelines for formal feedback.

Anupam Rama of JPMorgan Chase & Co. asked for a mechanistic explanation of why the ORIC-101 thesis failed, particularly given previously reported positive signals from Corcept Therapeutics in ovarian cancer and ORIC's own prior data showing stable disease in PDAC.

Answer

Chief Medical Officer Pratik Multani explained that ORIC's trial population was different and more refractory than Corcept's, requiring prior progression on a taxane-based therapy and having more prior lines of treatment (4 vs. 2.5). He also noted ORIC's regimen was designed to avoid prophylactic GCSF support. CEO Jacob Chacko added that this high bar was set deliberately in a late-line population to get a clear efficacy signal quickly for the single-arm combination study.

Anupam Rama of JPMorgan Chase & Co. questioned the specific learnings expected from the EOS-448 and pembrolizumab combination trial that would inform the subsequent study with dostarlimab.

Answer

CMO Joe Lager explained that the pembrolizumab combination study, which was planned prior to the GSK partnership, could be initiated sooner, allowing its data to help optimize dose selection and potentially accelerate the development timeline for the dostarlimab combination. He added that understanding the drug's performance with different PD-1 partners is also valuable.

Anupam Rama of JPMorgan Chase & Co. questioned the strategic rationale for studying EOS-448 in combination with pembrolizumab when a combination trial with GSK's dostarlimab is also planned.

Answer

President and CEO Michel Detheux and Chief Medical Officer Joe Lager clarified that the pembrolizumab combination study is intended to accelerate the program and generate data more quickly while the dostarlimab combination studies are being initiated.

Anupam Rama of JPMorgan Chase & Co. noted a comment in the corporate deck about a new formulation for the A2A program (EOS-850) entering Phase 1 and asked for additional details.

Answer

Chief Medical Officer Dr. Joe Lager confirmed the development of a new salt formulation for inupadenant, which is expected to improve properties such as dissolution at high pH. He stated that a clinical trial for this new formulation is anticipated to begin within the next couple of months.

Anupam Rama from JPMorgan Chase & Co. requested clarification on the 2021 data release strategy for the PTG-300 Phase 2 trial and asked about the drug's potential positioning within the polycythemia vera (PV) treatment paradigm.

Answer

CEO Dinesh Patel and Chief Medical Officer Samuel Saks confirmed that data updates for PTG-300 would be presented at medical conferences throughout the year, not just at ASH. Regarding market positioning, Saks explained that the drug is intended for patients who require frequent phlebotomies despite other treatments, as this indicates poor hematocrit control and leads to iron deficiency. Patel added that their market data shows a majority of PV patients fall into this category where current therapies are ineffective.

Anupam Rama of JPMorgan Chase & Co. inquired about the number of clinical sites and enrollment pace for the Pompe program, and whether initial biomarker data could be expected in 2020 for both the Pompe and DMD programs.

Answer

CEO Matt Patterson stated that while the exact number of sites for the Pompe program is not finalized, site reception has been strong and a screening study is underway to accelerate enrollment. He confirmed the company anticipates initial proof-of-concept data, including safety and biopsy information, for the Pompe program in the second half of 2020. He added that it is also a reasonable assumption that preliminary proof-of-concept data for the DMD program could be available in 2020.

Anupam Rama of JPMorgan Chase & Co. inquired about the identification status of the eight patients for the pivotal ASPIRO cohort and asked what additional analyses would be presented at the upcoming World Muscle Society update.

Answer

Chairman and CEO Matt Patterson confirmed that the eight patients for the pivotal cohort have been identified from the ongoing INCEPTUS natural history study. Regarding the World Muscle Society update, he stated that while it will be a meaningful update, it may not be as extensive as the data presented at ASGCT.

Anupam Rama from JPMorgan Chase & Co. inquired about the primary reasons and strategic thinking behind the decision to out-license the Crigler-Najjar program.

Answer

Matt Patterson, Chairman and CEO, explained that the decision was driven by a strategic focus on neuromuscular diseases, where Audentes has developed significant expertise in clinical execution, regulatory affairs, and high-quantity manufacturing. While still believing in the potential of the Crigler-Najjar program, the company aims to concentrate its resources to maximize patient impact and shareholder value within its core strength. Audentes will seek a partner to advance the program and recover its investment.

Anupam Rama from JPMorgan Chase & Co. asked about the final preclinical gating factors for the Pompe program's IND filing and the expected scope of the Q2 update for the Crigler-Najjar Syndrome program.

Answer

President and CEO Matthew Patterson outlined that the final steps for the Pompe program include completing mouse model analysis, large-scale manufacturing of AT845, and a 12-week non-human primate toxicology study, targeting a Q3 IND filing. For Crigler-Najjar, he acknowledged enrollment delays and stated the Q2 update would be as comprehensive as possible at that time.