Summary of Scholar Rock Holding Conference Call Company Overview - **Company**: Scholar Rock Holding (NasdaqGS:SRRK) - **Event**: Jefferies London Healthcare Conference - **Date**: November 18, 2025 Key Points Industry and Product Focus - Scholar Rock is focused on developing therapies for spinal muscular atrophy (SMA) using their lead monoclonal antibody, ipilimumab, which targets myostatin [2][3] Regulatory Challenges - A positive Phase III study for ipilimumab led to a Biologics License Application (BLA) submission in January 2025, but a Complete Response Letter (CRL) was received on September 22, 2025, due to compliance issues at the GMP manufacturing facility [3][4] - The compliance issues were related to the Novo Catalent facility in Bloomington, Indiana, which received an Official Action Indicated (OAI) notice [4][10] - The FDA and Scholar Rock had a Type A meeting to discuss the path forward, with Novo presenting a robust remediation plan [4][10][12] Remediation and Inspection Timeline - Novo reported that approximately 90% of the remediation work has been completed, focusing on quality management systems [10][11][16] - The FDA is expected to communicate their impressions of the remediation progress soon, with a reinspection planned for early 2026 [12][21] - If the reinspection is successful, Scholar Rock anticipates resubmitting the BLA promptly, with hopes for approval in 2026 [13][30] Market Potential and Launch Strategy - There are over 11,000 SMA patients in the U.S., with two-thirds currently on SMN-targeted therapies [45] - Scholar Rock expects initial patients to be those already on SMN therapies, as ipilimumab is anticipated to be an add-on therapy [46][47] - The company plans to launch ipilimumab as the first monthly IV infusion for SMA, which may change the treatment paradigm [49] Pricing and Market Expansion - The market opportunity in SMA is significant, with Scholar Rock planning to price their product in the U.S. first before expanding to Europe, Japan, and South America [52][54] - The company is aware of the challenges in negotiating prices outside the U.S. but sees the necessity of entering these markets [53] Financial Position and Runway - Scholar Rock ended Q3 2025 with approximately $369.6 million in cash and raised an additional $91.7 million through an ATM and $50 million in loans [58] - The cash runway extends into 2027, assuming no revenue from ipilimumab and not accounting for potential monetization of a Priority Review Voucher (PRV) [58][59] Future Developments - Scholar Rock is working on a NextGen product targeting myostatin, with Phase I data expected next year [55] - There is significant interest in their anti-mystatin portfolio from companies in the obesity space, indicating potential for future collaborations [57] Additional Insights - The meeting highlighted the urgency and collaborative nature of the discussions with the FDA, emphasizing the importance of addressing the unmet need in SMA [23][25] - The company is committed to maintaining a high-quality manufacturing process and is optimistic about overcoming current challenges [18][19]

Core Insights - The NEO-CYT trial is a randomized, multi-centre study evaluating MDNA11 as a neoadjuvant immunotherapy for early-stage melanoma patients, sponsored by Fondazione Melanoma Onlus and led by Professor Paolo A. Ascierto [1][2] - MDNA11 is believed to significantly reduce the risk of cancer recurrence post-surgery, based on positive results from the ABILITY-1 study [1][2] - The trial will assess MDNA11 in combination with nivolumab and possibly ipilimumab, focusing on Major Pathologic Response (MPR) as a primary endpoint, which is indicative of long-term survival [1][2] Company Overview - Medicenna Therapeutics is a clinical-stage immunotherapy company developing Superkines for cancer treatment, with MDNA11 being a long-acting IL-2 Superkine designed to activate immune effector cells while minimizing immunosuppressive effects [6][8] - The company has a cash runway expected to last until at least mid-2026, ensuring continued operations and development of its clinical programs [1] Clinical Development - The NEO-CYT trial aims to provide early, actionable data on the efficacy of MDNA11 in enhancing standard cancer immunotherapy, potentially expanding its market to include high-risk melanoma patients [2][5] - The trial is positioned to evaluate the combination of MDNA11 with established checkpoint inhibitors, which may improve pathologic responses and curative benefits post-surgery [2][5] Research and Collaboration - The Fondazione Melanoma Onlus, a non-profit organization, is sponsoring the NEO-CYT trial, emphasizing the collaborative effort in advancing melanoma research and treatment [7] - The trial is expected to generate significant clinical data that could redefine the role of IL-2 in early-stage melanoma treatment [2][3]

Delcath Systems (NasdaqCM:DCTH) Update Summary Company Overview - **Company**: Delcath Systems - **Industry**: Oncology, specifically focusing on treatments for metastatic uveal melanoma Key Points from the Call Chopin Trial Results - The Chopin trial involved 76 patients randomized to receive either percutaneous hepatic perfusion (PHP) alone or a combination of PHP with ipilimumab and nivolumab [6][8] - **Primary Endpoint**: One-year progression-free survival (PFS) was 54.7% in the combination group versus 15.8% in the PHP group [9] - **Overall Survival**: The combination therapy showed a median overall survival of 23.1 months compared to 19.6 months for PHP alone [9] - **Response Rates**: Best overall response rates were 76.3% for the combination group versus 39.5% for PHP alone [9] - **Adverse Events**: Grade 3 or higher treatment-related adverse events were more frequent in the combination group (81.6% vs. 40.5%) but were manageable [9][18] Implications for Clinical Practice - The results are considered practice-changing, suggesting that the combination of ipilimumab and PHP should be offered to eligible patients [21] - There is a need for further studies to understand the immune versus cytotoxic mechanisms behind the observed efficacy [20] - The combination therapy may be particularly beneficial for patients with both hepatic and extrahepatic disease [21] Financial Results and Guidance - **Q3 2025 Preliminary Results**: Revenue of $20.5 million, gross margins of 87%, net income of $0.8 million, and positive adjusted EBITDA of $5.3 million [32] - **Cash Position**: As of September 30, 2025, the company reported $88.9 million in cash and equivalents [33] - **Revenue Guidance**: The company lowered its revenue guidance for 2025 to $83 million to $85 million due to a slowdown in new patient starts and the impact of 340B discounts [35] - **Treatment Volume Projection**: Total HEPZATO KIT treatment volume is projected to increase by approximately 150% compared to 2024 [36] Market Dynamics - There was a noted decrease in new patient starts per site, attributed to seasonality and scheduling issues [34][50] - The company is optimistic that the Chopin trial data will encourage quicker adoption of combination therapies among oncologists [39][41] - Interest from major cancer centers remains strong, with expectations to have 40 operational centers by the end of next year [33] Additional Insights - The combination therapy's efficacy may lead to a shift in treatment paradigms for other cancers with liver metastases [27][29] - The company is focused on training additional healthcare professionals to administer HEPZATO KIT to mitigate scheduling conflicts [34] - The feedback from oncologists indicates that HEPZATO KIT addresses a significant unmet need in the treatment landscape [35] Conclusion Delcath Systems is positioned to leverage the positive results from the Chopin trial to enhance its market presence and treatment adoption for metastatic uveal melanoma. The financial outlook reflects challenges but also opportunities for growth as the company navigates the complexities of patient recruitment and treatment administration.

Core Insights - The interim data from the Phase 1b/2 clinical trial of ciforadenant in combination with ipilimumab and nivolumab shows feasibility and tolerability as a potential first-line therapy for metastatic renal cell cancer (RCC) [1][4][5] Group 1: Trial Overview - The trial enrolled 50 patients with newly diagnosed or recurrent stage IV clear cell RCC, with 8 in Phase 1b and 42 in Phase 2 [2][3] - Patients received ciforadenant 100 mg orally twice daily, ipilimumab 1 mg/kg every three weeks for twelve weeks, and nivolumab 3 mg/kg every three weeks [2] Group 2: Key Findings - The deep response rate was 34%, which is an improvement compared to historical data for the combination of ipilimumab and nivolumab alone [4] - The overall response rate (ORR) was 46%, including two complete responses and 21 partial responses [4] - The median progression-free survival (PFS) was reported at 11.04 months [4] Group 3: Patient Characteristics - The median age of patients in the trial was 61.5 years, with only 54% having undergone prior nephrectomy, indicating more unfavorable disease characteristics [4] - 82% of patients had a poor or intermediate prognosis according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria [4] Group 4: Future Directions - The company plans to continue following the 19 patients who remain on therapy to better understand the potential benefits of this treatment approach [2][5]

Summary of Arcus Biosciences FY Conference Call (September 10, 2025) Company Overview - **Company**: Arcus Biosciences (NYSE: RCUS) - **Industry**: Biotechnology, specifically focused on oncology Strategic Priorities - **Execution of Phase III Programs**: The primary focus is on the global Phase III program for casdatifan, a HIF2 inhibitor, with two studies targeting earlier line settings in renal cell carcinoma (RCC) [2][3] - **Funding and Partnerships**: The company has received significant funding from partners like Gilead Sciences, AstraZeneca, and Taiho Pharmaceutical, allowing them to operationalize only two of five Phase III studies [2] - **Capital Preservation**: The company has over $900 million in cash and is focused on conserving capital by pausing less strategic initiatives [8] Pipeline Highlights - **Casdatifan**: - Targeting RCC with a market opportunity of approximately $5 billion in G7 countries [4] - Data from 90 patients showed clear differentiation from Merck's belzutifan on efficacy measures [3] - Upcoming data presentation on 120 patients expected to provide more follow-up information [4][12] - **Domvanalimab**: - An Fc-silent anti-TIGIT antibody being evaluated in combination with anti-PD-1 and chemotherapy in first-line gastric cancer [5] - Expected readout in 2026 from a 1,000-patient study [5] - **Quemliclustat**: - A small molecule CD73 inhibitor in combination with chemotherapy for first-line pancreatic cancer, with a 600-patient study expected to provide data soon [5] Competitive Landscape - **FDA Interactions**: The company reports steady communication with the FDA, with no significant impact from recent changes in agency policies [10] - **Benchmarking Against Belzutifan**: - Casdatifan has shown a confirmed overall response rate (ORR) of 33%, significantly higher than belzutifan's 18%-22% [14] - Progression-free survival (PFS) for casdatifan was reported at 9.7 months, compared to belzutifan's 5.6 months [15][16] Market Opportunities - **Gastric Cancer**: The market opportunity for TAP greater than 5 is estimated at $3 billion in G7 countries [70] - **Lung Cancer**: The lung cancer market is projected to exceed $10 billion, with potential for multiple players [77] Collaboration and Partnerships - **Collaboration with AstraZeneca**: AstraZeneca is operationalizing the Evolve study, which is capital-efficient for Arcus, allowing them to retain all economic rights [48] Intellectual Property - **IP Duration**: Casdatifan has a patent life extending to 2041, providing a long-term competitive advantage [51] Conclusion - Arcus Biosciences is strategically positioned with a robust pipeline and significant market opportunities in oncology, particularly with casdatifan and its combination therapies. The company is focused on execution, capital preservation, and leveraging partnerships to enhance its operational efficiency and market presence.

Financial Data and Key Metrics Changes - In Q1 2025, total revenues reached $3.03 billion with non-GAAP diluted earnings per share at $8.22, reflecting strong financial performance [40]. Business Line Data and Key Metrics Changes - DUPIXENT's net product sales grew 20% globally on a constant currency basis compared to Q1 2024, with a 19% increase in the US, indicating strong demand across all approved indications [40][41]. - EYLEA faced challenges due to new competition, but enhancements are expected to strengthen its market position [41]. - Libtayo grew 21% in the US compared to the previous year, establishing itself as a cornerstone therapy in oncology [42]. Market Data and Key Metrics Changes - The branded anti-VEGF category contracted in Q1 2025, presenting challenges for EYLEA, while Libtayo is gaining market share in advanced non-small cell lung cancer [41][42]. Company Strategy and Development Direction - The company focuses on scientific innovation, investing over 30% of revenues into R&D, which is significantly above the industry average [31]. - Regeneron aims to expand its manufacturing capacity with a $3 billion investment in North Carolina and a $3.6 billion expansion in New York [48][49]. Management's Comments on Operating Environment and Future Outlook - The management acknowledges headwinds in the industry but emphasizes resilience and the importance of advocacy for fair pricing and patient access [33][34]. - The company is optimistic about its pipeline, with approximately 45 candidates in development, and believes in the potential of its existing products to drive future growth [39][43]. Other Important Information - Regeneron has secured regulatory approval for 14 homegrown medicines and has built a robust clinical pipeline [39]. - The company emphasizes the importance of protecting innovations through patents and ensuring that developed nations contribute fairly to the costs of innovative treatments [36][37]. Q&A Session Summary Question: What will happen with the drug last week that failed to meet its primary endpoint in the study? Will you conduct a new drug trial? - The drug candidate ipilimumab showed promising data initially, but efficacy waned during the trial. The company is analyzing the data and considering future steps based on findings [54][56][58]. - The management remains optimistic about the therapeutic candidate's potential and is in discussions with regulators regarding the next steps [59].

Financial Data and Key Metrics Changes - The company is preparing for the PDUFA date of September 22 for apategromab in SMA, indicating a significant milestone in its financial outlook [11] - The management has emphasized a strong cash position, with a runway extending into early 2027, allowing for strategic investments without immediate equity issuance [42][44] Business Line Data and Key Metrics Changes - The company has seen robust clinical development for ipilimumab in SMA, with a Phase III SAFIRE trial enrolling 188 patients, demonstrating clinically meaningful benefits [12][13] - The obesity program is set to share Phase II data from the EMBRAZE trial, focusing on the preservation of lean mass in patients receiving tirzepatide [28][29] Market Data and Key Metrics Changes - The company is under review with the FDA and the European Medicines Agency, with plans for a substantial launch in the U.S. and thoughtful expansion into Europe and Asia Pacific [25][26] - There are approximately 35,000 patients worldwide who have received at least one SMN targeted therapy, highlighting a significant market opportunity for the company's products [26][40] Company Strategy and Development Direction - The company aims to scale its growth into global commercialization, focusing on the approval of ipilimumab in multiple countries [3][25] - The strategy includes leveraging existing assets while exploring new indications for ipilimumab and SRK-439 in rare neuromuscular disorders [9][38] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of ipilimumab to reverse the trend of motor function loss in SMA patients, positioning it as a new standard of care [15][19] - The company is committed to making a meaningful difference for patients and ensuring that no patient is left behind in accessing their therapies [27][44] Other Important Information - The company is considering the implications of pricing strategies based on the rarity and severity of diseases like SMA, as well as the clinical benefits demonstrated [39][40] - The management is cautious about the investment in cardiometabolic and obesity indications, focusing instead on rare severe neuromuscular disorders [33][44] Q&A Session Summary Question: What are the expectations for the label regarding apategromab in SMA? - Management expects a broad label based on the robust data from the Phase III SAFIRE trial and the consistency of results across patient subgroups [12][13] Question: How does the drug fit into the existing treatment paradigm for SMA? - The company believes ipilimumab can provide significant benefits beyond existing SMN targeted therapies, particularly for patients who have started to lose motor function again [14][15] Question: What is the company's strategy for the obesity program? - The company plans to present Phase II data from the EMBRAZE trial, focusing on the preservation of lean mass in patients receiving tirzepatide [28][29] Question: How does the company view the regulatory pathway for obesity treatments? - Management acknowledges the evolving view of the FDA and the need to demonstrate both weight loss and preservation of lean mass in future trials [32][33] Question: What is the current cash position and runway for the company? - The company has a strong cash position with a runway extending into early 2027, allowing for strategic investments without immediate equity issuance [42][44]

Financial Data and Key Metrics Changes - Scholar Rock reported a strong start to 2025, with significant progress in bringing up epitigromab for SMA patients globally [6][9] - The company ended the quarter with $364.4 million in cash, and has an additional $100 million available under its debt facility to support the upcoming launch [25][26] Business Line Data and Key Metrics Changes - The phase three SAPPHIRE trial for epitigromab showed a statistically significant improvement in motor function, indicating its potential to reverse SMA progression [7][13] - The company is preparing for a U.S. commercial launch of epitigromab anticipated in Q3 2025, with plans to expand into Europe, Asia Pacific, and Latin America [9][20] Market Data and Key Metrics Changes - Approximately 10,000 SMA patients in the U.S. and around 35,000 globally have received SMN-targeted therapies, highlighting the market potential for epitigromab [21][22] - Market research indicates that 90% of SMA patients are seeking new treatment options that improve muscle strength, emphasizing the demand for epitigromab [20] Company Strategy and Development Direction - Scholar Rock aims to establish itself as a fully integrated global biopharmaceutical company, focusing on the launch of epitigromab and expanding its pipeline into other neuromuscular disorders [9][28] - The company is also exploring the EMBRAZE study to understand its role in treating obesity, indicating a diversification of its research focus [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming U.S. launch and the potential for sustainable growth driven by epitigromab and its pipeline [9][28] - The management team is committed to ensuring that no patient with SMA is left behind, reflecting a strong patient-centric approach [29] Other Important Information - The BLA for epitigromab was granted priority review by the FDA, with a PDUFA date set for September 22, 2025 [8][15] - The company is actively engaging with U.S. payers and preparing for reimbursement discussions in Europe, indicating proactive market access strategies [30][35] Q&A Session Summary Question: How receptive are U.S. payers to coverage of combination therapy for SMA patients? - Management indicated that early discussions with U.S. payers have been positive, with a focus on the need for better therapeutic options for SMA patients [32][34] Question: Can you comment on interactions with the FDA regarding the upadacumab review? - Management reported that interactions with the FDA have been routine and constructive, with no issues anticipated for the September 22 PDUFA date [38][39] Question: What are the expectations for the EMBRAZE study data in June? - Management confirmed that the primary focus will be on the 24-week data, with additional follow-up information provided as necessary [42][43] Question: How are you evaluating the potential to secure a commercial partner for Europe? - Management stated that they do not prioritize finding a partner outside the U.S., as they feel well-equipped to serve patients directly [88][89] Question: What are the launch dynamics and early demand expectations for epitigromab? - Management expressed optimism about the launch, citing the 100% newborn screening for SMA in the U.S. and the concentration of patients in centers of excellence [69][70]

Financial Data and Key Metrics Changes - Scholar Rock reported a strong start to 2025, with significant progress in bringing up epitigromab for SMA patients globally [6][9] - The company ended the quarter with $364.4 million in cash, indicating a solid financial position to support upcoming initiatives [25] Business Line Data and Key Metrics Changes - The phase three SAPPHIRE trial for epitigromab showed statistically significant improvement in motor function, with patients treated having a threefold higher chance of a three-point or greater increase in Hammersmith Scale compared to placebo [7][13] - The company is preparing for a U.S. commercial launch of epitigromab anticipated in Q3 2025, with plans to expand into Europe, Asia Pacific, and Latin America [9][22] Market Data and Key Metrics Changes - Approximately 10,000 SMA patients in the U.S. and around 35,000 globally have received SMN-targeted therapies, highlighting the market potential for epitigromab [21] - The company is focusing on the dual modality treatment approach for SMA, combining SMN-targeted therapies with muscle-targeting therapies [20] Company Strategy and Development Direction - Scholar Rock aims to establish itself as a fully integrated global biopharmaceutical company, with a focus on SMA and potential expansion into other neuromuscular disorders [9][27] - The company is also exploring the EMBRAZE study to understand its role in treating obesity, indicating a diversification of its research focus [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming U.S. launch of epitigromab and the potential for sustainable growth through the end of the decade [9][27] - The company is committed to ensuring that no patient with SMA is left behind, emphasizing its responsibility to patients and families [28] Other Important Information - The BLA for epitigromab was granted priority review by the FDA, with a PDUFA date set for September 22, 2025 [8][15] - The company has an additional $100 million under its debt facility to support the upcoming launch, extending its financial runway into 2027 [25][26] Q&A Session Summary Question: How have discussions with U.S. payers gone regarding coverage for combination therapy? - Management indicated that early discussions with payers have been positive, with a focus on the need for better therapeutic options for SMA patients [31][34] Question: Can you provide an update on interactions with the FDA regarding the upadacumab review? - Management reported that interactions with the FDA have been routine and constructive, with no issues anticipated for the September 22 PDUFA date [36][37] Question: What are the expectations for the EMBRAZE study data in June? - Management confirmed that the primary focus will be on the 24-week data, with additional follow-up information provided as necessary [41][42] Question: How do you evaluate the potential to secure a commercial partner for Europe? - Management stated that they do not prioritize seeking a partner outside the U.S., feeling confident in their ability to serve patients directly [86] Question: What are the expectations for launch dynamics and early demand post-approval? - Management noted that while they will not provide specific guidance, they are optimistic due to the existing infrastructure and patient population [68][70]

Financial Data and Key Metrics Changes - The company ended the quarter with $364.4 million in cash [25] - The company has an additional $100 million under its debt facility that can be drawn down this year to support the upcoming launch, extending its anticipated runway into 2027 [26] Business Line Data and Key Metrics Changes - The company is focused on the commercial launch of epitigromab for SMA, with a PDUFA date set for September 22, 2025 [6][13] - The company is preparing for a global launch, starting in the US in Q3 2025, and is also evaluating expanding the study of upitigramab into other rare neuromuscular disorders [7][8] Market Data and Key Metrics Changes - Approximately 10,000 patients with SMA are in the US, with about two-thirds having received SMN-targeted therapies [20] - Globally, around 35,000 patients have received SMN-targeted therapies, indicating a significant market opportunity for epitigromab [20] Company Strategy and Development Direction - The company aims to establish itself as a fully integrated global biopharmaceutical company, focusing on SMA and exploring additional indications for its therapies [7][14] - The company is committed to ensuring that any patient with SMA who can benefit from epitigromab has access to it, indicating a patient-centric approach [7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming launch and the potential of epitigromab to transform the treatment landscape for SMA [19] - The company is aware of the competitive landscape and the need for dual modalities to address both motor neuron and muscle degeneration in SMA patients [20] Other Important Information - The EMBRAZE proof of concept study is ongoing, focusing on the role of the company in treating obesity and preserving lean mass [9][10] - The company is on track to share top-line results from the EMBRAZE study in June 2025 [10] Q&A Session Summary Question: How have discussions with U.S. payers gone regarding coverage for combination therapy? - Management indicated that early discussions with payers have been positive, and they expect that the budget impact for any single payer will be limited due to the rarity of the disease [31][34] Question: Can you comment on interactions with the FDA regarding the upadacumab review? - Management reported that interactions with the FDA have been routine and constructive, with no issues anticipated for the September 22 PDUFA date [38] Question: What are the expectations for the EMBRAZE study data in June? - Management confirmed that they will provide the 24-week data as the main study outcome and will include any necessary follow-up information [43] Question: How quickly will the company be able to launch after the PDUFA date? - The company is prepared to launch the day after the PDUFA date, with ample supply to meet demand [60] Question: How is the company evaluating the potential to secure a commercial partner for Europe? - Management stated that they do not prioritize finding a partner outside the U.S. and feel well-equipped to serve patients directly [86]