Summary of Protara Therapeutics FY Conference Call Company Overview - **Company**: Protara Therapeutics (NasdaqGM:TARA) - **Date of Conference**: September 09, 2025 Key Industry and Company Insights Lymphatic Malformations - The largest data set on lymphatic malformations was generated by the University of Iowa, involving over 550 patients across 27 centers [1] - Protara is preparing a registration package for FDA submission, leveraging this data set and experience from Japan to seek accelerated approval [1] - TARA-002 is positioned as a treatment for BCG-unresponsive patients, with a focus on its unique mechanism of action compared to BCG [2][3] Mechanism of Action - TARA-002 acts as a TLR2/NOD2 activator, differing significantly from BCG, which is a TLR4 activator [2] - TARA-002 has demonstrated three-year stability at refrigerated temperatures and can be administered easily without special handling [2] - The drug upregulates key cytokines such as TNF-alpha, interferon-gamma, and IL-12, which are important for immune activation, while down-regulating IL-8, associated with recurrence [3][4] Clinical Trials and Data - Protara is currently enrolling patients in an Advanced II study for NMIBC (non-muscle invasive bladder cancer) and plans to publish interim data in February [4] - The company has reported a complete response rate of over 70% at six months and over 40% at twelve months in BCG-naive patients [6] - A significant portion of BCG-eligible patients (approximately 35%) do not receive BCG treatment, presenting an opportunity for TARA-002 [5] Safety and Efficacy - TARA-002 has shown no treatment-related grade 3 adverse events, with common side effects being mild and related to administration [7] - The administration process is straightforward, with efficacy comparable to other products in development [8] IV Choline Chloride Program - Protara is also developing IV Choline Chloride as a therapy for patients on parenteral support, addressing metabolic deficiencies [9][10] - The pivotal study aims to demonstrate elevated choline levels in serum as a primary endpoint, with interim data expected in mid-2026 [10][11] Market Potential and Future Directions - The incidence of lymphatic malformations is estimated at 1 in 2,000 to 1 in 4,000 live births, with a significant portion being macrocystic [15][16] - Protara aims to expand TARA-002's application to other maxillofacial cysts, potentially addressing a larger patient population [17] - The company holds $146 million in cash, sufficient to fund operations through 2027 and multiple catalysts in 2026 [18] Additional Important Points - Protara is actively engaging with the FDA regarding study designs for BCG alternative settings [5] - The company is focused on differentiating its product profile to drive adoption in a competitive market [7] - The ongoing studies and data collection are critical for establishing TARA-002's efficacy and safety in various patient populations [12][14]

Financial Data and Key Metrics Changes - The company is preparing to file its New Drug Application (NDA) for bitopertin in October, with a potential PDUFA date between June and October of the following year, marking a significant milestone for the company [4][5] - The company reported a P-value of less than 0.001 for the reduction in protoporphyrin-9 (PP9), indicating a clinically meaningful reduction in patients with erythropoietic protoporphyria [9][10] Business Line Data and Key Metrics Changes - The lead program, bitopertin, is in the accelerated approval pathway with the FDA, focusing on rare diseases related to red blood cell biology [4][5] - The second program is expected to present data on anemia of myelofibrosis and anemia of chronic kidney disease at upcoming conferences [5][6] Market Data and Key Metrics Changes - The company identified approximately 14,000 diagnosed patients in the U.S. for the target disease, with enrollment in trials not being a problem due to strong patient advocacy [18][23] - The company plans to leverage claims data to identify and validate physicians treating these patients, enhancing their market access strategy [23][24] Company Strategy and Development Direction - The company is focused on increasing disease awareness and ensuring that patients and physicians are informed about available therapies, as historically there have been no options for these patients [22][23] - The company aims to build a self-sustaining entity driven by revenues from bitopertin, with plans to explore additional indications within their iron modulation programs [60][61] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the regulatory pathway for bitopertin, citing positive interactions with the FDA regarding the use of PP9 as a surrogate endpoint [10][11] - The management highlighted the importance of continuous engagement with healthcare providers to ensure that patients receive appropriate care and treatment options [26][30] Other Important Information - The company has a strong financial position with $650 million on the balance sheet, which is expected to fund operations into 2028 [60] - The company has orphan protection for bitopertin, providing seven years of exclusivity in the U.S. plus potential pediatric extensions [36] Q&A Session Summary Question: Can you recap the interactions with the FDA regarding the accelerated approval path for bitopertin? - Management detailed a series of meetings with the FDA that led to the decision to pursue an accelerated approval pathway, emphasizing the strong rationale for using PP9 as a surrogate endpoint [10][11] Question: What are the key differences between the Apollo and Aurora trials? - Management explained that the Apollo trial will focus on measuring the time patients can spend in light, which is a clinically meaningful endpoint, alongside the reduction in PP9 levels [18][19] Question: How does the company plan to address the patient population for bitopertin? - Management discussed the importance of identifying engaged patients who regularly seek healthcare, estimating about 6,000 such patients, while also planning to reach out to the remaining diagnosed but less engaged patients [26][27] Question: What is the expected market opportunity for the company's anemia treatments? - Management indicated that there is a significant unmet need for anemia treatments in myelofibrosis, with an estimated market of about 22,000 patients, and potential pricing similar to existing therapies [42][44] Question: How does the company view its capital position and future financing needs? - Management expressed confidence in their capital position, indicating that they are well-funded to support ongoing trials and commercial preparations without immediate need for additional equity financing [60][61]

Regulatory & Clinical Strategy - Larimar Therapeutics expects to submit a BLA seeking accelerated approval for Nomlabofusp in Q2 2026[4, 5, 33, 34] - The BLA submission will include a safety database with at least 30 participants exposed for 6 months and a subset of at least 10 participants exposed for 1 year, with the majority on the 50 mg dose[4, 5, 34] - The FDA is open to using increases in skin FXN concentrations as a reasonably likely surrogate endpoint (RLSE) for accelerated approval, pending BLA review[5, 34] - A global Phase 3 study is intended as the confirmatory study, evaluating clinical outcomes including upright stability and mFARS, expected to be underway at the time of BLA submission[5] - The START Pilot Program continues to expedite the clinical and regulatory development of Nomlabofusp[29] Nomlabofusp & Friedreich's Ataxia (FA) - Nomlabofusp is a potential disease-modifying therapy designed to address the underlying FXN deficiency in FA[7, 34] - Friedreich's Ataxia affects approximately 20,000 patients globally, with about 5,000 in the U S[6] - Most FA patients produce only approximately 20-40% of normal frataxin (FXN) levels[6] - In the OLE study, Nomlabofusp 25 mg daily increased skin FXN levels to 72% of healthy volunteers at Day 90, compared to 16% at baseline[20, 19] - Larimar had $157.5 million in cash and investments as of March 31, 2025, with a projected cash runway into Q2 2026[35]

Del-brax Development and Regulatory Pathway - FDA has confirmed an accelerated approval pathway for delpacibart braxlosiran (del-brax) in the US [8] - The primary endpoint for accelerated approval is the reduction in the circulating biomarker cDUX [10, 59, 76] - A global confirmatory Phase 3 FORWARD trial has been initiated with 200 participants in a 1:1 randomized, double-blind, placebo-controlled design [10, 79] - The company anticipates topline data from the biomarker cohort of the FORTITUDE trial in Q2 2026 and a BLA submission in H2 2026 [10, 74] - The confirmatory Phase 3 FORWARD trial is designed to support full approval, with approximately 45 global sites [80, 83] FORTITUDE Trial Data - 12-month topline data from the FORTITUDE trial showed improved functional mobility in del-brax treated participants compared to placebo, as measured by 10MWRT and TUG [35, 39, 57] - Participants treated with del-brax also demonstrated improved muscle strength measured by QMT and improved upper limb function measured by RWS compared to placebo [42, 44, 57] - Del-brax showed a favorable long-term safety and tolerability profile in the FORTITUDE trial and its open-label extension (OLE) [10, 19, 57] - Over 60% of patients express that slowing or stopping the loss of muscle function would be the most meaningful outcome [30] cDUX Biomarker - cDUX is elevated 6- to 9-fold in people living with FSHD compared to healthy volunteers [59] - Del-brax treatment resulted in rapid and statistically significant reductions in cDUX and creatine kinase (CK) levels [59, 64]

Summary of the Conference Call for Disc Medicine (IRON) Company Overview - **Company**: Disc Medicine (Ticker: IRON) - **Event**: 2025 Jefferies Global Healthcare Conference - **Date**: June 05, 2025 Key Points Discussed Industry and Regulatory Environment - **FDA Interactions**: Positive and consistent interactions with the FDA regarding the NDA submission for Erythropoietic Protoporphyria (EPP) treatment, with alignment on using Protoporphyrin IX (PP9) as a surrogate endpoint for accelerated approval [4][11] - **NDA Timeline**: Projected NDA filing in the second half of 2025, with a pre-NDA meeting scheduled without issues [8][12] Market Opportunity for EPP Treatment - **Patient Population**: Estimated 20,000 patients in the U.S. with EPP, with 14,000 patients seeking treatment based on claims data [16][17] - **Engagement with Healthcare**: Approximately 6,000 patients show a higher degree of engagement with the medical system, indicating a target population for the launch [18] - **Commercial Strategy**: Plans to utilize advocacy groups and marketing strategies to activate the full patient opportunity [18][19] Launch Trajectory and Market Dynamics - **Launch Expectations**: Anticipated launch curve similar to other successful rare disease therapies, with high patient engagement and awareness [21] - **Disease Modifying Therapy**: The treatment is positioned as a disease-modifying therapy, addressing the underlying cause of EPP rather than just symptoms [23][24] Clinical Data and Efficacy - **PP9 Reduction**: Significant reduction in PP9 levels is expected to be a key indicator of treatment efficacy, with a robust response anticipated from KOLs [24][28] - **Phototoxic Reactions**: Previous trials showed a 75% reduction in phototoxic reactions at the highest dose, which would be impactful if replicated in larger trials [28][29] Competitive Landscape - **Other Treatments**: Awareness of competitors like Dursomelagon and other early-stage assets targeting EPP, but limited activity in the space [31][32] - **Anemia Program (974)**: Focus on anemia associated with chronic inflammation, particularly in myelofibrosis (MF) and chronic kidney disease (CKD) [35][36] Upcoming Data and Regulatory Path - **Data Readouts**: Anticipated data from EHA and ASH conferences, with a focus on long-term efficacy and safety [42][45] - **Regulatory Path for Anemia**: Clearer regulatory path established with the FDA for different patient groups in myelofibrosis, including non-transfusion dependent and lightly transfused patients [67][72] Patient Stratification and Efficacy - **Identifying Responders**: Potential to identify high responders based on baseline ferritin and EPO levels, which may guide treatment decisions [82][84] Additional Insights - **Market Dynamics**: The treatment landscape for anemia in myelofibrosis is evolving, with a focus on addressing unmet needs in patient care [39][60] - **Long-term Vision**: The company aims to position its therapies as first-line treatments for anemia in myelofibrosis, differentiating from competitors that target more niche populations [64][66] This summary encapsulates the critical discussions and insights from the conference call, highlighting the company's strategic direction, market opportunities, and clinical developments.