Company Overview - Rein Therapeutics is a clinical-stage biopharmaceutical company focused on developing first-in-class therapies for orphan pulmonary and fibrosis indications [3] - The lead product candidate, LTI-03, is a synthetic peptide targeting alveolar epithelial cell survival and inhibiting profibrotic signaling, currently in clinical development [3] - The second product candidate, LTI-01, has completed Phase 1b and Phase 2a trials for loculated pleural effusions and has received Orphan Drug Designation in both the U.S. and E.U. [3] Upcoming Events - Chief Scientific Officer Cory Hogaboam will present at the IPF Summit 2025 on August 19-21, 2025, discussing the role of immune cells and inflammation in idiopathic pulmonary fibrosis (IPF) [2] - CEO Brian Windsor will present on August 21, focusing on innovative clinical trial design and lessons learned from the LTI-03 trial [2] Research and Development Focus - The presentations will cover the modulation of lung-resident macrophages and the potential of Caveolin-scaffolding domain (CSD) peptides in targeting multiple drivers of fibrosis [5] - Rein's Phase 2 trial of LTI-03 aims to enroll up to 120 patients, assessing safety, tolerability, and lung function as key outcomes [5] - The company is strategizing around patient recruitment and trial design to ensure relevance in a rapidly evolving treatment landscape [5]

Financial Data and Key Metrics Changes - United Therapeutics reported record total revenue of $799 million, reflecting a 12% growth over 2024, marking the twelfth consecutive quarter of double-digit year-over-year revenue growth [12][10] - The Tyvaso DPI device achieved record total revenue of $315 million, representing a 22% growth over 2024, with record patient shipments for both Tyvaso DPI and the total Tyvaso franchise [12][13] Business Line Data and Key Metrics Changes - The Tyvaso franchise continues to perform strongly, with double-digit revenue growth for nebulized Tyvaso, Orenitram, and Unituxin [14] - Orenitram achieved record total revenue and patient shipments during the quarter, while Remodulin remains a top five product in total patient shipments [14] Market Data and Key Metrics Changes - The company noted strong underlying dynamics with record levels of referrals and starts for Tyvaso DPI during the quarter [14] - The competitive landscape includes a new treprostinil dry powder inhaler launched by Liquidia, prompting United Therapeutics to address misinformation regarding Tyvaso DPI's dosing and tolerability [15][16] Company Strategy and Development Direction - United Therapeutics is focused on sustaining growth in its foundational business while progressing its innovative small molecule pipeline and organ alternative technologies [11] - The company has authorized a share repurchase of up to $1 billion, reflecting confidence in its commercial business and upcoming catalysts [10][71] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the future of the business, anticipating sustained growth driven by the foundational business and upcoming clinical catalysts [11] - The company is optimistic about the potential of its TETON studies in idiopathic pulmonary fibrosis and advanced outcome studies in pulmonary arterial hypertension, with results expected to start reporting in September [8][30] Other Important Information - The company has launched a new pipeline website to provide detailed information about its pipeline candidates [9] - United Therapeutics is on track to conduct the first transplant in its EXPAND U kidney clinical study shortly [8] Q&A Session Summary Question: Comments on Utopia uptake in PH and ILD - Management indicated that the launch is proceeding as expected, with strong shipments and orders in June, and July looks promising [53] Question: Variability in FVC decline in IPF studies - Management has implemented central reading of SEC results and training at site levels to standardize measurements and reduce variability [62] Question: Reading across from IPF subgroup data - Treprostinil has multiple mechanisms of action that may benefit IPF patients, and management believes it can work on fibrosis, leading to efficacy in IPF [70] Question: Share repurchase authorization - The Board authorized a share repurchase due to the strength of the commercial business and confidence in upcoming catalysts, viewing the stock as an excellent investment opportunity [72] Question: Clinically meaningful FVC results from TETON trial - The study is powered to detect an 80 milliliter change in FVC, and management anticipates a clinically meaningful effect greater than this threshold [98] Question: Background therapy use in TETON studies - There is a higher background therapy use in TETON studies compared to previous studies, which may mute the efficacy of the investigational drug, but management remains optimistic [104]

Summary of GRI Bio Conference Call Company Overview - **Company**: GRI Bio - **Focus**: Clinical stage biotech company targeting inflammatory fibrotic and autoimmune diseases through regulation of invariant natural killer T (NKT) cells [2][5] Core Program - **Lead Program**: GRI o six two one (GRI621) - **Type**: Small molecule inhibitor of type one invariant NKT cells - **Indication**: Treatment of idiopathic pulmonary fibrosis (IPF) - **Current Stage**: Phase 2a study with top line data expected in Q3 2025 [6][17] Mechanism of Action - **NKT Cells**: Critical lymphocytes involved in chronic inflammation and fibrosis - Inhibition of NKT cells shown to be therapeutic across various preclinical models of fibrosis [8][9] - Increased NKT cell activity correlates with worsening fibrotic disease, suggesting potential as a biomarker [9][12] Clinical Trial Details - **Trial Design**: - 36 patients, randomized 2:1 (GRI621 vs. placebo) - Duration: 12 weeks, with patients allowed to continue background therapy [18][19] - Primary endpoints: Safety, tolerability, pharmacokinetics, biomarkers of fibrosis, and pulmonary function tests [19][25] - **Enrollment Status**: Approximately 80% enrolled [20] Interim Results - **Recent Findings**: Positive recommendation from the Independent Data Monitoring Committee (IDMC) for continued trial [24] - **Early Data**: Indication of antifibrotic signal observed in initial 12 patients after two weeks [24] Challenges in IPF Treatment - **Current Landscape**: - Existing treatments (nantenadib and profinidone) slow lung function decline but do not improve overall survival [32] - Significant side effects limit patient compliance [32] - **Focus on Upstream Targets**: GRI Bio aims to address earlier stages in the inflammatory cascade rather than late-stage targets like TGF beta [33][34] Market Potential - **Market Size**: IPF is an orphan indication; nantenadib generated approximately $4 billion in sales last year [38] - **Competitive Landscape**: Other drugs in development face challenges, including drug-drug interactions and tolerability issues [39][40] Future Considerations - **Regulatory Pathways**: Potential for expedited approval due to existing safety data from other indications [47] - **Pipeline Opportunities**: GRI Bio is developing additional programs, including GRI o eight zero three (GRI803) targeting systemic lupus erythematosus [49][50] Conclusion - GRI Bio is positioned to address significant unmet needs in the treatment of IPF through innovative targeting of NKT cells, with ongoing clinical trials and a robust pipeline of future therapies [52]

Summary of GRI Bio Conference Call Company Overview - **Company**: GRI Bio - **Focus**: Clinical stage biotech company targeting inflammatory fibrotic and autoimmune diseases through regulation of NKT cells [2][5] Lead Program - **Product**: GRI o six two one - **Type**: Type one invariant natural killer T cell antagonist - **Indication**: Treatment of idiopathic pulmonary fibrosis (IPF) - **Current Stage**: Phase 2a study with top line data expected in Q3 2025 [6][18] Mechanism of Action - **NKT Cells**: Critical lymphocytes involved in chronic inflammation and fibrosis - **Therapeutic Approach**: Inhibiting NKT cell activity to interrupt disease progression and restore immune homeostasis [5][8] - **Biomarker Potential**: Increased NKT cells correlate with worsening fibrotic disease, suggesting their role as a useful biomarker [9][39] Clinical Trial Details - **Trial Design**: - 36 patients, 2:1 randomization (24 on GRI o six two one, 12 on placebo) - Duration: 12 weeks, with primary endpoints focusing on safety and tolerability [16][18] - **Enrollment Status**: Approximately 80% enrolled, with interim data expected in Q2 2025 [18][22] Data and Results - **Interim Analysis**: Positive recommendation from the Independent Data Monitoring Committee (IDMC) after 12 patients completed two weeks [21] - **Early Signals**: Antifibrotic signal observed in pro-collagen type III (pro C3) after two weeks [21][26] Market Context - **Market Size**: IPF is an orphan indication; Nintanadib, one of the approved drugs, generated approximately $4 billion in sales last year [35] - **Challenges**: Current treatments slow disease progression but do not improve overall survival; significant side effects limit patient compliance [29][30] Competitive Landscape - **Current Treatments**: Nintanadib and Perfinetone are the two approved drugs, both with limitations in efficacy and tolerability [35][36] - **Future Positioning**: GRI o six two one aims to address the disease earlier in the inflammatory cascade compared to existing therapies [30][31] Regulatory Considerations - **Expedited Approval**: Potential for a single registration trial due to existing safety data from other indications [43][44] Pipeline Opportunities - **Future Programs**: GRI o eight zero three targeting type two NKT cells for systemic lupus erythematosus; additional 500 compounds in the library for future development [46][47] Conclusion - GRI Bio is positioned to potentially disrupt the IPF treatment landscape with GRI o six two one, focusing on early intervention in the inflammatory process and leveraging NKT cells as biomarkers for disease progression [5][39]