Summary of Jasper Therapeutics (JSPR) Update / Briefing July 07, 2025 Company Overview - **Company**: Jasper Therapeutics (JSPR) - **Focus**: Development of therapies for chronic spontaneous urticaria (CSU) using the drug vaprolimab Key Points Industry and Company Context - The conference call was focused on updated data from the BEACON trial and initial data from the open label extension study evaluating vaprolimab in patients with CSU [4][20] Core Findings from the BEACON Trial - **Efficacy**: - A greater than 25 drop in UAS7 (Urticaria Activity Score over 7 days) was observed in the 240 mg and 360 mg single dose cohorts, with 78% complete response and 89% well-controlled disease by week four [4][21] - In the open label extension study, 73% of patients achieved complete response and 82% well-controlled disease at the 12-week assessment with a mean reduction in UAS7 scores of greater than 25 points [17][22] - **Safety Profile**: - Vaprolimab demonstrated a favorable safety profile with no dose-limiting toxicities reported. Treatment emergent adverse events were similar in both active and placebo groups [13][22] - Mild transient adverse events were observed, including taste changes and neutrophil count reductions, but these were self-resolving and did not lead to discontinuations [14][15] Issues Identified - **Confounding Results**: - Two cohorts (240 mg Q8 weeks and 240 mg followed by 180 mg Q8 weeks) showed confounded results due to an issue with a specific drug product lot (lot A34954), which resulted in lower than expected drops in mean tryptase levels and no discernible effect on UAS7 in 10 out of 10 patients dosed with this lot [5][12] - An investigation into the affected lot is ongoing, with results expected in the coming weeks [6][20] - **Next Steps**: - Additional 10 to 12 patients will be enrolled in the affected cohorts to ensure a robust data set for the Phase IIb CSU study expected to commence mid-2026 [6][20] Financial and Operational Insights - **Cash Runway**: - Current guidance into the fourth quarter remains unchanged, but the company is evaluating its cost structure and may need to raise additional capital to extend its runway [54] - **Regulatory Communication**: - The company is in communication with the FDA regarding the lot issue, but there are no safety concerns associated with the affected lot [48][41] Additional Observations - **Durability of Responses**: - The data suggests that the depth of triptase reduction correlates with the depth of UAS7 reductions, indicating a potential for durable effects with the 180 mg dosing regimen [55] - **Patient Management**: - Patients who received the inactive dose from the compromised lot will be transitioned to a new drug product that has demonstrated efficacy in other cohorts [20][48] Conclusion - Jasper Therapeutics is optimistic about the potential of vaprolimab as a differentiated therapeutic option for CSU, despite the setback from the compromised drug lot. The company is taking proactive steps to address the issue and continue its clinical development program.

COVID-19 Related Opportunities - OraSure has multiple near-term COVID-19 opportunities, including two oral fluid self-collection devices for molecular testing that have received EUAs and CE-IVD marks[3] - The company is pursuing EUA for a lab-based oral fluid antibody test and developing a rapid antigen self-test[3] - OraSure is expanding manufacturing capacity to meet anticipated demand for COVID-19 tests, aiming to reach 55 million total tests per year by Q1 2021 and 70 million total tests per year by Q3 2021[28] - The company aims to increase total capacity for all molecular collection kits to 75 million units per year by Q2 2021 and 80 million kits per year by Q3 2021[29] - OraSure is also expanding capacity for Sars-Cov-2 Oral Fluid Antibody Tests from 10 million units per year to 20 million tests per year by Q4 2021[29] HIV Self-Testing - 21% of the 38 million people with HIV do not know their status, highlighting the need for accessible testing[32] - OraSure is the international HIV self-test market share leader with oral fluid self-collection and in-home results[33] - The Plan for America continues with $267 million in FY 2020 funding and a meaningful increase proposed for FY 2021 to end the HIV epidemic[35] Other Growth Drivers - Market leading microbiome products and services offer tremendous growth potential[3] - The company has $263.7 million in cash on the balance sheet with no debt, supporting ongoing business development activities[3] - Multiple research reports project mid-teens growth for the microbiome market from 2019-2024[39]

Summary of CalVista Pharmaceuticals FDA Approval Call Company and Industry - **Company**: CalVista Pharmaceuticals (KALV) - **Industry**: Hereditary Angioedema (HAE) Treatment Core Points and Arguments 1. **FDA Approval Announcement**: CalVista announced the FDA approval of sebitralstat, now branded as ECTRLY, as the first and only oral on-demand treatment for hereditary angioedema (HAE) attacks in patients aged 12 and older [3][6][39] 2. **Significance of Approval**: This approval marks a major milestone for both CalVista and the HAE community, being the first new on-demand therapy in over a decade [6][39] 3. **Treatment Landscape**: HAE is a rare genetic condition affecting approximately 8,000 people in the U.S. The current treatment landscape has been dominated by injectable therapies, which present barriers to timely treatment [9][10][13][14] 4. **Efficacy and Safety Profile**: ECTRLY is designed to be taken at the earliest recognition of an HAE attack, with a recommended dose of 600 mg. It has shown a rapid response time and a favorable safety profile, with headaches being the only notable adverse reaction [17][22][23] 5. **Market Opportunity**: The on-demand segment of the HAE market is expected to grow by 70%, reaching $1.2 billion by 2030, largely driven by the introduction of ECTRLY [39][40] 6. **Commercial Strategy**: CalVista plans to drive demand through a well-prepared sales force, patient education programs, and partnerships with healthcare professionals. The company has already engaged with key prescribers and plans to leverage patient summits for awareness [30][31][37][88] 7. **Patient Access Programs**: The Quick Start program allows patients immediate access to ECTRLY at no charge while their claims are processed, ensuring that they can treat attacks promptly [34][36] 8. **Global Expansion Plans**: Following U.S. approval, CalVista is preparing for global expansion, with plans to launch in Germany and Japan in 2026 [40] Important but Possibly Overlooked Content 1. **Patient Compliance**: The approval of ECTRLY is expected to improve patient compliance with treatment guidelines, as it overcomes barriers associated with injectable therapies [15][16] 2. **Real-World Data**: In the ongoing CONFIDENCE trial, a median time to treatment of 10 minutes and a median time to end of attack progression of 19.8 minutes were reported, indicating a rapid response to treatment [25][26] 3. **Physician Engagement**: The company has been actively engaging with physicians since February, ensuring a high level of awareness and readiness for the launch [84][85] 4. **Patient Satisfaction**: Early feedback from patients in the CONFIDENCE trial indicates high satisfaction levels with ECTRLY, which will be further analyzed and reported in future updates [90][91] This summary encapsulates the key points discussed during the call, highlighting the significance of ECTRLY's approval and the strategic plans for its commercialization and market penetration.

Investment Highlights - OraSure Technologies (OTI) is positioned to return to growth in its core business in 2025[5] - OTI has a differentiated product pipeline aligned with long-term healthcare trends, with potential product milestones expected to accelerate growth in 2025 and beyond[5] - OTI has an opportunity for significant operating margin leverage as volumes grow[5] - As of Q3 2024, OTI has $279 million of cash and no debt[5, 37] Strategic Transformation - OTI is focused on strengthening its foundation, elevating core growth, and accelerating profitable growth[7, 42] - OTI aims to improve access, quality, and value of healthcare with innovation in effortless tests and sample management solutions[9] - OTI is expanding its diagnostics portfolio with new tests and next-generation platform expansion, prioritizing instrument-free tests[12, 13] - OTI's acquisition of Sherlock Biosciences strengthens and broadens its diagnostic portfolio with molecular testing capabilities[19] - OTI anticipates submitting Sherlock's disposable self-test for CT/NG to the FDA by the end of 2025, targeting a $1.5 billion and growing market[22] Financial Performance - OTI is targeting a path to 50% adjusted gross margin[40] - The company's non-GAAP gross margin was 40% in FY23 and an estimated 40% in FY24[38] - Core revenue was $143 million in FY23 and an estimated $138 million in FY24, while COVID-19 revenue was $115 million in FY23 and an estimated $45 million in FY24[38]

Financial Highlights - Eledon had $1402 million in cash, cash equivalents, and short-term investments as of December 31, 2024[6] - The company forecasts sufficient funds to support operations through the end of 2026[6] Tegoprubart Clinical Development - The Phase 2 BESTOW trial of tegoprubart in kidney transplantation has completed enrollment, with top-line data expected in 4Q 2025[8] - Interim data update from the investigator-sponsored Phase 2 trial in islet cell transplantation for Type 1 diabetes is expected in Q4 2025[8] - A Phase 1b kidney transplant trial is ongoing, with an interim data update expected in mid-2025[8] Kidney Transplantation Market - The U S Medicare expenditure for end-stage renal disease and transplant is $50+ billion annually, including kidney transplantation costs of $440,000+ per transplant[23] - The global organ transplant immunosuppressant market size is estimated at $53+ billion[23] - Approximately 60% of organ transplants in the U S are kidney transplants[15] - Over 30-50% of kidney transplants fail within 10 years on the current standard of care immunosuppression[25] Islet Cell Transplantation - Approximately 2 million Americans live with Type 1 diabetes (T1D)[58] - Around 12% of people with T1D experience recurrent severe hypoglycemic events annually[58]

Transaction Overview - CoreWeave will acquire Core Scientific in an all-stock transaction at a fixed exchange ratio of 0.1235 CoreWeave share per Core Scientific share[9] - The acquisition is expected to result in CoreWeave owning less than 10% of the combined entity at close[9] - The deal is expected to close in Q4 2025, subject to regulatory approval and customary closing conditions[9] Financial Impact and Synergies - The acquisition is projected to immediately eliminate over $10 billion in future lease overhead for existing contractual sites[9] - CoreWeave anticipates over $500 million in fully ramped, annual run rate cost savings by the end of 2027 through streamlined operations[9, 22] - The transaction is expected to be leverage neutral, while providing access to diverse financing sources at a more attractive cost of capital[9] Assets and Capacity - Core Scientific's assets include over $760 million in fixed assets and right-of-use assets, and over $770 million of cash and liquid digital assets[10] - Core Scientific has a current portfolio of 1.3GW of power capacity with over 1GW of potential expansion gross power available[10] - Core Scientific has approximately 500MW of mining data center gross power capacity, which can be optionally converted to HPC[11] Strategic Benefits - The acquisition will give CoreWeave direct control over approximately 1.3GW+ of gross power, with the majority already under CoreWeave contract[18] - CoreWeave can unlock approximately $5B of committed capex for more efficient financing[25] - CoreWeave will gain greater control over a critical power footprint and optionality for future power capacity[15]

Bezuclastinib Program - Bezuclastinib is a potential best-in-class selective KIT mutant inhibitor, showing promise in pre-clinical studies and Phase 1/2 trials for GIST patients[10, 115] - KIT mutations drive up to 80% of GIST and over 90% of SM cases[27] - Bezuclastinib exhibits minimal brain penetration, with a brain to plasma ratio of 007, compared to 20 for avapritinib[37] - Cogent is conducting a Phase 2 clinical study (APEX) of Bezuclastinib in patients with Advanced Systemic Mastocytosis, with initial clinical results expected in 1H 2022[47, 48] FGFR2 Program - FGFR2 and FGFR3 are collectively altered in up to 41% of cancers[55] - Cogent is developing FGFR2 selective inhibitors with a target profile of <10 nM FGFR2 Cell IC50 and >200 nM FGFR1 Cell IC50[64] - CGT0292, a lead compound, demonstrates ~30x selectivity between FGFR1 and FGFR2 in cellular assays[80] - CGT0292 does not show serum phosphorus increase at a 5 mg/kg dose in the SD Rat Model of Hyperphosphatemia[84] ErbB2 Program - Significant unmet need remains for patients with non-exon 20 ErbB2 mutations[95] - Cogent is developing an ErbB2 mutant selective drug which covers key mutations while sparing wtEGFR, with a target Mutant Cell IC 50 of <10 nM and EGFR WT Cell IC 50 of >200 nM[104, 105] - Cogent has identified several novel series with promising enzyme selectivity for ErbB2 over EGFR WT[114] Financial Status - Cogent Biosciences had a cash balance of $2197 million as of December 31, 2021[12, 117]

Bezuclastinib Clinical Programs - Bezuclastinib combined with sunitinib demonstrated a 12-month median Progression-Free Survival (mPFS) in heavily pre-treated Gastrointestinal Stromal Tumors (GIST) patients[10] - In the APEX study, initial data in Advanced Systemic Mastocytosis (AdvSM) patients shows promising clinical activity with Bezuclastinib[10] - In Apex study, the Overall Response Rate (ORR) of CR + CRh + PR + CI was 73% (8 out of 11 patients) per CRRC assessment in TKI therapy-naïve AdvSM patients[27] - In Apex study, 88% of patients achieved a ≥ 50% reduction in serum tryptase levels[35] - In Apex study, 100% of patients with at least 2 cycles of treatment achieved a ≥ 50% reduction in bone marrow mast cell burden[35] - In Apex study, 92% of patients with at least 2 cycles of treatment achieved a ≥ 50% reduction in KIT D816V VAF[35] Market Opportunity - The global Total Addressable Market (TAM) potential for Bezuclastinib exceeds $3.5 billion, including $1.5 billion for NonAdvSM, $700 million for 2nd-line GIST, and $300 million for AdvSM[14] - Approximately 90% of Systemic Mastocytosis (SM) patients present with non-advanced systemic mastocytosis (NonAdvSM)[18] - Approximately 10% of patients present with advanced systemic mastocytosis (AdvSM)[18] Pipeline and Financials - The company's research pipeline includes novel, small-molecule targeted therapies for rare diseases, including an FGFR1-sparing, pan-mutant FGFR2 and a CNS-penetrant ErbB2[7] - The company's cash runway is expected to fund operations into 2025, with $289.1 million in cash as of September 30, 2022[7, 83]

Summary of Apogee Therapeutics Conference Call Company Overview - **Company**: Apogee Therapeutics - **Focus**: Development of APG-777 for atopic dermatitis Key Industry Insights - **Market Potential**: The atopic dermatitis market is projected to be worth $50 billion, with APG-777 positioned to potentially transform treatment paradigms [doc id='9'][doc id='33']. Core Points and Arguments 1. **Phase II APeX Study Results**: - APG-777 met or exceeded all key objectives in the Phase II APeX study for atopic dermatitis, demonstrating significant efficacy and a favorable safety profile [doc id='4'][doc id='15]. - 66.9% of patients achieved an EZ-75 response by week sixteen, surpassing results from existing treatments like Dupixent [doc id='15'][doc id='72']. 2. **Dosing and Administration**: - APG-777's induction regimen requires only four dosing days compared to nine for competitors, representing over a 50% reduction in injection days [doc id='14']. - The potential for maintenance dosing every three to six months could lead to 70-90% fewer injections compared to current standards [doc id='26']. 3. **Efficacy Metrics**: - The study showed a greater than 70% absolute percent change from baseline in EASI scores, with rapid lesion reduction observed as early as week two [doc id='15']. - Statistically significant improvements in itch relief were noted, with over 50% decrease from baseline at week sixteen [doc id='17']. 4. **Safety Profile**: - APG-777 demonstrated a promising safety profile, with lower rates of treatment-emergent adverse events compared to placebo [doc id='21']. - No injection site reactions were reported, enhancing the drug's appeal for patients [doc id='23']. 5. **Future Development Plans**: - Multiple data readouts are expected in the coming quarters, including maintenance data and results from the accelerated Part B of the APeX study [doc id='5'][doc id='29']. - Plans to initiate Phase III studies next year, contingent on regulatory alignment [doc id='32']. 6. **Market Positioning**: - APG-777 is expected to be a market leader, with 94% of patients preferring it over existing options if efficacy is equal [doc id='71']. - The company aims to establish APG-777 as a first-line biologic treatment for atopic dermatitis [doc id='73']. Additional Important Insights - **Combination Studies**: Ongoing studies are testing APG-777 in combination with IL-13 and OX40 ligand against Dupixent, which could further differentiate the product in the market [doc id='11'][doc id='44']. - **Regulatory Considerations**: The company is preparing for potential regulatory filings in early 2029, following Phase III trials [doc id='98']. - **Patient and Physician Preferences**: There is a strong demand for fewer injections and improved efficacy, which APG-777 aims to address [doc id='26'][doc id='72']. This summary encapsulates the key points discussed during the conference call, highlighting the promising results of APG-777 and its potential impact on the atopic dermatitis market.

Cogent Biosciences (COGT) Conference Call Summary Company Overview - **Company**: Cogent Biosciences - **Focus**: Development of bezuclastinib for the treatment of non-advanced systemic mastocytosis (SM) Key Industry Insights - **Industry**: Rare disease treatment, specifically systemic mastocytosis - **Current Treatment Landscape**: Limited options for patients with non-advanced SM, highlighting the unmet medical need for effective therapies Core Findings from the SUMMIT Trial - **Trial Results**: The SUMMIT trial demonstrated positive top-line results, meeting all primary and key secondary endpoints with statistically significant benefits compared to placebo [5][24][54] - **Patient Population**: The trial included 179 patients with moderate to severe symptoms of non-advanced SM, with a significant percentage being female [20][22] - **Primary Endpoint**: The mean change in total symptom score at week 24 was significantly better in the bezuclastinib group (24.32) compared to placebo (15.41), with a placebo-adjusted effect size of 8.91 [25] - **Secondary Endpoints**: Significant reductions in serum tryptase levels and other markers of mast cell burden were observed, with 87.4% of patients achieving at least a 50% reduction in serum tryptase [26][54] Safety Profile - **Adverse Events**: Bezuclastinib showed a favorable safety profile, with 98% of patients experiencing treatment-emergent adverse events (TEAEs) compared to 88% in the placebo group [29] - **Serious Adverse Events**: Serious AEs were low, with 5% in placebo versus 4.2% in the bezuclastinib cohort [29] - **Common AEs**: Hair color changes (69%), altered taste (23.7%), and nausea (22%) were among the most common TEAEs [30] Future Outlook - **Regulatory Submissions**: Cogent plans to submit a New Drug Application (NDA) for bezuclastinib later in 2025, aiming for commercial approval [6][54] - **Upcoming Trials**: Results from two additional pivotal trials (APeX and PEAK) are expected later in 2025, which could further establish bezuclastinib's role in treating advanced SM and gastrointestinal stromal tumors (GIST) [9][51] - **Market Potential**: The company is positioned to become a leader in the treatment of non-advanced SM, with a strong financial position to support its initiatives [54] Competitive Landscape - **Comparison with Avapritinib**: The conference highlighted the potential for bezuclastinib to outperform avapritinib in terms of efficacy and safety, with physicians expressing interest in switching patients who are not well-controlled on avapritinib [60][88] - **Patient Preferences**: Patients currently on avapritinib expressed satisfaction but showed a strong interest in switching to bezuclastinib based on the promising SUMMIT trial results [93] Additional Considerations - **Patient Quality of Life**: The trial results indicate not only symptomatic relief but also potential disease modification, which is crucial for improving patients' overall quality of life [96][98] - **Ongoing Research**: Further analysis of the SUMMIT trial data is anticipated, which may provide deeper insights into specific symptom domains and long-term outcomes [87][90] This summary encapsulates the key points from the Cogent Biosciences conference call, focusing on the promising results of the SUMMIT trial and the potential impact of bezuclastinib in the treatment landscape for systemic mastocytosis.