Summary of ORIC Pharmaceuticals Conference Call Company Overview - **Company Name**: ORIC Pharmaceuticals - **Ticker**: NasdaqGS:ORIC - **Focus**: Development of small molecule drugs in oncology, specifically targeting solid tumors like prostate cancer and lung cancer [2][3] Key Points and Arguments Lead Programs - ORIC is currently focused on two lead programs in prostate cancer and lung cancer, both in dose optimization and expected to start pivotal phase three studies in 2026 [2][3] ORIC-944 Program - Recent data showed encouraging results for the ORIC-944 program, particularly in combination with apalutamide and daralutamide, with impressive PSA response rates [3][4] - ORIC-944 has a 20-hour half-life compared to Pfizer's memoremedistat, which has a five-hour half-life, suggesting a potential safety advantage [3][19] - The ability to clear ctDNA was observed in 59% of patients, which correlates strongly with long-term outcomes like PFS and OS [5][9] Safety Profile - The safety profile of ORIC-944 appears favorable, with only one grade 3 adverse event reported in 20 patients, compared to multiple grade 3 events in Pfizer's studies [13][15] - A clean safety profile is crucial for future development, especially in earlier lines of treatment for prostate cancer [14][15] Market Opportunity - The metastatic CRPC market is estimated at approximately 50,000 patients, with a total addressable market (TAM) of about $3.5 billion in the US for each of the post-AR inhibitors and post-abiraterone populations [29][30] - Historical data suggests that even with an undifferentiated profile, a second-to-market drug can capture about 35% of the market [30] Future Development Plans - ORIC plans to submit dose optimization data to regulators in early 2026 to align on pivotal study design [25][26] - The first phase three study is expected to start in the first half of 2026, with primary readout anticipated in the second half of 2027 [27][28] Pipeline Asset ORIC-114 - ORIC-114 is focused on non-small cell lung cancer, with updates expected at ESMO Asia in December, including data from multiple cohorts [35] - The drug is designed to be CNS-penetrant, which may lead to longer PFS outcomes for patients with brain metastases [36][37] Financial Position - As of the third quarter, ORIC had $413 million in cash and investments, providing a runway into the second half of 2028, covering pivotal studies for both ORIC-944 and ORIC-114 [42] Additional Important Information - ORIC maintains strong relationships with Bayer and Johnson & Johnson, which are crucial for future collaborations [31][32] - The company is exploring the potential of PRC2 inhibitors in other oncology indications beyond prostate cancer, including breast cancer and lung cancer [33][34]

Core Insights - ORIC Pharmaceuticals announced additional efficacy and safety data from the Phase 1b trial of ORIC-944 in combination with androgen receptor inhibitors for metastatic castration-resistant prostate cancer (mCRPC) [1][2] Efficacy Data - The trial demonstrated a 55% PSA50 response rate and a 20% PSA90 response rate among patients [6] - Rapid and deep circulating tumor DNA (ctDNA) reductions were observed in 76% of patients, with 59% achieving ctDNA clearance, indicating potential long-term treatment benefits [1][7] - PSA responses and ctDNA reductions were consistent across all ORIC-944 dose levels and in combination with both apalutamide and darolutamide [4][5] Safety Profile - The combination of ORIC-944 with apalutamide or darolutamide showed a safety profile compatible with long-term dosing, with most adverse events being Grade 1 or 2 [8] - As of the cutoff date, only one patient experienced a Grade 3 treatment-related adverse event, with no Grade 4 or 5 adverse events reported [8] Next Steps - ORIC has selected provisional recommended Phase 2 doses for ORIC-944 to be tested in combination with darolutamide and apalutamide, with ongoing enrollment in the dose optimization portion of the trial [9] - Preliminary dose optimization data is expected to be announced in Q1 2026, ahead of initiating the first global Phase 3 registrational trial in mCRPC in the first half of 2026 [2][9] Company Overview - ORIC Pharmaceuticals is focused on developing treatments that address mechanisms of therapeutic resistance in cancer, with ORIC-944 being an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) [11]

Medical Innovation - A doctor is advocating for a more precise, humane, and effective alternative treatment for prostate cancer [1] - The alternative aims to improve the binary choice faced by men with prostate cancer: living with the cancer versus living with the consequences of removing it [1]

Core Insights - EDAP TMS SA's Focal One Robotic HIFU treatment was highlighted during Prostate Cancer Awareness Month, reaching millions through national television exposure [1][2] - The treatment offers a non-invasive option for prostate cancer patients, allowing them to maintain their quality of life while effectively targeting cancer [3] Company Overview - EDAP TMS SA is a leader in robotic energy-based therapies, developing and distributing minimally invasive medical devices using ultrasound technology [4] - The Focal One system is positioned as a leading prostate focal therapy, with potential applications beyond prostate cancer [4] Patient Experience - A patient named Peter D. shared his positive experience with Focal One Robotic HIFU, emphasizing minimal disruption to his daily life and a quick return to normal activities [2] - Dr. Eric Giesler, Peter's urologist, noted the importance of non-invasive treatment options in improving patient outcomes and quality of life [3] Awareness Campaign - The national exposure from the television segment is part of a broader campaign to raise awareness about prostate cancer treatment options among patients, caregivers, and healthcare professionals [3]

Summary of Oric Pharmaceuticals Conference Call Company Overview - **Company**: Oric Pharmaceuticals (ORIC) - **Industry**: Biotechnology, specifically oncology - **Focus**: Development of small molecule drugs targeting solid tumors, particularly prostate cancer and lung cancer [4][5] Key Pipeline Developments - **ORIC-944**: A PRC2 inhibitor in combination with AR inhibitors (apalutamide and darolutamide) for prostate cancer, currently in dose optimization and preparing for Phase 3 studies [5][6][7] - **ORIC-114**: A brain-penetrant small molecule targeting lung cancer, focusing on patient populations with EGFR exon 20, atypical mutations, and HER2 exon 20, also in dose optimization [5][6][7] Financial Position - The company has strengthened its balance sheet through capital raising, providing a cash runway until 2028, which covers the primary data readouts for both programs [7][8] Market Opportunity - The prostate cancer market is significant, with existing AR inhibitors (enzalutamide, apalutamide, darolutamide) showing strong efficacy but limited options for patients who progress on these therapies [11][12][13] - ORIC-944 aims to resensitize patients to AR inhibitors, potentially improving progression-free survival (PFS) outcomes [13][14] Competitive Landscape - Current AR inhibitors have similar efficacy profiles, but ORIC-944's better tolerability and dosing regimen (once daily with a 20-hour half-life) may provide a competitive edge [20][21][23] - The company aims to differentiate itself through improved drug properties and potentially better patient outcomes [25][26] Clinical Data Insights - Early clinical data showed ORIC-944 achieving higher rates of confirmed PSA50 (47%) and PSA90 (24%) compared to Pfizer's data (34% and 12%, respectively) [37][38] - The drug's toxicity profile appears favorable, with lower incidence and severity of expected toxicities compared to competitors [39][40] Future Plans - The company plans to initiate the first Phase 3 study in the first half of next year, selecting one AR inhibitor (either apalutamide or darolutamide) for the trial [49][50] - Upcoming updates will provide clarity on dosing regimens and additional clinical data, including ctDNA metrics [46][48] ORIC-114 Development - ORIC-114 (enozertinib) targets EGFR exon 20, atypical mutations, and HER2 exon 20, with a focus on CNS activity and a clean safety profile [57][64] - The company has made strategic decisions to prioritize first-line settings over second-line due to market size and cost considerations [69] Regulatory Considerations - The company is observing regulatory feedback from the FDA regarding competitive products in the space, particularly concerning atypical mutations [74][75] Conclusion Oric Pharmaceuticals is positioned to make significant advancements in oncology with its innovative drug candidates, particularly ORIC-944 and ORIC-114, while maintaining a strong financial position and strategic focus on market opportunities. The upcoming clinical data and Phase 3 study initiation will be critical in determining the company's trajectory in the competitive oncology landscape.

Summary of Radiopharm Theranostics (RADX) Update / Briefing Company and Industry Overview - **Company**: Radiopharm Theranostics (RADX) - **Industry**: Prostate cancer treatment and radiopharmaceuticals Key Points and Arguments 1. **Prostate Cancer Treatment Landscape**: - Significant advancements in prostate cancer treatments, particularly with radiotherapy options like radium-223 combined with enzalutamide and targeted therapies such as PSMA radiotherapeutics like Pluvicto [3][4] - Pluvicto has shown efficacy in prostate cancer patients both before and after chemotherapy, as evidenced by the PSMA-4 and VISION trials [3] 2. **Unmet Medical Needs**: - Despite advancements, there remains a substantial medical need for new therapies, especially targeted radiotherapy, as all patients receiving PSMA-targeting treatments will eventually relapse [4] 3. **Introduction of Betabart**: - Betabart, a monoclonal antibody targeting B7-H3, is being developed as a new treatment option. It has a modified half-life to reduce side effects while maintaining strong target affinity [4][5] - The upcoming study will enroll patients with various tumors, including those with prostate cancer who have previously received Pluvicto [5] 4. **KLK3 Targeting**: - KLK3 (PSA) is identified as a promising new target for prostate cancer therapy, with a focus on its specific expression in prostate tissues compared to PSMA, which is expressed in multiple organs [7][8] - The KLK3-targeted study is set to begin in Australia early next year [8] 5. **Preclinical Data**: - Preclinical studies show that KLK2 and KLK3 are highly specific to prostate tissues, with KLK3 exhibiting higher expression levels than KLK2 [9][19] - The therapeutic efficacy of KLK2-targeted therapies has been demonstrated in advanced mouse models, showing significant tumor reduction [13][14] 6. **Mechanism of Action**: - The therapeutic approach exploits the upregulation of androgen receptors (AR) in response to DNA damage, which increases the expression of KLK2 and KLK3, enhancing the targeting efficacy over time [16][29] 7. **Comparison with Other Therapies**: - KLK3-targeted therapies are positioned as a more advanced approach compared to KLK2, with a higher expression level and a more extensive research background [20][29] - The antibody developed for KLK3 is designed to avoid targeting PSA in circulation, focusing instead on the free form of PSA in tissues [28] 8. **Clinical Development Plans**: - RAD402 (KLK3 targeting molecule) is expected to enter clinical studies in Australia before the end of the year, alongside RV-01 (B7-H3 targeting molecule) in the U.S. [48] Additional Important Content - **Market Potential**: - The arrival of radiopharmaceuticals has significantly changed the metastatic prostate cancer treatment landscape, with improved patient survival rates [45] - There is a recognition that existing treatments like Pluvicto are not perfect, indicating a need for further scientific advancements [46] - **Future Directions**: - The company is exploring new targets and approaches to enhance treatment efficacy and patient outcomes in metastatic prostate cancer [46][47] - **Community Engagement**: - The webinars have attracted significant interest, indicating a strong community engagement and support for ongoing research and development in prostate cancer therapies [45]

Summary of Radiopharm Theranostics (RADX) Update / Briefing August 26, 2025 Company and Industry Overview - **Company**: Radiopharm Theranostics (RADX) - **Industry**: Oncology, specifically focusing on prostate cancer treatment and radiopharmaceutical therapies Key Points and Arguments 1. **Prostate Cancer Treatment Landscape**: The treatment of prostate cancer has evolved significantly, moving from traditional methods like surgery and chemotherapy to incorporating genetics, molecular imaging, and targeted therapies, including immunotherapy and radiopharmaceuticals [11][12][30] 2. **B7-H3 as a Target**: B7-H3 is highlighted as a promising new target for prostate cancer treatment, being highly expressed in various tumors, including 93% of castrate-resistant prostate cancer cases. This makes it a viable alternative to PSMA-targeted therapies, especially in cases where PSMA expression is low [39][41][43] 3. **Need for New Therapies**: There is a critical need for more effective therapies for metastatic castration-resistant prostate cancer, as current treatments often provide limited survival benefits [18][30] 4. **NCCN Guidelines**: The National Comprehensive Cancer Network (NCCN) guidelines are discussed, emphasizing the importance of treatment sequencing and the variety of options available based on prior therapies [19][20] 5. **Theranostics Concept**: The concept of theranostics is introduced, where ligands are designed to bind to specific cancer cell targets, allowing for both diagnosis and treatment using radiopharmaceuticals [24][25] 6. **Clinical Trials and FDA Approvals**: The presentation mentions several clinical trials demonstrating survival benefits from new therapies, including the FDA approval of Plavicto (lutetium-177) for prostate cancer treatment [27][28][51] 7. **BetaBART Development**: The development of BetaBART, a humanized monoclonal antibody targeting the four Ig isoform of B7-H3, is presented as a novel approach in radioimmunotherapy, with plans for a Phase 1 trial in 2025 [51][66] 8. **Competitive Landscape**: The competitive landscape for B7-H3 targeting is discussed, noting that while there are other modalities like ADCs and CAR T-cell therapies, the unique properties of BetaBART provide a competitive advantage [75][78][87] 9. **Immunological Memory**: Evidence of secondary immune memory from prior treatments suggests that BetaBART may not only target tumors but also enhance the immune response against them [64][66] 10. **Market Potential**: The potential market for B7-H3 targeting therapies is significant, with opportunities extending beyond prostate cancer to other solid tumors [46][51] Other Important but Overlooked Content 1. **Challenges with Current Therapies**: The limitations of existing therapies, including the need for better options post-Plavicto treatment, are emphasized, highlighting the urgency for innovation in this space [30][102] 2. **Mechanism of Action**: The mechanism of action for BetaBART is discussed, focusing on its ability to selectively target the four Ig isoform of B7-H3 while minimizing off-target effects and toxicity [49][66] 3. **Future Directions**: The discussion includes the need for randomized control groups in future trials to better assess the efficacy of new treatments [31] This summary encapsulates the critical insights from the briefing, focusing on the advancements in prostate cancer treatment, the significance of B7-H3 as a target, and the innovative approaches being developed by Radiopharm Theranostics.

Financial Data and Key Metrics Changes - Total revenue for Q2 2025 was $79.2 million, representing a growth of 48% compared to Q2 2024 [21] - U.S. revenue for Q2 was $69.6 million, reflecting a growth of 46% year-over-year [21] - Gross margin for Q2 2025 was 65.4%, an increase of 640 basis points year-over-year [25] - Net loss for Q2 2025 was $19.6 million, compared to a net loss of $25.6 million in Q2 2024 [26] - Adjusted EBITDA loss was $8 million, an improvement from a loss of $18 million in the prior year [26] Business Line Data and Key Metrics Changes - U.S. handpiece and consumable revenue for Q2 2025 was $43.1 million, a growth of 58% compared to Q2 2024 [21] - Approximately 12,750 handpieces were sold in Q2 2025, representing a year-over-year unit growth of 59% [22] - U.S. system revenue was $22.1 million, with 48 new HydroS robotic systems sold [23] - International revenue reached $9.6 million, marking a growth of 69% compared to the prior year [24] Market Data and Key Metrics Changes - The company expects to exit 2025 with an estimated installed base of 715 systems, with only 20% procedural share in the hospital market, indicating significant room for expansion [4] - The 2026 proposed Medicare physician fee schedule includes a category one code for Ag population therapy, which is expected to enhance adoption and reimbursement consistency [14][15] Company Strategy and Development Direction - The company aims to become a global leader in urology, focusing on evidence-based innovation and expanding Hydro's adoption in greenfield accounts [10][34] - A leadership transition is underway, with Larry Wood set to become the new CEO, emphasizing a commitment to innovation and growth [10][36] - The company is eliminating the role of Chief Commercial Officer to strengthen commercial execution, creating two new leadership positions [20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to achieve long-term profitability despite current tariff challenges, estimating a potential gross margin headwind of $1 million to $2 million in 2025 [31][92] - The company remains optimistic about the stability of the capital environment, with no indications of hospitals slowing or pausing capital spending [91] - Management highlighted the importance of clinical outcomes in driving adoption and utilization of their systems, despite recent reductions in physician fee schedules [60] Other Important Information - The company is actively pursuing operational strategies to mitigate tariff exposure, with a focus on maintaining gross margins and profitability [16][31] - Enrollment in the WATERFORT trial is progressing well, with expectations for full enrollment by 2026 [17] Q&A Session Summary Question: Guidance confidence and system placements - Management confirmed slight increases in guidance, with confidence stemming from strong sales force execution and visibility into the sales funnel [41][46] Question: Disruption from leadership changes - Management reassured that the experienced sales team will maintain focus and execution despite leadership transitions [48][49] Question: CCO role split rationale - The decision to split the CCO role aims to enhance commercial execution and support long-term growth objectives [52] Question: Utilization growth in accounts - Management noted that longer tenure in accounts correlates with increased utilization of aquablation procedures, with examples of it becoming the standard of care [55] Question: Impact of physician fee schedule reductions - Management emphasized that clinical outcomes will drive continued adoption, despite reductions in resective procedure payments [60] Question: System placements and future expectations - Management indicated that replacement sales are expected to pick up in 2026, aligning with the useful life of the systems [62] Question: International market strength - The UK remains the primary driver of international revenue growth, with emerging progress in Japan and Korea [68] Question: Hydros rollout and customer reception - Early feedback on the Hydros system has been positive, with expectations for utilization metrics to improve as accounts ramp up [75]

Financial Performance & Guidance - PROCEPT BioRobotics reported Q1 2024 global revenue of $445 million, an 83% year-over-year increase [22] - International revenue in Q1 2024 reached $43 million, a 65% year-over-year increase [22] - The U S installed base grew to 354 systems, an 84% year-over-year increase [22] - U S handpiece sales reached 6800, a 100% year-over-year increase [22] - The company projects total revenue for 2024 to be approximately $2135 million, representing a 57% year-over-year growth [26] - The company anticipates a gross margin of approximately 58% to 59% for 2024 [26] - Adjusted EBITDA loss is projected to be approximately $70 million for 2024 [26] - As of March 31, 2024, the company had a total cash and cash equivalents balance of $226 million and a debt balance of $52 million [27] Commercial Strategy & Market Expansion - The company aims to convert all resective BPH hospital-based procedures to Aquablation Therapy [39] - The company reports that over 95% of U S covered lives are now under signed majority IDN contracts [43] - Aquablation Therapy cases at Georgia Urology have increased 95x since 2019 [67] Prostate Cancer Research & Development - Approximately 1/3 of men with BPH also have prostate cancer, representing 300000 diagnoses per year [89] - Initial Aquablation impressions for prostate cancer show promise, with real-time imaging and surgeon confidence [113, 114] - Early results from a study (n=5) show 0% incontinence and 0% erectile dysfunction, as well as 0% actionable disease and 0% residual tumor on MRI [138, 148]

Core Viewpoint - ORIC Pharmaceuticals' shares increased over 20% in pre-market trading following the announcement of promising preliminary efficacy and safety data for its prostate cancer treatment candidate, ORIC-944 [1] Group 1: Study Results - ORIC-944 is being evaluated in a phase Ib study in combination with J&J's Erleada and Bayer's Nubeqa for treating metastatic castration-resistant prostate cancer (mCRPC) [2] - The study reported that 59% of the 17 previously-treated mCRPC patients showed a 50% drop in PSA levels (PSA50 response), with a confirmed PSA50 rate of 47% [4] - Additionally, 24% of patients demonstrated a 90% drop in PSA levels (PSA90 response), all of which were confirmed [4] - PSA responses were consistent across all dosage levels and combinations with either Erleada or Nubeqa, indicating a well-tolerated safety profile with mild to moderate adverse events [6] Group 2: Future Plans - ORIC Pharmaceuticals aims to complete the phase Ib dose exploration by mid-2025 and plans to test two potential recommended phase II doses in the second half of 2025 [7] - The results from the dose optimization phase will inform the best ORIC-944 dose for the first global phase III study, expected to start in the first half of 2026 [8] Group 3: Financial Aspects - ORIC Pharmaceuticals announced a $125 million private placement to fund operations through the second half of 2027, covering expenses until the primary endpoint data readout from the phase III mCRPC study [9]