Kyntra Bio Inc. (NASDAQ:KYNB) , formerly Fibrogen, shares fluctuated in Tuesday’s premarket session as the company announced data from a Phase 1b/2 study of FG-3246 in combination with enzalutamide for treating metastatic castration-resistant prostate cancer.Prostate Cancer Data Shows Response Rate Of 21%The data presented showed a median radiographic progression-free survival (rPFS) of 10.1 months in patients who had progressed on only one prior androgen receptor pathway inhibitor (ARPI).The study included ...

In mCRPC patients with androgen receptor (AR) mutations, treatment with MRT-2359 in combination with enzalutamide led to a 100% PSA response rate (5 of 5 patients) and a 100% disease control rate, including 2 patients with RECIST partial responses and 3 with stable disease, all showing reduction in size of target lesions Across all 15 evaluable patients, the overall RECIST disease control rate was 67%, and 10 of 15 patients showed tumor size reductions of target lesions Combination of MRT-2359 and enzalutam ...

FG-3246 and enzalutamide combination therapy, in biomarker unselected patients with androgen receptor pathway inhibitor (ARPI)-treated, taxane-naïve metastatic castration-resistant prostate cancer (mCRPC), led to a median radiographic progression free survival (rPFS) of 7.0 months in the overall study cohort, with median rPFS of 10.1 months observed in patients who progressed on only one prior ARPIHigher tumor uptake of FG-3180, a CD46 directed PET imaging agent, demonstrated a trend towards higher probabil ...

Summary of ORIC Pharmaceuticals FY Conference Call Company Overview - **Company Name**: ORIC Pharmaceuticals (NasdaqGS:ORIC) - **Industry**: Oncology - **Mission**: Overcoming Resistance in Cancer, focusing on developing therapies for cancer patients [2][3] Key Pipeline Assets - **Rinsey-Metastat**: A PRC2 inhibitor for prostate cancer, expected to have a phase three data readout in the second half of 2027 [3][11] - **Enosertinib**: A brain-penetrant TKI for lung cancer, targeting EGFR exon 20 and PAC mutations, with a phase three dose selected [5][35] Financial Position - **Cash Runway**: Well-funded with cash runway extending into the second half of 2028, allowing for continued development of both pipeline assets [3][11] Clinical Development Highlights Rinsey-Metastat - **Combination Studies**: Being developed in combination with apalutamide (J&J) and daralutamide (Bayer) [4][7] - **Safety Profile**: Demonstrated a differentiated safety profile compared to competitors, which is crucial for long-term dosing [8][29] - **Efficacy Data**: - Confirmed PSA response rates of 40% for PSA 50 and 20% for PSA 90, significantly higher than expected rates for AR inhibitors alone [24] - ctDNA clearance rate of 59%, indicating strong activity [26][27] Enosertinib - **CNS Activity**: Achieved a 100% intracranial objective response rate (ORR) in patients with measurable disease, highlighting its potential in treating CNS metastases [10][33] - **Patient Enrollment**: Allowed patients with active untreated CNS metastases, which is uncommon in competitor studies [34] Competitive Landscape - **Main Competitor**: Pfizer's mevrometostat, which has shown promising results but comes with higher toxicity [6][28] - **Market Opportunity**: The prostate cancer market is substantial, with AR inhibitors generating $11 billion in global revenue [16][17] Future Milestones - **Phase 3 Studies**: Expected to initiate one or two phase 3 studies within the year for both Rinsey-Metastat and Enosertinib [46] - **Data Releases**: Anticipated data from dose optimization studies in Q1 2026, focusing on efficacy and safety [50] Additional Insights - **Long-term Durability**: The combination of Rinsey-Metastat with AR inhibitors aims to extend the durability of treatment, addressing a significant unmet need in prostate cancer [17][19] - **Broader Applications**: Potential future development of PRC2 inhibitors in other cancers, including lung and breast cancer [30] Conclusion - ORIC Pharmaceuticals is positioned to make significant advancements in oncology with its innovative pipeline, particularly in addressing unmet needs in prostate and lung cancer, while maintaining a strong financial position to support its development efforts [46]

Clinical Trial Results of MRT-2359 - MRT-2359 combined with enzalutamide demonstrated a 100% PSA response rate in heavily pre-treated mCRPC patients with AR mutations[5, 38, 59] - Among the 4 patients with AR mutations, 2 patients showed PSA90 responses and 2 patients showed PSA50 responses[5, 38] - Two patients with AR mutations achieved RECIST partial responses (1 confirmed, 1 unconfirmed), and two had stable disease, resulting in a 100% disease control rate in the AR mutant population[5] - An overall disease control rate (DCR) of 64% was observed in 14 evaluable patients, including 5 patients without AR mutations who had stable disease[5, 59] Safety and Tolerability - The combination of MRT-2359 and enzalutamide was well-tolerated, with the most frequent adverse events (AEs) being mild or moderate manageable GI symptoms[5, 33, 59] - Treatment-related AEs occurring in >15% patients included fatigue (50%), diarrhea (45%), nausea (35%), arthralgia (30%), decreased appetite (30%), vomiting (30%), neutropenia (25%), and muscular weakness (20%)[31, 32] Future Plans - The company plans to initiate a signal-confirming 2-stage Phase 2 study (MODeFIRe-1) of MRT-2359 in combination with a 2nd generation AR inhibitor in 2026, targeting AR-mutated mCRPC[2, 56, 59] - Updated data from the Phase 1/2 study is expected to be presented at the ASCO Genitourinary Cancers Symposium in February 2026[59]

Core Insights - Monte Rosa Therapeutics announced positive interim data from a Phase 1/2 clinical study of MRT-2359 in combination with enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC), showing a 100% PSA response rate in patients with androgen receptor (AR) mutations [1][2][3] Study Results - The combination treatment resulted in a 100% disease control rate in AR mutant patients, with 4 out of 4 patients showing PSA responses, including 2 patients achieving PSA90 responses and 2 achieving PSA50 responses [1][3] - The overall disease control rate in the study population was 64%, with 9 out of 14 evaluable patients demonstrating stable disease or tumor size reductions [3][4] - The treatment was generally well-tolerated, with primarily Grade 1-2 adverse events reported [1][4] Future Plans - The company plans to initiate a new Phase 2 study in 2026, targeting AR mutant and AR signaling-dependent patients, to further evaluate the efficacy of MRT-2359 in combination with a second-generation AR inhibitor [1][6] - Updated data from the ongoing Phase 1/2 study is expected to be presented at the ASCO Genitourinary Cancers Symposium in February 2026 [2][5] Mechanism of Action - MRT-2359 is designed to degrade GSPT1, impacting MYC and E2F signaling pathways, suggesting a mechanism of action that may be independent of AR signaling [3][10]

Summary of Oric Pharmaceuticals FY Conference Call (December 03, 2025) Company Overview - Oric Pharmaceuticals is a clinical stage oncology company focused on overcoming resistance in cancer, specifically targeting prostate cancer, lung cancer, and breast cancer [2][3] Key Accomplishments in 2025 - Two data updates on ORIC-944, an allosteric PRC2 inhibitor for prostate cancer - Upcoming significant update on ORIC-114 at ESMO Asia - Successfully raised capital, providing a cash runway into the second half of 2028 [3] ORIC-944 Developments - ORIC-944 is being studied in combination with apalutamide and daralutamide for prostate cancer - Recent data showed PSA 50 response rate of 40% and PSA 90 response rate of 20%, slightly outperforming Pfizer's data [5][8] - Safety profile of ORIC-944 is favorable, with significantly lower rates of on-target toxicity compared to Pfizer's agent [5][9] Market Context and Competition - The prostate cancer market is substantial, with multiple AR inhibitors (enzalutamide, apalutamide, daralutamide) generating significant revenues [7][21] - Even if ORIC-944 enters the market later, there is ample opportunity due to the large patient population [22] Future Plans for ORIC-944 - Phase 3 study planned for the first half of 2026, focusing on post-ABI and post-ARPI patient populations [17][18] - The company aims to retain operational control while considering potential partnerships in the future [23] ORIC-114 Developments - ORIC-114 targets EGFR exon 20 mutations in lung cancer, with a focus on CNS activity, which is a key differentiator [26] - Upcoming data presentations at ESMO Asia will include results from various patient populations, with benchmarks set for response rates [30][31] Market Opportunity for ORIC-114 - The lung cancer market for targeted therapies remains significant, with unmet needs in specific mutation subsets [33] - The potential patient population for ORIC-114 is estimated at 10-12,000 annually in the U.S., indicating a multi-billion dollar market opportunity [34] Conclusion - Oric Pharmaceuticals is well-positioned with promising data for both ORIC-944 and ORIC-114, targeting large and unmet needs in oncology - The company is strategically planning its next steps while maintaining a focus on safety and efficacy to differentiate its products in competitive markets [22][34]

Summary of Oric Pharmaceuticals FY Conference Call Company Overview - **Company**: Oric Pharmaceuticals (NasdaqGS:ORIC) - **Industry**: Clinical stage oncology - **Mission**: Overcoming Resistance in Cancer - **Focus Areas**: Prostate cancer, lung cancer, and breast cancer - **Clinical Programs**: - **ORIC-944**: Allosteric PRC2 inhibitor for prostate cancer in combination with apalutamide and daralutamide - **ORIC-114**: Selective brain penetrant EGFR HER2 exon 20 program for non-small cell lung cancer [2][3] Financial Position - **Cash and Investments**: $436 million as of Q2, providing a runway into the second half of 2028, assuming success in clinical programs [3] Clinical Development Insights - **ORIC-944**: - Targets AR-dependent tumors transitioning to AR-independent states, aiming to resensitize them to AR inhibitors [4] - Clinical data from competitors (e.g., Pfizer) shows significant improvements in progression-free survival (PFS) with PRC2 inhibitors [6][7] - Pfizer's data indicated a tripling of PFS benefit in certain patient populations, validating the mechanism [7][8] - **Physician Feedback**: - Positive feedback on the randomized control study by Pfizer, indicating a promising profile for new agents in prostate cancer [10][11] - **Comparative Data**: - ORIC-944 shows higher PSA response rates and better safety profiles compared to Pfizer's mevrometostat [13][14] - ORIC-944 designed specifically for prostate cancer with optimized drug properties [14][15] Market Opportunity - **Prostate Cancer Market**: - Significant unmet need with a large patient population; existing AR inhibitors generated $11 billion in sales last year [16][17] - Even with a similar profile to competitors, the market opportunity remains substantial due to the high number of patients [17][18] Phase III Trials - **Timeline**: Planning to start the first phase III study in the first half of next year, approximately 18 months behind Pfizer [18][32] - **Patient Population**: Focus on post-abiraterone patients, with expectations for FDA labeling to reflect this [33][34] EGFR Program (ORIC-114) - **Upcoming Updates**: Data expected at ESMO Asia, focusing on three patient populations: EGFR exon 20, HER2 exon 20, and EGFR atypical [38] - **Benchmarks**: Expected response rates of 35% for EGFR exon 20 and atypicals, and 50% for HER2 exon 20 in second-line settings [39] Combination Therapy - **Amivantamab Collaboration**: Exploring combination therapy with Amivantamab, leveraging its success in classical EGFR settings [42][43] - **Rationale**: Aiming for dual inhibition of EGFR to manage safety and potentially extend PFS and overall survival [43] Conclusion - Oric Pharmaceuticals is positioned to capitalize on significant market opportunities in oncology, particularly in prostate cancer and lung cancer, with promising clinical data and a strong financial position to support ongoing and future trials. The company is focused on differentiating its therapies through optimized drug properties and strategic collaborations.

Summary of ORIC Pharmaceuticals Conference Call Company Overview - **Company Name**: ORIC Pharmaceuticals - **Ticker**: NasdaqGS:ORIC - **Focus**: Oncology, specifically small molecule drug development for solid tumors, with a focus on lung cancer and prostate cancer [3][4] Key Programs ORIC-944 (Prostate Cancer) - **Mechanism**: Small molecule inhibitor of PRC2, targeting the EED subunit, in combination with androgen receptor (AR) inhibitors [4][8] - **Current Status**: In dose optimization, aiming to start Phase 3 studies next year [4][26] - **Efficacy**: Early data shows a confirmed PSA 50 response rate of 47% and a PSA 90 response rate of 24%, outperforming Pfizer's data [20][21] - **Safety Profile**: ORIC-944 shows a differentiated safety profile with less toxicity compared to Pfizer's Mezigdomide, particularly in terms of hematologic and gastrointestinal toxicity [22][23] - **Half-Life**: ORIC-944 has a 20-hour half-life, allowing for once-daily dosing, which is expected to reduce Cmax-related toxicities [15][16] ORIC-114 (Lung Cancer) - **Focus**: Developed for non-small cell lung cancer, targeting multiple genetic mutations including EGFR exon 20 and HER2 exon 20 [49][50] - **Differentiation**: Emphasizes safety, tolerability, and CNS activity, which is crucial as many lung cancer patients present with brain metastases [52][53] - **Upcoming Data**: Substantial data readouts expected in the second half of this year and early next year, with a focus on three cohorts of patients [55][56] Financial Position - **Funding**: The company is well-funded, with a cash runway extending past the Phase 3 data readouts for both programs [4][72] - **Market Opportunity**: The prostate cancer market is significant, with an estimated $3.5 billion treatable market in the U.S. for the targeted populations [47][48] Competitive Landscape - **Comparison with Pfizer**: ORIC-944 is positioned as a potential competitor to Pfizer's Mezigdomide, with expectations of capturing 35% to 40% market share as a second entrant [46][48] - **AR Inhibitors**: ORIC has supply agreements with apalutamide and darolutamide, both of which are viewed as having similar efficacy but better safety profiles compared to enzalutamide [39][40] Upcoming Milestones - **Data Updates**: Incremental updates expected in the second half of this year, with a more substantial update in Q1 2026 [28][30] - **Phase 3 Study**: Plans to initiate a pivotal study for ORIC-944 in the first half of next year, with a focus on the CRPC setting [34][66] Conclusion - **Investor Attention**: ORIC Pharmaceuticals is positioned for significant data releases and has a strong financial foundation, making it a company to watch in the oncology space over the next 6 to 12 months [75][76]

Summary of ORIC Pharmaceuticals Conference Call Company Overview - **Company**: ORIC Pharmaceuticals - **Focus**: Development of small molecule drugs targeting resistance in oncology, specifically for solid tumors like prostate and lung cancer Key Programs - **Lead Programs**: - **ORIC-944**: A small molecule PRC2 inhibitor for castration-resistant prostate cancer (CRPC), currently in dose optimization and expected to enter phase three studies next year - **ORIC-114**: A small molecule TKI targeting non-small cell lung cancer (NSCLC) with brain metastases, also in dose optimization Core Insights - **Market Potential**: The combined market for AR inhibitors in prostate cancer is approximately $7 billion in the U.S. alone, with each patient population (post-abiraterone and post-ARPI) representing about $3.5 billion [doc id='36'][doc id='37'] - **Comparison with Competitors**: ORIC-944 has a 20-hour half-life and better drug properties compared to Pfizer's Mavrimodastat, which has a 4-5 hour half-life. ORIC-944 shows higher PSA response rates (47% confirmed PSA 50 rate vs. Pfizer's 34%) and lower toxicity [doc id='10'][doc id='13'][doc id='14'] - **Safety Profile**: ORIC-944 exhibits a lower incidence and severity of toxicities compared to Pfizer's drug, with no reported alopecia, which is significant for prostate cancer patients [doc id='15'] Clinical Data and Updates - **Phase One Data**: ORIC-944 showed promising early efficacy with a small sample size (n=17), indicating potential for longer-term durability [doc id='12'][doc id='13'] - **Upcoming Updates**: The second half of the year will provide incremental updates on dose selection and rationale for ORIC-944, with a more substantial update expected in Q1 2026 [doc id='24'][doc id='30'] Competitive Landscape - **CNS Activity**: ORIC-114 is positioned as a CNS-active agent, which is crucial as many lung cancer patients present with brain metastases. This could lead to longer progression-free survival [doc id='42'][doc id='43'] - **Market Dynamics**: The AR inhibitor market is large, with significant sales from existing drugs. ORIC aims to capture market share through better efficacy and safety profiles [doc id='36'][doc id='39'] Financial Position - **Cash Runway**: ORIC ended Q2 with $436 million in cash, providing a runway into the second half of 2028, which covers the phase three readouts for both ORIC-944 and ORIC-114 [doc id='56'] Strategic Considerations - **Partnership Opportunities**: ORIC is open to various forms of partnerships, including drug supply agreements and potential collaborations for broader development, especially for ORIC-944 in CSPC [doc id='54'] Conclusion - ORIC Pharmaceuticals is advancing its lead programs with promising clinical data and a strong financial position, positioning itself competitively in the oncology market, particularly in prostate and lung cancer treatments. The company is focused on optimizing its drug candidates while preparing for upcoming phase three studies.