Casdatifan (HIF-2α) Program - Casdatifan 100mg QD tablet showed a 33% confirmed ORR (Overall Response Rate) with short follow-up[15,19] - Casdatifan 100mg QD tablet showed a 15% primary progressive disease (PD) rate[15] - Casdatifan 50mg BID cohort showed a median Progression Free Survival (mPFS) of 9.7 months[15,25] - Casdatifan 50mg QD cohort showed mPFS not reached with 12 months follow-up[15,25] - The PEAK-1 Phase 3 study for Casdatifan is on track to initiate in Q2 2025[33] Domvanalimab (Anti-TIGIT mAb) Program - Domvanalimab plus Zimberelimab in 1L Gastric Cancer showed ~13 months mPFS vs 7-8 months for benchmark data[11] - In 1L PD-L1 High NSCLC, Domvanalimab + Zimberelimab vs Zimberelimab showed OS Hazard Ratio of 0.64[11,58] - EDGE-Gastric data showed 13.8 months median PFS in TAP ≥5% and 11.3 months median PFS in TAP < 5%[47] - STAR-221 is a Phase 3 study evaluating Domvanalimab + Zimberelimab + Chemo in 1L Gastric/GEJ/EAC, with data expected in 2026[51,52] CD73-Adenosine Axis Programs - Quemli ± Zim + G/nP in 1L Metastatic PDAC showed 15.7 months mOS vs 9.8 months for Synthetic Control Arm, representing a 37% reduction in risk of death[70]

Summary of the Conference Call Company and Industry - **Company**: Arcus Biosciences - **Industry**: Oncology, specifically focusing on clear cell renal cell carcinoma (CCRCC) Key Points and Arguments 1. **Clinical Trial Data Announcement**: Arcus announced data from the cascadafan plus cabozantinib combination cohort of the Phase 1b ARC20 clinical trial in CCRCC, presented at the ASCO conference on June 1, 2025 [2][4] 2. **Efficacy of Combination Therapy**: The initial data from the CAS plus CABO cohort showed a confirmed overall response rate (ORR) of 46%, which is significantly higher than the benchmarks for cabozantinib monotherapy (20-40%) and belzutafan plus cabozantinib (31%) [8][21] 3. **Durability of Responses**: All responders in the CAS plus CABO cohort remain on treatment, indicating durable responses even with a median follow-up of only five months [9][21] 4. **Safety Profile**: The adverse event (AE) profile for the combination therapy is consistent with expectations for each agent alone, with only 5% of patients discontinuing due to AEs, and no patients discontinuing both drugs [10][28] 5. **Strategic Positioning**: Arcus owns the rights to cascadafan, providing significant strategic flexibility and optionality in its development and commercialization [6] 6. **Phase III Study Initiation**: The company is preparing to initiate its first Phase III study (PEEK-one) for cascadafan, expecting rapid enrollment due to strong investigator enthusiasm [5][31] 7. **Market Opportunity**: The market for HIF2 alpha inhibitors in CCRCC is growing, with belzutafan sales reaching over $560 million in the last twelve months. Arcus believes cascadafan could capture a significant share of this market due to its superior profile [34][36] 8. **Combination with Other Therapies**: The potential for cascadafan to be combined with various standard-of-care agents in RCC is highlighted, particularly due to its lack of overlapping toxicities with other treatments [38][39] 9. **Future Development Plans**: Arcus plans to expand its development program for cascadafan, targeting both first-line and second-line settings in CCRCC, with the goal of establishing it as the preferred HIF2 alpha inhibitor [32][41] Other Important Content 1. **Patient Demographics**: The majority of patients in the trial had received prior immunotherapy (IO), with 83% having one prior line of therapy, indicating a contemporary treatment paradigm [20] 2. **Regulatory Filings**: The data presented will support the company's IND filing for the initiation of the PEEK-one study [19] 3. **Collaboration with AstraZeneca**: The EVOLVE RCC-two study, sponsored by AstraZeneca, is designed to assess the safety and efficacy of a TKI-free combination for RCC patients, enhancing resource efficiency [16][60] 4. **Long-term Follow-up**: The company expects to present more mature results from ongoing cohorts over the next 18 months, including ORR and progression-free survival (PFS) data [29][30] This summary encapsulates the critical insights from the conference call, focusing on the company's clinical advancements, market positioning, and future strategies in the oncology sector.

Casdatifan (Cas) & Cabozantinib (Cabo) Combination Therapy - The combination of Cas and Cabo shows a confirmed Overall Response Rate (ORR) of 46% in patients eligible for a minimum of 12 weeks follow-up [32] - In the Cas + Cabo cohort, 98% of patients experienced any treatment-related Adverse Events (AEs) [46] - The median duration of follow-up for patients on Cas 100mg QD + Cabo 60mg QD was 37 months [43] Casdatifan Development and Market Opportunity - Arcus Biosciences has $1 billion in cash to fund pivotal readouts for Domvanalimab (dom), Quemliclustat (quemli), and Casdatifan (cas), including the PEAK-1 trial [12] - Belzutifan prescriptions have grown 154% from December 2023 to April 2025 [74] - Belzutifan achieved LTM sales of >$560 million in the US, with run rate sales based on April Rx's at $720 million+ [75] Clinical Trial and Future Development - PEAK-1, a Phase 3 study, is expected to initiate imminently for post-IO ccRCC, randomizing patients to either 100mg Casdatifan + Cabozantinib or Placebo + Cabozantinib in a 2:1 ratio with approximately 700 patients [67, 68] - Arcus is targeting a $3 billion market opportunity in IO-naive metastatic ccRCC with Casdatifan + Volrustomig (volru) [85] - Arcus is also targeting a $2 billion market in post-IO metastatic ccRCC with Casdatifan + Cabozantinib [85]

Company Performance - Arcus Biosciences reported a quarterly loss of $1.14 per share, which was worse than the Zacks Consensus Estimate of a loss of $1.02, and compared to a loss of $0.05 per share a year ago, indicating a significant decline in performance [1] - The company posted revenues of $28 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 14.24%, and a sharp decline from year-ago revenues of $145 million [2] - Over the last four quarters, Arcus Biosciences has surpassed consensus EPS estimates two times and topped consensus revenue estimates three times [2] Stock Performance - Arcus Biosciences shares have lost about 40% since the beginning of the year, significantly underperforming the S&P 500, which declined by only 3.9% [3] - The current consensus EPS estimate for the coming quarter is -$1.08 on revenues of $30.7 million, and for the current fiscal year, it is -$4.13 on revenues of $123.83 million [7] Industry Outlook - The Medical - Biomedical and Genetics industry, to which Arcus Biosciences belongs, is currently ranked in the top 31% of over 250 Zacks industries, suggesting a favorable industry outlook [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can impact the stock's performance [5]

Financial Data and Key Metrics Changes - The company reported cash of $1 billion at the end of Q1 2025, an increase from $992 million at the end of 2024, bolstered by a $150 million equity financing completed in February 2025 [34] - GAAP revenue for Q1 2025 was $8 million, down from $36 million in Q4 2024, primarily driven by collaboration with Gilead [35] - The company expects to recognize GAAP revenue of $75 million to $90 million for the full year 2025 [35] Business Line Data and Key Metrics Changes - The late-stage portfolio is focused on casdadefan, with ongoing studies expected to generate significant data over the next two years [6][11] - The Fc silent anti-TIGIT antibody, domvanilumab, is on track for its first Phase III study readout in 2026, while the PRISM-one trial for the small molecule CD73 inhibitor is expected to be fully enrolled by the end of 2025 [14][17] Market Data and Key Metrics Changes - The addressable patient population for casdadefan in the IO naive setting is approximately 13,000 in the U.S. and 20,000 in other major markets, with a combined market opportunity estimated at $5 billion [31][32] - TKI-based regimens dominate the clear cell RCC market, holding approximately 65% share in the first line and 75% in the second line setting [32] Company Strategy and Development Direction - The company aims to bring casdadefan to market as quickly as possible, focusing on its advantages over existing therapies [6][11] - There is a strategic collaboration with AstraZeneca to develop a TKI-free combination option for first-line RCC, which is expected to enhance the market position of casdadefan [12][96] - The long-term vision includes developing casdadefan in earlier lines of therapy to displace TKIs, driven by a better safety profile and efficacy [11][12] Management's Comments on Operating Environment and Future Outlook - Management acknowledges the tumultuous macro environment but emphasizes a commitment to efficient execution and resource allocation [5][6] - The company expects a steady flow of data for casdadefan over the next couple of years, reinforcing its competitive advantages [6][10] Other Important Information - The company has a strong balance sheet with $1 billion in cash and investments, allowing it to fund operations through pivotal readouts [17][34] - The company is prioritizing its late-stage programs while maintaining a sustainable pipeline with minimal investment in early-stage programs [43] Q&A Session Summary Question: Can you elaborate on pipeline reprioritization and the adenosine inhibitor program? - Management confirmed that while there is a path forward for the adenosine modulator, current plans do not include moving forward with it at this time [41][42] Question: What should be expected in the ASCO presentation regarding the CAS data? - The ASCO presentation will feature more recent data than the abstract, including safety and efficacy data from approximately 40 patients [44][45] Question: Are there plans to ramp up investment in the TIGIT program? - Management expressed confidence in the current investments and highlighted ongoing discussions for potential future studies based on positive Phase II readouts [52] Question: What is the expected efficacy benchmark for CAS in the second line? - Management indicated that they are looking for meaningful reductions in tumor size and a safety profile that encourages investment in CAS for earlier lines of therapy [55][57] Question: What is the timeline for the PEEK-one study? - Management stated that while it is too early to provide specific timelines, they expect the study to enroll quickly and anticipate a readout that could narrow the gap with competing studies [66][68]

Financial Data and Key Metrics Changes - The company reported cash of $1 billion at the end of Q1 2025, an increase from $992 million at the end of 2024, bolstered by a $150 million equity financing completed in February 2025 [34][36] - GAAP revenue for Q1 2025 was $8 million, down from $36 million in Q4 2024, primarily driven by collaboration with Gilead [35] - The company expects to recognize GAAP revenue of $75 million to $90 million for the full year 2025 [35] Business Line Data and Key Metrics Changes - The late-stage portfolio is focused on the casdadefan program, which is the top priority, with ongoing data generation expected to reinforce its advantages over competitors [4][5] - The Fc silent anti-TIGIT antibody, domvanilumab, is advancing towards its first Phase III study readout, expected in 2026 [14] - The PRISM-one trial of QEMLi, a small molecule CD73 inhibitor, is enrolling rapidly and is anticipated to be fully enrolled by the end of 2025 [16] Market Data and Key Metrics Changes - The addressable patient population for the IO naive setting is approximately 13,000 in the U.S. and 20,000 in other major markets, with a combined market opportunity estimated at $5 billion [30][31] - TKI-based regimens dominate the clear cell RCC market, holding approximately 65% share in the first line and 75% in the second line settings [31] Company Strategy and Development Direction - The company aims to develop casdadefan in TKI-free regimens, targeting earlier lines of RCC treatment to improve patient quality of life [11][12] - Collaborations with AstraZeneca are focused on combining casdadefan with their anti-PD-1/CTLA-4 bispecific antibody for first-line RCC, marking a strategic move towards TKI-free options [12][96] - The company is prioritizing late-stage programs while maintaining a sustainable pipeline with minimal investment in early-stage programs [43] Management's Comments on Operating Environment and Future Outlook - Management remains focused on execution amidst a tumultuous macro environment, ensuring resource deployment reflects ongoing assessments of priorities [4][5] - The company anticipates a steady flow of data for casdadefan over the next couple of years, reinforcing its competitive position [5][10] - Management expressed confidence in the ability to fund operations through pivotal readouts, with a strong balance sheet supporting ongoing development [34][36] Other Important Information - The company is exploring additional cohorts in the ARC20 study to evaluate casdadefan in various settings, including TKI-free regimens [13][19] - The competitive landscape for anti-TIGIT antibodies has shifted, with the company and AstraZeneca's candidates dominating the Phase III landscape [15] Q&A Session Summary Question: Can you elaborate on pipeline reprioritization and the adenosine inhibitor program? - Management confirmed that while there is a path forward for the adenosine modulator, current plans do not include moving forward with it at this time, focusing instead on late-stage programs like casdadefan [39][41] Question: What should be expected in the ASCO presentation versus the abstract? - Management indicated that the ASCO presentation will feature more recent data, including safety and efficacy for a population of about 40 patients, with compelling results anticipated [44][46] Question: What is the plan for the Peak One study and its primary endpoint? - Management stated that it is too early to provide specific timelines for the Peak One study's PFS primary endpoint, but they expect rapid enrollment and are focused on collecting OS data as a key secondary endpoint [66][68] Question: Will the company consider commercialization partnerships post-Peak One? - Management expressed intent to commercialize casdadefan independently, with potential consideration for a partner in Europe, emphasizing confidence in their capabilities [108]

COMBINING TO CURE ® Arcus is at the forefront of designing combination therapies, with best-in-class potential, in the relentless pursuit of cures for cancer. May 6, 2025 CORPORATE PRESENTATION Notice of Trademark: The Arcus name and logo are the property of Arcus. All other trademarks used herein are the property of their respective owners and are used for reference purposes only. Such use should not be construed as an endorsement of Arcus. Forward-Looking Statements/Safe Harbor Forward Looking Statements ...

Revenue Generation - The company has not generated any revenue from product sales and does not expect to do so for the foreseeable future, with all revenue recognized to date coming from research, collaboration, and license arrangements [145]. - Total revenues for the three months ended March 31, 2025, decreased to $28 million, down 81% from $145 million in the same period of 2024 [156]. - License and development services revenue fell to $20 million, a decrease of 85% compared to $135 million in the prior year [156]. Clinical Programs - The company has seven clinical programs targeting unique indications, including HIF-2α, TIGIT, and PD-1, with significant collaboration agreements in place with Gilead [137]. - The median progression-free survival (mPFS) for the 50mg twice-a-day casdatifan monotherapy cohort reached 9.7 months, with confirmed objective response rates ranging from 25% to 33% [149]. - Most patients (81-87%) experienced disease control with either a partial response or stable disease while on treatment [143]. - The company retains full global development and commercial rights for the HIF-2α program after Gilead's option rights expired [141]. - The company is not pursuing a Phase 3 study for etrumadenant at this time, despite promising results from the ARC-9 study [144]. Financial Performance - Research and development expenses increased by 12% to $122 million for the three months ended March 31, 2025, up from $109 million in 2024 [158]. - Early-stage R&D and preclinical program expenses surged by 68% to $42 million, compared to $25 million in the previous year [158]. - Net cash used in operating activities was $132 million for the three months ended March 31, 2025, compared to $2 million in the same period of 2024 [171]. - General and administrative expenses are expected to remain stable for the remainder of the year [153]. Funding and Cash Position - In February 2025, the company issued 13.6 million shares at $11.00 per share, resulting in total gross proceeds of approximately $150 million [141]. - Cash provided by financing activities amounted to $142 million, primarily from the issuance of common stock in February 2025 [173]. - As of March 31, 2025, the company had $210 million in deferred revenue related to performance obligations with Gilead [178]. - The company has a term loan facility of $250 million, with $50 million drawn at closing and an additional $100 million available [168]. - Gilead acquired approximately 29.7% of the company's outstanding common stock as of March 31, 2025, following a stock purchase agreement [166]. - The company believes its cash and investments will be sufficient to fund operations for at least twelve months following the report date [164]. Future Expectations - The company expects R&D expenses to peak in 2025 and then decline significantly as programs advance towards regulatory approval [151]. - The company anticipates significant growth in development capabilities and infrastructure as it advances clinical-stage programs [151].

Financial Performance - Revenues for Q1 2025 were $28 million, a decrease from $145 million in Q1 2024, with an expected full-year GAAP revenue of $75 million to $90 million[12] - The net loss for Q1 2025 was $112 million, compared to a net loss of $4 million in Q1 2024[15] - Total revenues for Q1 2025 were $28 million, a decrease of 80.7% compared to $145 million in Q1 2024[24] - The net loss for Q1 2025 was $112 million, compared to a net loss of $4 million in Q1 2024, indicating a significant increase in losses[24] - The company reported a basic and diluted net loss per share of $1.14 for Q1 2025, compared to $0.05 for Q1 2024[24] Research and Development - Research and Development (R&D) expenses increased to $122 million in Q1 2025 from $109 million in Q1 2024, primarily due to higher costs in early-stage development[12] - Research and development expenses increased to $122 million in Q1 2025, up from $109 million in Q1 2024, reflecting a 11.9% rise[24] - The company is focused on advancing its pipeline, including the initiation and design of future studies such as PEAK-1 and the eVOLVE study[20] - Casdatifan, a HIF-2a inhibitor, is expected to have data presented at the 2025 ASCO Annual Meeting, with ongoing trials in multiple settings for clear cell renal cell carcinoma (ccRCC)[5] - The Phase 3 trial PEAK-1 for casdatifan is planned to initiate in Q2 2025, evaluating its efficacy against cabozantinib in IO-experienced ccRCC patients[11] - The company expects to present additional data from ARC-20 cohorts evaluating casdatifan monotherapy in fall 2025[11] Cash and Assets - Cash, cash equivalents, and marketable securities totaled $1.0 billion as of March 31, 2025, up from $992 million at the end of 2024, mainly due to net proceeds from an offering[12] - Cash, cash equivalents, and marketable securities totaled $1,005 million as of March 31, 2025, up from $992 million at the end of 2024[26] - Total assets increased slightly to $1,156 million in Q1 2025 from $1,150 million at the end of 2024[26] - Total liabilities decreased to $625 million in Q1 2025 from $665 million at the end of 2024, showing a reduction of 6%[26] - The total stockholders' equity increased to $531 million in Q1 2025 from $485 million at the end of 2024, reflecting a growth of 9.5%[26] Operational Efficiency - General and Administrative (G&A) expenses decreased to $28 million in Q1 2025 from $32 million in Q1 2024, reflecting cost reductions related to prior agreements[15] - Arcus is advancing its pipeline with a focus on casdatifan, supported by a strong balance sheet and operational plans to fund its development through initial pivotal readouts[5] Collaborations - Arcus is collaborating with AstraZeneca to evaluate casdatifan in combination with their investigational bispecific antibody in IO-naive ccRCC patients[11] - Arcus is dependent on collaborations with third parties like Gilead and Taiho for the successful development and commercialization of its investigational products[20]

Core Insights - Arcus Biosciences (NYSE: RCUS) has experienced mixed developments since last year, with the stock continuing to decline into April 2025 [1] - The company maintains sufficient cash reserves and has a broad pipeline of projects, indicating potential for future growth despite current challenges [1] Financial Position - The company has sufficient cash, which may provide a buffer against ongoing market pressures [1] - The broad pipeline suggests that there are multiple avenues for potential revenue generation in the future [1]