Summary of Cardiff Oncology Conference Call - October 09, 2025 Company Overview - **Company**: Cardiff Oncology (NasdaqCM:CRDF) - **Lead Asset**: Onvansertib, a small molecule targeting PLK1, a known cancer therapy target Industry Context - **Disease Focus**: Colorectal cancer, the third most common cancer globally, with increasing incidence, particularly in individuals under 50 in the U.S. - **Market Need**: High unmet need in RAS-mutated metastatic colorectal cancer (MCRC), with limited innovation in the last 20 years Key Points and Arguments 1. **Onvansertib's Mechanism**: - First-in-class PLK1 inhibitor that is well tolerated and can be combined with chemotherapy for colorectal cancer treatment [2][3] - Demonstrates 5,000-fold greater specificity for PLK1 compared to other PLKs, contributing to its tolerability [3] 2. **Clinical Trial Insights**: - The CARDIFF-004 trial is a Phase II study focusing on first-line RAS-mutated MCRC, combining onvansertib with standard chemotherapy [7] - Confirmed objective response rate of 49%, a nearly 20% improvement over control [8] - Early signs of progression-free survival (PFS) separation observed, particularly in the 30 mg dose group [11][12] 3. **Patient Response**: - Significant depth of response noted, with some patients previously considered unresectable being referred for curative surgery [11] - High patient compliance due to the oral administration and low toxicity profile [13] 4. **Safety Profile**: - Minimal additive toxicity observed when combined with standard chemotherapy, with no significant increase in grade III or higher adverse events [13] 5. **Strategic Partnerships**: - Pfizer invested $15 million in Cardiff Oncology in 2021 and has a member on the Scientific Advisory Board, indicating strategic interest in onvansertib [19] - Pfizer is acting as a contract research organization for the ongoing trial, while Cardiff retains full ownership of onvansertib [20] 6. **Financial Position**: - As of June 30, 2025, Cardiff had $71 million in cash, funding operations into early 2027 [21] - Anticipated updates from the CARDIFF-004 trial in Q1 2026, expected to provide more data on durability and PFS [27] 7. **Commercial Opportunity**: - Analysts estimate peak sales for onvansertib between $2 billion and $3 billion annually, with a favorable competitive landscape in first-line RAS-mutated MCRC [31] - Rapid adoption expected if efficacy is demonstrated without additional toxicity [32] 8. **Market Positioning**: - Onvansertib targets RAS-mutated MCRC, which constitutes about 50% of the patient population, while competitors like Meris focus on RAS wild type patients, thus not seen as direct competition [35] Additional Important Content - **Future Directions**: Cardiff is exploring other indications for onvansertib, including triple-negative breast cancer and small cell lung cancer, while maintaining focus on colorectal cancer [24] - **Research Findings**: Novel findings regarding the synergy between onvansertib and bevacizumab published in top journals, with patents extending the commercial runway for onvansertib [18] This summary encapsulates the critical insights from the conference call, highlighting Cardiff Oncology's strategic positioning, clinical advancements, and market potential for onvansertib in treating colorectal cancer.

Core Viewpoint - Akeso, Inc. has initiated a Phase III clinical trial for ivonescimab as a first-line treatment for advanced metastatic colorectal cancer (mCRC), addressing a significant unmet clinical need in this area [1][2][7]. Industry Overview - Colorectal cancer is the third most common cancer globally and the second leading cause of cancer-related deaths, with over 1.9 million new cases and approximately 904,000 deaths reported in 2022 [3]. - About 95% of mCRC cases are classified as microsatellite stable (MSS) or proficient mismatch repair (pMMR), which traditionally show poor responses to immunotherapy [3]. - Current standard treatments for mCRC include chemotherapy combined with targeted therapies, but the overall efficacy remains limited, with a five-year survival rate for advanced patients of less than 20% [4]. Company Initiatives - The Phase III trial (AK112-312/HARMONi-GI6) aims to validate the clinical benefits of ivonescimab, which has shown promising Phase II efficacy data in combination with chemotherapy for MSS/pMMR-type mCRC [5][7]. - The combination of ivonescimab with FOLFOXIRI demonstrated an overall response rate (ORR) of 81.8% and a disease control rate (DCR) of 100%, indicating compelling anti-tumor activity in this difficult-to-treat patient population [6]. Future Prospects - If successful, ivonescimab could provide a novel first-line immunotherapy treatment option for patients with advanced mCRC, potentially improving outcomes compared to existing therapies [7].

Core Insights - Innovent Biologics has presented promising clinical data for IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, at the 2025 ASCO Annual Meeting, demonstrating its potential to convert "cold tumors" into "hot tumors" in advanced colorectal cancer [1][2][10] Clinical Data Summary - IBI363 monotherapy showed a median overall survival (OS) of 16.1 months in patients with advanced colorectal cancer, significantly better than standard treatments which range from 6.4 to 9.3 months [6][10] - In Phase 1 studies, IBI363 combined with bevacizumab resulted in a confirmed objective response rate (cORR) of 15.1% and a disease control rate (DCR) of 61.6% among 73 participants [9] - The combination therapy showed a median progression-free survival (PFS) of 4.7 months, with a notable increase in efficacy for patients without liver metastases, achieving a cORR of 31.3% and a DCR of 81.3% [9] Mechanism of Action - IBI363 operates by blocking the PD-1/PD-L1 pathway while activating the IL-2 pathway, specifically targeting tumor-specific T cells, which enhances its therapeutic efficacy in treating colorectal cancer [11][12] - Tumor immune cell infiltration analysis indicated that higher levels of CD8+ T cells were associated with improved clinical responses to IBI363, supporting its mechanism of action [8] Future Development - Innovent is conducting further clinical studies in multiple countries to explore IBI363's efficacy across various tumor indications, including immune-resistant and cold tumors [12] - The company has initiated a pivotal trial for IBI363 targeting unresectable locally advanced or metastatic mucosal or acral melanoma [12][13] Company Overview - Innovent Biologics, founded in 2011, focuses on developing high-quality biopharmaceuticals for various diseases, including cancer, and has launched 15 products to date [14][15] - The company has received fast track and breakthrough designations from regulatory authorities for IBI363, indicating its potential in treating specific cancer types [13]

Core Viewpoint - Cardiff Oncology has received a patent for the use of onvansertib in combination with bevacizumab for treating all bev-naïve metastatic colorectal cancer (mCRC) patients, which is expected to enhance its market opportunities and growth potential [1][2]. Group 1: Patent and Treatment Scope - The newly issued patent covers the combination treatment of onvansertib and bevacizumab for all bev-naïve mCRC patients, including those with RAS mutations and RAS wild type, across all lines of therapy until at least 2043 [1]. - This patent expands the applicability of onvansertib beyond the current focus on first-line RAS-mutated patient populations, potentially redefining the standard of care for mCRC [2]. Group 2: Clinical Development - Onvansertib is currently being evaluated in a Phase 2 clinical trial (CRDF-004) in combination with FOLFIRI and bevacizumab or FOLFOX and bevacizumab for RAS-mutated mCRC patients [2]. - Initial data from the ongoing CRDF-004 trial was announced in December 2024, with additional clinical data expected in the first half of 2025 [2]. Group 3: Company Overview - Cardiff Oncology is a clinical-stage biotechnology company focused on developing therapies leveraging PLK1 inhibition for various cancers, with onvansertib as its lead asset [3]. - The company is targeting treatment-resistant tumors and aims to deliver superior clinical benefits compared to standard of care in indications such as mCRC, metastatic pancreatic ductal adenocarcinoma, small cell lung cancer, and triple-negative breast cancer [3].

Core Viewpoint - Galmed Pharmaceuticals has initiated a research collaboration with Virginia Commonwealth University to explore the potential of Aramchol in overcoming drug resistance in gastrointestinal cancers, particularly colorectal and hepatocellular cancers, aiming to enhance treatment efficacy against these aggressive tumors [1][5]. Group 1: Collaboration Details - The collaboration involves VCU scientists studying Aramchol in preclinical models, focusing on its ability to prevent or reverse resistance to standard therapies such as targeted kinase inhibitors and chemotherapies [1][2]. - The project is based on recent research highlighting the role of lipid metabolic pathways, specifically Stearoyl-CoA Desaturase 1 (SCD1), in driving drug resistance in GI tumors [2][5]. - Galmed will provide funding and Aramchol materials, while VCU will conduct the studies, leveraging its expertise in cancer biology and drug resistance [7]. Group 2: Market Implications - This partnership marks a strategic expansion for Galmed beyond its historical focus on fibrotic liver diseases into oncology, targeting a significant market with high unmet needs [4][5]. - Aramchol is the most clinically advanced SCD1 inhibitor, with a strong safety profile demonstrated in previous trials, presenting a unique opportunity in cancer treatment [4][5]. - The collaboration aims to generate proof-of-concept data that could lead to further clinical development in oncology, potentially expanding Galmed's pipeline and enhancing its commercial prospects [6][7]. Group 3: Clinical Context - A significant proportion of patients with advanced hepatocellular carcinoma (HCC) do not benefit from current second-line therapies due to drug resistance, with most developing resistance within six months [3][6]. - Targeting lipid metabolism with Aramchol is seen as a promising strategy to overcome resistance to tyrosine kinase inhibitors (TKIs), which are pivotal in treating advanced HCC [6][3]. - The collaboration aims to develop safe drug combinations that can block and circumvent drug resistance in HCC, addressing a critical need in cancer treatment [3][6].