Cardiff Oncology (CRDF) investor relations material

Pipeline and clinical data

• Focus on PLK1 inhibitor onvansertib, an oral molecule advancing to phase III for frontline RAS-mutated metastatic colorectal cancer, with promising phase II data presented at ASCO.

• Phase II showed 72% ORR in the FOLFIRI/bev arm versus historical 42% for controls, with median PFS not yet reached in the active arms and a hazard ratio around 0.55.

• Mechanistic synergy between onvansertib and irinotecan (FOLFIRI) likely drives superior efficacy compared to FOLFOX, due to effects on angiogenesis and DNA damage repair.

• Several patients in the 30mg cohort achieved 100% lesion reduction, with some proceeding to curative surgery, contributing to observed PFS benefit.

• Confidence in reproducibility of results for phase III is supported by consistent hazard ratios across two studies and robust analysis methods.

Regulatory and phase III development

• Completed end of phase II meeting with FDA, which endorsed moving forward with 30mg onvansertib plus FOLFIRI/bev in phase III.

• Phase III will randomize 640 patients globally, comparing onvansertib plus FOLFIRI/bev to FOLFIRI/bev alone, powered >90% for PFS and ORR differences.

• Study designed for potential accelerated approval based on ORR and durability, with PFS as the primary endpoint for full approval.

• Recruitment expected to be strong globally, with enthusiasm from both U.S. and ex-U.S. clinicians, and no anticipated issues switching from FOLFOX to FOLFIRI.

• Awaiting EMA guidance and finalizing CRO selection; enrollment timelines to be clarified after site feasibility assessments.

Market positioning and strategic outlook

• Onvansertib is positioned as a differentiated, well-tolerated agent in a space with little innovation for two decades, addressing a significant unmet need.

• Tolerability allows first-line use, which is rare for new agents in this setting.

• Current pan-RAS inhibitors face toxicity challenges in colorectal cancer, making onvansertib's profile attractive for broad RAS-mutated populations.

• Commercial opportunity is substantial, with estimated per-patient study costs of $200,000–$300,000 and ongoing efforts to secure both dilutive and non-dilutive funding.

• Exploring additional indications such as CMML, where early monotherapy activity has been observed.