Cardiff Oncology (CRDF) Company presentation summary

Market opportunity and clinical rationale

• Onvansertib is a first-in-class, highly selective oral PLK1 inhibitor targeting RAS-mutated metastatic colorectal cancer (mCRC), a large, underserved market with high unmet need and limited innovation.

• Approximately 150,000 new CRC cases are diagnosed annually in the U.S., with RAS mutations present in about 50% of first-line mCRC cases.

• The drug is designed to avoid toxicity and has shown robust efficacy, especially in bevacizumab-naïve patients, suggesting synergistic biology.

• FDA alignment has been achieved for a registrational program supporting both accelerated and full approval pathways.

Clinical trial results and efficacy

• In the ongoing Phase 2 CRDF-004 trial, onvansertib plus standard of care (SoC) demonstrated dose-dependent increases in objective response rate (ORR), with 49% confirmed ORR at 30mg vs. 30% for SoC alone.

• Deeper and more durable tumor regression was observed with onvansertib, with a greater proportion of patients achieving early tumor shrinkage and depth of response compared to control.

• Several patients achieved complete responses and were referred for curative surgery, highlighting the potential for significant clinical benefit.

• Initial progression-free survival (PFS) data show separation between the 30mg onvansertib and control arms, with median PFS not yet reached.

Mechanism of action and preclinical data

• Onvansertib acts through multiple mechanisms: synthetic lethality in RAS-mutant backgrounds, synergy with chemotherapy, and synergy with bevacizumab via antiangiogenesis.

• Preclinical models show that onvansertib combined with bevacizumab or chemotherapy results in greater tumor regression and reduced vascularization than single agents.

• Onvansertib inhibits the hypoxia signaling pathway by downregulating HIF1a, restricting tumor adaptation to hypoxia and strengthening intellectual property protection.