Cardiff Oncology (CRDF) Oppenheimer 36th Annual Healthcare Life Sciences Conference summary

Program overview and clinical rationale

• Lead program is an oral, highly selective PLK1 inhibitor, onvansertib, targeting first-line RAS-mutated metastatic colorectal cancer (mCRC), a high unmet need area.

• Onvansertib shows strong efficacy signals, with a confirmed overall response rate (ORR) of 72% at the higher dose in combination with FOLFIRI and bevacizumab, representing a 30% improvement over standard of care.

• Median progression-free survival (PFS) has not yet been reached in the onvansertib arm, with favorable dose-dependent trends and robust hazard ratios.

• The drug is being considered for expansion into other RAS-driven cancers, such as chronic myelomonocytic leukemia (CMML).

• Onvansertib is the only program specifically designed for the entire RAS-mutated mCRC population, with no approved therapies currently available for this group.

Clinical trial data and competitive landscape

• Phase II study in first-line RAS-mutated mCRC randomized 110 patients to standard of care or two doses of onvansertib with FOLFIRI/bev; included patients with aggressive disease and liver metastases.

• The 30 mg onvansertib arm achieved a 72.2% ORR versus 43.2% for combined standard of care, with deeper and more durable responses.

• Median PFS has not been reached in onvansertib arms, while standard of care reached 11 months; hazard ratios indicate significant risk reduction and statistical significance in the 30 mg arm.

• No significant additive toxicity observed when onvansertib is combined with standard chemotherapy regimens.

• Preclinical and clinical data suggest synergy between onvansertib, chemotherapy, and bevacizumab, enhancing anti-angiogenic effects.

Regulatory and development plans

• Finalizing the path to registration for onvansertib in frontline RAS-mutated mCRC, with plans to meet with the FDA and provide a full plan within the first half of the year.

• Phase III trial design will focus on 30 mg onvansertib with FOLFIRI-bev, aiming for both Accelerated and full approval, with global enrollment planned.

• Pfizer is the CRO partner for the ongoing trial and has invested $15 million, but full program rights are retained.

• Additional indications, such as CMML, are being explored through investigator-initiated studies, with promising single-agent activity.

• More detailed phase II data and regulatory feedback are expected in the first half of the year, with phase III trial initiation planned for the second half.