Cardiff Oncology, Inc. (NASDAQ:CRDF) is a clinical-stage biotechnology company leveraging Polo-like Kinase 1 (PLK1) inhibition to develop novel therapies across a range of cancers. The company's lead asset, onvansertib, is an oral and highly selective PLK1 inhibitor that is being evaluated in combination with standard of care (SoC) therapeutics in clinical programs targeting indications such as RAS-mutated metastatic colorectal cancer (mCRC), as well as investigator-initiated trials in metastatic pancreatic ductal adenocarcinoma (mPDAC), small cell lung cancer (SCLC), and triple negative breast cancer (TNBC).

In the first quarter of 2024, Cardiff Oncology presented promising data at the American Association for Cancer Research (AACR) Annual Meeting that further validated the company's clinical development strategy for onvansertib in first-line RAS-mutated mCRC. The data demonstrated onvansertib's ability to enhance the efficacy of standard of care treatments, particularly in bevacizumab (bev)-naive patients, providing a strong rationale for the ongoing CRDF-004 trial.

Business Overview

Cardiff Oncology's lead program is focused on the development of onvansertib in RAS-mutated mCRC. Onvansertib is a highly potent and selective PLK1 inhibitor with a 24-hour half-life, allowing for flexible dosing and scheduling. Preclinical studies have shown synergistic effects when onvansertib is administered in combination with various standard of care cancer agents, including irinotecan, 5-fluorouracil (5-FU), and bevacizumab.

The company's clinical development strategy in mCRC is centered around the CRDF-004 trial, a Phase 2 open-label, randomized multi-center clinical trial evaluating onvansertib in combination with FOLFIRI and bevacizumab or FOLFOX and bevacizumab for the first-line treatment of patients with RAS-mutated mCRC. The primary objective of the trial is to evaluate onvansertib's safety and efficacy in combination with standard of care, as well as to evaluate two doses of onvansertib, 20mg and 30mg, against standard of care alone. The primary endpoint is objective response rate (ORR), with progression-free survival and duration of response as secondary endpoints.

In addition to the CRDF-004 trial, Cardiff Oncology has several other ongoing and planned clinical trials evaluating onvansertib in various cancer indications, including mPDAC, SCLC, and TNBC.

Financials

For the full year 2023, Cardiff Oncology reported annual revenue of $488,000 and a net loss of $41,441,000. The company's annual operating cash flow was -$30,887,000, and its annual free cash flow was -$31,469,000.

In the first quarter of 2024, the company reported total revenues of $205,000, compared to $83,000 in the same period of 2023. Research and development expenses decreased by $1.0 million, while selling, general, and administrative expenses increased by $47,000 compared to the prior-year quarter.

As of March 31, 2024, Cardiff Oncology had $67.2 million in cash, cash equivalents, and short-term investments, which the company believes will be sufficient to fund its operations into the third quarter of 2025, well beyond the expected initial data readout from the CRDF-004 trial.

Promising Data from AACR Supports First-Line mCRC Strategy

At the AACR Annual Meeting in March 2024, Cardiff Oncology presented five posters that provided strong scientific rationale for the clinical development of onvansertib across multiple tumor types and various combinations.

One of the key highlights was the data from the company's lead program in RAS-mutated mCRC. The poster presented both clinical data from the Phase Ib/II trial and subsequent preclinical studies that support the scientific rationale for the company's clinical findings. Notably, the data showed that bevacizumab-naive patients within the Phase Ib/II trial had a higher objective response rate and longer progression-free survival compared to historical controls.

The additional preclinical data disclosed at AACR provided further evidence that onvansertib and bevacizumab have their pharmacological effect at two different nodes of the hypoxia pathway, suggesting a synergistic mechanism of action. In vivo combination studies in KRAS-mutant mCRC xenograft models confirmed the positive results, with the combination of onvansertib and bevacizumab resulting in significantly superior antitumor activity and greater decreases in tumor vascularization compared to either agent alone.

Collectively, the clinical and preclinical data presented at AACR in RAS-mutated second-line mCRC provided further validation of Cardiff Oncology's ongoing CRDF-004 trial, which is evaluating onvansertib in combination with standard of care in the first-line setting for patients with RAS-mutated mCRC.

CRDF-004 Trial Update

The CRDF-004 trial is a Phase 2 open-label, randomized multi-center clinical trial evaluating onvansertib in combination with standard of care FOLFIRI and bevacizumab or FOLFOX and bevacizumab for the first-line treatment of patients with RAS-mutated mCRC. The trial is being conducted in partnership with Pfizer Ignite and is expected to enroll approximately 90 evaluable patients.

In the first quarter of 2024, Cardiff Oncology announced that the first patient had been dosed in the CRDF-004 trial. The company initially forecasted that it would be able to share initial data from the trial in the second quarter or third quarter of 2024. However, based on the actual enrollment trends at the activated sites over the past few months, the company's expectation for the timing of an initial data readout is now in the third quarter or fourth quarter of 2024.

Despite the slight delay in the initial data readout, Cardiff Oncology remains highly confident in the ongoing site activation and enrollment efforts, as well as the resources provided by its partnership with Pfizer Ignite. The company anticipates that the initial data release will include objective response rate for approximately half of the 90 patients expected to be enrolled in the trial.

Contingent upon the results of the CRDF-004 trial, Cardiff Oncology plans to initiate CRDF-005, a Phase 3 randomized trial with registrational intent. The FDA has agreed that a seamless trial with ORR at an interim point is an acceptable endpoint to pursue accelerated approval, with progression-free survival and trend in overall survival being the endpoints for full approval.

Broader Clinical Pipeline and Preclinical Data

In addition to the RAS-mutated mCRC program, Cardiff Oncology presented promising preclinical data at AACR supporting the potential of onvansertib in other cancer indications.

In RAS wild-type mCRC, onvansertib displayed robust antitumor activity as a monotherapy and in combination with the EGFR inhibitor cetuximab, which is the standard of care for RAS wild-type mCRC patients. The combination of onvansertib and cetuximab induced tumor stasis or regression in 90% of the patient-derived xenograft (PDX) models evaluated.

Furthermore, the company presented preclinical data demonstrating onvansertib's potential in small cell lung cancer and ovarian cancer. In small cell lung cancer, the combination of onvansertib and paclitaxel, one of the standard-of-care treatments, showed synergistic inhibition of tumor proliferation in cell lines and was well-tolerated and highly effective in PDX models. In ovarian cancer, the combination of onvansertib with carboplatin or gemcitabine, both standard-of-care agents, exhibited antitumor activity in platinum-resistant PDX models.

These preclinical findings support the continued clinical development of onvansertib in a broader range of cancer indications, beyond the company's primary focus on RAS-mutated mCRC.

Liquidity

As of March 31, 2024, Cardiff Oncology had $67.2 million in cash, cash equivalents, and short-term investments, which the company believes will be sufficient to fund its operations into the third quarter of 2025. This cash runway extends well beyond the expected initial data readout from the CRDF-004 trial in the third or fourth quarter of 2024.

For the full year 2023, Cardiff Oncology reported annual revenue of $488,000 and a net loss of $41,441,000. The company's annual operating cash flow was -$30,887,000, and its annual free cash flow was -$31,469,000. In the first quarter of 2024, the company reported total revenues of $205,000, compared to $83,000 in the same period of 2023.

Risks and Conclusion

Cardiff Oncology's clinical development efforts are in their early stages, and the company faces the inherent risks associated with drug development, including the long duration of clinical testing, the specific performance of proposed products under stringent clinical trial protocols, extended regulatory approval and review cycles, and the ability to raise additional capital.

However, the promising data presented at AACR, the ongoing CRDF-004 trial, and the company's strong financial position provide a solid foundation for Cardiff Oncology's continued progress in developing onvansertib as a potential treatment for RAS-mutated mCRC and other cancer indications. The initial data readout from the CRDF-004 trial, expected in the third or fourth quarter of 2024, could represent a significant value inflection point for the company and the nearly 50,000 patients diagnosed with RAS-mutated mCRC each year in the United States.