By John Vandermosten, CFA
NASDAQ:CRDF
READ THE FULL CRDF RESEARCH REPORT
We are initiating coverage of Cardiff Oncology, Inc. (NASDAQ:CRDF) with a valuation of $8.50 per share. This value is based on our estimates for successful development and commercialization of onvansertib for first line treatment of patients with metastatic colorectal cancer (mCRC). Onvansertib is a Polo-Like kinase 1 (PLK1) inhibitor and the subject of a Phase II study which has reported favorable efficacy results. An update on the program is expected in 1Q:26 where further clarity will be provided on the design of a registrational Phase III trial that will support accelerated and full approval.
Cardiff’s clinical resources are focused on the indication in mCRC; however, there are investigator-sponsored studies that are evaluating other indications. This includes the University of Kansas Medical Center studies in metastatic pancreatic ductal adenocarcinoma (mPDAC), University of Maryland studies in small cell lung cancer (SCLC), and Dana Farber Cancer Institute work in triple negative breast cancer (TNBC). While we do not expect Cardiff to pursue these in the near term, the indications may become candidates when the mCRC indication has exited the clinic.
Polo-Like Kinase 1 is a serine/threonine kinase enzyme that plays a central role in cell division. If PLK1 is dysregulated, it can drive cancer by promoting excessive cell proliferation and overriding cell cycle checkpoints. Patients with high PLK1 expression in tumors have a poor prognosis. Blocking the expression of PLK1 can inhibit the proliferation of tumor cells and induce apoptosis, especially in combination with other therapies. This has led to development of numerous inhibitors of the enzyme, including onvansertib. Onvansertib builds upon the science underlying previously developed Polo-Box Kinase inhibitors by narrowing its specificity to the PLK1 enzyme. It offers fewer off-target effects than previous generations of PLK inhibitors, which were associated with poor tolerability. No other PLK inhibitors have been approved.
We anticipate that the onvansertib mCRC program will begin a Phase III registrational study next year and generate sufficient data to submit a new drug application by 2029. Following FDA review, approval could be granted by 2030 in the United States. We anticipate registrational submissions in other developed regions around the world in subsequent years. Our model assumes approvals in the EU, Asia, Oceania, and other countries in 2031 and beyond. We forecast that an established pharmaceutical company will either buy the company or license global commercialization rights to onvansertib and assume commercialization activities.
Cardiff has demonstrated clinical activity and initial safety for onvansertib and is in the process of developing a Phase III study with the FDA that will demonstrate further efficacy and satisfy requirements for both accelerated and full approval. Data to date has shown that both 20 mg and 30 mg doses of onvansertib in combination with bevacizumab and chemotherapy produces a better overall response rate (ORR) and progression free survival (PFS) compared to standard of care. If these results are replicated in a Phase III study, we expect FDA approval following the achievement of the study’s accelerated endpoints.
Cardiff is working closely with partners such as Pfizer to develop onvansertib. Pfizer initially invested in Cardiff in 2021 through its Breakthrough Growth Initiative program. It provided $15 million in capital and a Pfizer representative to participate on Cardiff’s Scientific Advisory Board. This investment gives Pfizer the right of first access to data prior to publication and could potentially set up this large pharmaceutical company to be an acquiror. In 2023, Pfizer took another step closer to Cardiff by having Pfizer Ignite’s clinical development infrastructure provide its expertise to run onvansertib’s mCRC trial.
Despite being the 3rd or 4th most common cancer around the globe and in the US, mCRC represents an unmet need, especially in the metastatic setting, where mortality is high and approved therapies provide progression free survival (PFS) of around a year or less. The addressable market for onvansertib in the current setting for mCRC is just under 30,000 in the United States and about 84,000 in the developed world.
Cardiff has a strong balance sheet with sufficient capital to support the completion of its Phase II trial and begin its registrational Phase III. With over $60 million at the beginning of 4Q:25 and a cash burn rate of about $40 million per year, we see sufficient funds available to support company operations into 2027. In addition to strong relationships with the banking community, Cardiff also has access to an at-the-market (ATM) facility with Jefferies that can augment registered offerings at low cost.
We expect further updates from Cardiff in the new year as Phase II mCRC data continue to mature and as the team has an opportunity to meet with the FDA to design a registrational trial. Assuming the two parties can agree on next steps, we anticipate the clinical trial to generate registrational data by 2029, which will be subsequently submitted to the FDA for accelerated approval.
Key reasons to own Cardiff Oncology shares:
- Onvansertib has demonstrated remarkable overall response rate (ORR) in bevacizumab naïve mCRC
- Prior trial in second line KRAS-mutated mCRC showed a material improvement in ORR in combination with standard of care
- ORR of 77% & median PFS of 14.9 months[1]
- Compares with standard of care 2nd line of 20% ORR & PFS of 7 months
- Addresses gap in effective treatments for RAS-mutated mCRC
- Mechanism of action inhibits angiogenesis cascade
- Dose dependent response
- Agent is highly specific to PLK1 with low off target binding affinity
- Brings new treatment to indication lacking innovation for last 20 years
- Colorectal cancer is 3rd or 4th (Global and US) most common cancer
- 154,000 estimated new cases of CRC in 2025
- Addressable market is approximately 19% of the total
- Adverse event profile for combination onvansertib is similar to standard of care
- Onvansertib expected to begin registrational Phase III trial 1Q:26
- Designed for accelerated and full approval
- FDA awarded Fast Track designation
- Multiple efficacy surrogates predict long term outcome
- Early tumor shrinkage
- Depth of response
- Balance sheet provides sufficient cash to support operations until 2027
- Robust intellectual property
- Patent portfolio addressing multiple indications and combination therapies
- Patents extend until 2043, with eligibility for five years of patent term extension
Our initiation report on Cardiff Oncology provides the information necessary for an investor to evaluate the company and determine whether or not it is an appropriate investment based upon their tolerance for reward and risk. In the report, we define the use of targeted therapy in oncology and dive into PLK1 inhibitors and how they work in combination with other agents. We examine the ways in which PLK1 inhibitors differ from other types of targeted therapy and how onvansertib specifically addresses an unmet need in RAS-mutated mCRC.
The report follows with a review of Cardiff’s clinical trials for onvansertib in mCRC and summarizes endpoints and safety metrics. The review highlights the unexpected and serendipitous finding that bevacizumab-naïve patients in the second line setting perform better than patients that had received the VEGF inhibitor as part of their prior first line therapy. After the introduction to onvansertib, we take a thorough look at colorectal cancer, including the most important types, the incidence and prevalence of the disease, risk factors, screening, symptoms, diagnosis, and standard of care. The next section introduces peers and competitors in the space who have developed other PLK1 or Polo Box domain inhibitors or are pursuing new therapies in mCRC.
The report then examines Cardiff’s corporate history and milestones achieved, followed by a review of 2025 financial performance. The next section discusses risks faced by life sciences companies in general and for those at the smaller end of the spectrum. This includes financial, partner, regulatory, manufacturing, and other risks. The final section of our report discusses the data and assumptions underlying our valuation for onvansertib in first-line, RAS-mutant metastatic colorectal cancer. Our work generates a Zacks Small Cap Research valuation of $8.50 per share.
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[1] Ahn, D. et al. Onvansertib in Combination With Chemotherapy and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Single-Arm, Phase II Trial. Gastrointestinal Cancer. October 2024.