Cardiff Oncology (NASDAQ: CRDF) this past week trumpeted positive data via press release from a Phase II trial of its lead pipeline candidate, onvansertib, in two standard-of-care (SoC) combination regimens in first-line RAS-mutated metastatic colorectal cancer (mCRC).
But another announcement issued the same day by Cardiff jolted investors enough to spark a stock selloff that sent the cancer drug developer’s shares nosediving 45% over two days: Cardiff’s CEO Mark Erlander, PhD, and CFO James Levine have stepped down, with Erlander succeeded by an interim CEO, Mani Mohindru, PhD, a member of Cardiff’s board since 2021.
Cardiff has begun searching for a permanent CEO and CFO, though in the meantime, it has promoted Brigitte Lindsay, a 14-year Cardiff veteran who had been senior vice president of finance, to the role of chief accounting officer—a move the company said will ensure continuity within its finance operations.
Cardiff described the C-suite moves as a “leadership transition designed to support the company’s next phase of growth and advancement toward late-stage development and key clinical and corporate milestones.”
The company highlighted Mohindru’s lengthy resume: founder of Roshon Therapeutics, a private biotech focused on developing novel therapies for cancer and inflammatory diseases; a current board member of CytomX Therapeutics; former CEO and board member at Novasenta and CereXis; and a senior executive at biotechs including Cara Therapeutics and Curis.
Investors, however, viewed both the change of leadership and even the Phase II data less positively. Cardiff shares tumbled 32% from $2.94 to an even $2 on the day of the announcements. The following day, Cardiff shares slid another 19% to $1.62, before dipping another 0.3% to $1.615 on Thursday, then rebounding 8% to $1.75 at the close of trading Friday.
Market cap drops 46%
The sharp slide has shrunk Cardiff’s market capitalization (share price times the number of outstanding shares) by roughly half (46%), from nearly $200 million to $108.787 million at the close of trading Thursday.
“The mgmt transition announcement today at the same time as the data update came as a surprise and appears to be largely driven by the board’s desire to advance into late‑stage studies w/ a new team that has relevant late‑stage development experience,” observed Maury Raycroft, PhD, an equity research analyst with Jefferies specializing in biotechnology, in a research note.
The clinical data announcement from the Phase II CRDF-004 trial (NCT06106308) reported on an intent-to-treat analysis showing dose-dependent benefits across several measures of efficacy in patients receiving onvansertib with the combination of chemotherapy drug Folfiri and bevacizumab (Folfiri/bev), the monoclonal antibody cancer therapy marketed by Roche and its Genentech subsidiary as Avastin®. The trial compared onvansertib plus Folfiri/bev to two SoC regimens, Folfiri/bev alone and a combo of chemo drug Folfox and bevacizumab (Folfox/bev).
Based on CRDF-004 results, Cardiff said, it has selected the 30 mg dose for a planned registrational trial of onvansertib with Folfiri/bev in first-line patients with RAS-mutated mCRC. While that study will compare that combination to Folfiri/bev and Folfox/bev, Cardiff made no mention of any registrational study of onvansertib with Folfox/bev.
Plans for the registrational trial, as well as final data from CRDF-004, are expected in the first half of this year, pending work with the FDA to finalize the design of the trial. In that study, Cardiff said, it expects to compare onvansertib with FOLFIRI/bev to SoC regimens, FOLFIRI/bev, or FOLFOX/bev.
“We believe a detailed analysis will help clarify the key risks around the program, and could meaningfully move the stock, we est +>100%/–50%,” Raycroft predicted.
“Negative direction”
“Overall, given the abrupt management changes in the absence of a smooth transition plan, coupled with a narrowed focus on onvansertib in combination with Folfiri, as opposed to both Folfiri and Folfox, we view the update slants in a negative direction,” Andy T. Hsieh, PhD, a partner and biotechnology analyst with William Blair, wrote in a research note.
Hsieh cited William Blair’s conversations with key opinion leaders (KOLs), which revealed that about 30% of frontline U.S. patients receive a Folfiri-based regimen, and the rest, a Folfox-based regimen. By comparison, the percentages of patients whose chemo regimens are based on Folfiri or Folfox are more evenly split.
“Assuming regulatory alignment with the FDA, focusing on the onvansertib plus Folfiri and Avastin reduces the total addressable market in the frontline setting to 12–20% from 40–50% previously,” Hsieh predicted.
Under that old percentage range, analysts had predicted peak-year sales for onvansertib ranging from just over $1 billion to nearly $3 billion. Raycroft offered the low estimate in a June 24, 2025, research note: “Assuming 11% mkt penetration, we model onvansertib could reach peak sales of $1.1B by 2034.” H.C. Wainwright analyst Raghuram Selvaraju, PhD, a managing director and senior healthcare analyst at the firm, offered the high-end estimate of $2.9 billion.
Metastatic cases account for 20% of total cases of colorectal cancer (CRC), the third most common cause of cancer mortality worldwide, with more than 1.85 million cases and 850,000 deaths annually. In the United States, CRC accounts for 150,000 new cases and 50,000 deaths annually. Another 25% who present with localized disease will later develop metastases, with Cardiff citing additional studies from 2023 and 2025.
As a result of Cardiff narrowing its total addressable market for onvansertib, Hsieh lowered from 50% to 45% William Blair’s projection of the probability of Cardiff achieving clinical success with onvansertib plus Folfiri/bev.
Notwithstanding that lower projection of success and “negative direction” talk, William Blair maintained its top-tier “Outperform” rating on Cardiff’s stock. Similarly, H.C. Wainwright kept its “Buy” rating, as well as its 12-month price target of $10 on Cardiff shares.
72% response rate
In the CRDF-004 trial, 18 of 92 confirmed responding patients received the 30 mg dose of onvansertib plus Folfiri/bev. Within that cohort of patients, 13 (72.2%) showed a confirmed objective response rate (ORR), nearly double the ORR shown by each of the other three cohorts: Onvansertib 20 mg + Folfiri/bev – (8 responders, 44.4%); SoC (Folfiri/bev + Folfox/bev; 16 responders, 43.2%); and Folfiri/bev alone (8 responders, 42.1%).
Also potentially promising amid the data: The 30 mg cohort showed a progression-free survival (PFS) hazard rate of 0.38 compared with Folfiri/bev—meaning that patients treated with onvansertib showed a 62% lower risk of disease progression or death at any given time compared to the control group. That hazard rate dips further to 0.37 when compared with SoC, for a 63% lower risk.
While the hazard rate appeared promising, “the lack of detailed data and the small n [number of patients studied] limit our ability to draw firm conclusions at this stage,” Raycroft commented.
“The early HRs of 0.38 (30 mg) and 0.56 (20 mg) vs FOLFIRI/bev suggest that the data are trending in the right direction,” Raycroft added, even though Cardiff acknowledged that median PFS had not yet been reached for either the 20 or 30 mg cohorts of onvansertib, given PFS rates of 9.72 for 30 mg and 7.49 for 20 mg.
Both SoC and Folfiri/bev showed median PFs of 10.97 months.
“While we continue to review data from the ongoing trial, our plan is to rapidly move forward with the onvansertib 30 mg dose in combination with Folfiri/bev, and we believe confirmatory data from a registrational trial has the potential to make this regimen a new SoC for [first-line] treatment of RAS-mutated mCRC,” Mohindru said in a statement.
Leaders and laggards
- Regenxbio (NASDAQ: RGNX) shares slid 18% from $13.41 to $11.01 Wednesday after the gene therapy developer acknowledged that the FDA placed a clinical hold on the company’s program to develop RGX-111 (clemidsogene lanparvovec) for Mucopolysaccharidosis Type I (MPS I), also known as Hurler syndrome, as well as its program to develop RGX-121 for MPS II, also called Hunter Syndrome. The FDA cited similarities in products, study populations, and shared risk between the clinical studies of both candidates. The holds were placed following a preliminary analysis of one case of neoplasm (intraventricular central nervous system [CNS] tumor) in a patient treated with RGX-111 in a Phase I/II study (RGX-111-002; NCT03580083). A preliminary genetic analysis of the resected tumor detected an AAV vector genome integration event associated with overexpression of a proto-oncogene (PLAG1). The patient continues to be asymptomatic, REGENXBIO said, with positive developmental advancements noted by the treating physician.
- Revolution Medicines (NASDAQ: RVMD) shares skidded 17% from $117.63 to $97.78 on January 26 after The Wall Street Journal reported that Merck & Co. (NYSE: MRK) had ended talks to acquire the developer of RAS-addicted cancer therapies “after the two couldn’t come to an agreement on price,” according to unnamed sources cited by the news outlet. The companies reported discussed a deal in the $30 billion range—adding weight to Merck chairman and CEO Robert A. Davis’ remarks at the recent J.P. Morgan 44th Annual Healthcare Conference that the company was interested in acquisition deals in the “multi tens of billions of dollars.” The Wall Street Journal previously reported Revolution was close to being bought out by AbbVie (NYSE: ABBV), a story that sent Revolution’s shares soaring 29% before AbbVie denied the story. The Financial Times earlier this month reported that Merck had proposed a buyout of Revolution ranging from $28 billion to $32 billion.
