Cardiff Oncology Inc. (NASDAQ: CRDF) experienced a significant decline in its stock price on Tuesday, closing approximately 32% lower, after disclosing abrupt executive changes alongside updates from a pivotal Phase 2 clinical trial. The company revealed that Mani Mohindru, who has been a board member since 2021, has been appointed as interim chief executive officer effective immediately. This leadership shift follows the departure of Mark Erlander as CEO and James Levine as chief financial officer, signaling a notable reshuffling at the executive level.
To ensure continued financial oversight, Cardiff promoted Brigitte Lindsay to the position of Chief Accounting Officer. Ms. Lindsay has dedicated over fourteen years to Cardiff Oncology and most recently held the role of Senior Vice President of Finance. The organization has initiated a search process for permanent replacements for the CEO and CFO positions, underscoring the temporary nature of the current appointments.
In a statement released on Tuesday, Cardiff Oncology indicated that the leadership transition is intended to underscore the company’s strategic emphasis on execution and clinical progression as its development programs advance toward maturity.
Alongside the management changes, Cardiff Oncology provided the latest data from its CRDF-004 study. This randomized, dose-finding Phase 2 trial assesses onvansertib in combination with standard of care (SoC) chemotherapy regimens—specifically FOLFIRI (folinic acid, fluorouracil, irinotecan) combined with bevacizumab or FOLFOX (folinic acid, fluorouracil, oxaliplatin) with bevacizumab—in patients newly diagnosed with first-line RAS-mutated metastatic colorectal cancer (mCRC).
The intent-to-treat analysis from the trial indicated dose-dependent clinical benefits in various efficacy endpoints favoring patients treated with onvansertib plus FOLFIRI/bevacizumab when compared to those receiving only the standard of care regimens.
Most notably, the 30 mg dose cohort exhibited a confirmed objective response rate of 72.2%, substantially higher than the 43.2% observed in the standard of care group. This difference approached statistical significance, with a reported p-value of 0.051.
Progression-free survival (PFS) data further supported these findings, with the 30 mg onvansertib plus FOLFIRI/bevacizumab arm achieving statistical significance compared to the SoC group, marked by a p-value of 0.048. At the time of data analysis, median PFS had not yet been reached in the onvansertib treatment arms, suggesting a potential extension in disease control duration.
Comparatively, onvansertib combined with FOLFIRI/bevacizumab outperformed combinations involving FOLFOX/bevacizumab. Consequently, Cardiff Oncology has selected the 30 mg onvansertib dose alongside the FOLFIRI/bevacizumab regimen to advance into future registrational trials intended for first-line patients harboring RAS-mutated mCRC.
Pending regulatory discussions and finalizing trial design with the Food and Drug Administration (FDA), Cardiff aims to initiate this registrational program later this year, with plans to compare onvansertib plus FOLFIRI/bevacizumab against existing standard of care regimens, including FOLFIRI/bevacizumab or FOLFOX/bevacizumab.
In terms of safety, the combination of onvansertib with both chemotherapy and bevacizumab regimens was well-tolerated. No significant or unexpected toxicities were reported, and no additive adverse events emerged. Grade 3 or higher treatment-emergent adverse events were uncommon, with neutropenia identified as the most frequent serious adverse event observed in both the combined treatment arms and the standard care groups.
The market response to these developments was influenced not only by the clinical data but also by an analyst perspective shared by William Blair on Tuesday. The firm noted that the sudden leadership upheaval, lacking a clearly communicated transition plan, combined with Cardiff Oncology narrowing its clinical focus exclusively on onvansertib with FOLFIRI rather than both FOLFIRI and FOLFOX regimens, casts the update in a "negative direction."
Analyst Andy Hsieh from William Blair subsequently lowered the estimated probability of regulatory success for onvansertib to 45%, down from a previous 50%. This adjustment reflects the potential impact of focusing the drug development program on onvansertib plus FOLFIRI and Avastin, which constrains the addressable frontline metastatic colorectal cancer market opportunity to roughly 12% to 20%, compared to an earlier range of 40% to 50% when both chemo options were included.
Despite the revised outlook, William Blair maintained an Outperform rating on Cardiff Oncology stock.
On Tuesday, Cardiff Oncology’s shares closed at $2.00, marking a fall of 31.9%, and trading near the lower end of its 52-week valuation range between $1.85 and $4.99, according to Benzinga Pro market data.