CytoDyn (OTCMKTS:CYDY) provided an update on its Phase II CLOVER study of leronlimab in metastatic colorectal cancer, highlighting early circulating tumor DNA, or ctDNA, data, preliminary clinical observations and plans for additional studies. The company also announced that CFO Robert Hoffman will become chief executive officer, succeeding Jay Lalezari, who will move into the role of head of research and translational sciences.
The open-label, randomized CLOVER trial is evaluating 350 mg and 700 mg doses of leronlimab alongside LONSURF and Avastin in 60 patients with microsatellite-stable metastatic colorectal cancer. Lalezari said enrollment was completed in April and noted that most participants had received at least three prior lines of treatment, placing many in the fourth-line or later setting rather than the intended third-line population.
Early ctDNA Findings
Lalezari said that among 28 patients with baseline and follow-up specimens analyzed through Natera’s Signatera assay, the median ctDNA decline at week two was 86%. He also said the company has observed an early dose-response signal and that activity appeared across patients with different prior-treatment histories, including patients with RAS mutations.
Reny Aniline, senior director of biopharma business development at Natera, presented a comparison with real-world patients receiving standard-of-care therapy. Natera examined 30 patients receiving LONSURF alone and 75 receiving LONSURF plus Avastin, using baseline and follow-up Signatera testing within four weeks of treatment initiation.
According to Aniline, the LONSURF-alone group had a median ctDNA increase of 22%, while the LONSURF-plus-Avastin group had a median decrease of 55%. In an initial set of 12 CLOVER patients processed by Natera, the company reported an average ctDNA decrease of 93%. Aniline cautioned that the CLOVER analysis remains limited to 12 patients but described the reductions as notable based on his experience with the platform.
Natera defines molecular complete response as undetectable ctDNA, molecular partial response as more than a 90% reduction from baseline, molecular stable disease as a reduction of 0% to 90%, and molecular progressive disease as an increase in ctDNA. Aniline said prior data from Natera’s database linked deeper molecular responses with improved real-world survival outcomes, though CytoDyn has not reported mature survival results from CLOVER.
Clinical Observations and Rollover Arm
Lalezari said approximately three-quarters of CLOVER participants with week-eight scans had either tumor shrinkage or stable disease. He also said no serious adverse events related to leronlimab had been reported in the study. The company plans to present updated clinical and biomarker data at the European Society for Medical Oncology Congress in Madrid on Oct. 25, followed by broader updates at the ASCO Gastrointestinal Cancers Symposium in January 2027.
Pashtoon Kasi, medical director of GI oncology at City of Hope Orange County and CLOVER’s lead investigator, said ctDNA trends appeared consistent with reported improvements in pain and quality of life among some patients. He emphasized that the findings are early and that further follow-up will be needed.
The study includes a rollover arm for patients whose disease progresses during the randomized phase. Those patients may receive leronlimab at 700 mg together with the PD-1 checkpoint inhibitor pembrolizumab. Kasi said two patients at his site had started treatment in the rollover arm, adding that early signs were promising but preliminary.
Kasi also reported that three of 36 patients enrolled at his site had been referred for surgery with curative intent after treatment. Two had liver metastases and one had lung metastases, he said. The patients had previously not been considered surgical candidates, and the company said their longer-term outcomes have yet to be determined.
Leadership Change and Next Steps
Hoffman said his CEO tenure would begin the day after the webcast. He said CytoDyn intends to complete CLOVER and assemble a data package for discussions with the U.S. Food and Drug Administration. Potential regulatory paths cited by Hoffman included Fast Track designation, Breakthrough Therapy designation and accelerated approval, contingent on continued supportive data.
The company said it expects to add a regulatory affairs leader and seek a chief medical officer with oncology experience. Hoffman also said CytoDyn plans to dose its first patient in a metastatic triple-negative breast cancer dose-escalation study and begin additional colorectal cancer studies in 2027.
Beyond CLOVER, Lalezari said CytoDyn is pursuing research collaborations in colorectal cancer, breast cancer, glioblastoma, pancreatic cancer, head and neck cancer, acute myelogenous leukemia and Alzheimer’s disease. Several of those programs remain in protocol-development or early enrollment stages.
On the financial front, Hoffman said CytoDyn reported cash of $16.4 million as of Aug. 31, with pro forma cash of approximately $18.3 million after subsequent financing activity. He said the company expects that cash to fund operations into the second half of 2027.
About CytoDyn (OTCMKTS:CYDY)
CytoDyn Inc is a biotechnology company focused on the development of leronlimab, an investigational monoclonal antibody that targets CCR5, a receptor involved in immune-cell signaling and the movement of certain cells through the body. The company’s research has explored potential applications in infectious diseases, oncology and inflammatory conditions.
Leronlimab, also known as PRO 140, has been studied primarily as a potential treatment for HIV infection, including in combination with existing antiretroviral therapies.
