Expanded Access And Rollover Design Help CytoDyn Reach High-Need Cancer Patients
A conversation among CytoDyn CFO Robert E. Hoffman, CytoDyn CEO Jay Lalezari, MD, and Clinical Leader Executive Editor Abby Proch
As researchers continue to explore the role of the immune system in cancer progression, increasing attention has turned to C-C chemokine receptor type 5 (CCR5), a receptor implicated in tumor growth, metastasis, and the tumor microenvironment across a range of solid tumors. Leronlimab, a monoclonal antibody targeting CCR5, was initially developed for HIV and is now being evaluated for its potential role in oncology.
CytoDyn’s oncology development program is focused on metastatic colorectal cancer (mCRC) and triple-negative breast cancer (TNBC), where the company is evaluating leronlimab’s potential to enhance anti-tumor immune responses and support combination treatment strategies. As part of this effort, CytoDyn is also exploring expanded access pathways for patients with limited treatment options while generating data to inform future clinical development and partnership opportunities.
In this Q&A, CEO Jay Lalezari and CFO Robert E. Hoffman discuss the company’s clinical programs and how CytoDyn balances patient needs with the requirements of drug development.
Clinical Leader: You've implemented an amendment to the CLOVER study providing a checkpoint inhibitor to patients with clinical progression. How does that work?
Jay Lalezari, MD: We have evaluated three doses of leronlimab: 350 mg, 525 mg, and 700 mg. It's given subcutaneously once a week. Patients administer it themselves, and there are no safety issues with this drug, which is not something you can say about any other cancer drug candidate.
We initiated the CLOVER study in patients with third line mCRC, evaluating two doses of leronlimab (350 mg vs 700 mg) on top of the standard-of-care backbone of Avastin and Lonsurf. We initially envisioned increasing everyone’s dose up to 700 mg and adding a checkpoint inhibitor as quickly as possible. However, we observed decreases in circulating tumor DNA in 100% of patients, which indicated potent anti-tumor activity with just leronlimab and the backbone regimen, even at the lowest dose of 350 mg.
As a result, we decided to further evaluate leronlimab's activity across the assigned dose cohorts before introducing a checkpoint inhibitor. We are now continuing to follow patients at their assigned dose level to better understand the activity of leronlimab without the confounding effects of adding a checkpoint inhibitor.
More recently, we submitted an amendment that allows patients who reach week 52 on their assigned dose and are doing well to continue treatment at that dose. In addition, we’re offering a rollover option that allows patients who experience clinical progression to increase their dose of leronlimab to 700 mg and add the checkpoint inhibitor.
You’re also expanding access to TNBC patients. Why did you decide to offer the Expanded Access Protocol?
Lalezari: In discussions with potential big pharma partners, one of the things they asked for was prospective confirmation that leronlimab would induce PDL1 and turn cold tumors hot — enabling treatment with an immune checkpoint inhibitor in a tumor with little to no immune cell infiltration. What that does is open up a huge market because most solid tumors are cold. When you use a checkpoint inhibitor, it often works, but it's only a small fraction of patients who are even eligible. If we can make those cold tumors hot, many patients with solid tumors suddenly become candidates.
Patients were also calling us wanting access. So, the two lines converged. The current path for access is through an emergency IND application, which requires a lot of paperwork and each individual physician is now the sponsor of an IND with the FDA. It’s really meant to discourage anyone from doing it.
However, the Expanded Access Protocol served both the patients’ and CytoDyn’s needs to give patients access to the drug, get readouts around their induction of PDL1, and then provide that information to doctors so they can try to get checkpoint inhibitor reimbursements from insurance companies.
How do you ensure that you're understanding patients' needs when preparing for or running trials?
Lalezari: I am still the medical director at Quest Clinical Research and we are involved with a number of cancer studies. I get reminded on a daily basis about patient perspectives and what they want and need.
For example, we have this ongoing colorectal cancer study, and we had a screening requirement that sometimes took up to six weeks to confirm that a patient’s tumor was CCR5+. At some point we realized that 100% of screened patients were coming back CCR5+, so we eliminated that screening requirement which enabled patients to start on treatment as soon as possible.
How realistic is it to be able to balance the needs of everyone involved, or do you have to bend to one party to move things along?
Lalezari: There's a difference between developing a drug and giving the best patient care — and I've had to navigate that. For example, in the CRC study, because of the breast cancer data, the higher dose looked much better. I really wrestled with whether to even include the lower dose because I thought it might be suboptimal. It turns out that lower dose is demonstrating encouraging activity in CRC, and it's unclear whether the higher dose is going to be better. So even if you think you know, you might not.
In the end, we know that the patients, the FDA, the investors, and CytoDyn want the same thing. We want solid data showing the drug works, as quickly as possible.
It's a competitive landscape. How do you differentiate yourself when talking to a prospective principal investigator or even patients?
Lalezari: Two ways. One, again, that safety profile: 1,600 patients treated in the CRC study. These are third-line, really fragile patients. There has been no serious adverse event related to leronlimab. There's been no dose adjustment or treatment limitation due to an adverse event with leronlimab. So, having a drug in oncology that is not causing adverse effect, that separates us.
The ctDNA data that we've generated is preliminary, but no one has ever seen anything quite like it in terms of a 70% decrease in at week 2. It's not enough for the FDA. And it's not quite enough yet for a partnership, but every oncologist I show that data seems pretty impressed. We now have quite a few academic oncologists come to us now proposing their own investigator initiated studies. When you add this early evidence of biologic activity with a benign safety profile and potential relevance throughout solid tumor oncology, you have a rather amazing story. And now I really don’t have to spend my time persuading anyone; the data has helped generate significant interest among investigators and potential collaborators. And we saw it in the enrollment, too. The study enrolled over a period of just a few months.
Robert E. Hoffman: Sadly, the bar is pretty low on colorectal cancer. The current standard of care, bevacizumab and LONSURF, saw an overall response rate of 6% and then no complete responses in the data in their study. Real-world data suggests it's maybe 3%. These patients are in dire need of anything at this point. Unfortunately, colorectal cancer is one of the fastest-rising cancers in patients under 50 in the U.S. There's just a huge unmet medical need, and it's a big market, too.
About The Experts:
CytoDyn CEO Jay Lalezari, MD, brings over 34 years of industry experience, including nearly 20 years of experience with leronlimab, also known as PRO 140. He previously served as interim CEO of CytoDyn from November 2023 to January 2024, CMO during 2020, and a member of the Company’s scientific advisory board for the past several years. Dr. Lalezari has been the CEO and medical director of Quest Clinical Research since 1996 and served as the CMO of Virion Therapeutics in 2018. Dr. Lalezari has also served as principal investigator for Phase 1, 2, and 3 clinical studies of new therapies for viral diseases. Dr. Lalezari received his MD from the University of Pennsylvania, his M.A. from the University of Virginia, and his B.A. from the University of Rochester. He also holds a board certification from the American Board of Internal Medicine.
CytoDyn Chief Financial Officer Robert E. Hoffman has decades of financial and leadership experience across biotech. Most recently, he was the president, CEO, interim CFO, and chairperson of the board of directors of Kintara Therapeutics, Inc. Prior to that, he served as CFO and SVP of Heron Therapeutics, Inc., CFO and EVP of Innovus Pharmaceuticals, Inc., and CFO of AnaptysBio, Inc.
Mr. Hoffman started his career at Arena Pharmaceuticals, Inc., rising to SVP, Finance, and CFO. Mr. Hoffman currently serves on the board of directors of Esperion Therapeutics, Inc., TuHURA Biosciences, and Fibrobiologics, Inc., and has previously served as a director of several public and private life sciences companies.
Mr. Hoffman is a former member of the steering committee of the Association of Bioscience Financial Officers and former director and president of the San Diego chapter of Financial Executives International. Mr. Hoffman holds a B.B.A. from St. Bonaventure University.