The shareholder letter is rich in content, has very careful wording and signaling, and is masterful in many respects. Though the whole letter is important, I’ve highlighted some of the points I found to be particularly important below. And the Science Supplement is chock full of details and summary of the recent science.
My opinion is that we have a CEO, Dr J, who has righted the ship (through herculean effort) and is giving it his all, so I continue to give him my full support and benefit of the doubt.
We are right at the gate to the locks, the gatekeepers will soon open the gates (with more PD-L1 elevation data), and we are about to sail out into open waters.
Enjoy the ride.
Keep on keeping on and staying long for the long haul
*************************
September 2025 Letter to Shareholders
https://www.cytodyn.com/newsroom/press-releas...areholders
VANCOUVER, Washington, Sept. 30, 2025 (GLOBE NEWSWIRE) --
Dear Shareholders,
As this pivotal year continues to take shape for CytoDyn Inc. (“CytoDyn” or the “Company”), I am pleased to share the progress we have made in advancing leronlimab as an innovative treatment in oncology. We remain confident that addressing critical unmet needs in this field is the best way to build value while improving the lives of patients. The foundation of our conviction in leronlimab rests on both preclinical and clinical evidence. From laboratory insights to encouraging patient survival observations, our story is compelling and one of consistent validation. The data presented over the past several months marks a watershed moment for both patients and our Company, providing evidence that leronlimab has the potential to reshape treatment paradigms in solid tumor oncology. With multiple clinical trials advancing, we are moving with discipline and urgency along a well-defined path forward.
Strengthening Our Leadership
To support this next chapter, we welcomed Robert E. Hoffman as our new Chief Financial Officer. An industry veteran with decades of financial and leadership experience, holding various executive and board positions in his biotech career, Robert has already brought significant value to CytoDyn. His expertise in capital markets and strategic planning strengthens our ability to execute, network, and expand our pipeline. We are delighted to have him aboard.
Scientific Progress and Clinical Development
At the heart of leronlimab’s promise is a novel mechanism of action (“MOA”) associated with prolonged survival observed in a group of patients with Metastatic Triple-Negative Breast Cancer (“mTNBC”). Supporting data, presented at a poster session at the European Society for Medical Oncology (“ESMO”) breast cancer meeting in Munich, suggest that leronlimab induces PD-L1 expression, creating synergy with immune checkpoint inhibitors (ICIs), a potential breakthrough in solid tumor treatment. This finding not only opens new therapeutic opportunities for leronlimab, but also represents a significant market opportunity for the Company. For additional information on this novel MOA and the status of our clinical initiatives and publications, please see the science update included with this letter.
One indication that carries the potential for significant value return is leronlimab in mTNBC, the most aggressive form of breast cancer, with 5-year survival rates around 15%. Based on the positive data presented at ESMO, we will shortly submit a follow-up Phase II proof of concept (POC) protocol for PD-L1-negative patients with mTNBC. These patients, currently ineligible for ICI therapy, will receive leronlimab plus standard chemotherapy, followed by a regimen of leronlimab with an ICI. We look forward to sharing more details after the FDA review of the protocol and briefing package that provides a complete summary of CytoDyn’s oncology data.
In parallel, we will be submitting an Expanded Access Protocol (“EAP”) to enable treatment for patients with second-line, or later, mTNBC, who are ineligible or otherwise unable to participate in our Phase II study. I am pleased to announce that we will be working with an individual benefactor to fund the launch of this compassionate-use program. This benefactor has also expressed interest in supporting an investigator-initiated study in patients with recurrent glioblastoma with an anticipated start date in 2026.
Beyond breast cancer, leronlimab continues to advance in the treatment of metastatic Colorectal Cancer (mCRC). Enrollment in our Phase II study is underway with five sites initiated and several more onboarding in the next several weeks. The enrollment of our fifth patient in the trial will trigger the Data Safety Monitoring Board (DSMB) safety review, which could then open study randomization to include the 700 mg dose. Importantly, we will be closely tracking PD-L1 levels of enrolled patients to further validate our MOA across solid tumors. With that in mind, we have prepared a rollover protocol to ensure that CRC patients who remain stable can continue leronlimab treatment beyond 48 weeks and to allow patients with disease progression the opportunity to receive leronlimab at a dose of 700 mg in combination with an ICI.
Finally, I am happy to share a very promising announcement as it relates to a patient who prospectively upregulated PD-L1 after having obtained access to leronlimab through an eIND application submitted by her treating physician. In early 2025, we received a compassionate access request for a patient with mTNBC who was previously unresponsive to treatment with Keytruda. This particular patient had two prior tissue biopsies, both of which were PD-L1 negative. In April, the patient started treatment with leronlimab, and in July blood tests confirmed an increase in PD-L1 levels. Our past clinical observations have shown that upregulating PD-L1 is the first step towards prolonged survival in this patient population and we are encouraged by this readout, which supports our working theory. This is the first of hopefully many PD-L1 upregulation readouts across our CRC and TNBC trial(s) in the coming year. I continue to have high hopes for our upcoming Phase II trials, as well as our expanded access program, as we look to reshape treatment paradigms in solid tumor oncology.
Update on Regulatory Matters, Resolution of SEC and DOJ Investigations
I am also pleased to share that we recently received confirmation from both the Securities and Exchange Commission (“SEC”) and Department of Justice (“DOJ”) that their respective investigations have now closed, and nothing further is required of the Company. I believe this positive conclusion for the Company is a reflection of our team here and our collective commitment to compliance and cooperation.
I remain confident that our collaborative relationship with the FDA has placed us on a productive trajectory. To accelerate progress in oncology, we established an oncology advisory board focused on pursuing the fastest and most responsible pathway(s) forward. The FDA recently granted our request for a meeting, and we look forward to discussing our retrospective data set and related observations in TNBC, as well as the next steps in our TNBC development plan. Maintaining strong relationships and credibility with the FDA and industry partners remains a top priority as we move forward.
Commitment to our Shareholders
Your support has carried the Company through the last several years and we remain committed to acting in your best interests. I want to thank you all again for your perseverance and patience. Your questions and feedback are always appreciated and best received through the Company’s IR email account: ir@cytodyn.com. In the coming months, we will be engaging in critical conversations with our key opinion leaders, potential industry partners and regulators. In support of these efforts, we ask our shareholders to be mindful of the process and respectful of our counterparties. Excessive outreach to these third parties can inadvertently hinder our progress. Our recent results and the novel MOA have attracted the attention of numerous patients, treating physicians, and others across the industry. Please know that we are actively pursuing collaborations to maximize the potential of leronlimab.
A Human Reminder of Our Mission
In closing, I’d like to share a brief personal anecdote. As the Company has worked to confirm the mTNBC survival observations and arranged for related follow-up testing, I’ve had the opportunity to speak with several of the surviving patients who accessed leronlimab during the Company’s prior oncology studies. These are individuals who had exhausted all other options yet are now enjoying more time with their families. I had the privilege of sharing a meal with one survivor and her spouse and it is difficult to put into words the emotions we all felt when reflecting on the remarkable sequence of events that brought us together that night, but I can name the most prominent – hope. Encounters like these remind us why our work matters and fuel our determination to accelerate progress for patients everywhere.
With Gratitude,
Jacob Lalezari, MD
CEO
My opinion is that we have a CEO, Dr J, who has righted the ship (through herculean effort) and is giving it his all, so I continue to give him my full support and benefit of the doubt.
We are right at the gate to the locks, the gatekeepers will soon open the gates (with more PD-L1 elevation data), and we are about to sail out into open waters.
Enjoy the ride.
Keep on keeping on and staying long for the long haul
*************************
September 2025 Letter to Shareholders
https://www.cytodyn.com/newsroom/press-releas...areholders
VANCOUVER, Washington, Sept. 30, 2025 (GLOBE NEWSWIRE) --
Dear Shareholders,
As this pivotal year continues to take shape for CytoDyn Inc. (“CytoDyn” or the “Company”), I am pleased to share the progress we have made in advancing leronlimab as an innovative treatment in oncology. We remain confident that addressing critical unmet needs in this field is the best way to build value while improving the lives of patients. The foundation of our conviction in leronlimab rests on both preclinical and clinical evidence. From laboratory insights to encouraging patient survival observations, our story is compelling and one of consistent validation. The data presented over the past several months marks a watershed moment for both patients and our Company, providing evidence that leronlimab has the potential to reshape treatment paradigms in solid tumor oncology. With multiple clinical trials advancing, we are moving with discipline and urgency along a well-defined path forward.
Strengthening Our Leadership
To support this next chapter, we welcomed Robert E. Hoffman as our new Chief Financial Officer. An industry veteran with decades of financial and leadership experience, holding various executive and board positions in his biotech career, Robert has already brought significant value to CytoDyn. His expertise in capital markets and strategic planning strengthens our ability to execute, network, and expand our pipeline. We are delighted to have him aboard.
Scientific Progress and Clinical Development
At the heart of leronlimab’s promise is a novel mechanism of action (“MOA”) associated with prolonged survival observed in a group of patients with Metastatic Triple-Negative Breast Cancer (“mTNBC”). Supporting data, presented at a poster session at the European Society for Medical Oncology (“ESMO”) breast cancer meeting in Munich, suggest that leronlimab induces PD-L1 expression, creating synergy with immune checkpoint inhibitors (ICIs), a potential breakthrough in solid tumor treatment. This finding not only opens new therapeutic opportunities for leronlimab, but also represents a significant market opportunity for the Company. For additional information on this novel MOA and the status of our clinical initiatives and publications, please see the science update included with this letter.
One indication that carries the potential for significant value return is leronlimab in mTNBC, the most aggressive form of breast cancer, with 5-year survival rates around 15%. Based on the positive data presented at ESMO, we will shortly submit a follow-up Phase II proof of concept (POC) protocol for PD-L1-negative patients with mTNBC. These patients, currently ineligible for ICI therapy, will receive leronlimab plus standard chemotherapy, followed by a regimen of leronlimab with an ICI. We look forward to sharing more details after the FDA review of the protocol and briefing package that provides a complete summary of CytoDyn’s oncology data.
In parallel, we will be submitting an Expanded Access Protocol (“EAP”) to enable treatment for patients with second-line, or later, mTNBC, who are ineligible or otherwise unable to participate in our Phase II study. I am pleased to announce that we will be working with an individual benefactor to fund the launch of this compassionate-use program. This benefactor has also expressed interest in supporting an investigator-initiated study in patients with recurrent glioblastoma with an anticipated start date in 2026.
Beyond breast cancer, leronlimab continues to advance in the treatment of metastatic Colorectal Cancer (mCRC). Enrollment in our Phase II study is underway with five sites initiated and several more onboarding in the next several weeks. The enrollment of our fifth patient in the trial will trigger the Data Safety Monitoring Board (DSMB) safety review, which could then open study randomization to include the 700 mg dose. Importantly, we will be closely tracking PD-L1 levels of enrolled patients to further validate our MOA across solid tumors. With that in mind, we have prepared a rollover protocol to ensure that CRC patients who remain stable can continue leronlimab treatment beyond 48 weeks and to allow patients with disease progression the opportunity to receive leronlimab at a dose of 700 mg in combination with an ICI.
Finally, I am happy to share a very promising announcement as it relates to a patient who prospectively upregulated PD-L1 after having obtained access to leronlimab through an eIND application submitted by her treating physician. In early 2025, we received a compassionate access request for a patient with mTNBC who was previously unresponsive to treatment with Keytruda. This particular patient had two prior tissue biopsies, both of which were PD-L1 negative. In April, the patient started treatment with leronlimab, and in July blood tests confirmed an increase in PD-L1 levels. Our past clinical observations have shown that upregulating PD-L1 is the first step towards prolonged survival in this patient population and we are encouraged by this readout, which supports our working theory. This is the first of hopefully many PD-L1 upregulation readouts across our CRC and TNBC trial(s) in the coming year. I continue to have high hopes for our upcoming Phase II trials, as well as our expanded access program, as we look to reshape treatment paradigms in solid tumor oncology.
Update on Regulatory Matters, Resolution of SEC and DOJ Investigations
I am also pleased to share that we recently received confirmation from both the Securities and Exchange Commission (“SEC”) and Department of Justice (“DOJ”) that their respective investigations have now closed, and nothing further is required of the Company. I believe this positive conclusion for the Company is a reflection of our team here and our collective commitment to compliance and cooperation.
I remain confident that our collaborative relationship with the FDA has placed us on a productive trajectory. To accelerate progress in oncology, we established an oncology advisory board focused on pursuing the fastest and most responsible pathway(s) forward. The FDA recently granted our request for a meeting, and we look forward to discussing our retrospective data set and related observations in TNBC, as well as the next steps in our TNBC development plan. Maintaining strong relationships and credibility with the FDA and industry partners remains a top priority as we move forward.
Commitment to our Shareholders
Your support has carried the Company through the last several years and we remain committed to acting in your best interests. I want to thank you all again for your perseverance and patience. Your questions and feedback are always appreciated and best received through the Company’s IR email account: ir@cytodyn.com. In the coming months, we will be engaging in critical conversations with our key opinion leaders, potential industry partners and regulators. In support of these efforts, we ask our shareholders to be mindful of the process and respectful of our counterparties. Excessive outreach to these third parties can inadvertently hinder our progress. Our recent results and the novel MOA have attracted the attention of numerous patients, treating physicians, and others across the industry. Please know that we are actively pursuing collaborations to maximize the potential of leronlimab.
A Human Reminder of Our Mission
In closing, I’d like to share a brief personal anecdote. As the Company has worked to confirm the mTNBC survival observations and arranged for related follow-up testing, I’ve had the opportunity to speak with several of the surviving patients who accessed leronlimab during the Company’s prior oncology studies. These are individuals who had exhausted all other options yet are now enjoying more time with their families. I had the privilege of sharing a meal with one survivor and her spouse and it is difficult to put into words the emotions we all felt when reflecting on the remarkable sequence of events that brought us together that night, but I can name the most prominent – hope. Encounters like these remind us why our work matters and fuel our determination to accelerate progress for patients everywhere.
With Gratitude,
Jacob Lalezari, MD
CEO
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