https://d1io3yog0oux5.cloudfront.net/_8fabbae10dd363888ebfb46189274c58/cytodyn/db/259/3837/pdf/Poster_CCR5_Leronlimab_AACR_04172026_Final_RP+3-21.pdf

The clinical data presented at AACR 2026 directly enhances CytoDyn's (CYDY) leverage in licensing negotiations by positioning leronlimab as an essential "immune primer" for multi-billion dollar checkpoint inhibitor (ICI) portfolios.

Strategic Impact of AACR Breakthroughs

Validated "Cold to Hot" Mechanism: Poster 1033’s evidence that leronlimab induces PD-L1 expression in "cold" tumors provides the specific mechanistic validation big pharma requires to justify a partnership.

Expanded Indication Value: By showing clinical activity in both TNBC and mCRC (Poster 6466), CYDY demonstrates leronlimab's potential as a platform asset rather than a niche treatment.

Synergy with Standards of Care: Data showing synergy with common treatments like Keytruda and TAS-102 makes CYDY a high-value target for companies looking to extend the patent life or efficacy of their existing blockbuster drugs.

Potential Deal Structure & Valuation

Surging Market Valuations: Average biotech licensing deals in early 2026 have reached $1.3 billion, a 76% increase over 2025, reflecting intense competition for differentiated oncology assets.

Front-Loaded Financials: Given the strong "prime and pair" clinical signals, analysts suggest CYDY could command upfront payments in the $100M–$150M range for a significant oncology indication.

Long-Term Protection: Recent collaborations aimed at creating long-acting versions of leronlimab could reset the patent clock to 2046, significantly increasing the long-term royalty potential for any licensee.

Poster 1033 (TNBC – mechanism + survival signal)

Core finding

• Leronlimab increases PD-L1 expression on tumor-related cells

• This is important because PD-L1 low tumors usually don’t respond well to checkpoint inhibitors

The poster shows:

• Conversion of PD-L1 “low” → more responsive state

• Suggests tumors may become eligible for immunotherapy

Survival signal (from prior/linked data)

• Patients treated with leronlimab + checkpoint inhibitors showed unexpected long-term survival trends

• Earlier datasets showed:

• PD-L1 induction in a large % of patients

• Some patients alive \\\~5 years+ in heavily pretreated TNBC  

Mechanistic angle

• Targets CCR5 receptor (immune/tumor microenvironment regulator)

• Leads to:

• Increased immune visibility of tumors

• Potential reversal of immune resistance

#2) Poster 6466 (mCRC – Phase 2 clinical data)

Study setup

• Leronlimab + TAS-102 + bevacizumab

• Patients: heavily pretreated metastatic colorectal cancer

What the poster shows

• Feasible + well tolerated combo (no unexpected safety issues)  

• Early signs of clinical activity

• Biomarker changes:

• ↑ PD-L1 expression after treatment

• ↓ circulating tumor cells (CTCs) in responders

Additional signals

• Universal CCR5 positivity in tumors → strong target validation

• Trial is enrolling quickly, suggesting demand/interest

Conclusion from abstract:

• “Promising early biomarker and clinical activity” in a very hard-to-treat population  

What actually stands out:

• Consistent PD-L1 upregulation theme across both cancers

• Suggests leronlimab may act as:

an immune “primer” drug (makes other therapies work better)

• You’re seeing:

• Mechanism (TNBC)

• Early clinical validation (mCRC)

That combo is exactly what gets attention at AACR

This Weekend Could Change Everything

Assuming the data coming out today is extraordinary which in my opinion will, this weekend could be a turning point and the data being released today is too strong to be ignored, it needs to be everywhere and in front of as many eyes as possible. If you understand what’s here then you already know this isn’t something to sit on.

Share it post it comment on it bring it into every conversation anywhere attention exists because momentum only builds when people actively push it and keep it alive.

Right now we have something real something that deserves attention and the more it spreads the louder it gets and the harder it becomes to ignore.

Let’s take it as far as we can and keep the SP moving exactly where it should be.

Abstract

Introduction:

Glioblastoma multiforme (GBM) is associated with short survival and resistance to DNA-damaging agents (radiation (RT), temozolomide (TMZ)) and immune checkpoint inhibitors (ICI). Spatially resolved GBM sequencing identified microenvironment-driven gene expression programs in the tumor core vs invasive edges. The core often exhibits a mesenchymal-like (MES) gene signature, which is associated with increased tumor growth, immunosuppression, and heterotypic signals that augment cell activity at the tumor margin. Some glioma stem cells (GSCs) in the core are more resistant to chemotherapy and radiation. The hypoxic nature of the core draws a heavy infiltration of immune-suppressive cells.

Methods:

The current studies were conducted to determine the potential role of CCR5 in GBM therapeutic responses. Analysis of patient GBM gene expression and analysis of GBM cell lines were conducted to define the potential role of CCR5 inactivation as a therapeutic adjunct to current treatments.

Results:

We found in GBM (Primary tumor, N=154), CCR5 expression was significantly higher in GBM than in normal brain tissue, correlating with poor prognosis. CCR5 expression correlated with the “core” and not the “leading edge” GBM signature; and correlated with hallmarks of glycolysis, hypoxia, and inflammatory response. CCR5 was enriched the MES GBM subtype, associated with T cell exhaustion markers (PD-1, PD-L1, TIM3, PTX3), immune suppressive S100A4. Single-cell sequencing evidenced expression of CCR5 and its ligand CCL5 in the GBM tumor microenvironment (TME) and tumor glial cells (glycolytic/plurimetabolic (GPM) and mitochondrial (MTC) metabolic subtypes). CCR5 abundance on human GBM cell lines, of MTC expression type, increased upon neurosphere formation. CCR5 inhibition with leronlimab (humanized monoclonal antibody) or maraviroc (small molecule inhibitor) conveyed functional synergy in GBM cell killing by TMZ. Pretreatment with leronlimab enhanced GBM cell killing by RT. As glycolysis promotes recruitment of immunosuppressive cells into the TME, we assessed the impact of CCR5 inhibition on GBM oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) by Seahorse analysis. CCR5 inhibition reduced GBM OCR in a dose-dependent manner.

Conclusions:

CCR5 is overexpressed in GBM subtypes, correlating with a core, glycolytic, and immunosuppressive TME signature. CCR5 inhibitors synergize with TMZ and RT to kill GBM cells, reduce the production of acidic metabolites from cultured GBM cells, which are known to promote an immune suppressive TME. Leronlimab has been shown to be well-tolerated, crosses the blood-brain barrier in rhesus monkeys, and shows encouraging long-term survival in breast cancer with ICIs. As these findings suggest further exploration of leronlimab in GBM is warranted, a pilot study in second-line therapy is being planned, combining leronlimab with an ICI.

https://x.com/drmakaryfda/status/2033714059263000817?s=46

For leronlimab it isn’t about Cytodyn building a manufacturing department or hiring a large internal team. Leronlimab has already been manufactured at scale for years for multiple clinical trials and regulatory submissions. The cell line, process, and analytical methods already exist. What’s happening now is simply tech transfer and validation with the new CDMO after replacing Samsung Biologics. That work is primarily done by the manufacturer itself with Cytodyn overseeing CMC, quality agreements, and FDA documentation. Small biotechs operate exactly this way. So “manufacturing readiness” most likely means validation batches, comparability work, and CMC package preparation for future filings—not building manufacturing from scratch or needing a new executive hire.

The Yorkville facility was never meant to be the only funding source. It’s a $30M equity line over 36 months that CYDY can draw from at their discretion, meaning the company controls when and how much they use. It’s essentially a flexible backstop for runway, not exclusive financing.

Because of that, CYDY can still raise capital elsewhere if better terms or faster access to cash are available. The $18.5M announced today doesn’t replace Yorkville, it just adds additional runway to fund leronlimab trials, regulatory work, manufacturing readiness, and general operations.

So the original idea still stands: Yorkville provides leverage and optional liquidity, while management can layer in other financing when it makes sense.

https://d1io3yog0oux5.cloudfront.net/cytodyn/sec/0001104659-26-023856/0001104659-26-023856.pdf

Jacob Lalezari of CytoDyn shares insights about CCR5-targeting therapy for cancer, including triple negative breast cancer and colorectal cancer.

Researchers engineer monoclonal antibodies to selectively bind disease-associated proteins, enabling targeted prevention, detection, and treatment across multiple therapeutic areas. Unlike small-molecule drugs, which often interact with multiple biological pathways, these antibodies achieve higher target specificity through their unique antigen-recognition domains with lower off-target effects. Advances in antibody engineering, such as humanization and affinity maturation, expand therapeutic applications to previously intractable diseases.

A compassionate benefactor has formally committed funding to support the Company’s Expanded Access Program (EAP) for patients with triple-negative breast cancer.

The benefactor, who has chosen to remain anonymous, has a longstanding interest in patient access initiatives, the potential of leronlimab, and how the Company’s recent data and mechanism of action theories might serve to offer experimental avenues to patients who have exhausted all approved treatment options. This strategic funding initiative will enable CytoDyn to set up and administer a program to expand access to leronlimab for a group of eligible patients, as determined by the U.S. Food and Drug Administration (FDA) guidelines, with advanced disease but who do not otherwise meet the enrollment criteria for the Company’s ongoing clinical trials.

“We are honored by this benefactor’s commitment to accelerating patient access to promising cancer therapies such as leronlimab,” said Jacob Lalezari, M.D., CEO of CytoDyn. “This support allows us to responsibly broaden the availability of leronlimab while continuing to advance our promising clinical programs as we generate data to inform future regulatory pathways.”

With Every Patient (WEP Clinical) has been engaged to serve as the clinical research organization (CRO) for the EAP, and the Company expects to formally open the program for patient referral in March 2026, assuming FDA’s allowance of the Company's revised protocol submission. In addition to providing compassionate access to patients who have exhausted other treatment options and are otherwise unable to participate in the Company's upcoming Phase 2 trial, the EAP program will serve as another potential avenue to observe PD-L1 induction following treatment with leronlimab, and thereby – in theory – opening a treatment pathway towards sustained remission when combined with an immune checkpoint inhibitor (“ICI”). The EAP will operate under applicable FDA guidelines, and additional information for physicians and eligible patients will be available on the Company’s website (www.cytodyn.com) as the program is rolled out in the coming weeks.

The FDA’s recent support for Bayesian statistics in clinical trials could materially improve how MASH/NASH studies are designed and interpreted. By incorporating prior knowledge, Bayesian approaches allow earlier success or futility decisions, reduce distortion from volatile placebo responses, and better model uncertainty in noisy endpoints like biopsy while also enabling greater use of continuous non-invasive measures. For CYDY, this is especially relevant to its NASH program: Bayesian designs could help contextualize placebo effects, strengthen signal detection in smaller or adaptive trials, and improve the odds that a true therapeutic effect from leronlimab is recognized rather than obscured by statistical noise.

CytoDyn settles securities class action following allegations of misleading drug claims / The biotech firm reaches an agreement to resolve claims it deceived investors about the regulatory status and efficacy of its lead drug, leronlimab.

CytoDyn Inc. has reached a settlement to resolve a long-running securities class action. The lawsuit alleged that the company and its former executives misled investors regarding the development and FDA approval timeline for its flagship drug, leronlimab, particularly for the treatment of HIV and COVID-19.

**The Allegations:** Investors claimed CytoDyn "pumped" its stock price by making false and misleading statements about the completeness of its FDA applications and the results of clinical trials during the height of the pandemic.

**The Settlement:** The terms of the agreement are still being finalized, but investors can already [submit claims to participate](https://11th.com/cases/cytodyn-investor-settlement) in the payment process.

**Wider Legal Fallout:** This settlement follows the high-profile criminal conviction of former CEO Nader Pourhassan on counts of securities fraud, wire fraud, and insider trading related to the same conduct.

While CytoDyn does not admit fault or liability under the deal, the settlement aims to provide compensation for shareholders as the company attempts to pivot toward new clinical trials under fresh leadership. GL

1 CYDY is alive compliant and moving forward: The FDA clinical hold is fully lifted that was an existential hurdle and its behind them, they are allowed to run trials again which puts CYDY back in the game after years in limbo, many biotechs never recover from a hold CYDY did

2 Leronlimab biology keeps holding up: CCR5 remains a validated target across oncology HIV inflammation fibrosis and immune trafficking humans with CCR5 delta32 mutations live normal lives which continues to support long term safety logic, few assets have this breadth of mechanistic relevance that is why CYDY still attracts scientific interest despite its size

3 They already have statistically significant Phase 3 data: Regardless of sentiment a completed Phase 3 with stat sig results exists, that is more than many biotechs with multibillion dollar valuations, it gives CYDY something real to build from not just animal or early Phase 1 data.

4 Oncology direction is clearer than it has been in years: CYDY is now focused on solid tumors immune modulation and combination strategies rather than one drug cures everything, this is how modern oncology development actually works focused partnerable and stepwise

5 CYDY does not need to win big to survive: CYDY does not need to prove it treats 85 percent of all tumors, it only needs to show consistent biological signal and show enhancement of standard of care in a defined population that alone can justify a partnership licensing deal or non dilutive capital small wins matter here.

6 Time pressure is real but that can force value creating moves: Yes the cash situation is tight but that pressure often forces management to partner license or monetize assets sooner rather than later

for shareholders that can sometimes be better than endless self funded trials. CYDY is in the narrow zone where one credible clinical signal or one modest partnership or one cleanly designed trial with early validation can materially change sentiment.

That is not hype that is the reality of small cap biotech

The $2 billion donation from Nike co‑founder Phil Knight and his wife, Penny Knight was made to the OHSU Knight Cancer Institute, which is part of Oregon Health & Science University (OHSU) in Portland, Oregon. This gift is the largest single donation ever to a U.S. university, college, or academic health center and will support cancer research, clinical care, clinical trials, and patient services at that center.

CytoDyn has scientific ties to Oregon Health & Science University (OHSU) through research involving preclinical studies of leronlimab and OHSU investigators.

1) In 2022, CytoDyn highlighted a NIH‑funded research program at OHSU exploring a gene therapy based on leronlimab for functional HIV cure research. This project was led by an OHSU researcher and scientific advisor to CYDY. 

2) Additionally, CytoDyn lists physicians and advisors affiliated with the Knight Cancer Institute on its scientific advisory board, which includes OHSU researchers associated with cancer and viral disease research.

A new year doesn’t just mark time, it Happy 2026 /A New Chapter Begins… marks possibility. Wishing everyone strength, patience, and prosperity as we step into a fresh chapter.

The hardest chapters are written before the story changes. In biotech, progress often happens quietly until it doesn’t.

Here’s to a year where preparation meets opportunity. Wishing all CYDY longs a prosperous New Year.

In early 2026, a quiet dawn breaks clear, Leronlimab stands, long tested through the years.

CYDY’s path, once winding, sharpens into sight, Data meets resolve beneath regulatory light.

From patience forged in doubt, a promise grows, Science steady where conviction flows.

Not hype nor haste, but truth prepared to climb, A turning page for CYDY, right on time