Vyrologix (leronlimab) / CytoDyn, Lantheus, Vyera Pharma, amfAR - LARVOL DELTA

Preliminary results of a phase 2 study of leronlimab in combination with TAS-102 and bevacizumab in previously treated metastatic colorectal cancer (AACR 2026) - "Leronlimab combined with TAS-102 and bevacizumab is feasible, showing promising early biomarker and clinical activity in heavily pretreated mCRC. Universal CCR5 positivity supports CCR5 as a potential therapeutic target. Updated outcomes and correlative data will be presented."

Combination therapy • IO biomarker • Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor • CA 19-9 • CCR5 • CTCs • PD-L1

Leronlimab induces PD-L1 expression and is associated with long‑term survival with an ICI in PD-L1 low metastatic TNBC (AACR 2026) - "CCR5 may promote ICI resistance in TNBC by upregulating immune checkpoints (sB7-H3) and sTyro3. Overall, 17.9% (5/28) of patients with mTNBC treated with leronlimab are currently alive after a median of >60 months follow-up."

IO biomarker • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCR5 • CD276 • CD8 • CTCs • PD-L1 • PROS1

Leronlimab is associated with long-term survival in metastatic TNBC: Enhancing PD-L1 expression, ICI response, and modulates T cell exhaustion (AACR-IO 2026) - "CCR5 may contribute to ICI resistance in TNBC by promoting T-cell exhaustion and driving immunosuppressive checkpoint pathways (including sB7-H3 and sTyro3). Leronlimab blocks CCR5 signaling, reduces exhaustion markers, suppresses multiple immunosuppressive mediators, and increases PD-L1 expression on tumor-associated cells; changes that may sensitize tumors to PD-1/PD-L1 blockade. Together, these findings support a mechanistic rationale for combining leronlimab with ICIs to enhance therapeutic responses in mTNBC."

IO biomarker • Metastases • Breast Cancer • Solid Tumor • Triple Negative Breast Cancer • CCR5 • CD276 • CD4 • CD8 • CTCs • CTLA4 • HAVCR2 • LAG3 • PD-L1 • TNFSF13B

CCR-CCL axes as key upstream influencers of pancreatic ductal adenocarcinoma: CCR2-CCL2, CCR5-CCL5, CCR4-CCL17/22, CCR6-CCL20, CCR7-CCL19/21. (PubMed, Front Immunol) - "We further detail past and ongoing therapeutic efforts and trials addressing these axes in both PDAC and relevant non-PDAC settings via several small-molecule antagonists and monoclonal antibodies: BMS-813160, Maraviroc, Leronlimab, FLX475, PF-07054894, IDOR- 1117-2520, and CAP-100. Despite continuous advances in the field, the current body of evidence remains limited and presents significant research gaps in areas such as spatial profiling, stage-specific analyses, and general mechanistic validation in PDAC-specific settings. Addressing these shortcomings will be key to developing a more comprehensive knowledge of the field and improving future therapeutic strategies to overcome PDAC."

IO biomarker • Journal • Review • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CCL19 • CCL2 • CCL20 • CCR2 • CCR4 • CCR6 • CCR7

Basket Study of Leronlimab (PRO 140) in Patients With CCR5+ Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P2 | N=16 | Completed | Sponsor: CytoDyn, Inc. | N=30 ➔ 16 | Trial completion date: Jul 2022 ➔ Jan 2025 | Active, not recruiting ➔ Completed

Enrollment change • Pan tumor • Trial completion • Trial completion date • Solid Tumor • CTCs

Prolonged survival following PD-L1/PD-1 immune checkpoint inhibitor therapy after leronlimab induced PD-L1 upregulation on cancer-associated macrophage-like cells and circulating tumor cells in patients with metastatic or locally advanced triple-negative breast cancer (SABCS 2025) - P, P1/2, P2 | "In clinical trials among previously treated mTNBC patients the median overall survival (mOS) has been reported as 6.6 months for ≥3rd line chemotherapy, 11.8 months for ≥2nd line sacituzumab govitecan, and 9.9 months for ≥1st line pembrolizumab. These findings support the hypothesis that LRM may enhance PD-L1 expression on CAMLs/CTCs, potentially priming tumors for improved responses to ICIs. In an evolving treatment landscape these data warrant prospective evaluation of LRM, particularly in combination with ICIs in mTNBC."

Checkpoint inhibition • Circulating tumor cells • Clinical • IO biomarker • Metastases • Tumor cell • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTCs

CytoDyn to Showcase PD-L1 Upregulation and Improved Survival in Metastatic Triple Negative Breast Cancer at the San Antonio Breast Cancer Symposium (CytoDyn Press Release) - "Median Overall Survival after starting leronlimab was 7.1 months (95% CI: 4.8–17.7 months) with survival at years 1, 2, 3, and 4 of 35.7%, 21.4%, 17.9% and 17.9%, respectively. Patients treated with either the 525 or 700 mg dose of leronlimab demonstrated significantly longer survival (HR 3.44, 95% CI: 1.2–9.9; P=0.0418) compared to patients treated with the 350 mg dose."

Retrospective data

CytoDyn to Present Prolonged Survival Data on Leronlimab...at the San Antonio Breast Cancer Symposium (GlobeNewswire) - "Company to deliver a poster presentation on clinical data demonstrating sustained remission following immune checkpoint inhibitor therapy with or after leronlimab treatment in patients with metastatic or locally advanced triple-negative breast cancer."

Clinical data • Triple Negative Breast Cancer

An Extension Protocol for Subjects Who Successfully Completed PRO140_CD02 or PRO140_CD02_Open Label Study (clinicaltrials.gov) - P2/3 | N=43 | Terminated | Sponsor: CytoDyn, Inc. | Active, not recruiting ➔ Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.

Trial termination • Human Immunodeficiency Virus • Infectious Disease • CXCR4

PRO 140_CD03 Extension: An Extension Protocol for Virologically Suppressed Subjects Who Successfully Completed PRO140_CD03 Study (clinicaltrials.gov) - P2/3 | N=56 | Terminated | Sponsor: CytoDyn, Inc. | Active, not recruiting ➔ Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.

Trial termination • Human Immunodeficiency Virus • Infectious Disease

An Extension of Protocol PRO 140_CD01 Study (clinicaltrials.gov) - P2 | N=20 | Terminated | Sponsor: CytoDyn, Inc. | Active, not recruiting ➔ Terminated; FDA required the sponsor to halt enrollment in the trial and transition participants to available therapies for the treatment of their disease. The trial was subsequently terminated once participants were transitioned.

Monotherapy • Trial termination • Human Immunodeficiency Virus • Infectious Disease

PRO 140 in Treatment-Experienced HIV-1 Subjects (clinicaltrials.gov) - P2/3 | N=6 | Completed | Sponsor: CytoDyn, Inc. | Active, not recruiting ➔ Completed | N=25 ➔ 6

Enrollment change • Trial completion • Human Immunodeficiency Virus • Infectious Disease

Leronlimab (PRO 140) Combined With Carboplatin in Patients With Cytokine Chemokine Receptor 5 Positive (CCR5+) mTNBC (clinicaltrials.gov) - P1/2 | N=10 | Terminated | Sponsor: CytoDyn, Inc. | N=48 ➔ 10 | Active, not recruiting ➔ Terminated; Study terminated prematurely due to business reasons. Participants are no longer examined or receiving intervention.

Enrollment change • Trial termination • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTCs • HER-2 • PD-L1

Evaluate the Efficacy & Safety of Leronlimab in Patients With Severe or Critical COVID-19 (clinicaltrials.gov) - P2 | N=484 | Completed | Sponsor: CytoDyn, Inc. | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2

Phase classification • Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Molecular targets of neuroplasticity in ischemic stroke: insights from GEO database, single-cell analysis and immune infiltration analysis. (PubMed, Front Aging Neurosci) - "Finally, the Leronlimab, Ulocuplumab, Burixafor, and MSX-122 are promising drugs to treat IS via targeting on CCR5 and CXCR4. In conclusion, our findings suggest that CCR5 and CXCR4 are promising targets for enhancing neuroplasticity post-ischemic stroke, thus providing potentially effective and reliable therapeutic targets for future interventional strategy."

Journal • Cardiovascular • Ischemic stroke • CD8 • CXCR4 • GRM1 • TIMP1

Chemokine receptor type-5: a key regulator of immunity, disease pathogenesis, and emerging therapeutic target. (PubMed, Inflammopharmacology) - "With therapeutic inhibition of CCR5 gaining attention, Maraviroc is approved for HIV treatment, while monoclonal antibodies such as leronlimab, genetic strategies (CRISPR), and dual CCR2/CCR5 antagonists such as cenicriviroc are under investigation for broader applications. Blocking CCR5 has shown efficacy in reducing metastasis and improving chemotherapy outcomes, reinforcing its therapeutic potential. Along with CCR5's role in disease pathogenesis, emphasizing its involvement in immune regulation and inflammatory processes, this review explores the multifaceted role of CCR5 in immunity, its contribution to disease pathogenesis, and innovative therapeutic interventions targeting CCR5 to modulate immune responses and treat diseases."

Journal • Review • Atherosclerosis • Breast Cancer • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • HER2 Breast Cancer • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammatory Arthritis • Inflammatory Bowel Disease • Oncology • Rheumatoid Arthritis • Rheumatology • Solid Tumor • CCL3 • CCR2 • CCR5 • HER-2

A Phase 2 Study of Leronlimab in Combination With TAS-102 + Bevacizumab in Previously Treated Participants With mCRC (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: CytoDyn, Inc. | Trial completion date: Aug 2028 ➔ Mar 2028 | Trial primary completion date: Jun 2028 ➔ Jan 2028

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

Observed survival following treatment with leronlimab in patients with metastatic colorectal cancer (ESMO-GI 2025) - P2 | "Four patients received leronlimab in combination with ongoing or new SOC regimens (n=2 FOLFOX, n=1 FOLFOX + bevacizumab and n=1 FOLFOXIRI + bevacizumab)... Leronlimab was generally well tolerated, with no related dose limiting toxicities observed and demonstrated potential clinical benefit in patients with relapsed mCRC. Though limited to 5 patients, these findings are encouraging and support further investigation of leronlimab in mCRC-MSS patients."

Clinical • Metastases • Colorectal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

CytoDyn Announces First Patient Dosed in Phase II Oncology Trial in Colorectal Cancer (GlobeNewswire) - "CytoDyn...announced that the first patient has been dosed in the Company’s clinical trial evaluating the efficacy of leronlimab in patients with relapsed/refractory microsatellite stable colorectal cancer ('CRC'). In partnership with Syneos Health, the Company has engaged eight clinical sites and counting, and patient enrollment and processing efforts are underway."

Trial status • Colorectal Cancer

CytoDyn Announces Encouraging Survival Data in Patients with Metastatic Colorectal Cancer Previously Treated with Leronlimab (CytoDyn Press Release) - P2 | N=30 | NCT04504942 | Sponsor: CytoDyn, Inc. | "CytoDyn Inc...announced encouraging clinical findings among patients with advanced metastatic colorectal cancer ('mCRC') previously treated with leronlimab. The final results indicate that 3/5 patients treated with leronlimab had at least a partial response, as measured by radiologic criteria, including one patient with a complete response who remains alive five years later....Dr. Benjamin Weinberg to present final results at the ESMO Gastrointestinal Cancers Congress 2025 in Barcelona, Spain."

P2 data • Colorectal Cancer

Clinical Trials Demonstrate Monitoring PD-L1 Upregulation Using LifeTracDx Blood Test Could Support New Treatment Path for Metastatic Triple Negative Breast Cancer (PRNewswire) - "Creatv Bio...in collaboration with CytoDyn Inc...presents promising four-year survival rates from a pooled clinical trial analysis of patients with metastatic triple-negative breast cancer ('mTNBC') treated with leronlimab and PD-L1 immune checkpoint inhibitors ('ICI')....Results indicated that leronlimab treatment correlated with increased expression of PD-L1 on circulating tumor associated cells, as measured using the LifeTracDx blood test from Creatv. The analysis also revealed promising survival observations among patients who experienced a significant increase in PD-L1 expression and subsequently pursued treatment with an ICI. Four year follow-up results were presented at the ESMO Breast Cancer meeting on May 15, 2025....In the trials presented at ESMO, results showed that monitoring the expressions of PD-L1 before and after induction of leronlimab using the LifeTracDx blood test identified upregulation of PD-L1 expression in 76% of patients after therapy induction."

Retrospective data • Triple Negative Breast Cancer

A Phase 2 Study of Leronlimab in Combination With TAS-102 + Bevacizumab in Previously Treated Participants With mCRC (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: CytoDyn, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2025 ➔ May 2025

Enrollment open • Trial initiation date • Colorectal Cancer • Oncology • Solid Tumor

Engineering an Endoplasmic Reticulum (ER) Stress Responsive RNA Structural Switch for mRNA and Gene Therapies (ASGCT 2025) - "Then, we replaced reporter genes with therapeutically relevant ER stress causing FVIII and Leronlimab (an anti-CCR5 monoclonal antibody being evaluated for HIV treatment)...Further testing and refinement of XBP1F modified therapeutic constructs in animal models with the goal of developing mRNA and gene therapies with decreased immunotoxicity and improved safety profiles is underway. Disease Focus of Abstract:None"

Gene therapy • Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia A • Human Immunodeficiency Virus • Infectious Disease • Rare Diseases • Thrombosis • ER • XBP1

Observed survival following treatment with Leronlimab in patients with metastatic triple-negative breast cancer (mTNBC) (ESMO-BC 2025) - P=N/A, P1/2, P2 | "Pretreated mTNBC has a poor prognosis whether treated with chemotherapy (French ESME program, ≥2 systemic therapies, median overall survival (mOS) ∼6 months, survival 1 year ∼25%, 2 years ∼10%, 3 years ∼7%), pembrolizumab + standard chemotherapy (mOS=10.8 months, 1 year ∼25%, 2 years 10%), or sacituzumab govitecan (ASCENT) (mOS=∼11.8 months, 1 year ∼25%, 2 years 20%). 28 patients with mTNBC were treated across three leronlimab clinical trials ((NCT03838367, N=10), (NCT04313075, N=16), (NCT04504942, N=2)). Treatment on NCT03838367 included leronlimab and carboplatin...4 patients who are currently alive without evidence of disease after 42, 48, 49, and 52, months, each had 4 prior lines of systemic therapy and were treated with leronlimab either in combination or subsequently, with checkpoint inhibitors: pembrolizumab (N=1) or atezolizumab (N=3) and chemotherapy (N=4). Leronlimab was well-tolerated... Leronlimab was well-tolerated. The encouraging pooled..."

Clinical • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

CytoDyn Releases ESMO Breast Cancer Meeting Poster (GlobeNewswire) - "CytoDyn Inc...today shared the Company’s poster presented at the European Society for Medical Oncology’s ('ESMO') Breast Cancer meeting on May 14-17, 2025, in Munich, Germany."

Clinical data • Solid Tumor