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

CCR5 Targeting Leronlimab in Combination With Hepatic Arterial Infusion Floxuridine and Systemic Therapy for the Treatment of Colorectal Cancer Liver Metastases, CHAMP Trial (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P1 trial • Colorectal Cancer • Oncology • Solid Tumor • PD-L1

Leronlimab (LRM) in combination with trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) in metastatic colorectal cancer (mCRC): The phase 2 CLOVER study (ESMO 2026) - No abstract available

Combination therapy • Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor

The guanine nucleotide exchange factor Rin-like is a repressor for renal uric acid excretion in human and mouse. (PubMed, Sci Transl Med) - "The hRINL (P139S) mutation inhibited proteasome-mediated degradation of hRINL in renal tubular epithelial cells, causing its accumulation, and the homologous mouse RINL (mRINL) Pro140→Ser (P140S) mutation up-regulated mRINL in mouse kidneys, indicating a gain-of-function mutation. We screened a library of 1500 natural products for RINL inhibitors and, after experimental validation, found that tetrahydrocurcumin bound to RINL and promoted its degradation, thereby ameliorating HUA induced by potassium oxonate treatment, uricase knockout, or secondary to severe malaria and chronic kidney disease in mice. These findings establish RINL as a repressor of UA excretion in both humans and mice and suggest that targeted degradation of RINL represents a promising strategy for HUA treatment."

Journal • Preclinical • Chronic Kidney Disease • Infectious Disease • Malaria • Nephrology • Renal Disease • RAB5C

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

Combination therapy with broadly neutralizing antibodies, antiretroviral therapy and CCR5 blockade limits viral reservoir seeding in infant macaque model of HIV. (PubMed, Nat Microbiol) - "Following the treatment of infants with viraemia at 72 h post-infection with the combination of broadly neutralizing antibodies, ART and leronlimab, no subsequent evidence of replicating or latent virus and antiviral immunity was observed 1 year after treatment interruption. These findings suggest a synergy between broadly neutralizing antibodies, ART and CCR5 blockade for preventing viral reservoir establishment and offer potential improvements over current therapies for newborns exposed to human immunodeficiency virus."

Journal • Human Immunodeficiency Virus • Infectious Disease

An ER stress-responsive RNA rheostat for programmable gene and mRNA therapies. (PubMed, Cell Chem Biol) - "We further demonstrate the regulation of Leronlimab expression in vivo using recombinant adeno-associated virus vectors. Together, these findings establish programmable RNA feedback control as a strategy for linking cellular proteostasis to therapeutic protein expression and improving the safety of gene and mRNA therapies."

Journal • Gene Therapies • ERN1 • XBP1

Leronlimab in combination with trifluridine/tipiracil (TAS-102) plus bevacizumab for patients with refractory metastatic colorectal cancer (mCRC): The phase 2 CLOVER study. (ASCO 2026) - P2 | "In the CLOVER trial LRM in combination with TAS-102 plus BEV has been well tolerated with no LRM-related DLTs. Rapid declines in ctDNA have been observed along with stable objective responses, with most patients having baseline liver metastases and RAS-mutant. At the time of abstract submission approximately half of the target number of patients have been enrolled and at the time of presentation the trial is expected to be fully or close to fully enrolled."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Breast Cancer • Colorectal Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCR5 • CTCs • PD-L1

CytoDyn Announces First Patient Dosed in Phase 2a Study in Collaboration with Weill Cornell Medicine Evaluating Leronlimab in Alzheimer’s Disease (GlobeNewswire) - "The study, known as SALIENT-AD (Safety Assessment of Leronlimab and Its Effect on Neuroinflammation Targets in Alzheimer’s Disease), is a Phase 2a, open-label, proof-of-concept study designed to evaluate the safety and biological activity of leronlimab in approximately 10 to 20 patients over the age of 50 with early-stage, biomarker-confirmed Alzheimer’s disease."

Trial status • Alzheimer's Disease

Safety and 5-year survival following treatment with leronlimab plus physician's choice combination therapy in patients with metastatic triple-negative breast cancer. (ASCO 2026) - P, P1/2, P2 | "In this post hoc analysis LRM was well tolerated with no LRM treatment-related TEAEs leading to treatment discontinuation and no LRM treatment-related TEAEs graded as CTCAE >2. A 5-year OS rate of 17.9% (5/28) in this advanced population is encouraging. All 5 patients with PD-L1 upregulation treated with LRM with an ICI, or followed by an ICI, remained alive at 5 years suggesting a correlation with durable responses."

Clinical • Combination therapy • IO biomarker • Metastases • Breast Cancer • Constipation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Neutropenia • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTCs

The Phase-2 CCR5-targeting Leronlimab With Oral Chemotherapy and VEGF-inhibitor Enriched Regimen Trial (CLOVER) (clinicaltrials.gov) - P2 | N=66 | Active, not recruiting | Sponsor: CytoDyn, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Oncology • Solid Tumor

SALIENT-AD: Safety Assessment of Leronlimab and Its Effect on Brain Inflammation in Alzheimer's Disease (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Weill Medical College of Cornell University | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation

Adeno-associated virus gene therapy-mediated CCR5 blockade suppresses virus replication long term in SHIV-infected macaques. (PubMed, Sci Transl Med) - "In the three macaques with uncontrolled SHIV viremia, short-term administration of exogenous leronlimab induced complete SHIV suppression in two and a 100-fold reduction in the third, indicating that a threshold of leronlimab expression is necessary to effectively halt SHIV replication. These results demonstrate the potential of gene therapy-mediated long-term antibody-based CCR5 blockade for HIV functional cure but highlight challenges in achieving sufficient antibody expression when targeting an abundant self-antigen."

Journal • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • CCR5 • CD4

SALIENT-AD: Safety Assessment of Leronlimab and Its Effect on Brain Inflammation in Alzheimer's Disease (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Weill Medical College of Cornell University

New P2 trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation

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

CytoDyn Presents New Leronlimab Data in Metastatic Colorectal Cancer at AACR Annual Meeting 2026 (CytoDyn Press Release) - "Among pre-screened patients with evaluable samples (N=33), CCR5 expression was detected in 100% of cases, supporting its potential as a therapeutic target in mCRC. Early clinical and biomarker responses were observed, including rapid and substantial reductions in circulating tumor DNA (ctDNA), with median declines of approximately 70% by week 2 across evaluable patients (N=19). The combination regimen has been well tolerated, with no leronlimab-related dose-limiting toxicities (DLTs) observed, and escalation to 700 mg dosing underway. The study continues to enroll toward full enrollment, reflecting significant unmet need in previously treated mCRC."

P2 data • Trial status • Colorectal Cancer

CytoDyn…announced the completion of enrollment in its Phase 2 clinical study (ClinicalTrials.gov Identifier: NCT06699836) evaluating leronlimab in combination with trifluridine and tipiracil (TAS-102) plus bevacizumab in patients with CCR5-positive, microsatellite stable (MSS), relapsed/refractory metastatic colorectal cancer (mCRC), also known as CLOVER (GlobeNewswire) - "Enrollment concludes with just over 60 patients participating across seven clinical sites located throughout the United States....CytoDyn plans to share topline data from the study as they become available."

Enrollment closed • Colorectal Cancer

An Open-Label, Multicenter, Non-Randomized Expanded Access Protocol (EAP) Designed to Provide Leronlimab to Patients With Locally Advanced or Metastatic Triple-Negative Breast Cancer (mTNBC) (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: CytoDyn, Inc.

New trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

CytoDyn…announced that it will be presenting two posters at the American Association for Cancer Research (AACR) Annual Meeting 2026 (GlobeNewswire) - "'The research being presented at AACR reflects the growing body of scientific work examining CCR5 biology and its role in the tumor microenvironment. Together, these studies help deepen our understanding of how leronlimab may enhance immune responses and inform our broader strategy to develop new treatment approaches for patients with difficult-to-treat cancers'."

Clinical data • Colorectal Cancer • Triple Negative Breast Cancer

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