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

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

CytoDyn Announces Data Suggesting Novel Mechanism of Action of Leronlimab for the Treatment of Solid Tumors (GlobeNewswire) - "CytoDyn analyzed data from its prior clinical trials of patients with metastatic Triple-Negative Breast Cancer ('mTNBC') and found that leronlimab treatment correlated with increased expression of an immune cell protein or 'checkpoint inhibitor' known as programmed death-ligand 1 ('PD-L1') on patient’s circulating tumor cells ('CTCs'). CytoDyn’s results indicate that 15/17 (88%) of patients who received a weekly dose of 525 mg or higher experienced a significant increase in PD-L1 expression on their CTCs over a 30-to-90-day period after starting leronlimab. Increasing expression of PD-L1 can be likened to turning 'cold' tumors 'hot', elevating PD-L1 levels to the level necessary for patients to potentially derive benefit from further treatment with a class of drugs known as immune checkpoint inhibitors ('ICIs')."

Retrospective data • Solid Tumor • Triple Negative Breast Cancer

Enhancing Transplacental Delivery of Monoclonal Antibodies Through FcRn Optimization (IMMUNOLOGY 2025) - "A single dose of leronlimab-PLS also ensured complete CCR5 receptor occupancy in mothers and newborns for nearly a month postpartum. These findings demonstrate that optimizing FcRn interactions can enhance transplacental mAb delivery and extend therapeutic efficacy, offering a novel approach to protect vulnerable populations during pregnancy and early life.Keywords: Animals Non-Human Primate; Infections AIDS; Molecules Antibodies"

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

Observed Survival Following Treatment With Leronlimab In Patients With Metastatic Colorectal Cancer. (ESMO-GI 2025) - No abstract available

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor

Addition of a short HIV-1 fusion-inhibitory peptide to PRO 140 antibody dramatically increases its antiviral breadth and potency. (PubMed, J Virol) - "CCR5-directed antibody PRO 140 is currently under clinical trials, but it only inhibits CCR5-tropic HIV-1 isolates. The designed fusion proteins by adding a minimum fusion-inhibitory peptide to PRO 140 enable dramatically increased activities in inhibiting both CCR5-tropic and CXCR4-tropic viruses, thus offering novel antiviral agents with a bispecific functionality that can overcome the drawbacks of PRO 140 antibody."

Journal • Human Immunodeficiency Virus • Infectious Disease • CCR5 • CXCR4

Study of PRO 140 SC As Single Agent Maintenance Therapy in Virally Suppressed Subjects with CCR5-tropic HIV-1 Infection (clinicaltrials.gov) - P2/3 | N=556 | Completed | Sponsor: CytoDyn, Inc. | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2/3

Phase classification • Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

CytoDyn Announces Promising Survival Observations in mTNBC Patients Treated with Leronlimab (GlobeNewswire) - P=NA | N=NA | "CytoDyn Inc...announced encouraging survival outcomes among a group of patients with metastatic triple-negative breast cancer ('mTNBC') treated with leronlimab. Although mTNBC typically has a poor prognosis, observed survival rates at 12, 24, and 36 months after treatment with leronlimab compare favorably with reported life expectancy after treatment with currently approved therapies. In addition, the Company confirmed that a small group of patients who failed treatment after developing metastatic disease survived more than 36 months after receiving leronlimab, are alive today, and currently identify as having no evidence of ongoing disease...CytoDyn...to summarize the findings and submit an abstract to the European Society for Medical Oncology (ESMO) Breast Cancer...from May 14 to 17, 2025....Based on these survival observations, the Company has initiated two pre-clinical studies in mTNBC that will evaluate possible treatment synergies between leronlimab..."

Clinical data • Preclinical • Triple Negative Breast Cancer

Leronlimab Treatment for Multidrug-Resistant HIV-1 (OPTIMIZE): a Randomized, Double-Blind, Placebo-Controlled Trial. (PubMed, J Acquir Immune Defic Syndr) - "Leronlimab resulted in significantly reduced plasma HIV-1 within one week after addition to failing ART. After 24 weeks combined with an OBT, most participants had plasma HIV-1 RNA levels <50 copies per mL plasma, suggesting utility of leronlimab as a component of salvage therapy."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease

CytoDyn Announces Findings of Statistically Significant Fibrosis Reversal Across Studies with SMC Laboratories (GlobeNewswire) - "CytoDyn Inc..announced today positive results from its preclinical studies with SMC Laboratories...The three studies demonstrated statistically significant reversal of liver fibrosis with leronlimab monotherapy (compared to an isotype IgG4 control arm with p-values across all 3 studies < 0.01). The first two studies, completed in late 2024, evaluated leronlimab in the STAM model of metabolic dysfunction associated steatohepatitis (MASH) with fibrosis in mice who received a single dose of Streptozocin at birth and were then fed a high fat diet from weeks four to twelve. The third study, concluded in January 2025, evaluated reversal of liver fibrosis in mice who received carbon tetrachloride, a liver fibrosis-inducing agent, from birth to sacrifice at day 35."

Preclinical • Fibrosis

A Phase 2 Study of Leronlimab in Combination with TAS-102 + Bevacizumab in Previously Treated Participants with MCRC (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: CytoDyn, Inc.

Combination therapy • Metastases • New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

Interventions for the management of long covid (post-covid condition): living systematic review. (PubMed, BMJ) - "Moderate certainty evidence suggests that CBT and physical and mental health rehabilitation probably improve symptoms of long covid."

Journal • Review • CNS Disorders • Depression • Fatigue • Mood Disorders • Novel Coronavirus Disease • Psychiatry

CytoDyn Announces FDA Clearance of Its Phase II Oncology Trial (GlobeNewswire) - "The study will evaluate the efficacy of leronlimab in patients with relapsed/refractory microsatellite stable colorectal cancer ('CRC')....Clearance for the Phase II oncology trial was achieved following productive feedback sessions with the FDA over the past few months and the submission of a final study protocol to the FDA in September 2024. As previously announced, the trial will be conducted in partnership with Syneos Health. A trial kickoff meeting has been set for late November 2024 and patient enrollment will begin in early 2025."

IND • New P2 trial • Colorectal Cancer

CytoDyn Engages Syneos Health as CRO For Its Phase II Oncology Trial (GlobeNewswire) - "CytoDyn Inc...announced today that it has engaged Syneos Health as the contract research organization ('CRO') for its upcoming Phase II oncology trial. The trial will evaluate the efficacy of leronlimab in patients with relapsed/refractory micro-satellite stable colorectal cancer ('CRC')....As previously announced, the Company’s final study protocol was submitted to the FDA for approval in September 2024, and CytoDyn expects to start screening patients in early 2025."

Commercial • Colorectal Cancer

Short-term combination immunotherapy with broadly neutralizing antibodies and CCR5 blockade mediates ART-free viral control in infant rhesus macaques (HIVR4P 2024) - "Here we evaluated whether a triple combination of early ART initiation with HIV broadly neutralizing antibodies (bNAbs) and the CCR5-blocking mAb Leronlimab could mediate virus clearance in simian-HIV (SHIV)-infected infant rhesus macaques. A total of 16 four-week-old infant rhesus macaques were orally infected with SHIV-SF162P3 and placed into the following treatment groups, with all treatments beginning at 72 hours after infection: 1) ART + bolus doses of the bNAbs PGT121-LS and VRC07-523-LS (n=2), 2) ART + Leronlimab for 8 weeks (n=6), or 3) ART + bolus doses of the bNAbs PGT121-LS and VRC07-523-LS + Leronlimab for 8 weeks (n=8). Finding a treatment that can prevent reservoir establishment and spread after the first 48 hours has been elusive. The results of this study suggest that the combination of ART, bNAbs, and CCR5 blockade via Leronlimab synergize in an undefined mechanism to prevent further seeding of of the reservoir early after infection, and may even..."

Human Immunodeficiency Virus • Infectious Disease

A Randomized Placebo-Controlled Trial of Leronlimab in Mild-To-Moderate COVID-19. (PubMed, Clin Ther) - P2 | "At the time the TEMPEST trial was designed although CCR5 was known to be implicated in COVID-19 disease severity the exact pathophysiology of SARS-CoV-2 infection was poorly understood. Today it is well accepted that SARS-CoV-2 infection in asymptomatic-to-mild cases is primarily characterized by viral replication, with a heightened immune response, accompanied by diminished viral replication in moderate-to-severe disease and a peak in inflammatory responses with excessive production of pro-inflammatory cytokines in critical disease. It is therefore perhaps not surprising that no differences between treatments were observed in the primary endpoint or in pre-specified secondary endpoints among participants with mild-to-moderate COVID-19. However, the results of the exploratory post hoc analysis showing that participants in the leronlimab group had greater improvement in NEWS2 assessment compared to placebo provided a suggestion that leronlimab may be associated with..."

Clinical • Journal • Cough • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Pulmonary Disease • Respiratory Diseases • CCR5

FcRn-enhancing mutations lead to increased and prolonged levels of the HIV CCR5-blocking monoclonal antibody leronlimab in the fetuses and newborns of pregnant rhesus macaques. (PubMed, MAbs) - "Further, a single dose of leronlimab-PLS led to complete CCR5 receptor occupancy in mothers and newborns for almost a month after birth. These findings support the optimization of FcRn interactions in mAb therapies designed for administration during pregnancy."

Journal • Human Immunodeficiency Virus • Infectious Disease

CytoDyn Announces Preliminary Findings in Study with SMC Laboratories (GlobeNewswire) - "CytoDyn...announced today a preliminary review of results from its preclinical study with SMC Laboratories. SMC Laboratories, a company specializing in preclinical drug efficacy evaluations using various models of inflammation and fibrosis in mice, conducted a study that assessed the optimal dosing of leronlimab in the MASH setting....Leronlimab monotherapy (700 mg) demonstrated statistically significant fibrosis reversal compared to an isotype IgG4 control arm (p<0.01); Leronlimab monotherapy appeared to demonstrate dose-dependent antifibrotic activity, with leronlimab 700 mg performing better at reversing liver fibrosis compared to leronlimab 350 mg..."

Preclinical • Fibrosis • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis

Biphenylsulfonamides as effective MMP-2 inhibitors with promising antileukemic efficacy: Synthesis, in vitro biological evaluation, molecular docking, and MD simulation analysis. (PubMed, Drug Dev Res) - "Apart from that, the MD simulation study also disclosed stable binding interactions of DH-18 and MMP-2 along with crucial interactions with active site amino acid residues namely His120, Glu121, His124, His130, Pro140, and Tyr142. In a nutshell, this study highlighted the importance of biphenylsulfonamide-based novel and promising MMP-2 inhibitors to open up a new avenue for potential therapy against CML."

Journal • Preclinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • MMP2

CytoDyn Announces Completion of FDA Meeting on Phase II Study of Leronlimab in Patients with Relapsed/Refractory Microsatellite Stable Colorectal Cancer (GlobeNewswire) - "CytoDyn...announced today that it completed a meeting with the U.S. Food and Drug Administration (FDA) to gain alignment on the rationale and proposed dosing for the Company’s Phase II study that will investigate the preliminary safety and activity of leronlimab in combination with trifluridine plus tipiracil (TAS-102) and bevacizumab in participants with CCR5+, microsatellite stable (MSS), relapsed or refractory metastatic colorectal cancer (mCRC). The Company intends to proceed with a submission of its final study protocol to the FDA, formal engagement of a clinical research organization (CRO), and related preparatory work towards initiating the proposed trial. This open label, randomized (1:1), multicenter trial will evaluate the anti-tumor activity (via overall response rate, ORR) of leronlimab at doses of 350 mg and 700 mg in combination TAS-102 and bevacizumab in approximately 60 patients with CCR5+, microsatellite stable metastatic CRC (mCRC)."

FDA event • New P2 trial • Colorectal Cancer

LS-variant anti-CCR5 monoclonal antibody provides long-lasting protection against intrarectal SHIV acquisition in rhesus macaques (AIDS 2024) - "These data demonstrate the ability of LS-variant Leronlimab to provide long-term protection against intrarectal SHIV acquisition and support development of long-acting CCR5 blockade for HIV PrEP."

Human Immunodeficiency Virus • Infectious Disease • CD4

Delivery and long-term expression of CCR5-blocking monoclonal antibody Leronlimab with AAV for ART-free remission from SHIV viremia (AIDS 2024) - "While further investigation is needed to develop AAV vectors and/or regimens that reduce the incidence of ADAs, the transgene reexpression phenomenon we have observed highlights the need to further investigate the interplay between AAV establishment and the development of ADAs. Overall, these data demonstrate the potential of AAV vectors for sustained antibody-based CCR5 blockade as a gene therapy approach for long-term ART-free HIV remission."

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

CytoDyn Announces Start of Preclinical MASH Study, Results Expected in Fall 2024 (GlobeNewswire) - "CytoDyn Inc...announced today that its preclinical MASH study with SMC Laboratories, Inc. ('SMC') has commenced, with results expected in the fall of 2024...To clarify the optimal dosing and evaluate the potential for combination therapy, SMC will be conducting a twelve-week preclinical mouse study evaluating both 350 and 700 mg dose levels, alone and in combination with Resmetirom, a drug recently approved by the FDA. The study will evaluate leronlimab’s potential role in preventing and/or reversing liver fibrosis."

Preclinical • Fibrosis • Metabolic Dysfunction-Associated Steatotic Liver Disease