MM-II / Moebius Medical, Sun Pharma - LARVOL DELTA

Patching of Damaged Meniscus and Cartilage of Osteoarthritic Animals by MM-II, a Dispersion of Empty Large Multilamellar Liposomes (ACR Convergence 2025) - P2 | "Pending on the KOA model, MM-II liposomes coat or patch OA cartilage and menisci. These observations, together with previous ones showing lubrication by MM-II, suggest a novel mechanism that may underlies MM-II clinical benefit in KOA."

Immunology • Musculoskeletal Pain • Osteoarthritis • Rheumatology

Clearance Kinetics and Cartilage Retention of MM-II, a Dispersion of Large Empty Liposomes, in Rat Knees (ACR Convergence 2025) - P2 | "IA injection in rat knees led to most MM-II liposomes clearing within 1–2 weeks, while a fraction persisted on cartilage and menisci for at least 28 days, supporting clinical findings of prolonged knee pain relief."

Preclinical • Musculoskeletal Pain • Osteoarthritis

Pharmacokinetic Profile of MM-II Following a Single Intra-Articular Injection in Patients with Knee Osteoarthritis in a Phase 2b Randomized, Controlled, Dose-Ranging Trial (ACR Convergence 2025) - P2 | "Based on these results, treatment of OA knee pain with a single IA injection of MM-II did not appear to increase circulating DMPC and DPPC levels compared with placebo within the time points analyzed. Further studies with additional sampling are necessary to enhance interpretation due to limited sampling time points and inherent variability in PK parameters."

Clinical • P2b data • PK/PD data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

LOCAL AND SYSTEMIC EFFECTS FOLLOWING REPEATED INTRAARTICULAR INJECTION IN RABBIT OF MM-II, A NOVEL DISPERSION OF LARGE, EMPTY, MULTILAMELLAR LIPOSOMES (EULAR 2025) - P2 | "MM-II related findings were limited to a reversible, non-adverse microscopic finding at the interim necropsy. NOAEL was determined as 35.7 mg/kg/dose cycle, once every three months for a total of 4 dose cycles. Toxicokinetic findings indicated that DMPC exposure appears to be transiently impacted by MM-II administration, with no accumulation between the dosing cycles."

Preclinical • Hematological Disorders • Musculoskeletal Pain • Ophthalmology • Osteoarthritis • Pain

COATING OF MENISCUS AND CARTILAGE OF OSTEOARTHRITIC RATS AND RABBITS FOLLOWING INTRAARTICULAR INJECTION OF MM-II, A DISPERSION OF EMPTY LARGE MULTILAMELLAR LIPOSOMES (EULAR 2025) - P2 | "MM-II’s empty large multilamellar liposomes, are reported here to coat both menisci and cartilage for at least 2 weeks in healthy and surgically induced OA knees in two species. Given previously demonstrated research that showed compression to enhance cartilage association of MM-II, the less pronounced coating in OA knees as compared to unoperated knees may be attributed to reduced weight bearing - and hence compression load - on the operated knee. In addition, the synovial localization and the reduced level in OA knees of these liposomes suggest that the liposomes are cleared by recruited mononuclear cells."

Preclinical • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

CLEARANCE KINETICS AND CARTILAGE RETENTION OF MM-II, A DISPERSION OF LARGE EMPTY LIPOSOMES, IN RAT KNEES (EULAR 2025) - P2 | "Following IA injection into healthy rat knees, a significant part of the injected MM-II liposomes cleared from knee joints within 1-2 weeks post-injection, likely due to uptake by synovial macrophages. Yet, a persistent amount of the liposomes remained associated with articular cartilage and menisci for at least 28 days. This data provides mechanistic support for the recent finding in a phase2b clinical trial showing reduction of knee pain lasting up to 6 months."

Preclinical • Musculoskeletal Pain • Osteoarthritis • Pain

Intra-articular MM-II for the treatment of knee osteoarthritis pain: Efficacy and safety results from a 26-week, phase 2b, placebo-controlled, double-blind, randomized dose-ranging trial. (PubMed, Osteoarthritis Cartilage) - P2 | "MM-II was safe, and the optimal effective dose for treatment of knee osteoarthritis pain was 3 mL."

Journal • P2b data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

"Empty Large Liposomes Reduce Cartilage Degeneration in Osteoarthritic Rats by Forming a Lubricative Coating". (PubMed, Osteoarthritis Cartilage) - "Reduction in cartilage degeneration by MM-II in OA rats is likely mediated through formation of a lubricative layer at the cartilage surface, though additional mechanisms could be mediating pain reduction demonstrated in clinical trials."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology

Efficacy and Safety of MM-II for Treatment of Knee Pain in Subjects With Symptomatic Knee Osteoarthritis (clinicaltrials.gov) - P2 | N=397 | Completed | Sponsor: Sun Pharmaceutical Industries Limited | Phase classification: P2b ➔ P2

Phase classification • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

DURATION OF CLINICALLY MEANINGFUL ANALGESIC RESPONSE TO INTRA-ARTICULAR MM-II, A NOVEL SUSPENSION OF LARGE, EMPTY, MULTILAMELLAR LIPOSOMES, IN PATIENTS WITH PAINFUL KNEE OSTEOARTHRITIS: ANALYSIS FROM A 26-WEEK PHASE 2B RANDOMISED CONTROLLED TRIAL (EULAR 2024) - "Currently available IA therapies either provide relatively short-term pain relief or are not convincingly superior to PBO. In contrast, in this study, a single IA injection of 3 mL of MM-II provided both relatively rapid and clinically meaningful pain relief for up to 26 weeks and appeared well tolerated. These data support MM-II as a possible long-lasting treatment for patients with knee OA."

Clinical • P2b data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology

Volume of intra-articular placebo injection has no effect on pain in knee osteoarthritic patients: Post hoc analyses from a phase 2b, double-blind, randomized trial (OARSI 2024) - "Purpose (the aim of the study): The effect of intra-articular injection volume on pain outcomes in osteoarthritis (OA) is controversial; relevant clinical data are scarce as few drugs are dosed based on volume. We aimed to determine the effect of volume of intra-articular placebo (PBO) injection on outcomes in a phase 2b trial that assessed the efficacy and safety of MM-II (empty liposomes) for painful knee OA."

Clinical • P2b data • Retrospective data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Efficacy and Safety of a Single Intra-Articular Injection of MM-II, a Novel Suspension of Large, Empty, Multilamellar Liposomes, in People with Painful Knee OA: Results of a 26-Week, Phase 2b, Placebo-Controlled, Double-Blind, Randomized Trial (ACR Convergence 2023) - "MM-II treatment was well tolerated and may provide durable, clinically relevant pain relief. These data support phase 3 studies."

Clinical • P2b data • Musculoskeletal Pain • Pain

INTRA-ARTICULAR MM-II, A NOVEL SUSPENSION OF LARGE EMPTY MULTILAMELLAR LIPOSOMES, IN PAINFUL KNEE OSTEOARTHRITIS: A 26 WEEK PHASE 2B RANDOMIZED TRIAL (EULAR 2023) - "Treatment with MM-II was well tolerated with low levels of adverse events. MMI-II may have the ability to provide durable and relevant pain relief, warranting confirmation in further clinical studies."

Clinical • P2b data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Cartilage-Bound Large Multilamellar Liposomes Show Potential Cartilage Protection From Inflammatory Stimulus By Attenuating Aggrecan Degradation (OARSI 2023) - "The aim of this study was to characterize possible protective effect of MM-II coating on bovine cartilage explants cultured ex vivo. This was investigated by applying MM-II onto cartilage explants in the presence or absence of mechanical load, removal of unbound liposomes followed by continuous stimulus with inflammatory cytokines and assessment of cartilage degradation by measurement of specific biomarkers of cartilage turnover in the conditioned medium."

Immunology • Osteoarthritis • Pain • Rheumatology • ACAN

Efficacy and Safety of MM-II for Treatment of Knee Pain in Subjects With Symptomatic Knee Osteoarthritis (clinicaltrials.gov) - P2b | N=397 | Completed | Sponsor: Sun Pharmaceutical Industries Limited | Active, not recruiting ➔ Completed | Trial primary completion date: Aug 2022 ➔ May 2022

Trial completion • Trial primary completion date • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Efficacy and Safety of MM-II for Treatment of Knee Pain in Subjects With Symptomatic Knee Osteoarthritis (clinicaltrials.gov) - P2b | N=348 | Active, not recruiting | Sponsor: Sun Pharmaceutical Industries Limited | Trial primary completion date: May 2022 ➔ Aug 2022

Trial primary completion date • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

LARGE MULTILAMELLAR NEUTRAL LIPOSOMES FORM A STABLE LAYER ON ARTICULAR CARTILAGE SURFACE UNDER EX-VIVO PHYSIOLOGICAL COMPRESSION (OARSI 2022) - "The above findings collectively suggest that application of exogenous phospholipids in the form of liposomes can compensate for the lost endogenous SAPLs through the formation of a coating layer on the cartilage surface which in turn provides lubrication to the damaged cartilage. The purpose of the current study was to assess ex-vivo whether physiologically relevant compression load is a key factor in the ability of MM-II liposomes to form this coating layer on the cartilage surface."

Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology

Efficacy and Safety of MM-II for Treatment of Knee Pain in Subjects With Symptomatic Knee Osteoarthritis (clinicaltrials.gov) - P2b | N=348 | Active, not recruiting | Sponsor: Sun Pharmaceutical Industries Limited | Recruiting ➔ Active, not recruiting | Trial primary completion date: Aug 2022 ➔ May 2022

Enrollment closed • Trial primary completion date • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Efficacy and Safety of MM-II for Treatment of Knee Pain in Subjects With Symptomatic Knee Osteoarthritis (clinicaltrials.gov) - P2b | N=348 | Recruiting | Sponsor: Sun Pharmaceutical Industries Limited | Trial completion date: Nov 2021 ➔ Aug 2022 | Trial primary completion date: Nov 2021 ➔ Aug 2022

Trial completion date • Trial primary completion date • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

[VIRTUAL] Intraarticular injection of MM-II liposomes lubricates cartilage in vivo and reduces friction and wear in ex-vivo cartilage models (OARSI 2021) - "As previously reported in a first-in-human clinical trial, MM-II, when injected intraarticularly, was shown to reduce pain up to 3 months post injection. This study aims to illustrate MM-II’s mechanism of action by studying the localization of the liposomes in the joint following an intraarticular injection into rabbits and using 2 ex-vivo cartilage models for evaluation of MM-II’s lubrication capabilities and its effect on reduction of friction and wear of the cartilage."

Preclinical • Osteoarthritis • Pain

[VIRTUAL] Local and systemic effects following intraarticular injection of MM-II liposomes. Results from two nonclinical toxicity studies in rabbits and dogs (OARSI 2021) - "Due to their unique characteristics, MM-II liposomes are retained on the cartilage surface, providing long-term lubrication and leading to a reduction in wear of the cartilage. The purpose of these preclinical studies was to evaluate the toxicity of MM-II, when administered via intra-articular (IA) injection into the stifle joint of rabbits and dogs."

Preclinical • Osteoarthritis • Pain

[VIRTUAL] Intraarticular injection of MM-II, a suspension of empty large liposomes, reduces cartilage degeneration in rat osteoarthritis model (OARSI 2021) - "Given the lubricating properties, cartilage wear reduction, and pain-lowering effect of MM-II, we hypothesized that IA administration of MM-II may also reduce OA progression. The purpose of the current study was to evaluate the effects of three consecutive IA injections of MM-II with dosing intervals of one per week, on cartilage degeneration in a rat meniscal-tear-induced model of osteoarthritis."

Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology

Moebius Medical Announces Dosing of First Patient in Global Phase IIb Clinical Trial of MM-II, a Novel Treatment for Knee Osteoarthritis Pain (PRNewswire) - "Israel-based Moebius Medical today announced that the first patient has been dosed in its Phase IIb clinical trial of MM-II, a novel candidate for the treatment of pain in knee osteoarthritis (OA). The Phase IIb clinical trial, which is expected to enrol approximately 312 subjects across the US, Denmark, and Hong Kong...Top-line data from the trial is expected to be available in mid-2022."

P2b data • Trial status • CNS Disorders • Osteoarthritis • Pain

Efficacy and Safety of MM-II for Treatment of Knee Pain in Subjects With Symptomatic Knee Osteoarthritis (clinicaltrials.gov) - P2b; N=312; Recruiting; Sponsor: Sun Pharmaceutical Industries Limited; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Moebius Medical Announces FDA Clearance of IND Application for Phase IIb Clinical Trial of MM-II, a Novel Treatment for Knee Osteoarthritis Pain (PRNewswire) - "...Moebius Medical today announced that the US Food and Drug administration (FDA) has cleared their Investigational New Drug (IND) application to initiate a global multi-center Phase IIb clinical trial of MM-II, a novel candidate for the treatment of pain in knee osteoarthritis (OA)....Enrollment of the trial's 312 subjects is expected to begin in US, Europe and Asia by the end of 2020, and top-line data is expected to be available in mid-2022."

Enrollment status • IND • New P2b trial • P2 data • CNS Disorders • Osteoarthritis • Pain