UBX0101 / Unity Biotech - LARVOL DELTA

Which Approach to Choose to Counteract Musculoskeletal Aging? A Comprehensive Review on the Multiple Effects of Exercise. (PubMed, Int J Mol Sci) - "Natural compounds such as resveratrol, rapamycin, quercetin, curcumin, vitamin E, genistein, fisetin, and epicatechin act on key signaling pathways, offering protective effects against musculoskeletal decline. On the other hand, molecules such as dasatinib, navitoclax, UBX0101, panobinostat, and metformin have been shown to be effective in eliminating or modulating senescent cells...Therefore, we have provided an overview of the main anti-aging compounds and examined the potential of physical exercise as a strategy in the management of age-related musculoskeletal disorders. Further studies should focus on identifying synergistic combinations of pharmacological and non-pharmacological interventions to optimize the effectiveness of anti-aging strategies and promoting healthier musculoskeletal aging."

Journal • Review • Immunology • Inflammation • Musculoskeletal Diseases • Osteoarthritis • Osteoporosis • Pain • Rheumatology • Sarcopenia

Emerging concepts and challenges in the development of disease-modifying osteoarthritis drugs - a more refined perspective. (PubMed, Arch Pharm Res) - "For this purpose, prime examples of different therapeutic groups, including the antioxidant NAC, senotherapeutic UBX0101, anti-inflammatory drug Anakinra®, Wnt inhibitor Lorecevivint®, chondroanabolic growth factor Sprifermin™, and various protease inhibitors, are discussed in detail. Moreover, this review addresses the challenges of patient stratification into different endotypes and phenotypes, the consideration of subgrouping in clinical trials, and the lack of suitable clinical outcome parameters. In summary, this review highlights potential reasons for the high failure rate of DMOADs in clinical trials and outlines key points for future improvement."

Journal • Review • Developmental Disorders • Immunology • Osteoarthritis • Pain • Rheumatology

Assessment of Differential Treatment Effect Between Predicted Endotype Subgroups of Knee Osteoarthritis in the MIV-711, UBX0101, and Oral Salmon Calcitonin Trials (EULAR 2025) - P2, P2a, P3 | "This study demonstrates the potential to predict OA endotypes using a small, targeted panel of biomarkers on trial data, offering a clinically practical tool to enhance trial recruitment. The observed responses to anti-resorptive treatments within OA subgroups highlight the potential benefits of aligning therapies with endotypes defined by the drug’s mode of action. Further investigation is needed to refine strategies for recruiting the right subgroups at the optimal time."

Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • CTSK

Advances and Challenges in the Pursuit of Disease-Modifying Osteoarthritis Drugs: A Review of 2010-2024 Clinical Trials. (PubMed, Biomedicines) - " Eleven DMOAD candidates are reviewed and critically analyzed for their potential benefit in OA treatment-Lorecivivint (SM04690), TissueGene-C, Cindunistat (SD-6010), Sprifermin, UBX0101, TPX-100, GLPG1972/S201086, Lutikizumab (ABT-981), SAR113945, MIV-711, and LNA043-and relevant challenges to their development are discussed. Six DMOADs have demonstrated statistically significant evidence of a structural or symptomatic benefit without major safety concerns in phase II and III randomized controlled trials post-2010."

Journal • Review • Developmental Disorders • Immunology • Osteoarthritis • Pain • Rheumatology

Senolytic treatment reduces oxidative protein stress in an aging male murine model of post-traumatic osteoarthritis. (PubMed, Aging Cell) - "We find that senolysis by a p53/MDM2 interaction inhibitor, UBX0101, reduces protein oxidative modification in the aged arthritic knee joint...These opposing responses include differing signatures of protein-by-protein oxidative modification and abundance change, disparate quantitative trends in modified protein network centrality, and contrasting patterns of oxidation-induced folding free energy perturbation between young and old. We develop a composite sensitivity score to identify specific key proteins in the proteomes of aged osteoarthritic joints, thereby nominating prospective therapeutic targets to complement senolytics."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology

Osteoarthritis drug pipeline rattles as FDA rejects top contender: What comes next? (Healio) - "'I am hopeful for lorecivivint,' Lane said. 'It's in phase 3 and it may be both an agent that may be able to reduce pain and prevent cartilage deterioration. So, I'm pretty excited. The phase-3 data will be very informative about whether it's a DMOAD'....'They were able to generate cartilage, with skeletal stem cells and inhibition of blood flow in the joint,' Lane said. 'It's a little bit out there, but it shows that it is important that we have to stimulate new cartilage formation - we have to get cells to make cartilage - but we also have to keep vascularity out of the joint. It's out there, but it's actually one of the most successful preclinical models of treating OA that we have yet.'"

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[VIRTUAL] A phase 2, randomized, double-blind, placebo-controlled study of senolytic molecule UBX0101 in the treatment of painful knee osteoarthritis (OARSI 2021) - P1 | "UBX0101 is a p53/MDM2 interaction inhibitor that can induce apoptosis of senescent synoviocytes. Results from a recent Phase 1 study (NCT03513016) suggested that IA UBX0101 had dose-dependent, clinically meaningful effects on pain and function in patients with knee OA."

Clinical • P2 data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • MDM2

Clinicians have 'reason for optimism' in novel osteoarthritis therapies (Healio) - "Lane said many rheumatologists encourage patients to lose weight and exercise more as a way of fending off the progression of osteoarthritis. 'But then we will work our magic with analgesics, anti-inflammatories and then injections, as needed,' she said....Given all of these potential avenues of osteoarthritis treatment, Lane believes the future is bright for management of this disease. 'There is reason for optimism for our patients,' she said."

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Long-Term Follow-Up Study of Patients With Osteoarthritis of the Knee Treated With UBX0101 or Placebo (clinicaltrials.gov) - P=N/A; N=161; Terminated; Sponsor: Unity Biotechnology, Inc.; Trial completion date: Jun 2021 ➔ Nov 2020; Enrolling by invitation ➔ Terminated; Trial primary completion date: Jun 2021 ➔ Nov 2020; Inability to achieve primary or secondary study objectives

Clinical • Trial completion date • Trial primary completion date • Trial termination • Immunology • Osteoarthritis • Pain • Rheumatology

A Study of Single and Repeat Dose Administration of UBX0101 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P1; N=35; Completed; Sponsor: Unity Biotechnology, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

A Study to Assess the Safety and Efficacy of a Single Dose of UBX0101 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P2; N=183; Completed; Sponsor: Unity Biotechnology, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

Unity shares untied as osteoarthritis of the knee drug fails phase II test (Bioworld) - "Shares of Unity Biotechnology Inc....fell 66.6% to $4.15 on Aug. 17 after UBX-0101, its one-time lead candidate, failed to best a placebo on an established measure of osteoarthritis pain in a phase II study."

P2 data • Stock price • CNS Disorders • Musculoskeletal Diseases • Osteoarthritis • Pain

UNITY Biotechnology Announces 12-week data from UBX0101 Phase 2 Clinical Study in Patients with Painful Osteoarthritis of the Knee (GlobeNewswire) - P2, N=183; NCT04129944; Sponsor: Unity Biotechnology, Inc.; "UNITY Biotechnology, Inc....today announced the 12-week results from the Phase 2 study of UBX0101, a p53/MDM2 interaction inhibitor, in patients with moderate-to-severe painful osteoarthritis (OA) of the knee. There was no statistically significant difference between any arm of UBX0101 and placebo at the 12-week endpoint for change from baseline in WOMAC-A, an established measurement of pain in OA....The company expects to complete collection of the Phase 2 24-week data, as well as that from the ongoing Phase 1b high-dose, repeat-dose study in the second half of 2020."

P2 data • Trial status • CNS Disorders • Musculoskeletal Diseases • Osteoarthritis • Pain

"L'un des grands espoirs de nouveau médicament pour l'arthrose, l'UBX0101, molécule sénolytique, échoue en phase 2. https://t.co/5Fw1W33TIG" (@Larhumato)

UNITY Biotechnology, Inc. Reports Second Quarter 2020 Financial Results and Clinical Program Updates (GlobeNewswire) - "In July 2020, UNITY announced that it expects to announce topline 12-week results from its Phase 2 study of UBX0101 in the third quarter of 2020. Consistent with prior guidance, 24-week results are also expected by the end of 2020....UNITY is also conducting a Phase 1b study of UBX0101 in patients with moderate-to-severe OA of the knee....Consistent with prior guidance, both 12- and 24-week results are expected in the second half of 2020."

P1 data • P2 data • Musculoskeletal Diseases • Osteoarthritis • Pain

UNITY Biotechnology announces upcoming catalysts for its lead programs (SeekingAlpha) - "UNITY Biotechnology...expects to announce 12-week results from Phase 2 study of UBX0101, a p53/MDM2 interaction inhibitor, in painful osteoarthritis of the knee, in Q3. Enrollment for the study was completed in Feb 2020."

P2 data • Musculoskeletal Diseases • Osteoarthritis • Pain

Unity Biotechnology, Inc. reports first quarter 2020 financial results and business updates (GlobeNewswire) - "Impact of COVID-19 Pandemic:...UNITY’s clinical and regulatory teams remain active and are working closely with its investigators in its ongoing clinical studies of UBX0101 to adapt to the current environment and ensure the studies remain on-track. UNITY is also following FDA guidance on clinical trial conduct during the COVID-19 pandemic, including with respect to the remote monitoring of clinical data. Further, UNITY has sufficient supply of UBX0101 for all ongoing clinical studies."

Clinical • CNS Disorders • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

Long-Term Follow-Up Study of Patients With Osteoarthritis of the Knee Treated With UBX0101 or Placebo (clinicaltrials.gov) - P; N=180; Enrolling by invitation; Sponsor: Unity Biotechnology, Inc.

Clinical • New trial • CNS Disorders • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

A Study of Single and Repeat Dose Administration of UBX0101 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P1; N=35; Active, not recruiting; Sponsor: Unity Biotechnology, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

UNITY Biotechnology Completes Enrollment in Phase 1b Study of UBX0101 (GlobeNewswire, Unity Biotechnology, Inc.) - "UNITY Biotechnology, Inc....today announced updates related to UBX0101. In February 2020, UNITY announced that it had dosed the first patients with moderate-to-severe osteoarthritis (OA) of the knee in a Phase 1b study...The study has now completed enrollment of 35 patients. Both 12- and 24-week data are currently expected in the second half of 2020. Also in February 2020, UNITY announced completion of enrollment of a Phase 2 study of UBX0101 in patients with moderate-to-severe OA of the knee. This study, now fully enrolled with 183 patients...The study currently remains on-track to report 12- and 24-week results in the second half of 2020."

Enrollment closed • P1 data • P2 data

UNITY Biotechnology Provides Pipeline and Business Updates (GlobeNewswire, Unity Biotechnology, Inc.) - "Recent Highlights and Business Updates: Osteoarthritis – UBX0101: In October 2019 UNITY announced that the first patient had been dosed in a Phase 2 study of UBX0101...in patients with moderate-to-severe osteoarthritis (OA) of the knee. The study is now fully enrolled with 183 patients....Both 12- and 24-week results are now expected in the second half of 2020....UNITY has also dosed the first patients in a Phase 1b study to explore the safety, tolerability and initial efficacy of a higher dose (8.0 mg) and repeated doses (4.0 mg x 2, separated by 1 month) of UBX0101. The study is expected to enroll approximately 36 patients with 12-week results expected in the second half of 2020."

Enrollment closed • Enrollment status • P1 data • P2 data

A Study to Assess the Safety and Efficacy of a Single Dose of UBX0101 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P2; N=183; Active, not recruiting; Sponsor: Unity Biotechnology, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

A Study of Single and Repeat Dose Administration of UBX0101 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Unity Biotechnology, Inc.

Clinical • New P1 trial

Safety, Tolerability, Pharmacokinetics, and Clinical Outcomes Following Single-Dose IA Administration of UBX0101, a Senolytic MDM2/p53 Interaction Inhibitor, in Patients with Knee OA (ACR-ARHP 2019) - "Single IA doses of UBX0101 up to 4.0 mg were well-tolerated by knee OA patients, and its PK was well-characterized. The activity of UBX0101 is supported by its effects on multiple BMKs, as well as the clinically meaningful and durable improvements in pain and function. UBX0101 as a senolytic agent may be an important future therapeutic option for pts with knee OA."

Clinical • Clinical data • Late-breaking abstract • PK/PD data

UNITY Biotechnology, Inc. reports third quarter 2019 financial results and business updates (GlobeNewswire) - "In October 2019, UNITY announced that the first patient had been dosed in a Phase 2 study of UBX0101 in patients with moderate-to-severe osteoarthritis (OA) of the knee. The study is expected to enroll approximately 180 patients with initial 12-week results expected in the second half of 2020....UNITY also plans to study the safety, tolerability and initial effectiveness of both a new higher dose and repeat doses in a Phase 1b study. The study is expected to enroll approximately 36 patients with initiation expected in the first half of 2020 with initial 12-week results expected in the second half of 2020."

Enrollment status • P1 data • P2 data • Trial status