Unity Biotechnology is the furthest ahead of the growing number of young biotech companies working on senolytic therapies that can selectively destroy harmful senescent cells in aged tissues. The company has already started human trials for osteoarthritis of the knee, using local rather than systemic administration of a small molecule senolytic drug. Other companies in the space, such as Oisin Biotechnologies, will be starting in on human trials for their approaches soon. As noted here, Unity Biotechnology recently announced results from their trial.
The accumulation of senescent cells throughout the body over the years is one of the causes of aging, and removing these cells reliably produces rejuvenation in mouse studies, meaning reversal of measures of aging, reversal of the progression of age-related diseases, and extended life spans. Senescent cells cause harm in a number of ways, one of which is the generation of chronic inflammation in surrounding tissues. Many age-related conditions with a strong inflammatory component appear to be caused in large part by senescent cells, and osteoarthritis is one of them.
The Phase 1 clinical trial of UBX0101 is a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability and pharmacokinetics of a single intra-articular injection of UBX0101 in patients diagnosed with moderate to severe painful OA of the knee. UBX0101 is a p53/MDM2 interaction inhibitor that targets selective elimination of senescent cells.
In Part A, 48 patients were randomly assigned to receive one of six dose levels of UBX0101 (between 0.1 mg to 4 mg) or placebo in a 3:1 randomization. Primary endpoints were safety and tolerability. Secondary and exploratory endpoints included plasma pharmacokinetics, synovitis as measured by MRI, pain, and measurement of senescence-associated secretory phenotype (SASP) factors and disease-related biomarkers present in synovial fluid and plasma.
In Part B, 30 patients were randomized to receive UBX0101 (4 mg dose) or placebo in a 2:1 randomization. Primary endpoints were safety and tolerability. Secondary and exploratory endpoints included changes in the levels of SASP factors and disease-related biomarkers present in synovial fluid and plasma, and pain. Synovial fluid samples were obtained at baseline and four weeks post-treatment.
In Part A, UBX0101 was well tolerated up to the maximum administered dose of 4 mg. There were no serious adverse events and no patients discontinued because of an adverse event. There were no dose-dependent adverse events or relevant clinical laboratory findings. The majority (66%) of adverse events were mild. In Part B, UBX0101 was well tolerated at the 4 mg dose. There were no serious adverse events and no patients discontinued because of an adverse event. The majority (75%) of adverse events were mild and there were no relevant clinical laboratory findings.
The study demonstrated that UBX0101 was safe and well-tolerated. Improvement in several clinical measures, including pain, function, as well as modulation of certain SASP factors and disease-related biomarkers was observed after a single dose of UBX0101. In approximately half the biomarkers measured in synovial fluid (treatment versus placebo) modulation was observed consistent with elimination of senescent cells and potential improvement in the tissue environment. Changes were observed in MMPs, tissue remodeling factors, and inflammatory cytokines.