UNITY Biotechnologies is the furthest ahead of the growing number of companies working on the development of senolytic therapies capable of selectively destroying senescent cells in old tissues. Senescent cells are generated constantly in the body, but are near all destroyed by programmed cell death processes or by the immune system. The few that linger, however, accumulate to cause serious issues via their inflammatory secretions. They disrupt tissue structure and function and provoke a sizable fraction of the chronic inflammation of aging.
Because senescent cells have systemic effects throughout the body, not just local effects in the tissue they reside in, and because the whole point of the exercise is to produce therapies that can be used off-label to produce rejuvenation for all aspects of aging, not just the very narrow aspect being trialed, the UNITY Biotechnology principals are thought by many in the community to be taking a poor approach to their first trials. They are using local injections to target arthritic joints, while it has already been shown that systemic administration in animal models is beneficial to not just arthritis but also near all other aspects of aging physiology. Nonetheless, the effect size for removal of senescent cells is so large that even this technically worse approach produced decent results in an earlier trial.
UNITY Biotechnology, Inc., a biotechnology company developing therapeutics to extend healthspan by slowing, halting or reversing diseases of aging, today announced details for the planned Phase 2 study of UBX0101 in patients with osteoarthritis (OA) of the knee. "In June, we announced promising results from our Phase 1 study of UBX0101 in patients with OA of the knee showing that our senolytic molecule had a dose-dependent response across multiple clinical endpoints. We look forward to substantiating the promising results we observed in Phase 1 in a larger Phase 2 study. We will also be gathering additional information on duration of effect out to 24 weeks, validating early safety and dose-finding, and characterizing potential disease-modifying effects on bone and cartilage."
In June 2019, UNITY announced results from its first-in-human Phase 1 study of UBX0101 in patients with moderate-to-severe OA of the knee. In this study, UBX0101 was well-tolerated. Improvement in several clinical outcomes, including pain and function, as well as modulation of certain senescence-associated secretory phenotype (SASP) factors and disease-related biomarkers was observed after a single dose of UBX0101.
UNITY plans to initiate a Phase 2 study of UBX0101 in patients with painful, moderate-to-severe OA of the knee. The study is expected to enroll approximately 180 patients with initiation expected in the fourth quarter of 2019 and initial 12-week results expected in the second half of 2020. This will be a randomized, double-blind, placebo-controlled study evaluating three doses (0.5mg, 2mg and 4mg) of UBX0101 administered via a single intra-articular injection. The primary measure will be an assessment of pain at 12 weeks using the WOMAC-A instrument. Secondary measures will include safety and tolerability, pain (by 10 point Numerical Rating Scale, or NRS) and function (by WOMAC-C) at 12 weeks, as well as similar measures at 24 weeks.