UNITY Biotechnology Scheduling Phase II Senolytics Trial for Late 2019

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.

Link: http://ir.unitybiotechnology.com/news-releases/news-release-details/unity-biotechnology-inc-announces-plan-phase-2-clinical-study

Comments

Good news. This one could reach the market by 2025, but I'm afraid this will be a prescription therapy. People with few OA won't be able to rejuvenate their knee. What do you think ?

Posted by: Jonathan Weaver at August 1st, 2019 6:19 AM

They have the bank roll to keep doing clinical trials, so they can keep at it (despite the stock now being at an all time low - and nowhere to go but down as we wait 24 more weeks - but that is another story)

I maintain that just eliminating senescent cells is not going to be the holy grail in humans that it is promoted as (despite the rodent data) unless backed up by other technologies for tissue repair such as stem cells, cross-link breakers in the joint, etc.

The concept that everything will just "normalize" on its own is such a fallacy that ignores everything we know about human biology

The OA market wants true disease modifying agents - not just another anti-inflammatory or pain killer

Posted by: David Permisov at August 1st, 2019 6:49 AM

David, I agree that some lay people who just read sensationalistic headlines might be under the wrong impression that senolytics alone will lead to indefinite lifespans, but the people who are actually familiar with rejuvenation research don't think that way.

You're correct; even though the removal of senescent cells might have larger benefits than initially expected, other rejuvenation therapies to repair the different kinds of underlying age-related damage will ultimately be necessary to achieve longevity escape velocity sooner rather than later.

Posted by: Quinn at August 1st, 2019 4:14 PM

Nontheless, senolytics with its limited effects will be welcome in the short term if they give us, as expected, health and a better quality of life ( and as a collateral effect, some more time, healthy people die less that frail/damaged-by-age people), until other therapies arrive in the middle-long term (20 years being optimistic?)

Posted by: Beta at August 2nd, 2019 3:47 AM

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