Unity Biotechnology Announces Results from a Senolytics Trial for Osteoarthritis

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.

Link: http://ir.unitybiotechnology.com/news-releases/news-release-details/unity-biotechnology-reports-promising-topline-data-phase-1-first

Comments

Good news. But still the results are a little too vague. Like how many percent of senescent cells were destroyed in the process would be better, unless they are planning to answer this during the phase 2. Admin do you know if and how we can get our hands on senolytics like quercetin/datasinib/fisetin and are they safe ? Thx.

Posted by: Jonathan Weaver at June 19th, 2019 6:28 AM

My reading of the data is that the placebo effect is so large it makes other results not particularly meaningful.

Posted by: JohnD at June 19th, 2019 10:32 AM

@JohnD: There was a large, statistically significant difference in self-reported pain versus the control, and results that were close enough to being significant on functional measurements to merit further study. It's worth keeping in mind that this was based off of just a single dose of the drug administered locally, and that even at the highest tested dose the drug was fully tolerated. They have the option of doing additional phase I studies at higher doses, or they could try doing multiple injections.

Posted by: Dylan Mah at June 19th, 2019 1:49 PM

Probably the results will be more impressive during the phase 2 , with better dosage. But anyway senescent cells in the knee doesn't hype me at all, won't help healthy people who are in their 30s or 40s. I would prefer someone test a senolytic which can help not just the elder's knee but overall health for everyone.

Posted by: Jonathan Weaver at June 19th, 2019 4:16 PM

This is a meaningless result, and they need to go back to the drawing board - a cheap steroid injection could achieve the same results for longer duration

To sugar coat this as they are doing in the press release is disingenuous

The finding that the drug was well tolerated is by no means surprising given short time course

The secondary endpoint of pain reduction was also a bit empty. The group that was controlled internally (participants take placebo for the first few weeks before being switched to drug) showed no improvement in pain. Group where patients were randomized to placebo or drug showed improvement in pain by 2 points on a scale of 0-10

https://finance.yahoo.com/news/apos-why-unity-biotechnology-dropped-184700856.html

Posted by: David Permisov at June 19th, 2019 4:32 PM

@Jonathan Weaver
>But anyway senescent cells in the knee doesn't hype me at all, won't help healthy people who are in their 30s or 40s

Most 30-40 years old don't have like problems. 60 -something, on the other hand do.

On top of that, if the treatment works for the knees it might work for the back pain too.

However, I don't know how well does this compound clear senecent cells.

@David Permisov

Yeah the tests are a bit underwhelming. But in fact, that is not a news. In this site there were comments expecting this result. Still might be a problem with the knees having inflammation which is not triggered by senecent cells alone

Posted by: Cuberat at June 19th, 2019 4:51 PM

@David Permisov

My goodness, what a miserable report that is in Yahoo finance! I on the other hand feel very heartened by the results. This was after all mainly a dose escalation safety study which was not powered to show long term efficacy. Having said that, there is a clear dose response relationship, which hopefully indicates that the mechanism of action seen in mice also holds true for humans. On top of that there were no major adverse events seen at the highest dose, which means that they could raise it if need be. Also it was a single injection, multiple injections will be trialed in the future. In addition, part B of the study, which did not reach significance, was specifically designed to harvest biomarkers and thus might have confounded the results.

If you've got 30 minutes spare, take a look at the investor conference call with power point presentation (need to register, but I just put in a fake company name):

https://edge.media-server.com/m6/p/63yyyzvi

The first generation of senolytics were never going to be perfect, however this study along with the small dasatinib/quercetin pilot study released in January at least tentatively indicate that senolytics could work in humans. And that fact alone is making me freaking excited! :-)

PS - I just wish I had some spare money to invest. Yesterday would have been a good day to pick up some Unity shares!

Posted by: Chris Linnell at June 19th, 2019 6:09 PM

@Chris Linnell

Thanks for the link

But I suggest you go beyond the commpany's materials to independent sources that can really dissect what the data shows

The sad truth is this program has a very long way to go

Senolytics, or more specifically UBX0101, is no where near a "fountain of youth", and at best at this point is a moderate anti-inflammatory / pain killer

Posted by: David Permisov at June 20th, 2019 7:30 AM

This was a safety & tolerability study and the drug appears safe and well tolerated. Also there appears to be some preliminary indication of dose-dependent symptom relief. Seems like pure good news.

Posted by: Justin Mallone at June 20th, 2019 7:56 AM

@David Permisov
>Senolytics, or more specifically UBX0101, is no where near a "fountain of youth"

It is not , but senolytics are the only thing (apart extreme CR) that can slow down, if not reverse the aging. That is not a small feat.

UBX0101, while not revolutionary, and probably weaker than fisetin/Dasatinib, if working will change the mainstream perception of what is possible. Wright's Brothers flight wasnt impressive at all, if you look at the distance and weight moved. And yet it was revolutionary...

Posted by: Cuberat at June 20th, 2019 9:02 AM

@Cuberat

Wright Brothers did not take US$300+ million form investors claiming a "fountain of youth"

Posted by: David Permisov at June 20th, 2019 9:10 AM

@David Permisov
Financial/investment success is not strictly tired to the scientific advances. You can have one without the other.

To attract venture capital you have to produce an immense quality of bulls*it. And you kinda have to believe it and make it believable. Here, from what I see in their study is that take the conversation stance and start small in a limiter and insulated area of the body with the hope to have a foothold in the senolytics market. Is that a during investment strategy? Sounds plausible. Are they putting the money to good use? That could be arguable. Do I suggest then as an investment? Rather not. Can they be used for speculation? Hell yes. After all the results of their study don't surprise the FA residents, so people with experience of speculation on small caps could make way money.

But what I really care about is that they advance the field without scaring the investors. Here are I didn't do my research on what did they promise.

Posted by: Cuberat at June 20th, 2019 11:01 AM

This is brilliant and a big marvelous medicine step! Could be great to know more about this and also I need know if are available a volunteer form to see the great progress of this drug on elders with knee malfunctions. My father have this problem many years ago and every year is worst and I read thus notice so he are agree to test this drug cause like he said " he have nothing to lose at that age"

Posted by: Christian Centeno at September 6th, 2019 8:37 PM

I have suffered a form of familial ostio arthritis from early adult. My father suffered this after years of heavy lifting, cold climate work. My son fell at age 28 damaging knee, resulting in severe pain. Now age 66 still walking but needs hip replacements. I am now age 91, 5 joint replacements, still walking on hip replacements from 1977, weigh 90 pounds. Ibuprophen ruined my upper intestines. I rely on Arnica Gel and now trying CBD cream with good results.
Wish I had the funds to back this endeavor .

Posted by: JEAN L KERN at October 6th, 2019 12:36 PM

I appreciate all this news to what seems to be a promising remedy for osteoarthritis but the what l as well as alot of other people really care about is WHEN WILL IT BECOME AVAILABLE to the general public?lt only seems that this remedy is forever getting tested while there are so many of us waiting for a solution that might be too late before it's ACTUALLY available.

Posted by: Hubert Alegre at November 26th, 2019 12:33 PM

I agree with several of above comments that various trials seem to go on forever spending enormous amounts of money but never seems to result in meaningful and approved results for treatment. I'm over 80 years old, surviver of heart bypass surgery over 26 years ago by determined swimming, walking, exercises ever since. Sadly I developed Osteoarthritis in my back approximately 6 years ago. I have since had treatment by various manipulation, pain injections and very recently denervation treatment. During all this time I've followed stem cell treatment development, senolytic trials, and even tried my own trials using Fisetin, without success. During all these years we get so many optimistic results but when they become real approved treatment for the public? Arthritis is the most common cause of problems in the world and possibly the greatest cost - surely more effort should be dedicated to a cure?

Posted by: Brian Jones at May 8th, 2020 11:04 AM

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