Big Pharma Senolytics Programs are Getting Underway

Biotech startups working in a new and credible field of clinical development only have a few years before large pharmaceutical companies take notice and begin to enter the arena. This shift in the competitive landscape is a good thing for patients, as a great deal more funding will be deployed to expand the space of possible therapies. Further, small companies with viable approaches are more likely to be acquired, increasing the odds that specific programs will continue through to clinical trials. It doesn't solve the problem of the burdensome regulatory system that slows all progress, but it does improve the odds of pushing something through the present roadblocks in the path of progress.

As today's news from Insilico Medicine indicates, this second phase of development, the interest of large pharmaceutical developers, is now underway for the field of senolytic therapies. These are treatments capable of producing rejuvenation via selective destruction of senescent cells in old tissues. Senescent cells secrete signals that disrupt tissue maintenance, structure, and function, generating chronic inflammation that accelerates the progression of aging. They are strongly implicated in the pathology of numerous age-related conditions. In mice, senolytic therapies have produced noteworthy examples of reversal of age-related disease. Biotech startups are presently working on approaches to senescent cell destruction: small molecules; immunotherapies; gene therapies; and so forth.

A few small human clinical trials of first generation senolytic drugs and supplements have taken place or are underway, awaiting publication of results. The results have been mixed. The dasatinib and quercetin combination looks promising for inflammatory lung disease and kidney disease, and has been confirmed to destroy senescent cells in humans in much the same way as it does in mice. A localized injection approach for osteoarthritis did not work, for reasons that are much discussed by the community - a poor choice of strategy, in that senescent cells throughout the body affect the inflammatory environment of joints, or a drug that doesn't do as well in humans as in mice, perhaps.

Looking at the past five years of work on senolytics, one may guess that the amount of effort needed to get Big Pharma interested enough to participate in a new line of work amounts to a few hundred million dollars in venture investment, half a dozen phase I and phase II clinical trials, ten to twenty biotech startups, and a few IPOs either taken place or on the horizon. At that point executives and boards in the pharmaceutical giants start to ask whether there might be something worthy of attention in this new part of the biotech industry.

Insilico partners with Taisho on end-to-end AI-powered senolytic drug discovery

Insilico Medicine announced today that Taisho Pharmaceutical Co., Ltd. and Insilico have entered into a research collaboration to identify novel therapeutics against aging. Insilico Medicine will utilize both the target discovery and generative chemistry parts of its Pharma.AI platform in this collaboration. It will use its proprietary Pandomics Discovery Platform to identify novel targets for senolytic drugs and Chemistry42 platform for a molecular generation. This collaboration brings together Insilico's state-of-art artificial intelligence (AI) technologies in drug discovery with Taisho's expertise in drug development, aimed to extend the human healthspan.

"We're delighted to collaborate with Taisho pharmaceutical, a well-recognized leader in the pharmaceutical industry and healthcare sector. It is believed that aging is a universal phenomenon that we cannot stop. However, emerging scientific evidence has shown that one may be able to reverse some of the age-associated processes. Through this collaboration, we will adopt our AI-powered drug discovery suites together with Taisho's validation platform to explore the new space of anti-aging solutions."

Under the terms of the agreement, Insilico Medicine will receive an upfront payment and milestone payments upon achievement of specified goals. Insilico Medicine will be responsible for early research phase target identification and molecular generation and Taisho will work collaboratively with Insilico in validating the results in various in vitro and in vivo assays. Taisho has the exclusive option to acquire Insilico's co-ownership of the successfully developed programs under agreed payment.

Comments

This is early discovery stage stuff and 10+ years from reality

Would be much better if Taisho invested in out-licensing a compound from say Unity, or SIWA, or Oisin, or a handful of other established senolytics companies with somewhat validated candidates

Otherwise the chance of ever seeing these discovery stage deals yield a finished drug is close to 0

Too much AI hype in the space IMHO

Posted by: qing song at October 15th, 2020 5:43 PM

This is actually a significant piece of news. One of the four questions any investor looking to start a new business should ask is - what is the competition? If there isn't any, then the investor is either way ahead of the curve, or is missing some obvious pitfall that others have already figured out is there.

I think big Pharma will now look at senolytics as a "validated" investment given that one of their own has invested in it. Expect more investment over the coming years, and more media attention as a result of this.

Of course Insilco and Taisho are looking for small molecule senolytics, which is a more risky approach than say Oisin's suicide gene therapy, as small molecules have more chance of side effects than antibody or gene therapies. And I don't really see "AI" as being much of an improvement over traditional computational models of small molecule interactions with proteins, so I don't think Insilco should be valued as any more than a traditional drug discovery biotech, but overall it is still a positive development.

Posted by: jimofoz at October 16th, 2020 3:02 AM

@jimofoz

Drug discovery is all well and good, but I too would have much rather seen a headline like "Novartis pays Unity $100MM to license UBX555 (random drug ID number)" - that would say to the world that this is "big pharma validated"

In-Silico means well and seems to want to spread the word about longevity, but those folks are a bit of self-promoters - what is this? the 20th pharma deal In-Silico has announced? have any of these candidates evolved into actual drug development?

Posted by: devon mcradle at October 16th, 2020 4:39 AM

Ongoing trial testing D + Q vs. dementia just started in Feb. Earliest results expected in 2022.

https://clinicaltrials.gov/ct2/show/NCT04063124

The purpose of this pilot study is to evaluate whether a combination of two drugs, dasatinib (D) and quercetin (Q) [D+Q], penetrate the brain using cerebrospinal fluid (CSF) in older adults with early Alzheimer's disease (AD). This combination of drug therapy has been shown to affect dying cells in humans with other chronic illnesses and in Alzheimer's mice models. The study team want to know if this combination of medications will reach the brain in order to evaluate if this intervention may be effective for treating AD symptoms in future studies. This is also known as a "proof of concept" study.

Posted by: nobody at October 17th, 2020 12:24 AM

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