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[reason]

UNITY Biotechnology made a big splash a few weeks ago to announce their venture funding and intent to develop a senescent cell clearance technology to treat age-related disease by removing one of its causes. The press linked the company to researchers involved in proof of concept work in mice that has been ongoing since 2011, using a clever system of genetic engineering to eliminate senescent cells first in an accelerated aging mouse lineage and then in mice that age normally. This culminated in a life span study showing 25% life extension in mice through this methodology, which clearly sets the stage for much greater interest in this approach to the treatment of aging as a medical condition. This is good news all round, since Strategies for Engineered Negligible Senescence (SENS) advocates and researchers have been calling for progress towards senescent cell clearance for more than a decade, and now the rest of the research community is finally catching up.

UNITY Biotechnology didn't emerge from nothing, and isn't just an outgrowth of the particular research group noted in the press material. It is more a union between that group, Buck Institute researchers who have been working on the same challenge, and a preexisting commercial venture with its own potential technology for senescent cell clearance. This makes sense, as the genetic engineering approach used in mice as a proof of concept would essentially have to be ripped up and rebuilt from scratch in order to be useful in humans. That is a poor alternative if there is some other approach to build on instead. As I pointed out last year, if you go digging there is a lot of dark matter out there from the past ten years when it comes to efforts to clear senescent cells. There are patents on a variety of approaches, and a number of dead, quiet, or dormant small companies that clearly never got to the point at which they could convince the venture community to fund their work.

One of these companies is Cenexys, started by the same successful entrepreneur who is at the helm of UNITY Biotechnology. There are relationships there with established biotechnology company Kythera Biopharmceuticals, and with the Buck Institute group run by Judith Campisi where a lot of senescent cell work has taken place in recent years. Cenexys was probably just a holding company for the senescent cell clearance intellectual property: if you take a look at relevant patent registrations, you'll find the following patents, and note that they are now assigned to UNITY Biotechnology.

Use of engineered viruses to specifically kill senescent cells (2013)

Polypeptides, viruses, methods and compositions provided herein are useful for the selective elimination of senescent cells. Method aspects include methods for inducing apoptosis in a senescent cell comprising administering to the cell a polynucleotide, virus, host cell, or pharmaceutical composition described herein. Other methods include expressing a pro-apoptotic gene in a senescent cell comprising administering to the cell the polynucleotide, virus, or pharmaceutical composition as described herein.

Immunogenic compositions for inducing an immune response for elimination of senescent cells (2013)

Provided herein are immunogenic compositions (vaccines) and methods for immunizing a subject with the immunogenic compositions for inducing an adaptive immune response directed specifically against senescent cells for treatment and prophylaxis of age-related diseases and disorders, and other diseases and disorders associated with or exacerbated by the presence of senescent cells. The immunogenic compositions provided herein comprise at least one or more senescent cell-associated antigens, polynucleotides encoding senescent cell-associated antigens, and recombinant expression vectors comprising the polynucleotides for use in administering to a subject in need thereof.

Compositions and methods for detecting or eliminating senescent cells to diagnose or treat disease (2014)

Disclosed are agents (e.g., peptides, polypeptides, proteins, small molecules, antibodies, and antibody fragments that target senescent cells) and methods of their use for imaging senescent cells in vivo and for treating or preventing cancer, age-related disease, tobacco-related disease, or other diseases and disorders related to or caused by cellular senescence in a mammal. The methods include administering one or more of the agents of the invention to a mammal, e.g., a human. The agents, which specifically bind to senescent cells, can be labeled with a radioactive label or a therapeutic label, e.g., a cytotoxic agent.

UNITY Biotechnology is the brand under which the final assembly of technology, money, and will for this line of research came together, after some years of groundwork, which clearly involved filing (arguably overly) broad patents on anything that looked promising. At any point in time over the past five years someone could have funded a senescent cell clearance approach and started good work on making it real. Things are always late, however, coming together well past the point at which they are obvious to many in the industry, especially when you have to convince outsiders to give you venture funding. This is why it is very rare for any company to emerge alone, and UNITY Biotechnology is only one of a number of efforts. There are competitors I know about, such as Oisin Biotechnology whose founders have assembled an impressive gene therapy approach, and no doubt competitors I don't know about because they are either quiet groups internal to Big Pharma entities, or scientists elsewhere in the world with nascent senescent cell clearance technology and the connections to launch a company sometime in the next year or two.

The breadth of these patents unfortunately doesn't give much of an indication as to what exactly the UNITY Biotechnology staff is working on for their first attempt at a senescent cell clearance technology, other than to suggest that they are indeed doing nothing with the genetic engineering proof of concept used in the mouse life span studies. Tagging senescent cells and then sending engineered immune cells to destroy them wouldn't be a terrible guess, however. Immunotherapy is certainly a very viable approach to targeted cell destruction; a lot of time and effort goes toward this sort of immunotherapy in the cancer research community, for example.

View the full article at FightAging

[reason]

UNITY Biotechnology and Oisin Biotechnologies are both early stage startups working on commercial development of therapies capable of clearance of senescent cells. Since accumulation of senescent cells is one of the root causes of aging and age-related disease, periodic removal of these cells is a narrowly focused form of rejuvenation. There are a number of other forms of damage and disarray that contribute to degenerative aging, and all will have to be fixed if aging is to be controlled by medicine, but an individual with fewer senescent cells is absolutely better off than one with more senescent cells regardless of the state of other forms of damage. Earlier this year researchers associated with UNITY Biotechnology published the results of the first life span study in normal mice engineered to destroy their own senescent cells, showing a 25% extension of median life span.

While the Oisin Biotechnologies principals have been pretty open on the topic of how their approach to senescent cell clearance works - it is a form of sophisticated gene therapy - the path chosen by UNITY Biotechnology remains less clear. In part this is because the public research based on gene therapy in mice that led to the life span study noted above is not something that could easily be adapted for use in human trials: it could be done, but almost every other option on the table would be both substantially easier to accomplish and more palatable to regulators. There is a trail of patents for other research leading in to the merger of groups that formed the company, but they cover a fairly wide selection of possible methodologies, including the use of immunotherapies and engineered viruses.

Gene therapies, immunotherapies, and more esoteric modern medical technologies are not the only possible approach to senescent cell clearance, however. In the past couple of years research groups have produced classes of drug - now called senolytic compounds - that can selectively drive senescent cells to self-destruct via the process of apoptosis. The combination of dasatinib and quercetin, for example, removes enough senescent cells in enough different tissues to produce meaningful benefits in mice. It isn't unreasonable to think that this type of result can be improved upon to the point at which it is a competitive option. Judging from recent news, it seems that UNITY Biotechnology will take the apoptosis-inducing drug development path, and, interestingly, is also setting up from the outset to deploy therapies outside the US in less heavily regulated regions:

Ascentage Pharma and UNITY Biotechnology Announce Collaboration for the Development of Senolytic Healthspan Therapies

China-based Ascentage - which is currently working on apoptosis-targeted cancer treatments - will work with UNITY Biotechnology to develop senolytic treatments for age-related diseases in an attempt to roll the back years for seniors. UNITY said it has also demonstrated in animal models that clearing senescent cells reverses or prevents many age-related pathologies, including: osteoarthritis, atherosclerosis, glaucoma, and kidney disease. "At UNITY, we have demonstrated that senescence is a key mechanism in aging and age-related disease. We have evaluated a wide panel of drug candidates that clear senescent cells, and Ascentage's compounds are some of the best we've seen. Access to their compound library through this collaboration will significantly accelerate our efforts to develop drugs to improve healthspan by halting or reversing several age-related diseases."

The biotech chose Ascentage as its partner in this anti-aging field "not only because of its cutting-edge technology, but also because this partnership will allow us to reach a global market." As part of the deal, the companies will also form a joint venture for the development and commercialization of senolytic drugs in China. Though specific terms are undisclosed, Ascentage has said it will acquire an equity interest in UNITY, and in return, the company will make an investment in Ascentage. Robert Nelsen, the co-founder and managing director of ARCH Venture Partners and a UNITY board member, will join the Ascentage board as an observer.

Ascentage Chairman and CEO Dr. Dajun Yang added, "We are one of the leading biopharmaceutical companies with clinical stage compounds targeting key proteins that control programmed cell death pathways. We will continue our efforts to advance clinical stage compounds for targeted anti-cancer therapy and are very pleased to work with UNITY for several unmet medical indications outside of the oncology space, with each aging-related disease potentially representing a multi-billion-dollar market."

View the full article at FightAging

[caliban]

Ascentage Pharma and UNITY Biotechnology Announce Collaboration for the Development of Senolytic Healthspan Therapies

 

Date:2016-04-25

 

 

    Ascentage Pharma, a clinical-stage biopharmaceutical company focused on apoptosis-targeted oncology drug discovery and development, and UNITY Biotechnology, a San Francisco-based biopharmaceutical company focused on the development of medicines to improve healthspan, announced a worldwide collaboration to develop senolytic treatments for age-related disease.

    The Ascentage team has been working for over a decade to create small-molecule drugs targeting programmed cell death and has established a best-in-class compound library and clinical-stage lead compounds for oncology therapeutics.

    UNITY Biotechnology, backed by ARCH Venture Partners, Venrock and Wuxi Healthcare Ventures, has been working for four years to elucidate the link between senescence and aging and has demonstrated in animal models that clearing senescent cells reverses or prevents many age-related pathologies, including osteoarthritis,   atherosclerosis, glaucoma, and kidney disease. 

    "At UNITY, we have demonstrated that senescence is a key mechanism in aging and age-related disease," said Dr. Nathaniel David, founder and CEO of UNITY Biotechnology. "We have evaluated a wide panel of drug candidates that clear senescent cells, and Ascentage's compounds are some of the best we've seen. Access to their compound library through this collaboration will significantly accelerate our efforts to develop drugs to improve healthspan by halting or reversing several age-related diseases."

    The Ascentage R&D team has a proven track record in structure-based drug design and lead optimization of small-molecule drug candidates targeting protein-protein interactions. "We chose Ascentage as our partner in this exciting anti-aging field not only because of its cutting-edge technology, but also because this partnership will allow us to reach a global market," David said.  As part of the deal, the companies will also form a joint venture for the development and commercialization of senolytic drugs in China.

    Though specific terms are undisclosed, Ascentage will acquire an equity interest in UNITY, and UNITY will make an investment in Ascentage.  Robert Nelsen, the co-founder and managing director of ARCH Venture Partners and a UNITY board member, will join the Ascentage board as an observer.

    "We have been tracking the science at Ascentage for some time and are incredibly pleased to enter this collaboration with them," Nelsen said. "We are confident that they will complement what we are doing at UNITY to drive major improvements in the treatment of diseases of aging to impact healthspan."

    Mr. Eric Zhao, partner of Oriza Seed Capital and Board member of Ascentage, said, "It is great to see two true innovative companies work together. I am sure they will bring extra value to everyone."

    Ascentage Chairman and CEO Dr. Dajun Yang added, "We are one of the leading biopharmaceutical companies with clinical stage compounds targeting key proteins that control programmed cell death pathways. We will continue our efforts to advance clinical stage compounds for targeted anti-cancer therapy and are very pleased to work with UNITY for several unmet medical indications outside of the oncology space, with each aging-related disease potentially representing a multi-billion-dollar market."

 

About Ascentage Pharma
    Ascentage Pharma is a China-based, global-oriented, clinical-stage biopharmaceutical company, dedicated to discovery and development of "first-in-class" and "best-in-class" targeted small-molecule cancer therapeutics. A rich portfolio of innovative small-molecule agents has been discovered and developed through the company's unique, robust, and world-class innovative drug development pipeline. Currently, Ascentage Pharma has four molecules in phase I-II trials in US, Australia and China, and another four molecules at IND reviewing or IND-enabling stages in US, Australia and China.

   Ascentage Pharma focuses on clinically validated cancer targets. Its established R&D pipelines include: inhibitors to a number of key proteins, including IAP, Bcl-2/Bcl-xL and MDM2-p53, that restore a tumor cell's apoptotic program; 2nd and/or 3rd generation of kinase inhibitors that overcome mutant resistance in cancer therapy; and inhibitors to epigenetic targets with enormous potential in oncology therapy. For more information, please visit www.ascentagepharma.com.

 

About UNITY Biotechnology
    UNITY Biotechnology is developing therapeutics that increase healthspan by preventing, halting or reversing diseases of aging. UNITY's initial focus is on creating senolytic medicines, which clear senescent cells that drive age-related afflictions such as osteoarthritis, atherosclerosis, eye diseases and kidney diseases. Backed by ARCH Venture Partners and Venrock, UNITY's world-class management team has experience building companies and developing medicines together and has collectively moved 91 therapeutic candidates into human clinical trials and developed 13 FDA-approved medicines. UNITY's mission is to build a future in which it doesn't hurt to be old — a future in which people stay healthy and mobile long into old age. More information is available a twww.unitybiotechnology.com.

 

 

 

[alc]

http://www.geekwire....ging-therapies/

 

 Senescent intimal foam cells are deleterious at all stages of atherosclerosis

 

http://science.scien...nt/354/6311/472

Edited by alc, 27 October 2016 - 11:33 PM.

[reason]

The whispers of late have had it that UNITY Biotechnology was out raising a large round of venture funding, and their latest press release shows that this was indeed the case. The company, as you might recall, is arguably the more mainstream of the current batch of startups targeting the clearance of senescent cells as a rejuvenation therapy. The others include Oisin Biotechnologies, SIWA Therapeutics, and Everon Biosciences, all with different technical approaches to the challenge. UNITY Biotechnology is characterized by a set of high profile relationships with noted laboratories, venture groups, and big names in the field, and, based on the deals they are doing, appear to be focused on building a fairly standard drug development pipeline: repurposing of apoptosis-inducing drug candidates from the cancer research community to clear senescent cells, something that is being demonstrated with various drug classes by a range of research groups of late. Senescent cells are primed to apoptosis, so a nudge in that direction provided to all cells in the body will have little to no effect on normal cells, but tip a fair proportion of senescent cells into self-destruction. Thus the UNITY Biotechnology principals might be said to be following the standard playbook to build the profile of a hot new drug company chasing a hot new opportunity, and clearly they are doing it fairly well so far.

UNITY Biotechnology Announces $116 Million Series B Financing

UNITY Biotechnology, Inc. ("UNITY"), a privately held biotechnology company creating therapeutics that prevent, halt, or reverse numerous diseases of aging, today announced the closing of a $116 million Series B financing. The UNITY Series B financing ranks among the largest private financings in biotech history and features new investments from longtime life science investors ARCH Venture Partners, Baillie Gifford, Fidelity Management and Research Company, Partner Fund Management, and Venrock. Other investors include Bezos Expeditions (the investment vehicle of Jeff Bezos) and existing investors WuXi PharmaTech and Mayo Clinic Ventures. Proceeds from this financing will be used to expand ongoing research programs in cellular senescence and advance the first preclinical programs into human trials.

The financing announcement follows the publication of research that further demonstrates the central role of senescent cells in disease. The paper, written by UNITY co-founders Judith Campisi and Jan van Deursen and published today, describes the central role of senescent cells in atherosclerotic disease and demonstrates that the selective elimination of senescent cells holds the promise of treating atherosclerosis in humans. In animal models of both early and late disease, the authors show that selective elimination of senescent cells inhibits the growth of atherosclerotic plaque, reduces inflammation, and alters the structural characteristics of plaque such that higher-risk "unstable" lesions take on the structural features of lower-risk "stable" lesions. "This newly published work adds to the growing body of evidence supporting the role of cellular senescence in aging and demonstrates that the selective elimination of senescent cells is a promising therapeutic paradigm to treat diseases of aging and extend healthspan. We believe that we have line of sight to slow, halt, or even reverse numerous diseases of aging, and we look forward to starting clinical trials with our first drug candidates in the near future."

So this, I think, bodes very well for the next few years of rejuvenation research. It indicates that at least some of the biotechnology venture community understands the likely true size of the market for rejuvenation therapies, meaning every human being much over the age of 30. It also demonstrates that there is a lot of for-profit money out there for people with credible paths to therapies to treat the causes of aging. It remains frustrating, of course, that it is very challenging to raise sufficient non-profit funds to push existing research in progress to the point at which companies can launch. This is a problem throughout the medical research and development community, but it is especially pronounced when it comes to aging. The SENS view of damage repair, which has long incorporated senescent cell clearance, is an even tinier and harder sell within the aging research portfolio - but one has to hope that funding events like this will go some way to turn that around.

From the perspective of being an investor in Oisin Biotechnologies, I have to say that this large and very visible flag planted out there by the UNITY team is very welcome. The Oisin team should be able to write their own ticket for their next round of fundraising, given that the gene therapy technology they are working on has every appearance of being a superior option in comparison to the use of apoptosis-inducing drugs: more powerful, more configurable, and more adaptable. When you are competing in a new marketplace, there is no such thing as too much validation. The existence of well-regarded, well-funded competitors is just about the best sort of validation possible. Well funded competitors who put out peer-reviewed studies on a regular basis to show that the high-level approach you and they are both taking works really well is just icing on the cake. Everyone should have it so easy. So let the games commence! Competition always drives faster progress. Whether or not I had skin in this game, it would still be exciting news. The development of rejuvenation therapies is a game in which we all win together, when new treatments come to the clinic, or we all lose together, because that doesn't happen fast enough. We can and should all of us be cheering on all of the competitors in this race. The quality and availability of the outcome is all that really matters in the long term. Money comes and goes, but life and health is something to be taken much more seriously.

Now with all of that said, one interesting item to ponder in connection to this round of funding for UNITY is the degree to which it reflects the prospects for cancer therapies rather than the prospects for rejuvenation in the eyes of the funding organizations. In other words, am I being overly optimistic in reading this as a greater understanding of the potential for rejuvenation research in the eyes of the venture community? It might be the case that the portions of the venture community involved here understand the market for working cancer drugs pretty well, and consider that worth investing in, with the possibility of human rejuvenation as an added bonus, but not one that is valued appropriately in their minds. Consider that UNITY Biotechnology has partnered with a noted cancer therapeutics company, and that the use of drugs to inducing apoptosis is a fairly well established approach to building cancer treatments. That is in fact why there even exists a range of apoptosis-inducing drugs and drug candidates for those interested in building senescent cell clearance therapies to pick through. Further, the presence of large numbers of senescent cells does in fact drive cancer, and modulating their effects (or removing them) to temper cancer progress is a topic under exploration in the cancer research community. So a wager on a new vision, or a wager on the present market? It is something to think about.

View the full article at FightAging

[Florian Xavier]

I KNEW it. It would be so absurd to have this kind of money and not investing in health and aging.

[reason]

What follows here is an inside baseball discussion relating to the companies working on senolytic therapies, biotechnologies capable of selectively destroying senescent cells. The presence of these cells is one of the causes of aging and age-related disease, and their removal is the first of a number of rejuvenation therapies based on the SENS vision that will emerge over the next few decades. Human trials of the first senolytics will be starting this year and next, and by the mid-2020s most people in the wealthier parts of the world will have the opportunity to remove this part of the burden of aging. This is a wondrous development: based on research to date, removing senescent cells from old individuals is a robust and reliable way to turn back the clock on many measures of aging and markers of age-related disease.

I should preface the rest of this post by noting that competition in the marketplace is a great thing, but only because some investors suffer meaningful losses. The threat of loss is necessary to the alchemy by which self-interest is turned into altruism. Only competition with real penalties for failure can drive the faster progress that benefits everyone. Yet regardless of who wins or loses in terms of the value of their shares, we all win when reasonably priced senolytic therapies become widely accessible. In that sense, investing in credible ventures aiming at the production of rejuvenation therapies is a great opportunity: even failure contributes to progress, and the outcome in the end is that we are all better off. Someone achieves the goal, someone deploys the treatment.

UNITY Biotechnology is presently at the head of the current crop of companies focused on treating aging and age-related disease through the clearance of senescent cells. They hold the leading position by virtue of the involvement of the principal research groups in the field, having big names from the pharmaceutical and biotech field running the show, and having recently raised more than $100 million to push the first of these therapies through the US regulatory progress and into the clinic. Yet I can't say as I think that their position is as enviable and commanding as it might first appear to be, however. From a competitive point of view, they actually have very little going for them at the moment aside from that war chest and the credibility it took to raise it.

Having made that statement, I should defend my position. The chief problem I see for UNITY is one of technology. They are taking a small molecule drug approach within the current regulatory system, and the currently available stable of senolytic drug candidates with which they entered the picture are chemotherapeutics with significant side-effects. Other drug candidates are emerging quite rapidly in the research community, some of which may have far fewer side-effects, but switching would mean starting fresh, or licensing fresh from current owners. It might also mean moving from a well-characterized drug with excellent pharmacology data, such as navitoclax, to a drug that still needs that data established. The situation is actually worse than this, however. Competitors with far better senescent cell clearance technologies, approaches with essentially zero side-effects, are emerging at the rate of one every year or so. Oisin Biotechnologies was the first, using a programmable gene therapy approach, and just this week another group announced their intent to form a company to develop their FOXO4-p53 interference method.

UNITY didn't emerge from thin air, and their precursor company does have a variety of patents and experience in trying to get immunotherapies and engineered viruses to work as senolytic treatments. They had plenty of time to try to get that to work and did not achieve those goals. With what is now a great deal of funding in comparison to the past, they could go back and try to make one of those approaches work. There is a great deal of uncertainty in that sort of endeavor, however. They should and no doubt will turn some of their funding to longer-term technology development with perhaps a five-year horizon, but when you take as much venture funding as this company has, the clock ticks very aggressively. They have to build a multi-billion-dollar valuation company pretty quickly, within the next couple of years. That has to be done on the basis of human trials starting right about now, since those clinical trials will take a year or so to run from idea to publication of results.

Another threat is that of medical tourism. Not everyone in this global industry is going to care about the opinions of the FDA. Given that existing senolytic drugs, and many of the new ones, can be purchased from established suppliers, there really is little to stop a large industry of medical tourism springing up for the very same drugs that UNITY is trying to put through the system. Or at the very least for drugs that are similar enough in effectiveness and side-effects. That will hamper UNITY's ability to charge regulatory capture prices; it is harder to do that when people can just go to Mexico at a tenth or less of the US price. That in turn will harm their valuation and ability to raise further funding needed to run treatments through the FDA gauntlet.

A final consideration is that everything UNITY spends money on today helps their competitors just as much as it helps them. One might argue that the big UNITY war chest is really largely a charity fund for industry development. Being a competitor to UNITY is one of the greatest places to be in modern for-profit biotechnology. They are doing all the work to prove out the industry, raise its profile, and demonstrate with ever-better clarity that targeted destruction of senescent cells successfully treats aging. They are doing more than their part to set a high initial valuation for any other new company with a credible technology for targeting senescent cells. This is all wonderful from the point of view of anyone waiting for the end result to emerge in clinics, but pretty terrible for UNITY from a competitive point of view. They'll be hip-deep in highly effective competing companies come this time in 2019.

As I see, it the UNITY management has a few options when it comes to strategy. Firstly they can forge ahead in the hope that regulatory barriers are good enough to allow a large valuation based on approval for a chemotherapeutic that is (a) inferior to a range other treatments only a little behind in time to market, and (b) also available on the open market for medical tourism. Secondly they can couple that approach with significant investment in development of new drugs that can be patented, variants of those already discovered. These two are more or less the standard playbook for a new pharmaceutical entity, so they may well do this and only this. If they do, I think that their competitors, already equipped with far superior products, will eat their lunch over the next few years, however. The third option is to continue to prove out the market, make life easy for competitors, run the first trials, pull in another even larger round of funding at some ridiculous valuation, and then use those funds to buy the best of the crop of competitors, solving the technology problem.

This last option seems plausible, and is not uncommmon. I think it quite likely that UNITY will kick off their chemotherapeutic trials, publish the promising initial results while downplaying the side-effects, raise series C in 2018, and then buy whichever of the young companies in the space with a better senolytic technology wants to sell for a quick turnaround. Despite the enormous size of the target market here, ultimately every adult human much over the age of 30 buying a treatment every few years, not every entrepreneur wants to spend a decade fighting the FDA to make progress towards a narrow, limit use of their therapy. A quick win and sudden wealth is a strong temptation; anyone starting up a senescence-focused biotech company these days will have an acquisition by UNITY somewhere in mind as an option - as will the investors who back those companies.

View the full article at FightAging

[johnross47]

I could see a couple of potential downsides to this scenario.

 

They fail to buy in a more successful product and go down, scaring off potential investors in the field, and, they do buy in a better product but have to sell it at a very high and mostly unachievable price.

[YOLF]

The way I see it, VCs aren't going to sink all their eggs into one basket. They probably invested in Unity and are also investing in the competitors. This is how you guarantee that you win in the long term. From their perspective, they aren't going to lose money, Unity is a stepping stone that will build a brand and will be the easy to beat competitor in the space for others to beat and this will add benchmarking value to their successful products. 

 

However, the lower the bar, the lower the quality of the products (though also the greater the impression of exponential growth). I think we need to see Unity benchmark drugs become obsolete as benchmarkers as quickly as possible.

 

Edited by YOLF, 06 April 2017 - 03:29 AM.

[reason]

It was only partially in jest that I recently noted Unity Biotechnology as a financial institution with a sideline in rejuvenation research, specifically the targeted destruction of senescent cells. The principals have raised a truly enormous amount of funding in the past year and a half, and recently filed for IPO. They have not yet presented even preliminary human data. Typically the ordering of these matters tends to be at least a little different; there are some raised eyebrows in the community. But if the Unity Biotechnology founders can raise the funds and use them well to advance the state of the art, then more power to them. From their SEC filings we know a little more than we did as to the specific classes of pharmaceutical developed at the company, or at least those they are prepared to talk about today. One is the line of development that started with Bcl-2 inhibitors such as navitoclax, and the other is a more novel approach to senescent cells, one that is as much about suppressing their harmful signaling as it is about destroying the cells.

In using pharmacological methods, Unity Biotechnology has an approach to senescent cell clearance that is objectively worse than, say, the programmable gene therapy pioneered by Oisin Biotechnologies. Pharmaceutical approaches are slow and expensive to tinker into better shape when they turn out to be overly tissue specific or have problematic side-effects. Nonetheless, it is entirely possible to build an enormous business on the back of a first generation senolytic pharmaceutical, because if it clears even 25% of senescent cells from just a few tissue types it will still be far more useful than any other class of medication for inflammatory, fibrotic, and other age-related diseases of those tissues. But the competition in the form of Oisin Biotechnologies will arrive in the clinic a couple of years later with a form of therapy that can destroy all senescent cells in all tissues, and that can be adapted quickly and at low cost.

The Unity folk know this, and the potential market is so very large (every human being much over the age of 40) that I think it probably won't dent their success all that much. There will be many enormous companies and many senolytic therapies coexisting in that market. It is plausible that the more interesting challenge for the Unity Biotechnology staff is to create a therapy that is meaningfully better than the dasatinib and quercetin combination, better enough to justify the very large cost multiple that the company will have to charge in order to keep their investors satisfied. Dasatinib is out of patent protection, its pharmacology is very well characterized in humans, and it runs to a $100-200 cost for a single dose that would be usefully taken perhaps once a year at most. Should the human studies, such as those running at Betterhumans, show it to be effective, that may cause issues for Unity or any other small molecule development concern. None of the other candidate drugs have yet done much better than dasatinib and quercetin in animal studies. The existence of dasatinib will drag down the prices it is possible to charge for anything that performs in the same class - which so far is everything, to a first approximation.

A Biotech Entrepreneur Aims To Help Us Stay Young While Growing Old

The idea behind Unity - preventing aging - sounds crazy, but it's backed by dozens of scientific papers. There are aging cells, called senescent cells, that build up throughout the body and contribute to what we think of as old age-things like achy joints, waning vision, even perhaps Alzheimer's. Kill those senescent cells with drugs, Nathaniel David reasons, and people might be able to grow old without becoming infirm. "Like, how awesome would it be? The problem is you have to take the first baby step to demonstrate it's possible. That's what chapter one is: demonstrate in a human being that the elimination of senescent cells takes a heretofore inescapable aspect of aging and can either halt it or reverse it." Unity's chief executive and chairman, Keith Leonard, 56, interrupts. "Just that. It's easier to talk to the FDA about treatment of a disease once it's diagnosed than it is to work really early and prevent disease. But prevention is what we'd love to get to."

It's an amazing goal, backed by great science, not to mention $222 million in venture capital and $85 million raised from a May initial public offering, which valued Unity at $700 million, flat with its last fundraising. When a medicine is just beginning human tests, the odds it will make it to market are 10%. But David's career has turned into a blueprint for success in biotech, transforming ideas from university laboratories into viable companies, investment gains and, maybe, drugs. David's five companies have raised $1.5 billion and made investors close to $2 billion without ever actually turning a profit. "He's probably the best person in the world at finding great academic science and shaping it into a fundable story and a sellable business plan," says Kristina Burow, managing director at Arch Venture Partners. She has known David since he was in graduate school and has backed four of his startups.

The idea for Unity arrived in David's email inbox in 2011, from multiple senders at the same time. Jan M. van Deursen had genetically engineered mice so that many types of senescent cells would die. The results of this experiment and of others that followed were striking. Van Deursen introduced David to Judith Campisi, at San Francisco's Buck Institute, who had helped establish the senescent-cell field. Arch founded Unity in 2011, with Van Deursen and Campisi as cofounders. For five years the company didn't even have offices; all the work was done at the scientists' labs.

There's a good reason for the skepticism, no matter how cool Unity's science is: Investors have been hoodwinked by antiaging science before. In 2007, a company called Sirtris went public based on the hype around antiaging compounds related to red wine. GlaxoSmithKline bought Sirtris for $720 million in 2008, but it never resulted in any drugs and was shut down in 2013. Unity needs to show that a medicine can have a clear effect in humans. Its first attempt, UBX0101, will target arthritis. Now, in the first human test, it will be injected into the knees of 30 patients, who will fill out surveys about how much pain they feel, have fluid removed from their knees and undergo MRI scans. They'll be compared with ten patients who will get a placebo injection. Any signs that the drug is making patients better will be seen as a reason to move into further studies. Unity expects to enter two more drugs into human studies by the end of next year. Candidate diseases include glaucoma, where killing senescent cells seems to lower the pressure that builds up in the eye, and lung diseases, where it may coax lung cells to stop making scarred, fibrous tissue.

Unity has raised so much money precisely because its executives know it may take multiple tries to find a medicine. It's not known what the risks of killing senescent cells are; it's possible they could include, for instance, slow wound healing. There's no way to know until human tests begin.

View the full article at FightAging

[reason]

The honor of running the first trial of a senolytic drug, albeit inadvertently, goes to one of the groups testing dasatinib or navitoclax back when those pharmaceuticals were first evaluated for cancer therapies. At that time nobody knew that these drugs could selectively destroy senescent cells, and were thereby far more valuable as a starting point for rejuvenation therapies than as cancer treatments. The first intentional human trial was started last year by Betterhumans, a non-profit organization. Now Unity Biotechnology has recently announced that their first human trial is underway, testing the ability of their initial candidate senolytic to treat osteoarthritis. You may recall that the evidence in animal models for the accumulation of senescent cells to be a primary cause of osteoarthritis is fairly compelling. We can hope that this holds up in humans; results will likely start to appear in a preliminary form next year.

UNITY Biotechnology, Inc., a biotechnology company developing therapeutics to extend healthspan by slowing, halting, or reversing diseases of aging, today announced the treatment of the first patient in the Phase 1 clinical trial evaluating UBX0101 in moderate to severe osteoarthritis of the knee. "For many people, we believe that osteoarthritis is the main reason why it hurts to get old. By designing a treatment to selectively eliminate senescent cells in the joints of patients diagnosed with painful osteoarthritis, our goal is to alter the otherwise disabling course of this disease. This is an important milestone for UNITY. This is the first time we have treated a patient with a drug to eliminate senescent cells. While this study is designed to establish safety, we are also looking for the earliest signals of reducing senescent cell burden in this disease of aging."

The Phase 1 clinical trial of UBX0101 is a randomized, double-blind, placebo-controlled, single ascending dose study that will evaluate safety, tolerability, and pharmacokinetics of a single intra-articular injection of UBX0101 in patients diagnosed with moderate to severe osteoarthritis of the knee. Patients will be randomly assigned to receive UBX0101 or placebo in 3:1 randomization by dose level cohort.

Cellular senescence is a natural biological state in which a cell permanently halts division. Senescent cells accumulate with age and secrete as many as 100 different biologically active proteins, including pro-inflammatory factors, proteases, pro-fibrotic factors, and growth factors that disturb the tissue microenvironment. This collection of secreted proteins is referred to as the Senescence Associated Secretory Phenotype, or SASP. In addition to its effects on tissue function, the SASP contains factors that induce senescence in neighboring cells, setting off a cascade of events that culminates in the formation of the functionally aged and/or diseased tissue that appears to underlie a variety of age-associated diseases. UNITY believes that the elimination of senescent cells will remove SASP factors - addressing a root cause of diseases of aging. Senolytic medicines, or treatments designed to selectively remove senescent cells, target the SASP at its source, and may have a more durable impact on disease than current therapies.

Link: http://ir.unitybiote...treated-ubx0101

View the full article at FightAging

[Rocket]

Good luck. Hope it works and is soon available. Once its on the market some clever people will find a way to obtain some for systemic use.

[ImmInst]

UNITY Biotechnology Adds Accomplished R&D Leader David L. Lacey, M.D., to Board of Directors http://prn.to/2BKj8NF 

UNITY Biotechnology Adds Accomplished R&D Leader David L. Lacey, M.D., to Board of Directors http://prn.to/2BKj8NF 

View the tweet

[ImmInst]

#ICYMI: Listen to $UBX CEO Keith Leonard's fireside chat at the Morgan Stanley Global Healthcare Conference last Friday. http://bit.ly/2p4ZO5u  pic.twitter.com/2t3RL8d5oV

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[ImmInst]

Enjoyed hearing our scientific co-founder Judy Campisi speak at the @BuckInstitute Inflammation & Aging event yesterday #agingbiology pic.twitter.com/1OCY9UYEsb

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[ImmInst]

#ICYMI: $UBX CFO Bob Goeltz presented at the Cantor Fitzgerald Healthcare Conference on Wednesday. Catch a replay here: https://bit.ly/2IeIbcg 

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[ImmInst]

We just announced our Q3’18 #financialresults – Get the details: https://bit.ly/2JKI6O7  $UBX

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[ImmInst]

Our Co-Founder and President @NathanielEDavid discussed the past, present and future of #aging research alongside a distinguished panel at #BAAM18 last Friday. Thanks for a great meeting! pic.twitter.com/SFzLgjPasj

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[ImmInst]

Mark your calendars! $UBX Investor and Analyst Event on Cellular Senescence will be webcast live on Dec. 11 from 9:00-11:30 a.m. ET. More details here: http://ow.ly/eIO550jGgj5  #agingbiology

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[ImmInst]

<p class="TweetTextSize TweetTextSize--normal js-tweet-text tweet-text" lang="en">Today we announced an additional cohort to evaluate a higher dose in our ongoing UBX0101 Phase 1 study in <a class="twitter-hashtag pretty-link js-nav" dir="ltr" href="https://twitter.com/...thritis</b></a>of the knee. Read the details here: <a href="https://bit.ly/2SsKrAG">https://bit.ly/2SsKrAG&nbsp;</a> <a class="twitter-cashtag pretty-link js-nav" dir="ltr" href="https://twitter.com/search?q=%24UBX&amp;src=ctag">$<b>UBX</b></a></p>

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[ImmInst]

We are excited to welcome industry leader Margo Roberts, Ph.D. to our board of directors. https://twitter.com/search?q=%24UBX&src=ctag">$UBX href="https://bit.ly/2rm8WE8">https://bit.ly/2rm8WE8 

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[ImmInst]

https://twitter.com/hashtag/ICYMI?src=hash">#ICYMIlast week, catch a replay of our investor and analyst event, The Science of Cellular Senescence, featuring Drs. Judy Campisi and Jan van Deursen. href="https://bit.ly/2QC1jYs">https://bit.ly/2QC1jYs  href="https://twitter.com/hashtag/agingbiology?src=hash">#agingbiology href="https://twitter.com/hashtag/healthspan?src=hash">#healthspan

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[ImmInst]

Today we announced selection of UBX1967 as our lead development candidate in https://twitter.com/hashtag/ophthalmology?src=hash">#ophthalmologyto advance into IND-enabling studies. Read more here: href="https://bit.ly/2H2zLIe">https://bit.ly/2H2zLIe 

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[ImmInst]

Today we announced we’re adding a cohort to our Phase 1 study in #osteoarthritis of the knee to further evaluate the impact of treatment with UBX0101 on SASP factors. Read more here: https://bit.ly/2AWJTfO  $UBX

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[ImmInst]

We’re looking forward to presenting at the https://twitter.com/hashtag/CowenHealthCare?src=hash">#CowenHealthCareConference in Boston on Mar. 11. Learn more: href="https://bit.ly/2tMV6Mf">https://bit.ly/2tMV6Mf  href="https://twitter.com/search?q=%24UBX&src=ctag">$UBX

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[ImmInst]

We just announced our full year and Q4 '18 #financialresults. Get the details: https://bit.ly/2SMa0w8  $UBX

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[ImmInst]

Today we announced an exclusive license agreement with @UCSF to continue to explore the therapeutic use of alpha-Klotho protein. Researchers including @DenaDubal have found that Klotho has the potential to slow age-related #cognitive decline. More details: https://bit.ly/2W4xMFy 

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[Engadin]

UNITY Biotechnology Reports Promising Topline Data from Phase 1 First-in-human Study of UBX0101 in Patients with Osteoarthritis of the Knee

 

SAN FRANCISCO, June 18, 2019 (GLOBE NEWSWIRE) --  UNITY Biotechnology, Inc. (UNITY) [NASDAQ: UBX], a biotechnology company developing therapeutics to extend healthspan by slowing, halting or reversing diseases of aging, today announced promising results from its first-in-human Phase 1 study of UBX0101 in patients with moderate to severe osteoarthritis (OA) of the knee. The study demonstrated that UBX0101 was safe and well-tolerated. Improvement in several clinical measures, including pain, 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.

 

"This Phase 1 study of UBX0101 is an important first step in exploring the potential of a senolytic approach in the treatment of a range of age-related diseases," said Keith Leonard, chairman and chief executive officer of UNITY. “We believe our novel approach to eliminating senescent cells has the potential to meaningfully impact healthspan.”

 

“New treatments for OA are desperately needed, especially an intervention that targets the biology of the condition that includes cell senescence,” said Richard F. Loeser, Jr., M.D., Director, UNC Thurston Arthritis Research Center Herman and Louise Smith Distinguished Professor of Medicine, Division of Rheumatology, Allergy & Immunology. “These exciting data are supportive of this very promising new approach for this chronic painful condition.”

 

 

Phase 1 Trial Design and Results

 

Trial Design

 

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 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.

 

 

Safety, Tolerability and PK

 

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.
             
UBX0101 demonstrated dose-proportional plasma pharmacokinetics. Model-based predicitons of concentrations within the knee suggested that doses at or above 1 mg may be pharmacologically active. This informed the prospectively defined low dose (0.1, 0.2, and 0.4 mg) and high dose (1, 2, and 4 mg) groupings for analyses.

 

 

 

..../....

 

 

 

[ImmInst]

Today we reported promising topline data from a phase 1 first-in-human study of UBX0101 in patients with osteoarthritis of the knee. Listen to the replay of the discussion here: https://bit.ly/2RiFhaQ  pic.twitter.com/GT3trJoTNk

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[Engadin]

S O U R C E :   Yahoo! Finance

 

 

Here's Why Unity Biotechnology Dropped as Much as 20.4% Today

 

What happened

 

Shares of Unity Biotechnology (NASDAQ: UBX) fell over 20% today, before sharply recovering. This came after the company reported data from a phase 1 clinical trial for its lead drug candidate, UBX0101, in moderate to severe osteoarthritis. The two-part study demonstrated mixed results.

 

In part A of the study, patients taking various doses of the drug candidate demonstrated significant improvements in pain reduction compared to placebo at the 12-week mark. In part B of the study, all patients were given the highest dose of UBX0101, but didn't report statistically significant reductions in pain compared to placebo at the four-week mark.

 

As of 2:09 p.m. EDT, the stock had settled to a 8.9% loss.

 

 

So what

 

Today's news suggests that the search for medicines to increase longevity and stave off age-related diseases is far from over. Researchers simply don't have a great understanding of the complex molecular interactions that take place within the body and contribute to age-related diseases. Developing a drug compound that interacts with just one part of those complex systems and chemical cascades -- the infamous "Can a biologist fix a radio?" dilemma -- is unlikely to yield much success.

 

That doesn't mean it's not worth trying. Unity Biotechnology's approach is to develop therapeutics for cleaning up old, inefficient, and senescent cells (cells that don't divide) that contribute to disease progression.

 

UBX0101 specifically aims to inhibit the interaction of two proteins in order to trigger the elimination of senescent cells. The results were mixed from the phase 1 trial in moderate to severe osteoarthritis, insofar as pain management is concerned. But the company noted that changes in various biomarkers indicated a reduction in the number of senescent cells in patients receiving the experimental therapy.

 

 

Now what

 

Open-minded investors realize that Unity Biotechnology is likely to encounter a healthy amount of failure in the clinic. The question is whether the data generated from those failures deepens the understanding of age-related diseases such that longevity-based medicines can be successfully developed.

 

Given the complexity involved in this approach, investors shouldn't allocate an irresponsible amount of their portfolios to the company -- if it has a place in their portfolios at all.