Notes on the 2019 Ending Age-Related Diseases Conference in New York

I recently attended the second Ending Age-Related Diseases conference in New York, hosted by the Life Extension Advocacy Foundation (LEAF). The mix of attendees was much the same as last year: an even split between scientists, entrepreneurs, investors, patient advocates, and interested onlookers, all focused on the treatment of aging as a medical condition. The presentations were similarly a mix of scientists talking about their research programs, entrepreneurs presenting on the data produced by their companies, and investors discussing the state of the industry.

For my part, I have already presented several times this year on the work taking place at Repair Biotechnologies, while we were raising our seed round. So rather talk again on a familiar topic, I chose instead to discuss the terrible state of clinical translation in the life science industry - the institutional, widespread, ongoing failure to develop promising research programs into therapies. This is particularly the case for the treatment of aging, given that translational research in gerontology was actively suppressed by leading scientists for much of the last 40 years. This was an overreaction to the "anti-aging" industry of fraud, supplements, and false hope established in the 1970s, and probably set us back decades.

Even now there is a great gulf between academia and industry, into which projects vanish. This gulf is built of many factors: scientists rarely have good connections to the people who could carry forward their projects; academic funding tends to stop once projects get close to the point at which they could be translated; universities do far too little to nurture new companies, and instead focus on being toll collectors; most investors sit around waiting for companies to form and come to them, rather than devoting their resources to helping companies form; and so forth. The result is that the research community is littered with credible projects in a dormant state, just waiting for someone to champion their development.

A number of fellow entrepreneurs in the longevity industry presented their latest data at the conference. Doug Ethell of Leucadia Therapeutics noted the proof of principle of his thesis on the roots of Alzheimer's disease, data obtained in ferrets. Partially occluding the cribriform plate in the skull, to mimic the process of ossification that occurs with age in humans, blocks drainage of cerebrospinal fluid, thus allowing amyloid and other molecular waste to build up in the brain and cause neurodegeneration and cognitive decline.

Greg Fahy of Intervene Immune presented quite a lot of data on what six to twelve months of treatment with growth hormone and DHEA does to the thymus and measures of immune system composition in older individuals. It makes for a compelling story, given their evidence for thymic regrowth and improvement in the immune system, for all that I remain dubious about growth hormone as a mode of treatment for aging. There is a lot of evidence to suggest that it isn't such a great plan. But perhaps undergoing a year of such treatment to have a somewhat larger, somewhat more active thymus going forward is a sensible trade-off, should these results hold up in larger patient groups.

John Lewis of Entos Pharmaceuticals gave a great presentation on the lipid nanoparticle (LNP) platform used by Oisin Biotechnologies to destroy senescent cells and by OncoSenX to destroy cancer cells. This platform is one of the candidate technologies to power all of the next generation of gene therapies, ensuring that most implementations can just work, comparatively simply, and with far less effort than is presently required. The presentation included the final study results from the mouse lifespan study run by Oisin Biotechnologies in which LNPs were set to target cells that expressed p16, p53, or both p16 and p53. That last group lived significantly longer, and had their first death at the point at which half of the control group had died.

Kelsey Moody presented on LysoClear, one of the ever growing number of subsidiary companies generated by the Ichor Therapeutics team. The company is developing an approach to treat macular degeneration by using compounds derived from bacterial enzymes to break down molecular waste that builds up in the lysosome, impairing cell function. His emphasis was on the need to be careful, conservative, and methodical in preclinical development, using LysoClear development as an example of always proving each step before moving on, building on well-proven existing work.

From the scientific community, Maria Blasco discussed at length her work on telomeres and telomerase gene therapy in mouse models. Her group sees loss of telomere length in tissues as a significant contributing cause of aging, with wide-ranging downstream effects, rather than a marker of aging that results from loss of stem cell function. Amutha Boominathan presented on her work at the SENS Research Foundation, moving mitochondrial genes into the cell nucleus in order to prevent the consequences of damage to mitochondrial DNA. In principle this can stop inevitable mitochondrial DNA damage from causing aging. Morgan Levine discussed epigenetic clocks based on DNA methylation, and what lies ahead in getting them to be useful to speed up development of rejuvenation therapies. The clocks and the therapies must develop in parallel, and many different clocks will likely be needed. The biggest task ahead is to understand exactly what it is that these epigenetic clocks are measuring.

From the investment community, Joe Betts-Lacroix noted that of the 1000 or so biotech startups out there, maybe 70 or so are credibly involved in working on aging and longevity. This industry is in its very earliest stages. One of the worthies in our community is presently assembling a database of those aging-focused startups, which I hope will be made publicly available fairly soon. There is a lot more that our community needs to do in order to help newly arriving entrepreneurs and investors become knowledgeable and productive quickly, and a database of companies is a good idea in this context.

Both James Peyer of the newly founded Kronos BioVentures and Sree Kant of Life Biosciences discussed how to invest in longevity, given the nature of the industry and its present constraints and peculiarities. James Peyer, as always, brought a very interesting set of ideas to the conference, and Life Biosciences is itself a sensible strategic response to the twin challenges of (a) a lack of entrepreneurs and (b) researchers who really don't want to leave academia. Life Biosciences wraps subsidiary companies around research teams, providing an environment that still feels like academia, and in which much of the trouble of running a company is abstracted away into the larger parent organization.

I have of course omitted mention of a number of other presentations and panels, and no offense is intended to the speakers. The above is really just a list of things that caught my attention, or that I happened to be there for rather than being caught up in meetings. All in all it was a good event, as was the case last year. The LEAF volunteers did a great job, and I encourage you to add this conference series to your 2020 agenda.

Comments

Hormones like GH usually display a complex pattern where intermittent and oscillating activation is beneficial but chronic low or high activation lead to deleterious effects.
The linear view of more is better is definitely bunk and the Intervene presentation I saw at Ending Aging 2018 seemed pretty suspicious, but I would write off that clever application of HGH can improve Health Span

Posted by: Johannes at July 17th, 2019 4:38 PM

Is there any published data on OISIN p16+p53 updates?

Posted by: Cuberat at July 17th, 2019 4:59 PM

@Reason, about Maria Blasco you say: "Her group sees loss of telomere length in tissues as a significant contributing cause of aging, with wide-ranging downstream effects, rather than a marker of aging that results from loss of stem cell function". What is your opinion? A cause or a marker?

Posted by: Josep at July 18th, 2019 7:05 AM

@Reason
What is the typical amount of money needed for a startup?

I think a crowd investing vehicle would be doing really well as the longevity community keeps growing. I for one won't donate my life savings but I would be willing to invest a good chunk of it if the risk is spread amongst 10+ startups. The chance of profiting from it and getting projects done is win-win and literally every person on this planet has an interest in doing so.

Posted by: Christian at July 18th, 2019 8:12 AM

"I think a crowd investing vehicle would be doing really well as the longevity community keeps growing. I for one won't donate my life savings but I would be willing to invest a good chunk of it if the risk is spread amongst 10+ startups. The chance of profiting from it and getting projects done is win-win and literally every person on this planet has an interest in doing so."

Excellent idea!

Posted by: Peter at July 18th, 2019 3:45 PM

I would shift a pretty large fraction of my investment funds into something like crowdfunder.com for any good anti-aging startups.

Posted by: Corbin at July 18th, 2019 5:20 PM

@Christian
Biotech startups in this and similar spaces typically require at least $25k as the minimum investment in seed or initial convertible equity rounds. Initial friends & family investors can sometimes give less but it's hard to be friends & family for 10+ startups. There are syndicates on AngelList and other platforms that allow investors to add as little as $1-5k to a pooled funds investment picked by the syndicate lead, but there are no syndicates I'm aware of that specialize in aging startups, and you typically have to pay carry to the syndicate decreasing returns but this is probably a rational thing to do in order to diversify across 10+ startups for anyone who doesn't have 250k to directly invest.

Most syndicates are for tech or other areas. The closest one I know of to aging is BioVerge, which operates via its own website. It's scope is startups at the intersection of bio/health & new technologies, so aging startups are mostly in-scope (since most involve some kind of new technology), but they do other things as well. Currently, one still has to be an accredited investor to join, but the last part of the jobs act from a few years ago is to pave the way for crowd-equity-investing and whenever the details of how that will work become clear things might open up to everyone.

Last year I wanted Reason to start a syndicate specifically for rejuvenation startups but he went and founded a new startup instead. If someone were to come along and start such a syndicate, I think it would be good for the space. I think it's likely within a few years.

It would be great to eventually have an narrow sector index to track the performance of aging companies and after that someday have an investable passive index fund, but these are not on the immediate horizon and would only track public companies, not pre-IPO startups. It would be difficult to make an index fund for private startups. Also, as aging projects become a sizable fraction of what big biotech/pharma companies do, it will be impossible to separate out those parts from the rest of what those companies do and thus any index or fund would only be an approximation of even the publicly-traded part of the commercial space.

Posted by: Karl Pfleger at July 18th, 2019 5:43 PM

I also would move ~half my investments into a well structured fund if one were available.

Posted by: Tom Schaefer at July 19th, 2019 9:48 AM

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