Fight Aging!

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.