FY#15: Getting closer to real anti-aging therapies

A conference report on Longevity Therapeutics 2019

I had the pleasure of attending the first year of the Longevity Therapeutics conference in San Francisco in January, on behalf of LEAF, where I am a volunteer writer. In full disclosure, my attendance was comped by the conference organizers.

Organized ably by Hanson Wade, with John Lewis, CEO of Oisín Biotechnologies, as program chair, the conference focused on senolytics for senescent cell clearance, big data and AI in finding new drugs (“in silico” testing), delivery systems for therapeutics like senolytics, TORC1 drugs, biomarkers of aging, and challenges with clinical trial development and FDA approval. In short: a smorgasbord of cutting-edge longevity research.

As the conference’s name implies, however, the focus most generally was on therapeutics for aging, rather than basic research or theory, which is a first for any science-based longevity conference that we know of.

Ned David, CEO of Unity Biotechnology, kicked off the conference with a talk about their latest research on senolytics, which clear away senescent cells (“zombie cells”) that spew out harmful chemicals that can cause neighboring cells to also become senescent. Unity has made the news recently with an extension request for its first-of-a-kind senolytics clinical trials with osteoarthritis patients. Their preliminary Phase 1 clinical trial results were deemed “safe,” a major step in obtaining FDA approval, so it will be exciting to see the full results later this year or in 2020.

Big data and AI was a major theme, with the “the young data Turks” from BioAge, Gero and Insilico, all making presentations about various ways to utilize increasingly large health and “omics” datasets to discover novel therapeutics. Other notable companies in the field of AI and biotech include Google’s DeepMind, recently making major advances in the protein folding problem, Atomwise and Recursion. This are of longevity research feels to me like it will quickly become an integral part of the field.

I had a conversation with Eric Morgen, Chief Science Officer for BioAge, about the evolution of aging and whether a better understanding of why we age, in an evolutionary sense, is important in developing better therapies for aging. He insisted that it didn’t really matter how various aging pathways evolved, implying that big data and machine learning could ferret out drugs and other therapies regardless of how evolution got us to where we are.

I suggested that an evolutionary understanding may help greatly in getting us to better therapies because understanding any problem’s history is likely to help us resolve that problem. I argued that understanding of proximate causes — biochemical pathways, for example — isn’t as effective an understanding as understanding the “deep time” evolutionary pathways that led to these biochemical pathways.

Time will tell, of course, who’s right on this. If BioAge or other machine learning companies are able to find effective therapies before long, based mostly on brute force, that will be an effective rebuttal to my argument (which, of course, is not at all original to me since many others, including Josh Mitteldorf, have made similar arguments for years).

Ron Kohanski from the National Institute of Aging, gave a talk on biomarkers for basic and translational research, and provided some commentary on the National Institute of Health (NIH) and National Institute on Aging (NIA), which is a division of NIH. In discussion with me after his talk, Ron let me know that NIA has received significantly higher funding from Congress in recent years, such that they’re actually having a hard time finding ways to usefully disburse it. Their research budget has increased from about $1 billion four years ago to $3.8 billion in 2018.

Steven Braithwaite, Chief Science Officer of Alkahest, talked about his company’s efforts to identify the active proteins in young plasma that has been shown in many parabiosis experiments to lead to significant anti-aging effects in mice. They have developed novel therapeutics, ALK6019 and ALK6021, which in various experiments have led to remarkable improvements in cognitive ability in mice tested in Barnes mazes — significantly better improvements than seen with young plasma alone, as the figure shows. These therapeutics suggest various plasma fraction treatments may become available “in the next few years” according to Braithwaite in response to my question on the likely timing of these therapeutics.

Mark Bamberger, Chief Science Officer at Stealth Biotherapeutics, talked about the role of elamipretide, a novel and first-in-class therapeutic, in improving mitochrondrial function and thus energy production and cellular function more generally.

Morgan Levine, a professor with the Yale School of Medicine, presented on her team’s work creating an improved version of the epigenetic clock developed independently by Steve Horvath and Gregory Hannum. She was a postdoc with Dr. Horvath so she knows his work well. She claims her clock is more predictive of biological age than either the Horvath (version 2) or Hannum clocks.

Joan Mannick, Chief Medical Officer of ResTORbio, gave a great talk about their latest research on TORC1 inhibitors, based on rapalogs and a proprietary drug called RTB101. They found that. A combination of rapalogs everolimus and sirolimus with RTB101, led to a remarkable 42% reduction in respiratory tract infections in the elderly (RTIs).

Kelsey Moody, CEO of Ichor Therapeutics, gave an impressive talk about a number of efforts that Ichor is working on. Ichor is a holding company with various daughter company spinoffs. Ichor creates, funds and spins off companies focused on specific aspects of aging and health. Moody also gave a half-day workshop on the first day of the conference on how to develop a pre-clinical drug pipeline for anti-aging therapies.

Lorna Harries, professor at University of Exeter, discussed her lab’s research on resveratrol and resveralogs in relation to gene splicing and dysregulation. One result that caught my attention was a remarkable increase in telomere length in their lab mice treated with a resveralog: 1.3–2.4 times “vehicle-only controls” as described in LaTorre, et al. 2017. There has been significant research in trying to induce telomere lengthening in lab animals and humans in the last few decades and results this large seem to indicate real promise for human therapeutics, though it is as usual impossible to say whether murine model results will translate well to humans.

There was also a “speed networking” session with five-minute get to know you sessions at each table, with forced rotations, which seemed silly at first but was actually pretty effective.

The organizers also included a “mastermind” group discussion session on the second day where groups of 10 or so people discussed a number of big picture questions, took notes, and provided them to the organizers for collation and summary. Again, this might have seemed awkward but was in fact quite effective at spurring productive discussion.

The first iteration of this conference was considered a success so it seems likely we’ll see further iterations in the coming years.