All Too Short Comments on the 10th Aging Research and Drug Discovery (ARDD) Meeting

I attended the 10th Aging Research and Drug Discovery (ARDD) conference in Copenhagen recently, alongside my Chief Scientific Officer at Repair Biotechnologies, Mourad Topors. If one wanted to take in all of the presentations and take notes, as I've done in the past, ARDD would be much more of a test of endurance than other longevity industry conferences. It is five 12 hour days, starting with networking at 8am, the last presentations going on past 8pm, and then socializing at nearby bars afterwards for the truly dedicated. This on top of jet lag for those coming in from the US in direction and Asia in the other. The intent of the organizers is for participants, and those following the livestream, to drop in for the topics that interest them, and take the time for other activities in between.

The mix of attendees was, as always, some combination of academics, the founders of biotech startups, visitors from Big Pharma, and investors, those being a mix of interested individuals and venture capitalists. Judging from discussions held in the corridors, the present view of the investment market for biotech startups is that while some people are raising funds with apparent ease, it is still not a great environment. Better than the start of the year, but not great. There were fewer institutional investors at ARDD than in past years, and the consensus appears to be to expect fiscal gloom until later in 2024. Expenditures are cut, timelines extended, and bridge rounds are raised, business as usual for lean times.

The Big Pharma interest in the conference varied from "to be honest, my boss told me an hour ago to come in and represent the company, I'm really not familiar with this," to department heads with interesting experience and well-considered positions on the field. As some of you may know, one of my areas of interest is the path to better gene therapies, and I had a lengthy conversation with the director of a gene therapy program in which our views aligned on many of the details. Viral vectors are going to be amazing in 2050, but are very much not amazing now; there would be a mass exodus from the development of mRNA therapies if only someone could find a way to deliver plasmids to the nucleus; the development of tissue-targeted delivery systems seems on the verge of becoming impressive, but still has a long way to go if your targets are small areas of the body; and so forth.

This year, I confess, I attended only a fraction of the many presentations in the program. Most of my time was taken up with networking. For those who didn't attend, I recommend looking through the program and waiting for the videos to be posted. There were some interesting talks. The role and details of cellular senescence in aging was a frequent topic. Both the academic and industry communities are rapidly digging in to the biochemistry of senescence, with new discoveries emerging and the debates shifting on a regular basis. The Deciduous Therapeutics program is becoming one of the most interesting in the industry, given that their approach to rousing the immune system to destroy senescent cells lasts for a considerable time following a single dose. At the same time, they are far enough along in their work that the supply of new details shared in public is drying up, as often happens.

We at Repair Biotechnologies shared that our LNP-mRNA therapy can rapidly reverse both atherosclerosis and nonalcoholic steatohepatitis (NASH) in animal models. We plan to submit our first pre-IND package later in the year. Maxwell Biosciences is making an appearance at most conferences these days as they ramp up their program; they produce a small molecule mimetic of the LL-37 antimicrobial peptide, a sort of too-good-to-be-true part of the innate immune system that improves just about every process the immune system touches when upregulated. It attacks bacteria, viruses, cancers, and even appears to improve aspects of tissue maintenance. Their program is focused on delivery as needed. It did occur to me that one could learn from the Minicircle approach to follistatin upregulation and use some form of long-lasting vector to turn a small volume of subcutaneous fat cells into a factory for LL-37, permanently upregulating it and its effects on immune defenses, but apparently this doesn't have the desired effect - hence the need for a mimetic rather than the original peptide.

Other fellow travelers on the conference circuit showing off their progress included some of the growing number of reprogramming ventures: Retro Biosciences, rapidly expanding their research footprint and likely to become a behemoth in the industry the next time they go out to seek investment; Life Biosciences, about which much the same might be said; the actual behemoth of Altos Labs; and smaller ventures such as Turn Bio. Epigenetic reprogramming to reset the biochemistry of aged cells is, as one might expect, another frequent topic at conferences these days. Arguably the majority of funding for research and development in the field of longevity is currently focused on forms of partial reprogramming, which at least offers the hope that a decade from now we'll have answers to all of the most important questions about this approach.

We do live in a barnstorming age for biotechnology, and so very much more can be accomplished than regulators would approve for widespread use. There are a lot of high-flying technical discussions going on behind the scenes. Anything that starts with "why can't we just..." usually ends with "well, we could, but it would be very hard to obtain approval." Passing through the regulatory process is, meanwhile, so very expensive than only the most conservative, safe, incremental programs have an easy road to finding the necessary funding. Biotech investors are, if anything, even more conservative than the regulators, very ready to anticipate difficulties and avoid investing in those programs.

To conclude, if you'd like a crash course on the state of the scientific field and the industry focused on treating aging as a medical condition, attending ARDD is one of the better options on the table.

Comments

Thank you so much for your review of the aging conference! I have a question: did this conference bring up ways to treat aging by cleaning up intercellular matter? I heard that this is quite a promising area.
As I understand, after the end of the organism's growth, long-aging factors accumulate in the intercellular substance. These factors are not removed by the immune system in time, which leads to clogging of the intercellular space. The cells try to destroy these factors themselves by lysis, but they fail. This leads to chronic inflammation. And because of the blockage of the intercellular space, the immune cells cannot destroy the cancerous foci, which leads to the development of cancer. The accumulation of such factors in the brain does not occur because of the constant cyclical cleansing of brain tissue during sleep. This explains the strong difference in espression of brain tissues and tissues in other organs (PMC7906136). Plus, such factors affect the elasticity of blood vessels and interfere with intercellular communication. It seems to me that this direction is quite promising for gerontological research.
English is not my native language, so I apologise for any mistakes с:

Posted by: Mikhail Ivanov at September 12th, 2023 12:20 AM

Mikhail, Just a reader of this blog but don't know much about what you asked about. Do you think plasma dilution through plasma donation would remove some of the bad stuff you are talking about or does it not end up in the blood circulation?

Posted by: Mike Best at September 12th, 2023 8:50 AM

Thanks for your question, Mike Best.
Collagen and elastin are examples of "Long-lived proteins" from the matrix that affect cell metabolism. During the aging process, these proteins undergo various chemical transformations, such as glycation, resulting in cross-linking, adduct formation, etc.
I have heard that diluting blood plasma with a mixture of saline and albuin can reduce the percentage of negative blood factors affecting aging (PMC7288913). But it seems to me that diluting blood plasma will not help to flush out glycated elastin or other long-aging matrix factors due to covalent cross-linking and tight packing.

Posted by: Mikhail Ivanov at September 13th, 2023 12:53 AM
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