New COO Michael Ringel says company is confident as it prepares for clinical studies in glaucoma and NAION later this year.
Back in 2020, a seminal paper in Nature showed that treatment with a partial epigenetic reprogramming restored vision in blind mice. Since then, the world has waited with bated breath for a human trial of the technology. And waited. And waited.
Now, nearly five years later, with billions invested in multiple companies seeking to harness the technology’s potential, it seems that the world is finally going to get what it wants. Life Biosciences, the company co-founded by the Harvard study’s lead author Dr David Sinclair, is gearing up to launch the first ever partial epigenetic reprogramming candidate into the clinic this year.
Longevity.Technology: As Life Bio readies for what will be one of the most eagerly anticipated clinical trials in years, it has appointed long-term advisor Dr Michael Ringel as its Chief Operating Officer. The timing makes sense – the former head of research and product development at Boston Consulting Group has spent decades advising biotech and pharmaceutical companies on their R&D strategy – and his strategic acumen, operational expertise, and industry insight will be invaluable as Life Bio moves into its clinical phase. We sat down with Ringel to learn more about the road ahead.
Expressing his excitement about “rolling up his sleeves” and getting stuck into the operational execution of Life Bio’s business, Ringel says that he felt the time was right to join the company due to a combination of both the long term and the short term potential.
“We are really at an exciting cusp, where enough evidence has accumulated on the long term potential of what can be done with rejuvenation,” he explains. “But, in the near term, we’ve got to make that real with therapeutics that address age related diseases for individuals. Of course, making that happen requires a lot of operational, technical know-how, and so I wanted to be able to contribute to that at this really critical point.”
Life Biosciences’ David Sinclair and Michael Ringel.
Primate studies drive optimism
In addition to the earlier mouse studies, Ringel cites the “incredible results” subsequently seen in studies in nonhuman primates as another key driver behind his appointment.
“We’re very close to getting into the clinic now, with real therapeutics that have the potential to benefit patients,” he says. “And if we’re successful, we’ll be the first partial epigenetic reprogramming agent on the market, so it’s a very exciting time.”
Assuming everything goes to plan, Ringel expects that Life Bio will enter clinical trials within a year with its ER-100 therapy, which leverages the expression of three transcription factors, Oct-4, Sox-2, and Klf-4 (OSK) to induce partial epigenetic reprogramming. The company plans to run trials for not one, but two ophthalmic indications: glaucoma, which affects millions worldwide, and non-arteritic anterior ischemic optic neuropathy (NAION), a rare disorder similar to a stroke of the eye that is characterized by painless yet sudden loss of vision.
“There are some good treatments for glaucoma, but unfortunately pretty much all of them eventually fail and the disease continues to progress, so there’s a need for a second line therapy,” says Ringel. “Although NAION is rare, there is an expectation the incidence is going to grow because it is an identified adverse event of GLP-1 therapy. And there’s currently no treatment at all for this disease, not even an off-label treatment, so there is a huge unmet need.”
According to Ringel, Life Bio has “good data” from its nonhuman primate studies, which gives the company confidence that it should be able to address both conditions in humans.
“Of course, primates are not people,” he cautions. “They’re a better translational model than mice, and a primate eye is quite similar to human eye, but you never know. There are no guarantees when it comes to drug development, but I’ve seen a lot of companies on the consulting side, and when I looked at Life Bio’s data package, it was as good as you could possibly get at this stage. We’ll learn more as we go into clinic, but I have a lot of confidence that our odds are very good.”
Trial safety will be key
As this will be the first time that an epigenetic reprogramming therapy has been tested in humans, there is no established protocol for clinical trials, and Ringel explains that Life Bio’s Phase 1 trials will be a little different.
“A typical Phase 1 trial is conducted in healthy people and powered to provide safety data, but our trials are going to be in patients,” he says. “We will still be looking primarily at safety – monitoring for adverse events and any of the concerns that people have around partial epigenetic reprogramming. But, because we’re in patients, we will also get some anecdotal data of efficacy, which it will be useful for us in our own decision making around Phase 2 and forward.”
On the safety point, Ringel says the company has been encouraged by the data seen in its preclinical studies.
“One of the concerns about partial epigenetic reprogramming is, are you going to see transformation events where you either get cells that essentially go all the way back to pluripotency, which could result in the formation of tumors,” he says. “We have dosed mice continuously over most of their lifespan, and seen no pluripotency and no tumorigenicity.”
Staying on safety Ringel says another key point about the ER-100 therapy is that it’s a “fully inducible” system.
“We deliver it via gene therapy, but it only turns on when you’re exposed to doxycycline, so you can turn it on for a period of time and then turn it off,” he explains. “That’s how we plan to use it therapeutically. This will be a short dosing in humans, so much less exposure than a mouse when given treatment for their entire life. And of course, one of the things we’ll figure out in Phase 2 is, what’s the titration of that – how long is the right amount to get a therapeutic benefit?”
Addressing the delivery challenge
While Life Bio’s initial focus is clearly on the eye, Ringel says, without being specific, that the company has “lots of other downstream indications” in its sights.
“We are definitely not just an ophthalmology company – partial epigenetic reprogramming seems to work throughout the body,” he says. “There are some organs that are easier to deliver to than others, and that’s part of the reason why we started with the eye, but there are other indications beyond the eye that we are pursuing. There are other organs that are also easy to deliver to.”
Delivery is a hot topic in the world of epigenetic reprogramming, and Life Bio and many others are engaged in exploring how to deliver therapies to specific organs and more systemically.
“We have some ongoing work around lipid nanoparticle technology, made famous by the COVID vaccines, which is able to deliver quite broadly, and that is a potential path forward,” says Ringel. “And there are other options, such as small molecule activators of reprogramming, where you don’t have to deliver the transcription factors, but you actually deliver small molecules that activate the transcription factors. We have some work going on there too, but we’re trying to stay focused on the trial, while not neglecting the longer term things that we know are eventually going to be important.”
“We’ve got quite a lot of data now around how that can affect multiple organ systems in multiple disease animal models, including nonhuman primates. So we have a lot of confidence that we have a good technology that’s going to allow us to reach a lot of diseases.”