Current therapies targeting multiple sclerosis (MS) primarily target the symptoms of the disease but do not repair neurological damage caused by the condition. This is something that Chris Loose, PhD, CEO and co-founder of Progentos Therapeutics, and his colleagues are hoping to remedy.
MS is a chronic, immune-mediated condition that results in the demyelination of neurons in the central nervous system. Some people have a relapsing-remitting version of the condition and others have a gradual progression of neurological symptoms with increasing disability over time.
Although many treatments, like anti-CD20 monoclonal antibodies, sphingosine-1-phosphate receptor modulators, and Bruton’s tyrosine kinase inhibitors, are available for treatment of MS, they almost exclusively target abnormal immune activity and do not repair tissue damage caused by the condition.
Progentos Therapeutics was founded last year by Loose and colleagues and is aiming to develop small molecule, oral drugs that can stimulate the regeneration of myelin in people with MS. Loose spoke with Inside Precision Medicine senior editor Helen Albert about his career, about building Progentos in a challenging time for the industry, and what he hopes to achieve going forward.
Q: What inspired you to become a scientist?
Loose: For as long as I can remember, I’ve been interested in helping to develop new medicines. I thought about whether I should be a doctor, or an engineer who can have a broader impact rather than seeing one patient at a time. Could I help create something that could help a great number of people? That’s been inspiring me for the last 20 years.
Q: What made you decide to move into the biotech industry?
Loose: After college, I had the chance to work in Merck’s research labs and loved the mission and being around smart people doing important work. I had the realization that to have a real impact, getting into a smaller environment like a startup would be a way to really maximize what I could contribute. And so, I came up to MIT with the goal of working with Bob [Robert] Langer, who became my PhD advisor. He has been so successful entrepreneurially, and I had the opportunity to just immerse myself in that culture. I was able to do two startups with Bob, and Progentos is now a spin-off of the last startup.
Q: Did attending MIT help you to become an entrepreneur?
Loose: I think it’s why I wanted to go there. From the middle of my graduate work, it was clear there could be a startup opportunity arising from my project. Immediately, I could find people from all different backgrounds, from finance and business, to marketing, to biology and chemistry. They all came together very quickly to join me and to try to move ahead with our idea.
We had success winning the business planning competition at MIT to get our start. It was fun and a good validator. It turned into a device company making safer vascular catheters called Semprus BioSciences that got two FDA approvals and also got to an acquisition.
That’s how I got started, but my heart had always been in making new medicines. That’s where I wanted to go, and so that’s where I started to pivot to.
Q: The second startup you founded was called Frequency Therapeutics, how was that experience for you?
Loose: It was working in drug development, so a very different world. We were focused on hearing restoration, which is a big unmet need, and we were able to carry a new approach into the clinic that looked very promising early on. Ultimately, while that didn’t pan out, we made a discovery relating to multiple sclerosis that was very encouraging.
While Frequency didn’t continue, we were able to spin that out into Progentos, where we think we’re working on what could be the first restorative therapy for multiple sclerosis, as well as a broader vision for regeneration in the body.
Q: This is your first CEO role, how has that been for you so far? Has it been a big change or was it the next logical step?
Loose: These startups are all teamwork. From the earliest days of my first startup, it’s all about a small group of people figuring out how to raise the money, how to set the strategy, how to recruit the right people. So, I think there’s been a lot of continuity in that regard. Obviously, I have a different set of responsibilities now, but I think I have been moving in that direction for a while.
It helps that I have a great co-founder in Sanjay Magavi, PhD, our CSO, who is an excellent scientist, and also just a great business partner as well.
Q: How did treatments for hearing restoration turn into a possible treatment for MS?
Loose: The science is actually quite distinct between the two. I think the connection was that we were looking for ways to achieve cellular regeneration inside the body. How do you trigger the body to restore a tissue? The reason we started working on multiple sclerosis is because inside the brain about 5% of the cells are oligodendrocyte precursor cells, or OPCs. They’re the regenerative cells that are there to repair damage. When someone has MS, what that is, is the body’s immune system attacking the myelin covering their nerves. You get degeneration, but the system can repair that. The problem is that in the state of disease, it doesn’t keep up with the damage.
We discovered distinct targets that could very effectively turn on this regenerative system. We’re really pushing a system that’s designed to be active, and really has been proven to be active, because when you look at MS, that system is why you have relapses, where patients get worse, but then go into remission—they get better as repair happens. We know that happens naturally, but we want to essentially turbo charge that system.
Q: Why is it important to have new therapies for MS?
Loose: There’s around 20 drugs for MS that all slow the body’s attack on the myelin. They slow down the immune attack, but nothing rebuilds the structure that’s been lost, and that is the enormous unmet need.
If you look at the best drugs that are out there, they slow down progression, and they very much reduce the relapses that happen. But none of them make you better. They don’t restore any function. And when you talk to patients and clinicians, that is absolutely clear, their number one need is restoration of neurological function that is impacted by the disease.
Q: I know the company is at a fairly early stage, but what are your future goals?
Loose: We discovered a new target that, to our knowledge, no one else is working on, that is giving some really profound preclinical efficacy. If you look at the history of remyelination, there have been attempts in the past that people have taken to clinic, and they have seen some signals of efficacy.
Our view was that we needed a much more effective target, and that’s what we have found. I think what sparked the interest of Progentos investors was the striking improvements in the degree of remyelination. We’re thinking with this much more effective target; we can make it clinically meaningful for patients.
The enormous goal is getting to human proof of concept. I think with the level of efficacy we’ve seen preclinically, our goal is to make sure we have the best candidate that we can to move into patients to demonstrate safety and get to that human proof of concept. Of course, we’ll be building backups, as you’d expect, but it’s really about getting to that big end point. We don’t have a specific timeline yet, but we’re working very swiftly, and I think we have a lot of good candidates to move ahead into clinical trials.
Q: Is anyone else doing anything similar to Progentos?
Loose: There are competitors in the space, one of which is in the clinic called Contineum Therapeutics. There are others who are pursuing some different pathways. We’ve been very excited by the preclinical data we’ve been able to produce head-to-head with the other pathways that are really being pursued. We think we have a really distinct approach with robust efficacy, and we’re excited to get into the clinic.
Q: How has the fundraising environment been for you since founding Progentos?
Loose: We were able to raise a $65 million Series A last year from some wonderful investors. That gives us support all the way through to human proof of concept, which is an enormous milestone for patients, as well as for the company. We’re very focused on driving to that.
It has been a very tough fundraising environment. I think people are looking for big advances right now. This would be a new category of medicine. It’d be the first restorative in MS. That’d be a big deal. I think investors are looking for big ideas that could have a large patient impact, a lot of value creation, and proven teams.
Q: Are you interacting with any MS patient groups?
Loose: Absolutely. We spend a lot of time, through the major conferences, working with both the key opinion leaders and patient spokespeople. It’s been striking that if you do surveys amongst patients the number one thing on their list is restoration of function. It’s what everyone wants.
The existing drugs have got about as good as immune modulators can get. They slow down attacks and progression, but patients still decline over time. Everyone wants to gain function back. By the time you’ve been diagnosed, you’ve likely already had some loss of function and people really want to get better.
Q: What have you been your biggest learning experiences since you’ve taken over this role?
Loose: I think it’s an interesting environment we’re operating within, notably in the current funding climate. I think figuring out ways to be very efficient and scrappy and creative is at a premium right now. We’ve been operating with a very lean team, while engaging the right experts to help us make efficient progress and stay very nimble.
I think that’s been a transition that a lot of companies are going through. It’s also a lot of just staying very focused and driven.
I think there are times when big platform stories are exciting, and there are times when a specific product story that you have just got to execute on is attractive. We’ve just had to be very disciplined and push very hard to get to where we want to be.
Q: What advice would you give young biotech founders trying to succeed in the industry right now?
Loose: Having really good advisors and supporters around you who’ve been successful and seen a lot of ups and downs solves a lot of problems. For example, we had the good fortune of recruiting Andrew Miller, the founder of Karuna Therapeutics, to chair our board. He founded that company and helped it progress all the way for 14 years through FDA approval and the acquisition by BMS. He has a ton of CNS drug development experience.
I think finding people like that in your environment who’ve been down the road you’re trying to go down and can give you real advice is super helpful, and it’s great to have such an experienced operator on the board. It is a big resource, both for me as well as the venture capitalists around the table.
Finding people who you can trust and have known for many years is also key. One of the advisors I continue to talk to most days was my advisor during the MIT business plan competition, starting in 2005. Having decades of history with someone where you can float new ideas, and they can push you and can give you super direct feedback are really important things to have around you. I encourage young entrepreneurs to keep assembling great people who will give them direct feedback and help them look around corners.
It’s also about focusing on fundamentals. Really strong science is still getting funded in the venture community. Make sure you have really good conviction in the targets you’re going after. They’re going to have a big impact for patients and investors. If you can articulate that, and you have a clear, differentiated approach, those deals are still getting done.
Q: Is there anything that you would do differently if you had to go back to the beginning?
Loose: I feel very fortunate about where we are. We’ve got great backers; we’ve got a great team. We’re working on a big problem that I think can have a real impact for patients. Science always adds ups and downs, but I think we’re in a great spot and I’m really excited to move ahead.
Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.
