ALS, also known as Lou Gehrig’s disease is a neurodegeneration disorder similar to MS, but with no known treatment. ALS Therapy Development Institute, is the first non-profit biotech seeking to find a treatment and potentially increase the quality of life for individuals living with this illness.
Founded in 1999 and based in Cambridge, Mass, ALS TDI is on the fast track to finding a successful drug that works. OneMedRadio had the pleasure of sitting down with CEO and CSO, Dr. Steve Perrin to discuss this debilitating disease and why its important to move quickly in discovering a treatment.
Strategically, the organization has done a good job in moving drugs through clinical trials but lacks venture capital funding. But the benefit investors stand to gain is a major stakehold in the drug with a low investment. Quite an opportunity.
To hear the full audio interview with Dr. Perrin, please click below and see a full transcript to follow.
Brett Johnson: Hi, this is Brett Johnson in New York City with OneMed Radio. Today, we are with Dr. Steve Perrin who is the CEO of the ALS Therapy Development Institute, a Cambridge, Massachusetts-based organization focusing on finding a cure for ALS. Thanks for joining us today, Steve.
Dr. Steve Perrin: Thank you much. Appreciate your time.
BJ: So can you go ahead and tell us first, what is ALS?
SP: Sure. ALS or amyotrophic lateral sclerosis, it’s also often called Lou Gehrig’s disease is a really devastating disease. It’s a progressive neurodegeneration of the motor neurons in the spinal cord that basically innervate all of the muscles in your body and when those nerves die, you basically progress up, we become more and more paralyzed. Usually, the disease appears somewhere in the fourth or fifth decade of life. There is no susceptibility difference between males and females so you’re as likely to get it if you’re a woman or a man. The incidence is increasing in younger folks. We have seen in the last decade or so people in their 18s, 20-year-olds getting this disease, which is also quite devastating.
There is no effective treatment at this point in time for the disease and within three to five years after your first signs or symptoms, they usually end up succumbing to the disease unfortunately. So it’s very, very devastating on the patient, families, and caregivers. It’s a huge and significant unmet need, you know, in the medical organizations in the US as well as around the world. It is sort of an orphan disease. There’s only about 30,000 people in the country with a formal diagnosis at any given time.
BJ: Interesting. So what has been the development of treatments in the past? I mean what’s the current status of what’s out there?
SP: So if you would ask the researcher in pharma or biotech 25 years ago how you were going to develop a drug to slow down or cure ALS, the focus really would have been on saving the motor neurons up in the spinal cord that I mentioned are dying during the disease. But we now know that that philosophy was pretty naïve and it was mainly because we just didn’t understand that much about the disease. The thing that’s really exciting that’s happened in the last decade for ALS patients and opportunities for drug development is we now understand that other cell types within the spinal cord are also players in the disease and we also know that there is some tissues such as skeletal muscle and peripheral nerves outside the central nervous system that are also affected by the disease, and that opens up new opportunities to develop drugs to slow down and stop those processes.
So we’re starting to see some better drugs moving towards the clinic because we understand the disease much better than we did even a decade ago, which is exciting for patients and, you know, pharmaceutical companies and biotechs that are working in this field.
BJ: So what role do you guys play in sort of the ecosystem or the development process of new drugs and treatments?
SP: Sure. So we are the only nonprofit biotech in the country actually, which is a very unique business model. So we are a true 5013c nonprofit, but we behave much more like a traditional biotech organization. So we were founded in 1999 so we’re not a fly-by-night organization. Our mission has never changed. Our goal is to facilitate the development of effective treatments for ALS patients and we’ve become the world leader in preclinical drug development for ALS. What I mean by that is we have several mouse models for the disease. We have 26,000 square feet of lab space here in Cambridge. We run more drugs in the animal models of ALS than the entire academic community combined. We’ve run about 200 drugs in the models since I’ve joined the company in 2006. We have two drugs now moving into phase 2 clinical trial so as a proof of concept for the rigor of our preclinical work, we’ve been quite successful and we will not stop until we have a host of successful drug candidates moving towards the clinic for patients.
So we have 32 full-time scientists in Cambridge. All of us have been trained and have experience in drug development in biotech or pharma so we have a lot of skin in the game and again, our passion and our drive is to really serve our constituents, which is our patient community.
So, you know, in order to achieve our goal, we’ve utilized both our nonprofit and for-profit strategies and capabilities. So as a nonprofit we can approach biotechs and pharmaceutical companies and ask to end license their drugs and test them in our animal model and again we don’t want a lot of return on investment because we’re a nonprofit. They can own most of it, but if we see positive data, our mandate is to make sure that the contracts are drawn up so that they will help us push it towards the clinic and towards our patient community.
We leverage our nonprofit status in other ways such as getting fee-for-service work. We’re only a 32-person company but we have the ability for instance to make protein biologics. We’ll make these stable cell lines here but obviously don’t have the manufacturing capability but we have a deal with Lanza and BioEXCEL to make our protein biologics in large scale once we make seed cultures and stable clones. They may do it at cost and take a tax write-off for the rest of it because we’re a 5013c. So we leverage our nonprofit status to really build our resources and build a community.
As a biotech, we have 32 scientists that are really skilled at the processes of sophisticated drug development from pharma. So we do full blown pharmacokinetics, pharmacodynamics, survival and efficacy studies. We do biomarker of drug efficacy in vivo to help facilitate clinical development. So we really understand the process of drug development as folks that have been trained in the biotech and pharma world.
BJ: So what kinds of organizations could really benefit from what you do? I guess private investors or venture capital funds or large pharma? I mean who can really capitalize on this that may not be capitalizing on it today?
SP: Yes. So that’s the key point of the folks that might not be capitalizing today. You know, strategically, we’ve done a pretty good job as we get compounds through preclinical and show proof of concept in animal models. We’ve done a pretty good job of trying to bridge that gap and getting it towards pharma hence we have two phase 2 trials that we’re initiating this year.
But where we haven’t done a great job and I think that folks either because they don’t understand our business model yet or we haven’t figured how to work with them is we don’t have angel funding yet, we don’t have any venture capital funding yet and I think that that’s a huge opportunity for those types of stakeholders as well as for us to invest in these early stage programs, but to really change the paradigm of the business model if you will because we’re not looking for tens of millions of dollars of investment there.
It typically costs us somewhere between $1M to $3M to go from a target that we think is exciting to developing a compound to hit that target making sure that that drug has functional activity in cell lines, doing pharmacokinetics in mice to look at biodistribution and understand dosing and half of the drug, executing very highly powered survival studies to see if the drug slows disease. That process takes us about 18 months to two years and costs again $1M to $3M. If somebody wanted to come in and invest in a piece of a program like that, we would give them a major stake hold of ownership in it. Again, it’s high risk because it’s very early on, but that’s not a lot of money to own 30% to 50% of a drug moving forward.
To own a drug in the ALS space is a huge business opportunity. It’s a billion-dollar market space for a disease-modifying drug and it’s a low hurdle through the FDA because there is no effective treatment. So it is high risk. It’s a low investment if you ask me and the upside if you get a compound that actually works is instantaneously a blockbuster disease indication. So there’s quite an opportunity. We run about 30 drugs per year through our pipeline so we have quite a robust capability that’s completely funded at this point by ALSTDI and a grassroots fundraising endeavor so —
BJ: How many drugs could you – I mean I guess can you minimize your risk by leveraging it across a broader spectrum or broader number of compounds that you’re going to pursue? How many could you develop? I mean how many could you test out? How many ideas are there that could be developed?
SP: So one of the things that we did when I first joined the organization back in ’07 is we did a lot of molecular profiling of three or four animal models of the disease as well as about 4000 ALS, human ALS biopsy samples. We identified about 150 druggable pathways that are going wrong during the disease in various tissues. Some of the pathways are going wrong in peripheral nerves, some of them are going wrong in skeletal muscle where the innervation happens, some of them are going wrong up in the spinal cord, some of them are immune targets that are upregulated in the spleen or in lymph nodes for instance. So out of each one of those pathways, there’s anywhere between 10 and 40 druggable targets.
So we start doing the math, you know, we’ve got a couple of thousand druggable targets that we’re systematically working our way through. Some of them obviously don’t pan out and they’re not promising and some of them are actually quite exciting, but drug development is always challenging. Even sometimes when you have a drug that hits a target and it works in cell based assays, when you start trying to put in mice it has toxicity and you have to go back in the drawing board and do some chemistry on that particular compound to make it suitable for chronic dosing. Those are the types of things that it’s this two steps forwards, two steps back process that you can’t always foresee.
But as far as capacity, I mean right now again we run about 30 compounds a year through the process. If we have the resources, we could probably double that number. Drug development is resource intensive and we are right now limited by our financial ability to screen more compounds than about 30 per year on our current budget.
BJ: Uh-hum. And what are the odds that from the 30 in a year that you can come across one that could end up getting to the market?
SP: Well our shots on goal are getting more and more accurate I might argue. You know, again as I said earlier in the conversation, ten years ago I would argue from a drug development perspective we were throwing darts at a dartboard with a blindfold on. We just didn’t understand the disease well enough. As I said in the last couple of years, we’ve now had two compounds out of about 150 that we’ve screened that are now – you know, they’ve both demonstrated the ability to slow down disease progression and improve survival in the animal model. We optimize dosing in the animal model. We identify biomarkers of drug response that are amenable to translation to the clinic so that can help with phase 2 clinical trial design and early prediction if the drug is working in people. So that was two compounds in the last three years so if we run about 30 a year it was 2 out of 90. It’s not a terrible hit rate in drug development.
So and again I think as we’re learning more about the disease, those odds are going to improve. It is still high risk; I’m not going to kid you. If 1 out of 30 per year starts to show promise and within 18 months after that we can get it moving towards proof of concept in man, I consider that to be an incredible success rate.
BJ: And the reward could be substantial, you know, if one of these gets all the way through. I mean what’s the return?
SP: The return is unbelievable. I mean again you can charge premium price point for a devastating disease like this. I mean you look at new drugs entering these types of markets either in the enzyme replacement field such as the Genzyme model, those were therapies that are disease modifying that are getting premium prices at $200,000 a year per patient. Even new drugs entering the MS space such as Gilenya from Novartis, the price point for that drug is $55,000 a year for a patient.
So, you know, if you look at the incidence rate of ALS compared to multiple sclerosis, it’s identical. There’s about 5000 new MS patients diagnosed per year. There’s about 5000 new ALS patients diagnosed per year. There’s about 600,000 people walking around with multiple sclerosis and there’s only about 30,000 people with ALS, but that’s because MS now has seven disease modifying drugs that are FDA approved that patients can take and it slows down their disease and it improves their quality of life. If we had seven drugs in the ALS space, you’d go from 30,000 patients to 300,000 or 400,000 patients really quickly. In the MS space in the US is a $12B a year field for people that have invested in it. So the upside is huge. The first disease modifying drug could instantaneously become a billion-dollar product.
BJ: Wow. So it sounds like there’s some considerable upside. So what would be a next step if an investor is interested in this? How do they proceed with your group?
SP: I think the best thing for an investor to do is to come up and learn about who we are. Come and visit our lab and sit down, we’ll walk you through our business model, walk you through what a nonprofit biotech research institute is, what our goals are, how we collaborate and work with other groups. Again, we have collaborations with six or seven small biotechs where they couldn’t afford to run their compounds in ALS but we thought that their compounds were interesting because they hit interesting targets. We’re running those compounds for free right now and we own half of those drugs if they worked going forward. They should come up and get a flavor of how we do business and how our drug development process works and how quickly we move.
We move much more quickly in our projects than traditional biotech and pharma does and that’s because our mission is driven by a very different paradigm. We don’t have a commercial organization that dictates what we should be working on and what we shouldn’t, our science team does that. So we make much quicker go, no go decisions on programs than what most folks are used to seeing and I think that’s a great first step. Come up and visit TDI, sit down with us, we’ll talk about our business model, we’ll talk about our project portfolio where things are in the value chain and how resources could help drive projects forward quicker.
BJ: So, Steve, could you take a minute and tell us a little bit about your background and how you get involved with ALS?
SP: Sure. I very early on in my career decided that academia wasn’t for me so shortly after becoming an assistant professor at BU medical school, I jumped into biotech because I really saw early on that I wanted to make a difference in patients and I really wanted to work on drug development. So I joined a very small biotech in Cambridge. I was there for quite a few years setting up a molecular profiling team. I moved on to what is now Sanofi Aventis, but at the time was Hoechst Marion Roussel and lived through several mergers with Hoechst Marion Roussel with other groups into Aventis, which later became Sanofi Aventis. I was director of molecular profiling there for about seven or eight years. I set up a high throughput sequencing core. I set up a high throughput gene expression profiling platform. I worked with a bioinformatics team on microarray development and other types of technologies for pretty much the entire Aventis organization.
After Aventis I moved to Biogen Idec. I had a very similar role there. I was director of biomarker development there for all of their preclinical and clinical programs and at one point in time, the organization wanted to expand its capabilities or commercial interests in other neurodegenerative diseases and ALS was on the radar screen. They made me head of the ALS program because the first goal was to identify druggable targets and that’s basically a molecular profiling exercise. So I ran Biogen’s ALS program for about four years or so which is how I got to know the people here at ALSTDI. Biogen’s headquarters is right down the street. We kept bumping into each other at meetings and when they were looking for a chief scientific officer, they really asked me to join and try to make an impact on their ability to more successfully move drugs through the process. So I joined TDI back in 2006 and I haven’t looked back. It’s been quite a rewarding experience.
BJ: Well it sounds terrific and I know you’ve been making some huge progress there developing the organization so. Thanks so much for joining us today.
SP: I really appreciate your time. Thank you.
BJ: That is Dr. Steve Perrin who is the CEO of ALS Therapy Development Institute, a Cambridge, Massachusetts nonprofit focusing on finding a cure for ALS. This is Brett Johnson in New York with OneMed Radio. Have a great day.