Courtney Young, CEO of MyoGene Bio
An in-depth interview with Courtney Young, PhD, on how she is developing her PhD research on muscle diseases into cutting-edge therapeutics as the co-founder and CEO of MyoGene Bio.
About Founding Bio: It is becoming increasingly common for academic trainees in the life sciences, both graduate students and postdocs, to found and lead companies based on their academic research, a movement termed founder-led bio. The idea of starting a company when your whole career has been in academia can be overwhelming. I want this Substack to be a resource for aspiring founders to read about the experiences of people who have been in their shoes.
“When the patent was submitted, was when I first started thinking about a startup … I was always interested in entrepreneurship, but I hadn’t thought I would become a founder right after my PhD.”
-Courtney Young, PhD, Co-founder and CEO of MyoGene Bio
Dr. Courtney Young, PhD is the CEO and co-founder of MyoGene Bio, a biotech startup developing CRISPR-based therapies for Duchenne Muscular Dystrophy. Duchenne is a devastating genetic disease with no cure. After a family member was diagnosed with Duchenne, Courtney became passionate about researching the disease and focused her PhD research at UC Los Angeles around a gene editing approach for Duchenne. Based on that research, Courtney and her two PhD advisors founded MyoGene to develop their early-stage academic research into what they hope will be one of the first uses of CRISPR for Duchenne. Courtney and I discuss how her academic grant writing skill has been key to funding MyoGene, why she moved MyoGene from Los Angeles to San Diego, and why she believes a gene editing approach is the most promising strategy for treating Duchenne.
1) Hi Courtney! Can you tell me a little about yourself and your journey to becoming a founder?
I'm Courtney Young, one of the co-founders and the CEO of MyoGene Bio. I got into science when I was in high school. I'd always been interested in math, engineering, and science and in high school realized I really liked biology. This was much to my parents' surprise since their background is in physics and engineering, but I was really interested in biology. When I was a senior in high school, my cousin was diagnosed with Duchenne muscular dystrophy. This was a disease our family had never heard of before and there was no family history. In his case, it was caused by a sporadic mutation, which actually happens in ~⅓ of Duchenne patients. We Googled it and learned it was a really devastating disorder. At the time, there were no effective treatments and patients typically die in their twenties or thirties. After reading about Duchenne I thought, “Well, I've always been interested in science, math, and engineering, so maybe this [researching Duchenne] is something that I should think about pursuing.”
I went to undergrad at Johns Hopkins University for an engineering degree, and during my second semester there, I began volunteering in a lab that was researching muscle diseases. The year after that, I switched to a different lab that was also working on muscle diseases. There, I started a small undergrad research project looking at a small molecule for muscle regeneration, which ultimately was tested in Duchenne but was not shown to be efficacious. But these research experiences solidified my interest in muscle disease research and I continued in the field of Duchenne therapeutics. I spent a summer fellowship at Leiden University Medical Center, working on strategies for exon skipping for Duchenne [See Question 3 for an overview of therapeutics strategies for Duchenne].
During undergrad, I also did two company internships. I spent a summer at Covidien, which is a medical device company, not focused on muscle diseases, and then a summer at Sarepta, which was developing an exon skipping therapy for Duchenne at the time [Sarepta developed the first FDA-approved exon skipping drug for Duchenne, Exondys 51, approved in 2016]. So I had dabbled in a couple areas of muscle disease research. I then decided to do my master's at University College London in the UK, rather than having spent any time abroad during undergrad. And when I went for my master's there, I wanted to look at muscle diseases from a different angle so I worked on a muscle stem cell-focused project.
After that, I started thinking about what I wanted to focus on for my PhD. I knew I wanted to do something besides exon skipping, small molecules, or stem cells for Duchenne. I started by looking for universities that had really good muscle disease research groups. I ended up choosing UCLA because they have a whole center for Duchenne. There's multiple labs that focus on the disease, a clinic that sees Duchenne patients, and even a student group promoting awareness of Duchenne. It was a very nice community of people working on a disease that I was really passionate about. When I started at UCLA, I was interested in joining the lab of Melissa Spencer, but her lab wasn't doing anything that I was super interested in at the time. I told her, “I want to do something really impactful for Duchenne. I've already tried small molecules, exon skipping, and stem cell approaches.” This was in 2013, so CRISPR had just been published for use in human cells. And we said, “Okay, well, maybe we should think about doing gene editing. Maybe we should think about trying CRISPR, this new approach that only a few people are using.”
If we were going to do this, I figured I should go get some experience with gene editing. So I rotated in Don Kohn's lab, working on a project for blood-borne diseases. We were comparing zinc fingers, TALONs, and CRISPR. And in that rotation, it was immediately apparent that CRISPR was the way to go. I went back to Melissa's lab for my main thesis. My unofficial co-advisor was April Pyle, her lab focuses on stem cells and muscle development and we were using the stem cells as a model system to test CRISPR in Duchenne patient cells. The goal was to develop a single approach that would have an impact on the disease for a large number of patients rather than targeting small subsets. We ended up using CRISPR to make a large deletion in the gene to restore the reading frame, encompassing a region that accounts for 50% of patient mutations with one approach. This deletion retains 87% of the protein coding sequence and is associated with a very mild form of a different muscle disease, Becker muscular dystrophy.
By the time I was nearing the end of my PhD, my advisors and I had decided we were going to start a company from this project. I stayed for a brief postdoc while we were getting that transition ready, working on a few other projects, and then we got a couple of grants to start doing work in the company. I moved into MyoGene full-time in mid-2019.
2) Before spinning out MyoGene, had you thought about becoming an entrepreneur?
As the project began to develop and we were able to show this was a good deletion to make and that we could use CRISPR to make the deletion, UCLA submitted a provisional patent application to protect the idea of this large deletion, as well as the specific guide RNA sequences. It was when the patent was submitted that I first started thinking about a startup. Before that, I had thought, “Oh, maybe I'll become a professor, then maybe I'll do a startup.” I was always interested in entrepreneurship, but I hadn’t thought I would become a founder right after my PhD.
My parents had started multiple companies in software, so becoming a founder is something I had thought about. I had seen the development of their first company where they had a successful exit and enjoyed working for themselves. When I was in high school, rather than getting a normal summer job, my parents said, “Oh, just start a company to make some money.” And so I started teaching cooking classes to kids out of our kitchen as my summer job, rather than getting a normal summer job. It wasn’t anything official, but that was my first little trial of running my own company, unrelated to science.
I like research and directing people. In grad school, I realized I didn't really want to be a professor but I had always liked the idea of being able to control a research project and being in charge of the development of science. When we had the patent filed, we began to think, “Oh, someone may license the patents from UCLA. We don't want somebody to come develop our product without our input.” We had invested a lot of time into developing this therapy and thinking about how it should be brought to patients. Melissa had been in the field for almost 30 years and we had seen multiple drugs in Duchenne go into clinical trials that were not well designed and fail. I'm very committed to helping patients, and we realized we didn't want to lose control of our project right away.
[How did you end up becoming the CEO of MyoGene?]
Becoming the CEO of MyoGene came both from the idea of wanting to direct development of our therapy, which we had invested a lot into, and try to do it right from our perspective. It also met my goal of being able to run a research project, but not in academia.
3) What are people trying for therapies for Duchenne and why do you think the CRISPR-based approach of MyoGene is a superior approach?
Duchenne is typically caused by out-of-frame mutations in the DMD gene, which is on the X chromosome, so it primarily affects males. This gene encodes for a protein called dystrophin, which normally protects muscle. These out-of-frame mutations will result in no dystrophin protein being produced, which leads to progressive muscle degeneration and ultimately cardiac or respiratory failure.
Although some approaches just target downstream effects, the overall goal of many therapies for Duchenne is to restore the dystrophin protein. I think the biggest impact for patients will be approaches targeting the underlying cause of the disease and restoring dystrophin, or something that can replace dystrophin's function, in muscle. Right now, there's a handful of approved drugs. There are corticosteroids, just addressing some of the downstream effects, exon skipping drugs, which have accelerated approval for 8-13% of patients, and one gene therapy, a gene replacement with micro-dystrophin [essentially a fragment of dystrophin that has partial functionality], that has accelerated approval for patients who are between four and five years of age. Thus there are currently only small patient populations applicable for these genetic medicines.
The way exon skipping approaches work is by targeting an exon next to the patient's mutation, which causes the next exon to be skipped and produces an in-frame, internally deleted transcript. But exon skipping therapeutics target mRNA transiently and have only shown modest efficacy, restoring less than 5% of dystrophin and slightly slowing the decline of the disease. Each drug also only targets one exon, so they only work for between 8% to 13% of patients, depending on what exon they target.
Gene replacement is limited by the size of the DMD gene which is very large and so the coding sequence doesn’t fit into AAV [AAV is a non-pathogenic viral capsid commonly used for delivery of gene therapies]. Currently, gene replacement approaches in trials utilize mini or micro-dystrophins that are about a third the size of the normal gene and are able to fit into an AAV. These are really small versions, so they may not have full functionality. It’s also not permanent and will just last until that cell dies. One gene replacement approach has accelerated approval and a couple of others are in clinical trials right now, still being tested [The one with accelerated approval is Elevidys, developed by Sarepta and approved in June 2023]. The benefit from that therapy was not statistically significant on the primary endpoint of that trial. There are a few other types of treatments being tested in clinical trials right now, mostly aimed at the downstream effects of the disease.
A big advantage of CRISPR is that it permanently changes the patient's own DNA. This means the normal gene regulation and sequence will be intact because it's in the endogenous gene locus, and then you're not limited by the carrying capacity of AAV, and so you can make much larger dystrophins. Some of the other CRISPR approaches for Duchenne that have been tested preclinically are targeting just one exon. Our approach at MyoGene is essentially a permanent multi-exon skipping where we make a large multi-exon deletion to encompass more patients and hopefully make a more functional dystrophin. Doing this using CRISPR is expected to be more effective than current exon skipping therapies. This idea of generating an internally deleted dystrophin has been around for a while and is actually based on patients who have an allelic disease called Becker muscular dystrophy, who have naturally occurring in-frame deletions in dystrophin but have a much milder phenotype than Duchenne. [For a comprehensive review on strategies for treating Duchenne, please see this review paper.]
4) How did you know it was time to spin out the company? What milestones had you achieved by the time you officially spun out?
We incorporated the company in 2018 and I went full-time into MyoGene in mid-2019. The biggest piece of data we thought that we needed to move the technology into a company was having some in vivo efficacy results [data with the CRISPR approach in a mouse model]. We had enough support, funding, and resources in academia to show in vivo efficacy and thus demonstrate the first proof of principle. That initial proof of efficacy in mice coincided with the end of my thesis project. The time between ending my thesis and then actually doing the spin-out also helped us sort out the logistics. We had to incorporate the company and get the various registrations to then apply for NIH SBIR grants which can take some time. While that was in progress, I stayed on for a brief postdoc at UCLA.
By the time we did spin out, our first two grants were about to start. A couple months later, we found lab space at the Magnify incubator on the UCLA campus. It was really convenient to be on campus to still collaborate with Melissa and April, and it gave us access to useful resources.
5) What level of support did you get from your PIs? Had they spun out companies before?
I was interested in starting a company and once I brought it up, my PIs were very supportive and jumped on the idea. They'd always been open to their trainees taking different types of career paths. Neither had done a startup before, so this was a first for all of us and we didn’t know that much about business. So it was definitely a steep learning curve in the beginning, and we’re still learning, but it’s been a great experience.
[How involved are Melissa and April now?]
MyoGene still collaborates with Melissa and April, and they are co-founders and on our scientific advisory board. We're all still good friends even though I don't see them as much now that I'm in San Diego, but we still are in touch a lot.
6) How did you make the decision to move MyoGene from Los Angeles to San Diego?
MyoGene was based in Magnify for the first two and a half years which was a great experience. However, when I started thinking about where MyoGene should be based, I looked at other biotech ecosystems in California, since we had just started a CIRM (California Institute for Regenerative Medicine) grant [which required MyoGene to be based in California]. It was really between the Bay Area and San Diego. I personally liked San Diego more, it’s smaller, the biotech ecosystem is more condensed, and I love that everyone here has been super friendly. Everyone has been so willing to help me, and it has been a very nice community.
7) Is there a patent for your technology? How long did it take to license out the IP? How did negotiations with the university go?
We did have a patent. Licensing out the patent, in general, was fairly positive, although it took a pretty long time, about nine to twelve months. We first did an option agreement that was very simple and fast, and then at least we had that in hand when we went to apply for grants to show we would be able to get the IP.
8) It can seem daunting to start a company, let’s talk about the logistics of how you got started.
[What resources did UCLA have for you? How did you incorporate your company and find a lawyer?]
There were some new initiatives [at UCLA] that were beginning to support startups. For example the technology office had a startup-in-a-box program that we used, where they introduced us to different lawyers who they had worked with before. The lawyers then might give the company a deal to help them start off easier. I also took a business of biotech class and participated in a summer program and multiple entrepreneurship boot camps.
Because we were initially just planning on going after grants, we incorporated as an LLC rather than a C Corp. If you are immediately going for investments, you'd want to incorporate as a C Corp. A lot of what I learned about the logistics of starting the company, I learned from one-day entrepreneurship boot camps and workshops. When you go to the first one, you don’t understand anything they are saying, but after a few, everything becomes more familiar and then you actually get the concepts once you’ve been to a few of these.
[Did you know anyone else spinning out their own company?]
There were other PIs who had startups, but they didn’t always have trainees going into those companies. But in my year [of PhD students], I knew multiple people who moved into a startup. They weren't all CEOs, or even all C-suite level people, but it was becoming more common. Melissa and April had always kind of deferred to me and they didn't want to be in charge of the company, so when the time came we all agreed I should run the company.
[How did you find your first employees?]
For the first three months, it was just me. Then, I hired a part-time employee, who was a great technician in April's lab, and he split time between April's lab and MyoGene. Six months after that, I hired a full-time employee, also someone I knew at UCLA. I was doing both business and lab work in the beginning. I started handing off more and more lab work, and that transition allowed us to grow. The initial hires were people I knew at UCLA and I think in the early days hiring people you know can be advantageous. When you're so small, you don't want to risk hiring somebody who's not going to really work out.
[How did you find your first lab space in the Magnify incubator?]
We had to do an application to get into Magnify. We knew some other PIs who had companies in the space and it was nice to initially be able to stay on campus. To get into Magnify, we had to do a pitch, and they helped us refine the pitch. That was the first time I had ever built a business pitch, and they helped me make it more business-like.
9) MyoGene has been awarded several SBIR grants. Why did you decide to pursue non-dilutive funding?
Coming from an academic background where we had grant funding for the project in the academic lab, we thought it would be a good idea to start with the same approach for the company. In grad school, I had helped Melissa and April write grants, so I had a decent amount of experience although they both helped me write the first grant for MyoGene. When we started, getting grant funding was the easiest thing for us to think about doing, because it’s what we knew as academics. SBIR grants are either a Phase I, which isn't very much money, but you don’t have to have much preliminary data, or a Phase II which is more money for a longer period of time. Because we had in vivo data, we went for a Fast-Track application, which links a Phase I and a Phase II SBIR. That was really beneficial because then you don't have to reapply for your Phase II. As long as you meet your Phase I goals, moving into Phase II is automatic in a Fast-Track grant.
We also hadn't built a new network of investors to try to go for equity funding. We talked to a few investors, but nothing immediately came of it. So we just continued with grants. Currently we have a grant from the California Institute of Regenerative Medicine (CIRM). And that's actually been really helpful because they will fund drug development studies, IND enabling studies, and then clinical studies, all of which they have different types of grants for. CIRM is specifically for programs that work on regenerative medicine or gene therapy. They have a discovery grant, if you're really early stage, and they have the Quest grant if you are doing in vivo efficacy. And then they have a translational grant and a clinical grant. So they provide funding at every step, hoping to funnel therapies into clinical trials.
[Looking forward, how are you thinking about going after grants versus VC funding?]
We are looking to raise money from VCs. We're still applying for grants because even if we did get VC money today, having additional non-dilutive funding is really valuable. The environment isn't great right now and there has been some waning interest in gene therapy but hopefully, it's going to change now. We have also some venture philanthropy investments.
10) How have you built your network as a founder?
I've done lots of pitch competitions. You usually get some sort of coaching with that, and you'll get feedback on your pitch, and meet people through that event. And then I've done the Mass Challenge accelerator program, Ad Astra bootcamp, and I'm currently doing the Creative Destruction Labs accelerator program. So these are free or low-cost programs where you're matched with mentors or you go to courses to help develop your startup. Programs like these are where I’ve found mentorship and connections to potential investors. I'm also in a CEO circle, so meeting more of my peers who are going through the same challenges, which has been really nice support to have.
11) What skills from your PhD have been most useful as a founder and what skills have you had to develop?
As far as what I picked up in academia, there were two things that have been really useful. One was grant writing, because that's how we started being able to fund MyoGene. I know lots of other companies where the CEO came from business and had no idea how to write a grant to NIH and struggled or had to use a grant writer. My experience has been that SBIRs are evaluated similarly to academic NIH grants, so coming from an academic lab where I was already writing grants has been hugely helpful.
The other skill I developed that was helpful was people management. I had a lot of people who helped me with my projects at UCLA, and I would direct them on different parts of the work. Right now, I’m the CEO and also acting as the CSO, so directing the research at MyoGene is a hugely important part of my job, and I developed some of those skills during graduate school. As a startup, you still direct research, like how you do in academia but your goals are different. Our goals in the company are to develop a product. We're not trying to answer a biological question. We need to know enough to know that it's working and that we can evaluate it. But I don't need to waste time on understanding why.
[On skills Courtney has had to develop.]
The biggest thing that was different, that I had to learn very quickly, was the language of how to pitch in business compared to academia. All the terminology that people use in business, and acronyms that VCs use, we’re never exposed to in academia. You have to learn how to craft business materials. For instance: How do you create your revenue projections? How do you give a business pitch? How do you talk about the competitive landscape? How do you create a chart on that? Changing the pitch, changing the language, and learning to present our goals differently was the biggest learning for me.