Rare Leader: Karen Chen, CEO, Spinal Muscular Atrophy Foundation

The Basics
Name: Karen Chen

Title: Chief executive officer

Organization: Spinal Muscular Atrophy Foundation

Disease focus: Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disease characterized by muscle atrophy and weakness. The disease generally manifests early in life and is the leading genetic cause of death in infants and toddlers. SMA is caused by defects in the Survival Motor Neuron 1 (SMN1) gene that encodes the SMN protein. The SMN protein is critical to the health and survival of the nerve cells in the spinal cord responsible for muscle contraction (motor neurons).

Headquarters: New York City

How did you become involved in rare disease: I was a researcher and executive working at drug companies, and I often got approached by headhunters. I was contacted by a headhunter for the SMA Foundation. I thought that was kind of odd since I had never had any experience working for non-profit foundations and at that point hadn’t even heard of SMA, but I dug a little deeper and found a little more about SMA and the organization and I flew to New York for an interview. I met with the founders, Dinakar Singh and Loren Eng and I became intrigued since the foundation wasn’t your typical nonprofit foundation. It functioned more like a pharma biotech company, at least at a high level. After the meeting with the founders, I even met their daughter who has SMA, and when I went home, I received a nice note from their daughter saying that she hoped I’d work on her disease. After that, I couldn’t say “no.” When I originally made the choice to work in biotech and pharma, versus pursuing an academic career, which was more common at that time in the late eighties/early nineties, most companies were focused on bigger diseases, such as stroke, or Alzheimer’s, rather than rare diseases. In the last 10 years, the focus has changed due to successes in getting effective drugs in these conditions because they’re more homogeneous and there have been blockbuster failures, as I call them, in clinical trials for the larger neurological diseases. Now there are more programs than ever in rare diseases and, in the last five years or so, I’ve tried to provide advice and guidance to other foundations and drug companies working in the other 7,000 rare diseases. Rare diseases have become a passion for me, and I hope I’m going to be able to continue contributing and finding cures for the rest of my career. It’s serendipity that I got into it, but I love the area.

Previous career: Biotech executive

Education: A.B. Biology from Harvard University, Ph.D. Neurosciences from the University of California, San Diego

The Organization
Organization’s mandate: Our mission is to accelerate the development of therapeutics for SMA. It’s very singularly focused. Our sole mission is to work on treatments and not to raise awareness or raise funds. It’s not even to interact in providing help to patients and families directly. It’s to develop drugs.

Organization’s strategy: Our strategy has been to partner with drug developers and other important stakeholders to develop these treatments. To make SMA the low-hanging fruit among the other diseases, we’ve tried to develop what I call tools and information needed to successfully develop an approved drug. These include cellular models, animal models, natural history data, biomarkers, and clinical endpoints. The foundation has also funded basic research that’s answered questions about when and where, meaning what cells should be targeted and at what point treatments need to be utilized—essentially any research that helps answer questions that would eventually accelerate therapeutics development. The foundation has also served as a hub to connect various stakeholders, such as clinicians, basic researchers, drug developers, regulatory agencies, as well as patients and families. We want it to be that one-stop shop for SMA drug development and to be able to assist in every step of the process. Many of us at the foundation had worked in drug development, so we knew what those steps would be and how to help.

Funding strategy: We’re self-funded, initially by the founders and now through the successful approvals and sales of drugs, which we helped fund and develop. We’re receiving a return on our investment on the research that led to those drugs. We have received other donations, which we’re grateful for, but we don’t rely on those donations to fund our operations. One hundred percent of those donations directly fund the research. We don’t have to focus any of our efforts on, or even hire personnel to work on fundraising. That’s why you’ll see that in the past, and even now, we have people who are not professional fundraisers or professional non-profit executives, but rather researchers and people who work in science.

What’s changing at your organization in the next year: We’ve been fortunate in SMA to have had three different drugs approved in the last two years. The first was Spinraza, which is an antisense oligonucleotide that needs to be directly injected into the fluid around the spinal cord. The second is the gene therapy Zolgensma, which also needs to be given into the central nervous system. But this past August, Evrysdi, which is an oral drug, was approved. All these drugs replace the missing SMN protein, in the SMA patients. It’s been transformative for the patients. The drugs all prevent the motor neurons and other cells from dying. When treated early enough, children develop normally and don’t exhibit any symptoms of SMA. Even for the patients who are older, when they’re first treated, the drugs halt the deterioration and worsening of the symptoms, but they still don’t restore function because obviously the earlier you treat with drugs, the better. In this next year, we’ll be changing our drug development focus and looking for ways to regenerate these lost nerve cells and muscle cells to gain back some of the lost function. There’s a lot of innovative research in regenerative medicine. We’re excited to see if we can test these different approaches in SMA. We hope that these therapies will be effective in SMA, but we think that they have the potential to have an impact in many different diseases.

Management Style
Management philosophy: Being at a nonprofit foundation that partners with biotech and pharma companies, but also works with clinicians and basic researchers, as well as collaborates with other foundations that are also focused on SMA, we need to be flexible. We wear many different hats in many different contexts. We don’t get a seat at the table because people are working for us or we’re their sole funder. We have to earn it. To earn our seat at the table, we have to demonstrate that we can provide valuable contributions, and everyone knows that we want what’s best for patients. I’ve tried to manage by example by trying to be a good partner and by being knowledgeable and helpful to our collaborators, and not trying to force ourselves on them. We find that the most meaningful contributions and collaborations are when they want us to participate and they value us. That’s an important example to set. I try to do that. Since we’re all at the foundation because of patients and families, I think about that all the time. It guides everything we do. It gives everything a sense of urgency and it’s not a job that we can leave at the office. We think about it all the time. If we put off doing something until tomorrow, it could mean the difference between treating a severely sick child a day earlier, which obviously has a profound impact on his or her life. Our sole mission is to accelerate the development of therapeutics for SMA. We want to put ourselves out of business and each one of us out of a job. The goal is to develop effective drugs. If we’re successful, the SMA foundation, hopefully, won’t be needed in the future.

Guiding principles for running an effective organization: We’re effective because we are knowledgeable, and we want everybody in the organization to be knowledgeable. We have an effective organization because there’s not a lot of bureaucracy and red tape. We’re very transparent. We tend not to have meetings because meetings are the bane of every organization. For example, we simply CC everybody on different emails so everybody is well-informed. I mentioned the sense of urgency. We are constantly reminded about this urgency with our interactions with families, as well as patients. The guiding principles are just to be transparent and communicative with everyone at all levels within the organization and to work with a sense of urgency.

Best way to keep your organization relevant: Frequent communications with important stakeholders, as well as key opinion leaders in SMA and more broadly in neuroscience drug development, and now, regenerative medicine. Keeping abreast of the latest developments in research. But it’s most important for us to understand what the unmet needs still are. I mentioned we had three drug approvals for SMA, and with each approval, the unmet need the patients and families might change. It’s very important for us to keep our finger on the pulse and know what that is in order to know what our next focus should be.

Why people like working with you: I try to be knowledgeable and helpful and do my job well, but I think it’s also important to be friendly and collegial. It’s often the case when we feel a sense of urgency and stress that we may forego being friendly, but I find, especially in our role as advocates for patients and families, it’s important to be collegial and to have people want to work with you. Of course, humor is also appreciated, though some people may not appreciate my puns.

Mentor: I’ve had a lot of scientific mentors, but since joining the SMA Foundation my mentor has been Loren Eng, the mother of a child with SMA and the co-founder and current president of the foundation. She doesn’t have a scientific background, but she’s able to understand all the science and research that’s presented, and is always able to step back and see the big picture and cut to the chase. I think it’s her strategic vision and her business acumen that’s made the SMA Foundation successful.

On the Job
What inspires you: SMA patients and their families. They’re all truly amazing, and not just in how they live with SMA, but so many of them are successful by any measure. They’re truly wonderful, compassionate people. They’re constantly inspiring.

What makes you hopeful: I’m hopeful that the ability of therapeutics to transform SMA as patients begin to take those three approved drugs. With treatment, they’re beginning to sit up, stand up and some are even walking. I see in the future, with early genetic testing and early treatment, there’s hope of eliminating the majority of SMA cases and hopefully with progress in regenerative medicine, even the patients that weren’t treated at a very early age will gain function that they’ve lost or achieve functions that they never had.

Best organization decision: It’s been to focus, focus, focus. We’re not an enormous organization. There are certainly large nonprofit organizations like the Michael J. Fox Foundation. We’ve always been a small one. We’ve had to focus just on the development of drugs, even though, of course, we’d love to be able to directly interact with, and help patients and their families more. And even within drug development, we’ve only had the bandwidth to focus on a limited number of programs because we want to just provide our partners, pharma and biotech companies, with everything, from A to Z. That’s a lot of time and resources. For example, when we collaborate with one of our pharma partners, it’s not uncommon for me to talk to them every day for hours. We can’t partner with tens or twenties of companies. We’ve had to focus and be selective.

Hardest lesson learned: No matter how much effort, time, money has been spent on a particular approach or a research program, it may not be successful. The best decision is sometimes just to kill a program early and not to keep going, no matter how much we have invested in, or how much we want that program to be successful. That’s a hard lesson—to know when to say stop.

Toughest organization decision: It’s probably the exact same answer I gave you about the best organization decision, which is to focus on just the development of therapeutics, and only on a limited number of drug programs. We wish we could do everything, but I think that’s to the detriment of all programs if we can’t just focus on a few that we think have the best chance.

Biggest missed opportunity: We’re constantly evaluating what we’re doing and keeping tabs on the research and progress in the community. We might have initially missed an opportunity, but as time went on, we found that maybe we should revisit that decision and we’ve then decided to invest in and start working on that program. I don’t think there’s been a large, missed opportunity. There might have been opportunities that we’ve re-evaluated later on. Even when we feel like we can’t take on an opportunity for a specific research program or funding, we’ve found ways to have other people do it. We have great connections with other organizations, other nonprofit foundations, as well as the companies with whom we collaborate. We’ve managed to find ways to get funding for that program or find others who can help that investigator or patient group move forward.

Like best about the job: It’s knowing that we may benefit patients. That’s certainly the goal and I’m kind of a people person. I love interacting with people. Collaborating with so many different groups and individuals has been great for me. I love that about my job. I originally became a neuroscientist because I like working in many different things. I make fun of my colleagues who are molecular biologists or biochemists because I tell them, you’re only focused on one technique. You’re just doing the one thing. You have many different problems, yes, but neuroscientists just have one. We usually are working on one question or problem and we bring many different techniques and learn whatever skill we need to get the job answered. What drew me to being a neuroscientist was doing different things every day. That’s exactly what I like about my job at the SMA Foundation. No two days are alike. Every day I’m doing something different—interacting with a different group of people. I love that variety.

Like least about the job: It’s what people like least about everybody’s jobs, which is those mundane, but necessary tasks and keeping the organization running—the budgets, the reports, the performance reviews. I don’t think I’ve talked to anybody who kind of loves the paperwork associated with their job.

Pet peeve: People at other organizations working in other diseases or at pharma or biotech companies that don’t have a sense of urgency and passion about what they do.

First choice for a new career: I can’t imagine doing anything else. It would just be the next chapter of what I’m doing now. Advisor or consultant to other nonprofits or working with a venture capital firm investing in rare diseases.

Personal Taste
Most influential book: It’s the books that made me want to be a neuroscientist. The Man Who Mistook His Wife for a Hat by Oliver Sacks, The Mind of a Mnemonist: A Little Book about a Vast Memory by A.R. Luria, and The Mind’s I by Douglas Hofstadter and Daniel Dennett.

Favorite movie: Airplane

Favorite music: Alternative rock, classical, and Led Zeppelin

Favorite food: Wine. I have, over 4,000 bottles in my wine cellar and I’m trying to keep it to that number. I keep trying to foist bottles on friends and say, “Oh, you’re having a party. May I bring all the wine that you’re going to need?”

Guilty pleasure: Going down rabbit holes on the Internet.

Favorite way to spend free time: Friends and family. I recently moved to Jackson, Wyoming and I discovered I love hiking.