Q: What are the challenges in research for Duchenne muscular dystrophy that Charley's Fund can help address?
The amount of capital we raise and fund into research is small compared to what the government contributes to basic science and what industry invests in later-stage research. But we step in at that critical point known as "the valley of death," after government funding usually stops but before a large industry player steps in. Many therapies languish there and never make it to patients.
We target research as well as systemic challenges that threaten to stall or slow the progress of promising therapies. Our value system prioritizes focus, efficiency, creativity, and leverage over recognition or financial return on investment. This gives us room to act in ways other stakeholders can't. Focus keeps us glued to what really matters; everything we do must have a yes in answer to "Will this help get medicines to kids who need them faster and more efficiently?" Efficiency keeps us lean and mean – from timelines to funding budgets (95 cents of every dollar spent since inception has gone to our research efforts). Creativity enables us to identify and solve problems others miss. Business-as-usual won't defeat Duchenne, so we aim to be nimble and bold in identifying bottlenecks and creating solutions. Leverage helps us make our small investments mighty: We seek strategic funding points where our dollars count extra because their impact de-risks greater follow-on funds, and we pursue leadership opportunities where our funding rallies additional funding from other patient organizations.
Q: Charley's Fund now funds clinical research, in addition to its initial focus on translational research. What motivated this expansion?
A simple and terrific reason: the research was moving into the clinic, and we wanted to be there to keep driving it forward as fast as possible.
Our mission is to accelerate the delivery of life-saving treatments in time to save Charley and all boys with Duchenne muscular dystrophy (DMD). When we say we "do whatever it takes," we mean it. When we started 10 years ago, Duchenne research wasn't at the clinical stage. Now it is, we're needed, and so we are involved. Our view is: if the science is promising, nothing gets in its way.
As one example really close to home, some years ago we identified a therapy developed for another disease that showed promise in animal models of DMD. But, the therapy had been shelved because of a complication: it brought serious gastrointestinal side effects in humans. The company lost interest, but we saw potential. We acquired the drug, and set to develop and test a new enteric-coated version without the side effects. We not only set to funding a clinical trial, we actually created a biotechnology company of our own that had the experience and expertise to run it. Now, the therapy is showing encouraging preliminary results in a Phase 1b/2a study, and if effective it will be the first for all boys with Duchenne, regardless of genetic mutation. And, the biotech — Akashi Therapeutics — is building a pipeline that already includes two more promising drugs.
Q: Tell us about how your innovative partnerships have sped drug development for DMD.
Let me start with an example. In 2008, we funded a biotech pursuing disease-modifying treatments for Duchenne. Out of our grant, they identified and began developing a particularly promising therapy. They succeeded in partnering that therapy with a large pharmaceutical company. But, when the therapy was tested in Phase 1 trial with healthy volunteers, it didn't distribute through the body as hoped. The pharma partner ended the deal and returned the therapy.
The biotech wanted to address the problem and keep the therapy moving forward. Charley's Fund didn't want to see yet another drug succumb to the Valley of Death if something could be done, so we hired a preclinical expert to help us evaluate the data. He agreed that the bioavailability problem could be overcome. We shared our analysis with other foundations and formed a coalition to provide the company with the funds needed to reformulate and retest the compound. Today, the company is building on success and data from this trial to move into two additional clinical trials and an expanded pipeline.
This is one example, but creativity and collaboration in our partnerships — with both industry and other foundations — are core to our approach. Sometimes we use creative partnerships to solve scientific challenges, sometimes to solve systemic challenges. This past year, we partnered with other patient organizations to form a research advocacy initiative called The Race to Yes. That initiative mobilized more than 100,000 people and led to action from both the Food and Drug Administration (FDA) and White House.
Q: What do you consider Charley's Fund greatest accomplishments over the last decade?
Number one, we've learned that what we're doing is working. When Charley was diagnosed, there was not even one clinical trial for a promising drug to treat Duchenne. Now, multiple clinical trials are underway, and treatments are approaching FDA approval. Today we can hope that boys with Duchenne will have more time, and we can use that time to continue building the cocktail of drugs that will turn Duchenne from an aggressive killer into a manageable chronic condition. We played a pivotal role in making this happen. We funded the two companies with therapies approaching FDA approval early on. We played a major role in influencing the FDA's decision to consider accelerated approval. We started the biotech that is developing likely the first therapy to benefit all boys with Duchenne, regardless of genetic mutation.
Number two, we've also had failures. I think this is crucial to our overall success. If we aren't failing sometimes, we're not taking enough risks, and we're not learning from failures and finding opportunities to get better. We led an effort called "Pilot Trials Now" to take approved therapies for other indications and test them in boys with Duchenne. We had good preclinical rationale and good trial design, but it turned out we did not get a viable therapeutic out of that effort. But we got definitive "no's" that helped us close the book on outstanding questions, and we learned a lot about a major area of research — drug repositioning — very much in play for Duchenne.
Q: What are your top research goals over the next year, and what will it take to reach those goals?
Ten years ago, we decided to plant a large number of seeds in various therapeutic areas. The individual seeds we planted have either flourished (like in exon-skipping, the category of the two drugs approaching FDA approval) or floundered. Additional players have taken up ploughshares and have begun nurturing certain sectors. This all enables us to tighten our focus on the best research opportunities and develop tools that will help all new drugs move faster.
Our goals for the next year center around those opportunities. Two areas of particular interest are muscle regeneration and tools to accelerate clinical research. A therapy that promotes healthy muscle regeneration will be an important component of the Duchenne medicinal "cocktail." This is a major need, but it's early stage, risky, and likely requires some creative thinking to jump ahead. Good clinical tools and a clear regulatory path are needed to ensure that new treatments move through clinical trials and approval as quickly, efficiently, and effectively as possible. There's little financial upside in pursuing field-wide solutions, so it is a prime opportunity for us to have a major, meaningful impact. We don't have one company's interest in mind — we have long, healthy lives for all boys with Duchenne in mind. So we have an opportunity as a neutral party to drive that conversation. The opportunity for a creative problem-solver to have an impact can't be overstated. We are energized by what we have accomplished, but we have much yet to do.