THE PEOPLE BEHIND THE PROGRESS CHARLEYâ€™S FUND 2016-2017
DEAR FRIENDS AND SUPPORTERS,
It feels strange and surreal to be writing you this letter. Every Autumn for the past 12 years, we have written about our quest to get safe and effective treatments developed and approved for kids with Duchenne. We knew it was possible, of course. Otherwise, we never would have embarked on this allencompassing endeavor. But at the same time — if we’re being totally honest — sometimes we felt like it would never happen. And then, this year, it finally did: The FDA granted conditional approval to Exondys 51, the first treatment to produce dystrophin, the protein boys with Duchenne are missing. Hallelujah, cheers, kudos, AMEN!!!! We celebrate this achievement, but it is important to put it in perspective. This first treatment can only help 13% of kids with Duchenne, Charley not among them. And the medicine is a treatment, not a cure; it is one
ingredient in what needs to be a robust cocktail of medicines. The past 12 years have seen a transformation of the DMD landscape. When Charley was diagnosed we faced a barren situation with scant hopeful prospects far off in the distance. Today we have a dynamic and productive research scene with new clinical trials popping up every year. You have helped turn despair into hope, and then real progress. This year’s annual news highlights some of the people who are driving this historic transformation. We hope you enjoy getting to know the scientists, physicians, donors, fundraisers and children who are working hard to help us transform the future for all kids with Duchenne. Thank you for being a part of this dedicated group!
nds and frie Charley al Park. tr in Cen t u o g in hang
While Charley looks forward to a brighter future than we ever thought possible, we cannot avoid the reality that he is living on borrowed time. This year, we lost too many precious lives. We said goodbye to Darius Weems. We suffered the loss of a young man who was participating in the same clinical trial as Charley. We saw too many memorial candles posted as Facebook profiles, a stark reminder that Duchenne steals lives every single day. This year, Charley needs to rest after walking one block whereas he used to last for two. At the end of the school day, he asks a friend to lift his wheely-backpack into the car; last year he did that himself. When trying to climb a couple of small steps, he leans his upper body to the side for support from a nearby wall — a compensation for leg weakness that we haven’t seen before. We know these small signs mean the clock is
ticking ever louder. That’s why we’re dedicated to making sure we build on every success and learn from every mistake so we can achieve our goal on the fastest possible timeline. Best wishes for a spectacular 2017! All our gratitude,
Tracy and Benjy
SCIENTISTS SEEKING SOLUTIONS
JUSTIN FALLON Professor of Medical Science at Brown University, Providence RI We met Dr. Fallon ten years ago, when one of our supporters heard him speak about a DMD treatment he was developing at Brown University. We funded laboratory studies that yielded positive results, and now his company Tivorsan Pharmaceuticals is preparing to start a human clinical trial. We wish this work could move faster, but it takes tens of millions of dollars to prepare for and conduct a clinical trial. The Tivorsan team is plugging away as quickly as funds allow.
With support from Charley’s Fund, some incredible scientists are working to turn exciting “eureka” moments into medicines and tools that can improve the lives of patients.
SEWARD RUTKOVE Chief, Division of Neuromuscular Disease at Beth Israel Deaconess Medical Center, Boston MA Dr. Rutkove is developing a tool with the potential to measure whether a treatment is having an effect on damaged muscles. This could be a quick, painless, inexpensive way to measure whether a new drug is stabilizing or improving disease progession. What are you working on with support from Charley’s Fund? My main focus is on improving biomarker tools to help judge the efficacy of new therapies in DMD. A better ability to judge a treatment effect means a better ability to tell if a drug is worthwhile or not. If we can do this in a shorter amount of time and with fewer boys needing to be studied, the sooner we can make major inroads toward curing this disease. My main interest has been on electrical impedance myography (EIM) but I am also exploring ultrasound and other simpler tools. How is this work important in speeding drug development? I’d like to think very important! We need better tools to assess efficacy. Simple, accurate measures of disease efficacy that potentially could even be used at home, could go a long way toward helping speed drug discovery.
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What are you working on that Charley’s Fund has supported? We are working on a disease-modifying therapy that could work for all patients, regardless of mutation. The therapeutic is based upon a naturally occurring protein called biglycan that recruits utrophin and nNOS to the muscle cell membrane. Charley’s Fund was one of the earliest supporters of our work and was instrumental in moving it from an academic laboratory into industry.
How has the DMD therapeutics landscape evolved over the past decade? The landscape has changed dramatically over the past decade. The approval of Exondys 51 was a major milestone, but there are many other therapies in development that could enhance the efficacy of this drug and help the patients who are not eligible for exon skipping. What impact does this first DMD drug approval have on your work? The approval is very important for our work. The regulatory pathway is now much better defined and there is an overall optimism in the entire Duchenne therapeutic ecosystem that will help support new therapies in the pipeline.
Charley’s Fund used a venture philanthropy model to fund Dr. Fallon’s work. Success will be a win-win for kids with Duchenne: a safe and effective treatment and a financial return on our investment so we can plow the funds back into additional promising science.
“ Exondys 51 is making a difference, but this is only the start . . . we continue to work to make this even better." — Steve Wilton
STEVE WILTON & SUE FLETCHER
Fun F act: Dr. Wil ton’s g ot a pup na med S t e lla, just lik e Cha rley.
Professors at Murdoch University, Perth Australia The DMD community now has one FDA-approved treatment under our belts, and these two very dedicated scientists deserve extra-special thanks for that! How did your work help advance the first DMD drug approval in the U.S.? Sue: Steve and I began working together in the early ‘90s. Steve was investigating the mechanism responsible for revertant fibres, which are fibres containing trace amounts of dystrophin. He suggested that if we could increase revertant fibres, we could reduce the severity of DMD. Steve's idea became a discovery on June 19, 1997. As a cell biologist, my major role has been to direct the preclinical experiments and manage the cell bank. This discovery and the work we did to refine it provided the basis for Sarepta to develop the newly approved treatment, Exondys 51. What does this first approval mean for boys with Duchenne? Steve: This is just the first “line in the sand.” We have set a standard and identified a compound that unequivocally makes some dystrophin after treatment. There are fold increases from baseline and I believe we can improve delivery to make this even more efficient. I am relieved, excited, proud and numb all at the same time. Exondys 51 is making a difference, but this is only the start. . . we continue to work to make this even better. Sue: The approval of Exondys 51 is the first step in making a difference for those with Duchenne, and it is not the end of our role. Our commitment to the research has been validated, which is very gratifying, however we remain mindful that for so many families, it has taken way too long. What are you working on or excited about next? Steve: Helping the boys who aren’t eligible for Exondys 51! We decided a long time ago we wanted exon skipping to be available for all DMD boys who may benefit from it. We are working on other rare dystrophin mutations and striving to identify the most efficient sequences, to deliver the best options for these mutations.
LAURENT BOGDANIK Study Director at The Jackson Laboratory, Bar Harbor ME We are working with Laurent and Jackson Lab (aka JAX) to refine and improve preclinical testing for Duchenne treatments. With more treatments in development each year, it is critical that we have a better “gateway to the clinic” to help determine which drugs should move into clinical trials. What is Jackson Lab? The Jackson Laboratory is an independent, non-profit institute focused on genetic research to improve human health. Our Bar Harbor headquarters campus conducts research in disease mechanisms in laboratory mice. The group focuses on neurological diseases, including DMD. We work with foundations, academic researchers, biotechs and pharmas to develop new drugs.
Fun Fa ct: Dr. Bog danik bakes a mean Tarte Ta tin.
What work are you doing with support from Charley’s Fund? We are testing the efficacy of a potential new multi-therapy for Duchenne muscular dystrophy. In collaboration with Charley’s Fund, we are using a new mouse model that we developed at JAX. With previous models, it has been difficult to mimic the human form of DMD. The locomotion and inflammation in this model is closer to what we observe in humans, so it could be a better predictor of what effect a new drug will have on kids with Duchenne. How is this work important in speeding drug development? When using animal models to research cures for human patients, it is always a bit difficult. Some widely used mice develop a form of muscular dystrophy that is much milder than in humans. This is an issue when testing new drugs because there is not much of a disease to cure. The new mouse that we developed has locomotor dysfunction more similar to that of Duchenne patients. Our work with Charley’s Fund on this mouse has potential to considerably hasten discovery of treatments.
$37 million dedicated to research since 2004
PHYSICIANS TESTING TREATMENTS When Charley’s Fund was founded in 2004, there were no clinical trials for promising new medicines. Today it’s a different world, thanks in large part to the progress you have fueled. A decade ago, a DMD doctor’s job was to provide the best possible care. Today, with our support, many physicians are testing new therapies that may result in longer, stronger lives.
supporters engaged to defeat DMD
BRENDA WONG Director, Comprehensive Neuromuscular Center at Cincinnati Children’s Hospital Dr. Wong is known to many Duchenne families (including Charley’s!) as a dedicated doctor who provides best-in-class integrated care. But she also has her hand in cutting-edge research. In November, she participated in our workshop alongside other esteemed experts to help assess the promise of Electrical Impedance Myography as a clinical trial outcome measure.
treatments in development with our support
clear goal: to accelerate research to save our boys
t: Fun Fac s e g r laxe Dr. Won e h g to r by talkin an and Afric orchids violets.
How does your work help advance the development of new treatments for Duchenne? Our clinical work with patients and families plays an important role in the advancement of the development of new treatments for DMD patients. The clinical information of DMD patients managed with standard of care interventions provides longitudinal data vital for the understanding of the variable rates of disease progression. The data we’re generating will improve trial designs and accelerate DMD drug development. What does the first treatment approval mean for boys with Duchenne? Approval of the first drug for patients with DMD is a milestone that is to be celebrated by all in the DMD community. This will be life changing as families with newly diagnosed boys with DMD will not hear the typical “there is no treatment for DMD apart from steroids.” What else are you working on/ what are you excited about next? We are keen to discover non-invasive biomarkers for DMD that can monitor disease progression and be used in clinical trials. There’s a lot of buzz around gene editing and gene therapy strategies for the next wave of treatment options.
JOHN JEFFERIES Fun Fac t: Dr. Jeffe ries does P9 0X!
Co-Director, Advanced Heart Failure and Cardiomyopathy at Cincinnati Children’s Hospital Dr. Jefferies specializes in treating the devastating heart troubles that develop in DMD as boys get older. Not only does he help provide optimal care now — he also plays a key role in helping test new medicines that could be life-saving game changers in the future.
As a cardiologist, what is your role in treating DMD patients and developing new treatments for them? I oversee the cardiovascular care in our Neuromuscular Comprehensive Care Center at Cincinnati Children’s Hospital Medical Center. I participate in numerous clinical trials directed at the heart disease seen in Duchenne muscular dystrophy. What are you working on now with Charley’s Fund’s support? I am working on an innovative project in conjunction with Phrixus Pharmaceuticals to assess the safety and efficacy of a novel drug therapy called P-188NF (Carmeseal-MDTM). This therapy offers the potential to repair damaged cell membranes, which could lead to a variety of benefits in boys and young men with DMD. There are years of preclinical data generated around this compound, and we are hopeful that this will translate into meaningful benefits in humans. What is your hope for this project? My hope for this project is that we identify another promising treatment that could favorably impact the heart, lungs, and skeletal muscle in our DMD population. What other treatments coming down the pike are you excited about? I am very excited about other potential therapies that could reverse some of the cardiac disease seen in Duchenne. Specifically, we are investigating the use of stem cell therapy in an attempt to mitigate the scar burden that accrues in the heart. We have completed enrollment for our initial study and are anxiously awaiting the results. I am also very enthusiastic about newer oral drug therapies that are available to treat adults with cardiomyopathy. Some of these therapies may have direct benefit in the Duchenne population with a low side effect profile.
“This therapy offers the potential to repair damaged cell membranes, which could lead to a variety of benefits in boys and young men with DMD.” How has the DMD therapeutics landscape evolved over the past decade? The landscape of therapeutic opportunities has continued to expand and there are exciting new options on the horizon. We are very enthusiastic about many of the evolving investigational therapies, including some that target the heart. With better monitoring strategies, we can see more direct effects of these treatments on the myocardium.
Last yea r Charle y suffere fracture da d hip. To d a y, he’s ba on his fe ck et and d etermine d to stay stro ng.
BOYS BEING BRAVE When we throw around scientific terms like “clinical trial” and “dystrophin production,” it may be easy to forget that at the heart of this historic endeavor are the single most important element of this process: boys. Boys who giggle like hyenas, boys who have a weakness for watermelon sour patch kids, boys who quarrel with their siblings. The courage that drives these kids and the sacrifices they make to help test new medicines are mind-boggling. We know kids who miss school once a week to fly across the country to be infused with either an experimental treatment or a saline solution. We know kids who have undergone general anesthesia four separate times for an invasive muscle biopsy just to see if their bodies are producing the missing protein. We know kids who have spent 2.5-3 hours every single doctor visit to painstakingly demonstrate their muscle function on a long, boring difficult series of tests: climb four stairs, walk for six minutes, stack cups on a table, rise from the floor, run ten meters, hook up electrodes, breathe into a tube, lie still in the MRI machine, and more. One mom summed things up pretty well: “I tell you, these DMD brave kids teach us more than they’ll ever realize. I could cry at their humanity and strength.”
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THE RACE TO YES with our partner Team Joseph to ensure that the FDA acts with flexibility, urgency and scientific integrity when it comes to Duchenne. After a drawn-out process costing way too much time and money, Exondys 51 was finally approved, but dysfunction persists. Next steps for R2Y: get to the core of these problems so kids with Duchenne get the treatment (and treatments!) they deserve.
LUKE GRECO Neptune NJ Luke is volunteering to help confirm that Sarepta’s exon skipping medicines slow Duchenne’s deadly progression. He just received his first infusion as part of a clinical trial. Before that, he flew with his parents to Iowa where he was put under general anesthesia and wheeled into surgery so doctors could extract some muscle tissue and test it for dystrophin. “In Iowa where the biopsy was done, we met a boy who was getting his 6th infusion,” Luke’s mom told us. “He showed Luke his biopsy scar and calmed his nerves. Totally put him at ease. I tell you, these DMD brave kids teach us more than they’ll ever realize. I could cry at their humanity and strength.”
“And it begins!!! 1st infusion of Essence for 53! Praying it’s the drug and not the placebo but only time will tell.” #lukestrong #curedmd53 — Kristen Weag Greco
AIDAN LEFFLER Bellevue WA Every Wednesday for two years, Aidan Leffler flew from Seattle to Vancouver to participate in a clinical trial. From the start, his family realized he was getting a placebo rather than the actual medicine. But they stuck it out, because kids in the placebo group would “cross over” to the treated group after one year. Today, after years of travelling, poking, prodding, testing and stressing, Aidan is finally getting treated with an FDA-approved medicine. He goes to his local doctor once a week after school for his infusion, and the medicine is covered by his insurance. Exondys 51 has given Aidan additional strength and more time on his feet. But this drug does not treat all kids with Duchenne, and it is a treatment not a cure. So we press on for more!
people showed up at the historic “ad comm” meeting
DMD experts signed a letter to the FDA in support of the data
brave boys were followed in a clinical trial for five long years
CHAMPIONS CHEERING US FORWARD Fueling this powerful engine of progress is a group of dedicated people digging deep to help in any way they can. Charley’s Fund champions donate money, host fundraisers, provide advice, volunteer their time, and even show up in Washington, DC to ensure the FDA follows the science. We are lucky to have enthusiastic supporters who make sure we have the funds we need to keep driving forward. The champions featured here represent our incredible extended family!
MARGO & JEFF BARBAKOW Santa Barbara, CA Margo and Jeff learned about DMD through the film Darius Goes West. Soon after that, they made the decision to help increase our impact by becoming Charley’s Angels (you can too with a gift of $50,000+!). Margo has also become Charley’s selfappointed fairy godmother. This summer she treated him to an incredibly relaxing vacation in Santa Barbara. How did you hear about Charley’s Fund? We became involved via Darius Goes West. Darius and the crew were in Santa Barbara for a screening at the Santa Barbara International Film Festival, of which Jeff is the chairman. You have now been supporting Charley’s Fund for nearly a decade (wow!). How have you see the organization evolve? I have seen outreach, events, research, fund- and friend-raising on the rise. When we became involved in 2007, none of our friends had ever heard of DMD. Now, because Charley’s Fund and Darius and his crew have spread the word, more awareness has been created. Darius was able to participate in a clinical trial sponosred by Charley's Fund, and he got to see the first treatment approved by the FDA. Progress! What has made you stick with Charley’s Fund over the years? CHARLEY and his amazing family. Simple.
Juan, left, with family
JUAN PEDRO ARBULU Lima Peru Juan Pedro Arbulu is one of several thousand people who follow Charley’s Fund through Tracy’s blog and on social media. When The Race to Yes needed to send a message to the FDA, Juan Pedro was part of the vast legions that sprang to action. Juan Pedro hails from Lima, Peru and his son Juan, 11 years old, has Duchenne. “I am impressed with how nformed and insightful you are on many DMD issues you write about. You are doing what I would love to do if I had the capability of living in the U.S. — speed things up as much as I could, do whatever it takes.”
“I know time is an enemy, but I know we can change this.”
Mirtha, center, with supporters Wicho Hernand ez and Margee Martin ez
ELLEN WILNER New York NY When, how, and why did you get involved in Charley’s Fund? I heard Tracy and Benjy speak at a Charley’s Fund event and thought they were the most incredible people doing the most amazing work. After learning more, I became convinced that it was just a matter of time and money to find a treatment for this horrible illness. I knew I had to get involved. How could I sleep at night knowing these kids didn’t have to die and could have a better and longer quality of life? I called Tracy and said, “You don’t know me but I’ve heard you speak and I would like to help. How about if we host a run in Central Park to raise money for Charley’s Fund?”
What’s next for you? Charley’s Fund is working on growing support from teens and young professionals. We already have an amazing core group! We are working with a teen committee in NYC to get involved in promoting ideas and strategies for their age group. We’re starting similar work with young professionals as a ‘next generation’ of Charley’s Fund planners and donors. I am happy to share the lessons I’ve learned in building an event and motivating people, and explore ways we can expand the ‘family’ through things like social media. The possibilities are endless!
What has made the RAGT such a success? The keys to the Race Against Time are personal connection, Charley’s Fund’s unique vibe, people not wanting to miss out on a great event, and fun! We find that once people meet Charley’s Fund and our amazing ‘family’ of supporters, they want to come back. One of the ways we’ve increased our participation and fundraising is by tapping into camp and school groups, corporate sponsors, families and young professionals to spread the word — and create some friendly competition.
What advice would you give to somebody who wants to help but doesn’t know where to begin? Just do it! Tracy and Benjy are so busy looking for new treatments and running their foundation. They, of course, will be amazing amplifiers and supporters of what you do, so find an idea you are passionate about and get started!
THE RACE AGAINST TIME started as a small run in Central Park with a handful of participants. Now in its seventh year, the event has become a powerhouse community activity through which hundreds of participants and thousands of supporters have raised more than $1 million to defeat Duchenne.
MIRTHA DE LOS REYES Miami FL When Mirtha’s son Nico was diagnosed with Duchenne, she contacted every organization she found on the Internet. “Charley’s Fund stood out for its tremendous drive,” she says. “It has been a force, emotionally and mentally. When I feel I can’t, I read your very first emails and I say I can!!” Mirtha’s passion is infectious. It wasn’t long before her friends and coworkers were helping her plan a cocktail party fundraiser. “Miami Loves Charley’s Fund” was emotional, inspirational, and lucrative. Go Mirtha!
MYRNA FREEDMAN Boston MA One of our first donors when we launched Charley’s Fund in 2005, Myrna has gotten more and more involved as we gain momentum. She follows our progress via Facebook and the monthly CHARLeNews, so she always knows what’s going on and how she can help. Myrna was the very first to join
CHARLEY’S COFFEE CLUB! Within minutes of the program's launch, she committed to an automatic monthly donation. Why’d she spring to action so quickly? “I thought that this was a clever way to raise money. You are always thinking constructively. And I really commend you for this!”
are a part of something huge!