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Dear Friends and Supporters,

On November 11, Charley celebrated his 13th birthday. In just a few months he will become a bar mitzvah, the occasion in Jewish life when a boy officially takes on the responsibilities of manhood. This seminal transformation in Charley’s life mirrors a major turning point at the foundation that bears his name. Over the past two years, we have built DART Therapeutics, a highly sophisticated biotechnology company that has full drug-development capability. The DART team’s expertise enables us to engage in developing new treatments from soup to nuts including: acquiring or collaborating on promising technologies, planning and implementing preclinical studies, conducting clinical trials that increase the likelihood of a successful outcome, and navigating the regulatory process to ensure the fastest path forward for promising new medicines. The “birth” of this unique biotech company has been covered by many industry publications as a prime example of the innovation that is needed to revolutionize the rare disease drug development enterprise.

DART Therapeutics is fast-tracking the development of several different treatments for Duchenne. The most advanced drug in DART’s pipeline is HT-100, now in a clinical trial for 30 boys with the disease including Charley. The company is prepping other promising therapies for clinical trials and building infrastructure improvements that will lead to faster, better drug development.

Charley’s Fund is also investing in more effective outcome measures, building relationships with clinical trial centers so they can get trials started very quickly, and running preclinical animal studies to determine which set of molecules should be next up to bat. As our activity level has dramatically increased, so has the associated budget. That’s where your help has been — and continues to be — critical to our success. The money you donate to Charley’s Fund goes directly to our medical research and drug development efforts.

When we started Charley’s Fund, our little boy was four years old. He was pint-sized, and the foundation wasn’t much bigger. We have grown from a small group of family and friends to a circle of supporters that is 8,000+ strong. Yet we still maintain a “lean and mean” model, only employing the skeletal staff that is absolutely necessary to drive us toward accomplishing our goal. That goal has been, and always will be, the same as it was when we started: to develop multiple treatments for Duchenne in time to save Charley’s life and many thousands of children like him. In November 2004, we set out to give Charley a better future than the one doctors told us to expect. Nine years later, we are a good way down that path. Until we reach the finish line, we will not waiver. We will not get side tracked. We will not rest. Thank you for providing the support we need to keep pushing full force toward that goal. We hope you will do the same this year.

May 2014 bring health, happiness and the first FDA-approved therapy for Duchenne!

All our gratitude,

Tracy Kramer Seckler and Benjamin Seckler, MD

FUNDRAISING

(L-R) At the Matt’s Promise Benefit Concert, recording artist David Gray with Matt’s daughters and wife; David Gray on stage; Benjy Seckler in a serious moment.

Riders line up at the start.

MATT’S PROMISE BENEFIT CONCERTMay 2013The annual Matt’s Promise benefit concert held in May at Cipriani Wall Street in NYC once again had a huge impact on Charley’s Fund. Proceeds from the night exceeded half a million dollars! David Gray sang his heart out, much to the delight of 800+ swaying, picture-snapping fans. Supporters raised their paddles to buy over-the-top trip experiences like a vacation to Paris to see Eminem live in concert and a set of “player’s tickets” to Superbowl XLVIII.

Mark your calendars for next year’s event, sure to be a sellout on May 8, 2014!

CHARLEY RIDEJune 2013Our annual Charley Ride keeps getting better with age. This year marked our third anniversary and thanks to some incredible volunteers we really stepped it up a notch. The Kids Discovery Challenge, planned and implemented by teenagers, brought in a whole bunch of smiling little ones hopping around on obstacle courses and creating structures out of wacky materials. At the other end of the spectrum, we added a “pro-62”, a faster paced ride for riders seeking an intense physical challenge. All told the event raised $22,000 and increased our exposure in Charley’s hometown. We’ve already picked up some new volunteers to help make next year’s event even more successful.

THE RACE AGAINST TIMEOct 2013NYC’s Central Park was blanketed in lime green and mega-smiles once again this year during the 4th annual Race Against Time. Event chair Ellen Wilner and her all-star committee recruited new runners and ran a seamless event that brought in upwards of $125,000. We were honored to have 62 cadets from the West Point Military Academy running this year in honor of Davis Cox, age 8. Cox hails from Florida and members of his extended family were major contributors to this year’s event. And brand new this year…The Race Against Time spread north! A local crew took it upon themselves to plan a Berkshire County version of the Race Against Time. More than 100 runners participated in the relay event and plans are already underway to make it even bigger and better next year.

CHECK IN WITH DARIUSDarius celebrated his 24th birthday in September, and continues to inspire teens all over the country. He’s been Skyping with schools and youth groups around the nation to educate kids about Duchenne and the fight for a cure. Darius participated in a clinical trial sponsored by Charley’s Fund to test whether a drug called Revatio could help heart function in young men with Duchenne. The results are in, and unfortunately the drug did not show benefit. That was not the answer we hoped for, but now we know to move on to testing other drugs. We are so grateful to Darius and all the other guys who travelled to Baltimore to help us. We will not stop until we find the medicines that can help Darius, Charley and thousands of boys and young men like them all over the globe. You can help us do that in a new way this year in honor of Big D — text DARIUS to 80100 to donate $10 to Duchenne research!!

news

FIGHTING DUCHENNE MUSCULAR DYSTROPHYCharley’s Fund

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RESEARCH UPDATE

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a good shop does a boy goodon a lighter note:

Stocking Stuffers and Gift Items!Have you checked out the Charley’s Fund online store recently?

Some new merch could be right up your alley for holiday gifting…

Charley’s muscles are tested with EIM.

To read the news on

all of our projects, make a donation or

shop our fun Charley’s Fund products

visit charleysfund.org.

Biovista CollaborationThis year we formed a partnership with Biovista,

a company with a proprietary computerized analysis system called COSS. COSS combed through more than 90,000 molecules in search of medicines that are already in the clinic or on the market for other diseases but may benefit kids with Duchenne. Biovista screened for drugs that have not been reported in the medical literature, but which might be a very good fit with Duchenne scientifically — in other words, truly novel findings.

This search resulted in over 20 candidates that we have reviewed in depth. We have prioritized those drugs and are moving ahead with four of them, which entails animal testing to validate their potential. No stone unturned, even if we have to look under 90,000 stones! Your support of our annual appeal will help pay for the preclinical studies on the four most promising “hits” from this collaboration.

SARMMuscle strengthening agents will be a critical

part of the “cocktail” of medications that ultimately ends Duchenne. For that reason, Charley’s Fund is supporting the development of DT-200, a Selective Androgen Receptor Modifier (SARM). Our clinical trial plan got a thumbs up from the MHRA, the UK’s equivalent of the FDA.

Added bonus: Our SARM drug has potential to help patients with other diseases, so we are talking to patient groups in other neuromuscular disease areas about working together to support the devel-opment of this promising medicine. Your support of our annual appeal will help finance final preparation for regulatory filings and clinical trial start-up.

RESULTSWe started funding medical research and drug

development in 2005. We follow through on every project we initiate to make sure we get an answer. We are committed to reporting results no matter what the outcome. This enables us to keep moving the most promising treatments forward and move on from leads that do not bear fruit. For full news on all of our projects, visit charleysfund.org.

Electrical Impedance Myography (EIM)

Now that several new medicines are entering clinical trials for Duchenne, we must make sure that we have the right tools in place to show if a drug works. Charley’s dad has always said, “The only thing worse than having no effective treatment for our son would be having an effective treatment but not being able to prove that it works.”

Currently the “gold standard” outcome measure for Duchenne clinical trials is the 6 minute walk test. It’s extremely simple, bordering on crude. Doctors measure how many meters a patient can walk in six minutes. As you can imagine, this test has many drawbacks including variability based on effort and failure to detect subtle changes in muscle improvement.

We are developing a new technology that could help us solve this problem called Electrical Impedance Myography (EIM). EIM is a noninvasive, painless, highly sensitive and objective measure of muscle integrity. With your support, we have shown that EIM can accurately measure muscle integrity in Duchenne patients. Your support of our annual appeal will help us continue to use this innovative tool as a supplemental outcome measure in the HT-100 trial.

“My hopes are all in that bottle you hold. You very well may hold the diamond in the rough. Praying that this works for your son and all the boys on it. Thank you for participating and making a difference in all our boys’ lives.” – parent of a child with Duchenne

“I almost couldn’t drive the two hours home because I just felt like crying for joy! This is a big and new day. Thank you!” – parent of a child in the HT-100 trial

THEY SAY a picture speaks a thousand words, and these photos are a prime example. It’s difficult to find adequate

words to express the hope, pride, and anxiousness we felt this summer when Charley took his first dose of HT-100. The story of this clinical trial is one for the history books. HT-100 is derived from an ancient Chinese herb known as chang shan. For decades, scientists have known of its healing properties. Many animal studies have demonstrated that this compound may reduce fibrosis and improve muscle function. But major hurdles blocked the path to getting this compound into a clinical trial for patients with Duchenne. For starters, the drug didn’t get very far in clinical trials for other diseases such as cancer because it caused severe nausea and vomiting. The company that owned the drug had shelved the compound due to lack of funding and shifting business priorities.

We believed in the promise of this compound and did not let those obstacles stand in our way. We assembled a team of drug development experts to conduct thorough due diligence to determine if this was indeed a good “shot on goal” as treatment for Duchenne. The answer was yes, so we then brokered a deal with the owners of the drug and took over development. Our safety and toxicology experts reformulated the drug with an enteric coating, which allows the medicine to bypass the stomach and release slowly into the bloodstream. We gathered all of the existing data on the drug, filled in the holes with the needed preclinical experiments, and earned a green light from the FDA to proceed with a clinical trial for boys with Duchenne.

FEATURED PROJECT

HT-100 Clinical TrialToday HT-100 is in a clinical trial at

five hospitals across the US. The goal of the trial is to help us determine the best dose for maximum safety and tolerability. Thanks to our supporters, we are on our way to finding out if this drug can delay disease progression and result in longer, healthier lives for children with Duchenne. To make the story even more amazing, the development of HT-100 has been 100% financed by nonprofit foundations. Led by Charley’s Fund and our partner the Nash Avery Foundation, 17 organizations have joined forces to keep this clinical trial on the fastest possible track. What a testament to the power of a patient community!

Next steps: Thirty boys are enrolled in the phase 1b/2a trial to test safety and tolerability of HT-100. The trial will be complete in mid-2014. If we can demonstrate that the drug is safe and tolerable at a dose that is expected to result in clinical benefit, we will move to the next step: A larger, international “pivotal” trial designed to show that the drug actually results in healthier muscles for boys with Duchenne. Provided we have adequate funding, that trial could start in the second half of 2014.

Exon Skipping Exon skipping is a therapeutic approach that

acts like a molecular “bandaid” to address a ge-netic mutation. Charley’s Fund has helped move this promising therapy forward with an investment of $4.5 million in the field. Results are finally rolling in, and it looks like our hefty contribution is paying off with the dividends we hoped for: a viable thera-py for boys with Duchenne! Results from a clinical trial run by Sarepta Therapeutics in Cambridge, Mass.: 12 boys who have been treated with Eteplirsen for two years have been holding steady. Anyone familiar with Duchenne knows that this is a HUGE win. Over the course of two years, boys with Duchenne between the ages of 7-10 generally experience dramatic decline in muscle function. The clinical improvement over untreated boys is not surprising, because Sarepta has also clearly shown that Eteplirsen produces dystrophin, the protein that boys with Duchenne are missing.

Drug development is a risky business, and the news isn’t always fantastic. Duchenne families experienced a setback this year when Glaxo Smith Kline reported that Drisapersen, their lead exon skipping drug, failed to meet its primary endpoint in a phase 3 clinical trial. The bottom line: kids on the drug did not do any better on the six minute walk test than kids who were not given the medicine.

It is crucial to note that this news does not doom exon skipping as a therapeutic approach. GSK is analyzing their data to determine if a subset of children benfitted from the drug and if there is a path forward. Also, there are vital differences amongst the different exon skipping drugs in development. Your support of our annual appeal will help us make our position clear to the FDA: We have enough data from Sarepta to approve Eteplirsen on an accelerated basis.

Pilot Trials Now Results are In

Together with other nonprofit foundations, we sponsored two clinical trials using FDA-approved drugs that patients are using for other diseases. The results are in for both:

REVATIO was tested in 15 young men with Duchenne to determine if it could improve heart health. Unfortunately, the drug did not result in any benefit. Although that is not the answer we hoped for, we are proud to say that we posed the question and implemented a trial that got us an answer. We will keep coming up to bat until we round the bases. Each time we take a swing we get better and better.

Thanks are due to our funding partners the Nash Avery Foundation, Action Duchenne, Hope for Javier, Zubin’s Wish, and Cure Duchenne for sup-porting the trial and to Drs. Kathryn Wagner and Dan Judge and their clinical team for giving young men with Duchenne the chance to help determine if Revatio could help our boys.

INCRELEX, a drug that is currently used to treat growth hormone deficiency, was tested in a clinical trial with 40 boys at Cincinnati Children’s Hospital Medical Center. The data suggest that Increlex did not improve muscle function, but boys on the drug grew a great deal more than the untreated control group. Stunted growth and delayed puberty are two side effects of chronic steroid treatment, which most boys with Duchenne are using for lack of a better treatment.

The information we gleaned from the Increlex trial gives doctors another set of data to make informed decisions about how to best manage care of kids with Duchenne.

UpdatesHighlightsCharley’s Fund’s sole mission is to direct money into the hands of researchers who have the best shot at developing a treatment or cure for Duchenne Muscular Dystrophy. Our goal is to cure DMD in time to save Charley’s life and the lives of thousands of boys like him.

“I Believe…” chocolate trufflesHand-crafted by Brinn Chocolates of South Burlington, VT these decadent truffles make the perfect gift for teachers, colleagues, or anyone else who appreciates a sweet smile.

Squeeze Away Stress!The holiday season is notoriously stressful. Now we can help you manage! Our new stress balls are prime shape and texture for optimum squishing and squeezing plus they sport our signature smile, which we hear is contagious! Stuff your kids’ stockings, pass them out at a party, or have them on hand at home for an indoor game of tossup when it’s too cold to play outside.

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Visit charleysfund.org/shopfor a wide variety

of great items for everyone on your list!

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