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You Make It Possible Every action brings us closer to ending Duchenne.

Whether you write to your representative in Congress, run a race, or become a monthly supporter, you can do something that will make a difference in the fight to end Duchenne. Join our Make It Possible photo campaign today! It’s a fun way to show that you are getting involved, taking action, and raising awareness. Stop by our photo station located near the 2013 Annual Connect Conference registration area to participate. Help us demonstrate the strength of our community and our determination to make a real difference. Together we will make it possible. Together we will end Duchenne.

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PPMD Research

2011-2013 • Investing in a Future for Duchenne REPLACING DYSTROPHIN $1.3M

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TREATING THE HEART $1.6M

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BLOCKING FIBROSIS $413K

Multi-exon skipping Improved exon skipping Utrophin upregulation (Summit, Tivorsan, PTC Therapeutics, U Penn) Travel support for Sarepta Trial Support for continued access to Ataluren

REBUILDING MUSCLE $1.9M

Eplerenone clinical trial SERCA2A gene therapy in preclinical model Microdystrophin functionality in heart Glyco–protein based therapeutic for heart function Tadalafil and Sildenalfil– Pilot Study Combining prednisone and sildenafil

GENETIC MODIFIERS & REPLACING STEROIDS $250K

Support for Halo Therapeutics HT–100 Preclinical studies of Spironolactone Wellstone Center supplement to support research on blocking fibrosis

SUPPORTING CLINICAL TESTING $658K

“To our Tivorsan team, PPMD represents the voice of the Duchenne community. This support is critical to our ability to navigate through the drug development process and achieve meaningful milestones.“

– Joel Braunstein, Tivorsan

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• • • • •

Follistatin gene therapy Wellstone Center supplement to support research on muscle regeneration Travel support for participants in Shire/ Acceleron Study Adult–derived muscle stem cells

Selective steroid receptor modulator without prednisone side effects (Weisman Fellow and Research Grant) Identification of genetic modifiers of Duchenne severity

Support for four TACT Review Meetings Review of Approved Drugs for Duchenne (RADD) Project Fluid Biomarker Identification MRI Biomarker validation Non-amulatory Endpoint Development

“PPMD understands that developing viable Duchenne therapies is a collective effort. Their funding of work aimed at identifying and developing new biomarkers could play a fundamental part in advancing promising medicines through clinical trials.”

– Jon Tinsley, Senior Director of R&D of Summit PLC

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Welcome PPMD Friends—

We are thrilled to have you at the 2013 Connect Conference! If this is your first time with us or if you’ve been a conference regular, thank you for joining us in beautiful Baltimore. We’ve accomplished so much together. When I think of all that our community has made possible over the years, all that we accomplished since our Ft. Lauderdale Connect Conference, and all that we’re doing today, my heart fills with appreciation and gratitude for each and every one of you— for your passion and commitment. Through our hard work and dedication, as well as that of clinicians, researchers, and industry who have joined our efforts and join us here at the conference, we’re finally seeing some of the moments we never thought we would see. Life with Duchenne is much different than it was when my sons were diagnosed in 1984. Today, people with Duchenne are walking longer than ever before, they’re graduating from college, they’re getting married, and they’re starting careers and families of their own.

BETTER

FASTER

NOW

Projects that will improve the quality of drug candidates entering clinical testing

Projects that will decrease the time required to test drugs for Duchenne and Becker

Reviewing and testing approved drugs to buy time for this generation of boys

The theme of this year’s conference is Better, Faster, Now. You will see this idea carried throughout your agenda. This is how we categorize projects in our research portfolio. But actually, Better, Faster, Now goes beyond research alone. Just like PPMD. We know that drug development is a complicated ecosystem that benefits from consistent care across centers, valid regulatory strategies, clinical infrastructure, current natural history data, availability of biomarkers, and an understanding of the socioeconomic burden of disease; these are just a few of the things that can impact the likelihood of success for new drugs. Although we put significant dollars directly into development efforts for particular drugs, this strategy alone will never move the needle fast enough. We have to enable drug development efforts across the whole ecosystem in a holistic manner. That’s why we won’t just be bringing you research updates and presentations from industry over the next three days. We will also be talking to you about advocacy, critical information on care, and how you can improve daily life for you and your family. Most importantly, PPMD exists to help you connect. There is strength in numbers and this conference unites you with other families on a journey similar to yours, speaking the same language. And on a larger scale, we hope that this conference unites the Duchenne community. Thank you for spending this time with us. You being here is hugely important. We will not rest until we end Duchenne. And with you on our team we know that we will continue to see the impossible become possible. Have a great conference and I look forward to reconnecting!

Pat Furlong, PPMD President & CEO

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Share the Experience

Want to share what you’re doing and learning at the Connect Conference?

Follow us on Twitter #PPMDconnect Enhance your 2013 Annual Connect Conference experience by joining conference attendees and PPMD staff on PPMD’s social networking channels. Follow the official PPMD Twitter channel, @ParentProjectMD

and use the Connect Conference hashtag, #PPMDconnect to join in the conversation. Your photos and insights will help us share what we are learning with the entire community!

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PPMD’s White Paper: Continuing the Quest for Accelerated Approval Putting Patients First: Recommendations to speed responsible access to new therapies for Duchenne

recommendations about how to effectively evaluate new therapies for Duchenne and other, rare, serious, and life-threatening disorders. The committee came up with the following recommendations to the FDA, to fully realize the potential to speed responsible access to new therapies for Duchenne:

Earlier this Spring, PPMD proudly produced Putting Patients First, a white paper outlining recommendations to speed responsible access to new therapies for Duchenne. Since we launched our advocacy efforts in 2000, we have seen continual progress in Washington. From the passing of the MD-CARE Act in 2001, to its reauthorization in 2008 (and hopefully again in 2013), to historic FDA related legislation, PDUFA and FDASIA, passed in July 2012. From virtually no funding to over $250 million leveraged in Duchenne-specific resources, the voices of this community continue to be heard in D.C. But now it is time to take our discussions with federal regulatory agencies to the next level. We have been working with the FDA and other regulatory agencies for the last decade to educate them on Duchenne and the catastrophic affect this disorder has on both patients and families. As our relationship continues to grow and build, and with the implementation of FDASIA, we are hopeful that the FDA will work with PPMD and the rare disease community to take advantage of the new opportunities created by this landmark legislation. To ensure we make the most of these new opportunities, PPMD brought together an expert Advisory Committee, including leading voices in academia, industry, and patient advocacy, to issue

Expand the use of accelerated approval for therapies intended to treat rare diseases, including Duchenne muscular dystrophy.

Issue clear guidance outlining the level of evidence required for the use of surrogate endpoints in order to expand the scope of acceptable endpoints, including novel surrogate and intermediate clinical endpoints, used to approve drugs for serious or life-threatening diseases with unmet medical need.

Pilot the use of adaptive approval for serious and life-threatening disorders with significant unmet medical need, using existing authority under current law.

Give greater weight to the demonstrated benefit/risk preferences of patients, as well as caregivers in the case of pediatric illness, when making risk benefit determinations. Subpart D considerations must be evaluated here, yet benefit/risk should also be addressed within the context of patients living with Duchenne.

Parent Project Muscular Dystrophy and the distinguished panel of advisors who contributed to this report stand ready to work alongside the FDA to strike a more appropriate balance between clinical certainty and patient access to potentially life-saving treatments. Patients and their families, frustrated by the slow pace of progress and desperate for access to new treatments for this devastating illness, deserve nothing less. Learn more and read the full white paper at

ParentProjectMD.org/PuttingPatientsFirst

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CLINICAL TRIALS: actively recruiting

ATALUREN

A Novel Drug for Nonsense Mutations by PTC Therapeutics, Inc. • What is the current status of ataluren?

»» PTC Therapeutics recently opened a Phase 3 trial of ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). This randomized, doubleblind, placebo-controlled trial is designed to confirm the safety and efficacy results seen in its Phase 2b study. The study will enroll 220 participants at approximately 50 sites in North America, South America, Europe, Israel, Asia, and Australia. »» Studies for nmDMD patients previously enrolled in ataluren trials are ongoing in each of their countries. »» PTC has applied for conditional approval of ataluren for nmDMD in Europe and expects a decision by regulatory authorities by second half of 2013. No such program is available in the US. »» Ataluren is also being studied in patients with cystic fibrosis (CF) in a Phase 3 trial. Data was presented at the European Cystic Fibrosis Society on June 8, 2012.

• What is nonsense mutation?

A nonsense mutation is a premature stop signal in the genetic code that interrupts the production of a protein. Proteins are essential to the proper working of every cell in the body. Nonsense mutations result in incomplete proteins that do not function properly and in turn cause a genetic disorder. For example, in nmDBMD, the muscle protein dystrophin is incomplete and non-functional, leading to muscle wasting and progressive loss of muscle strength.

• What is the goal or purpose of this research?

Ataluren is an investigational (experimental) drug that is designed to enable the formation of a functioning protein in a patient with a genetic disorder due to a nonsense mutation. Ataluren is taken orally and has the potential to treat the root cause of the disorder by overriding the premature stop signal so that a functional protein can be made. It does not alter a patient’s genetic code or introduce genetic materials into the body.

• Who is funding this research?

Ataluren was developed at PTC Therapeutics. The development of ataluren has been supported by the FDA Office of Orphan Products Development, Parent Project Muscular Dystrophy, the Muscular Dystrophy Association, Cystic Fibrosis Foundation Therapeutics Inc., and the National Center for Research Resources.

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• When will Ataluren be commercially available?

Ataluren is an investigational drug that is only available through clinical trials. It has not been approved for use by regulatory authorities in any country and thus cannot be legally purchased for use by a patient. Based on estimates regarding patient enrollment, initial, top-line data from the Phase 3 clinical trial are expected in mid-2015. If full trial results support approval and FDA approves our application, ataluren could be available in the US as early as the second half of 2016. PTC plans to apply for approval in other countries following US approval. If ataluren is granted conditional approval in the EU it could be available there as early as 2014.

• How can I find out if Ataluren would benefit my child?

Approximately 13% of boys with Duchenne have a nonsense mutation. You should discuss genetic testing with your child’s physician or a genetic counselor. Usually, only a small amount of blood is required to perform the test. The blood sample must be sent to a specialized laboratory that has expertise in Duchenne. Ataluren is specifically for patients with a nonsense mutation; therefore it will not benefit patients if the disorder is caused by a deletion or duplication.

• Where can I learn more about Ataluren?

»» You can learn more about ataluren at www.ptcbio.com. Information about the Phase 3 clinical trial is available on that site as well as on www.ClinicalTrials.gov (search term: NCT01826487) and www.DuchenneConnect.org. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: actively recruiting

Becker Natural History Study

Becker Muscular Dystrophy: A Natural History Study to Predict Efficacy of Exon Skipping • What stage is this research?

This study is actively recruiting participants.

• What is the goal or purpose of this study?

This is a natural history study to characterize the Becker muscular dystrophy (Becker) clinical presentation. Investigators will collect information on Becker patients whose in-frame mutations mirror those that would be generated in Duchenne muscular dystrophy (Duchenne) patients treated with skipping of exons 45, 51, or 53. Researchers will correlate specific abnormal dystrophin proteins with the range of clinical outcomes including physical development, mental development, and quality of life in patients with these specific mutations. Researchers will investigate the observed variability to deepen our understanding of molecular mechanisms relevant to the optimization of exon skipping therapeutic approaches.

• Who is funding this study?

This study is funded by the National Institutes of Health (NIH).

• Who is eligible to participate in this study?

To participate in this study you must be a male with Becker, age 4 and above, and have one of the following dystrophin gene deletions: exons 45-47, exons 45-48, exons 45-51, exons 45-53, or exons 48-51 where the boundaries of the mutations are confirmed.

• What do I have to do if I decide to participate in this study? At each study visit you will have a physical and neurological exam by a study physician, and review your health medication and cardiac history. You will have strength, function, and breathing testing performed by a physical therapist, and you will also complete quality of life questionnaires. At your first study visit you will also have a blood draw and a skin biopsy, and adults will have the option to have a muscle biopsy.

• Where does this study take place?

Texas Children’s Hospital in Houston, TX; the University of California, Davis, in Sacramento, CA; and Alberta Children’s Hospital in Calgary, Alberta, Canada. More sites will be added in the future so be sure to check www. ClinicalTrials.gov or the website for the CINRG group: www. cinrgresearch.org for updated site lists.

• How many visits to the study site are necessary? There will be a total of 4 visits–a baseline evaluation and 3 annual follow-up visits over a 3-year period.

• Can any visits be done locally? No, they must be done at a participating CINRG center.

• Is there any funding to help pay for travel? The study does not provide any funds for travel; however please inquire at each individual site as some CINRG sites may have alternative resources for travel reimbursement or assistance.

• Will I get paid for participating in this study? No, you will not be paid for your participation in this study. You will not be charged for additional tests and procedures that are performed only because you are participating in this research. Your responsibility to pay for other medical treatment will not be changed by your participation in this study.

• Why should I consider participating in this study? While no personal benefit can ever be guaranteed by participation in a study, there are other benefits, including allowing you to play an active role in your own health care (or that of your child), gaining access to medical specialists that are normally not available to you or your child, and helping others by contributing to the better understanding of Becker.

• Where can I learn more about this study? »» You can learn more about this study at www.cinrgresearch.org and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

This study will be run at participating centers of the Cooperative International Neuromuscular Research Group (CINRG) network. The participating CINRG centers include Children’s National Medical Center in Washington, D.C.; the University of Pittsburgh in Pittsburgh, PA; the University of Minnesota in Minneapolis, MN; Ann & Robert H. Lurie Children’s Hospital of Chicago in Chicago, IL;

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CLINICAL TRIALS: actively recruiting

Coenzyme Q10 and Lisinopril Clinical Trial of Coenzyme Q10 and Lisinopril in Muscular Dystrophies • What stage is this research?

This clinical trial is actively recruiting participants.

• What is the goal or purpose of this study?

This is a clinical trial to test a medication used for the heart, called Lisinopril (an angiotensin converting enzyme (ACE) inhibitor) and supplement called Coenzyme Q10, to ameliorate the decline in cardiac muscle functions that occurs in muscular dystrophies. The goal of this study is to determine if Coenzyme Q10 alone, Lisinopril alone, or a combination of Coenzyme Q10 and Lisinopril is more effective at delaying the onset of cardiac symptoms in patients with Duchenne, Becker, or Limb Girdle muscular dystrophy.

• Who is funding this study?

This study is funded by the Department of Defense (DOD).

• Who is eligible to participate in this study?

To participate in this study you must have a confirmed genetic diagnosis of Duchenne, Becker, or Limb Girdle muscular dystrophy (certain type 2 only), be 8 years of age or older, and have no clinical cardiac symptoms with a normal left ventricular fractional shortening (>28%) on echocardiogram. You cannot currently be taking Coenzyme Q10, Lisinopril, or beta blockers (a type of heart medication), and you cannot have used these medications in the past for longer than 6 months.

• What do I have to do if I decide to participate in this study? First you will have a screening visit. If you are eligible to participate in the study based on the results of your screening visit, you will be randomized to one of four study arms: Arm 1 – CoQ10 alone, Arm 2 – Lisinopril alone, Arm 3 – both CoQ10 and Lisinopril, or Arm 4 – Enhanced standard of care with no study medication. You will then have scheduled study visits, which include a physician exam, strength & breathing testing, spine x-rays, echocardiograms, electrocardiograms, and blood work.

• Where does this study take place?

This study will be run at participating centers of the Cooperative International Neuromuscular Research Group (CINRG) network. This study is currently approved at 8 CINRG sites: Children’s National Medical Center, Washington, D.C.; Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL; Carolinas Medical Center, Charlotte, NC; University of Pittsburgh, Pittsburgh, PA; University of Tennessee, Memphis, TN; University

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of California, Davis, Sacramento, CA; National Center of Neurology and Psychiatry, Tokyo, Japan, and Alberta Children’s Hospital, Calgary, Alberta, Canada. However, more sites will be added in the future so be sure to check www.ClinicalTrials.gov or the website for the CINRG group: www.cinrgresearch.org for updated site lists.

• How many visits to the study site are necessary? There are 6-7 visits during the 24 months of the study, which includes screening and months 0.5, 1.5, 6, 12, 18 and 24.

• Can any visits be done locally? No, visits must be done at a participating CINRG center.

• Is there any funding to help pay for travel? The study does not provide any funds for travel; however please inquire at each individual site as some CINRG sites may have alternative resources for travel reimbursement or assistance.

• Will I get paid for participating in this study? No, you will not be paid for your participation in this study. The study site will provide you with the study medication free of charge, should you be placed in an arm involving the use of a study medication. You will not be charged for additional tests and procedures that are performed only because you are participating in this research. Your responsibility to pay for other medical treatment will not be changed by your participation in this study.

• Why should I consider participating in this study? One benefit that may result from participation in this clinical trial is a delay in the development of heart problems associated with muscular dystrophy. We are doing this study to find out whether or not people with certain types of muscular dystrophy will do better with Lisinopril, CoQ10, or neither. We anticipate that there will be a benefit, but the amount of potential benefit is unknown. There is no greater or lesser benefit anticipated for any of the four randomization groups listed above. Everyone who participates in the study will benefit from more frequent doctors visits and closer medical monitoring. By watching you more closely, we may find problems and treat them earlier than if you were seen less often.

• Where can I learn more about this study?

»» You can learn more about this study at www.cinrgresearch.org and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: Actively recruiting

DP ARF Ultrasound

Double-Push Acoustic Radiation Force (DP ARF) Ultrasound for Monitoring Degeneration in Duchenne Muscular Dystrophy

• What stage is this research?

This study is actively recruiting participants.

• What is the goal or purpose of this study? This is a pilot clinical trial to assess the ability of a new ultrasound-based imaging method, Double-Push Acoustic Radiation Force (DP ARF) ultrasound, to monitor the progression of Duchenne muscular dystrophy (Duchenne).

• Who is sponsoring this study?

This study is sponsored by the University of North Carolina, Chapel Hill, in collaboration with the National Institute of Neurological Disorders and Stroke (NINDS).

• Why should I consider participating in this study? While no personal benefit can ever be guaranteed by participation in a study, a potential indirect benefit may be the satisfaction of being a part of the advancement of medical science to improve monitoring and treatment of Duchenne and the other 30+ types of muscular dystrophies in children and adults.

• Where can I learn more about this study? »» You can learn more about this study at www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• Who is eligible to participate in this study?

The study population will include 30 boys with Duchenne enrolling at ages 5 to 9 years. To be considered for enrollment, boys must have a clinical onset of Duchenne by age 5, and must have the ability to stand, either alone or with assistance.

• What do I have to do if I decide to participate in this study? All boys will be imaged 3 times annually for 4 years. In addition to DP ARF imaging every 4 months, the boys will undergo standard quantitative muscle testing (QMT) and timed function tests (TFT) of time to standing, 6-minute walk, and 30-feet walk. Age at loss of ambulation will also be recorded for each boy.

• Where does this study take place?

This study takes place at the University of North Carolina, Chapel Hill (UNC-CH).

• How many visits to the study site are necessary, and can any visits be done locally? A total of 12 visits – 3 per year for 4 years. All visits must be at UNC-CH.

• Is there any funding to help pay for travel? Yes, this study provides reimbursement for air travel (for the patient and an accompanying adult) and car travel (by the mile). Hotel accommodations in Chapel Hill are also provided.

• Will I get paid for participating in this study? No, there is no payment for participating, other than the funding to help with travel costs.

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CLINICAL TRIALS: actively recruiting

Duchenne Natural History Study Longitudinal Study of the Natural History of Duchenne Muscular Dystrophy • What stage is this research?

This study is actively recruiting Duchenne muscular dystrophy and healthy control participants.

• What is the goal or purpose of this research? »» The purpose of this study is to establish the largest longterm assessment of people with Duchenne muscular dystrophy (Duchenne). In this study, the investigators associated with the Cooperative International Neuromuscular Research Group (CINRG) will take a detailed look at Duchenne participant’s physical abilities, the medical problems they experience, and how they use health care services. Physical abilities will be compared to a group of healthy controls. »» The second purpose of this study is to find out whether small, normal differences in the genetic makeup of people with Duchenne (called “single nucleotide polymorphisms” or “SNPs”) affect how their disease progresses and relates to muscle strength/size and steroid response. »» The third purpose of this study is to study genetic variations associated with Duchenne. »» The final purpose of this study is to determine whether certain biomarkers are present in people with Duchenne and not in healthy controls.

• Who is sponsoring this research?

This study is sponsored by the U.S. Department of Education, National Institutes of Health (NIH), and Department of Defense. Parent Project Muscular Dystrophy is funding the study of the New Young Duchenne Cohort.

• Who is eligible to participate in this trial?

»» Researchers are now recruiting for the New Young Duchenne Muscular Dystrophy Cohort. 100 male Duchenne participants, age 4 – 7 years old, are needed. The diagnosis of Duchenne must be confirmed by genetic test and/or muscle biopsy. »» Researchers are now recruiting for the Healthy Control Cohort. 120 male healthy controls, ages 6-17 years old, are needed.

• What to I have to do if I decide to participate in this trial?

»» Duchenne Muscular Dystrophy Cohort: At each study visit you will have a physical and neurological exam by a study physician, and your health medication will be reviewed. You will have strength, function, and breathing

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testing performed by a physical therapist, and you and/ or your parent/legal guardian will also complete quality of life questionnaires. Optional saliva and/or blood samples will be collected for genetic and/or biomarker (markers that may help us understand more about Duchenne) analysis. »» Healthy Control Cohort: At each study visit you will have strength and function testing completed. Optional blood samples will be collected for biomarker (markers that may help us understand more about Duchenne) analysis.

• Where does this study take place?

»» This study will be run at 25 participating centers of the Cooperative International Neuromuscular Research Group (CINRG) network. The participating CINRG centers include 12 sites in the US and additional sites in Canada, Argentina, Puerto Rico, Italy, Sweden, India, Israel, and Australia. More sites may be added in the future so be sure to check www.ClinicalTrials.gov or the website for the CINRG group: www.cinrgresearch.org for updated site lists.

• How many visits to the study site are necessary? There will be up to 12 visits for Duchenne participants. There will be 2 visits for typically developing controls.

• Can any visits be done locally? No, they must be done at the participating CINRG center.

• Is there any funding to help pay for travel? The study does not provide any funds for travel; however please inquire at each individual site as some CINRG sites may have alternative resources for travel reimbursement or assistance.

• Will I get paid for participating in this study? No, you will not be paid for your participation in this study. You will not be charged for additional tests and procedures that are performed only because you are participating in this research. Your responsibility to pay for other medical treatment will not be changed by your participation in this study.

• Why should I consider participating in this study? While no personal benefit can ever be guaranteed by participation in a study, there are other benefits, including allowing you to play an active role in your own health care (or that of your child), gaining access to medical specialists


CLINICAL TRIALS: actively recruiting

that are normally not available to you or your child, and helping others by contributing to the better understanding of Duchenne.

• Where can I learn more about this study? »» You can learn more about this study at www.cinrgresearch.org and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

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CLINICAL TRIALS: actively recruiting

Duchenne Tissue Bank

Duchenne Muscular Dystrophy Tissue Bank for Exon Skipping • What stage is this research?

This study is actively recruiting Duchenne muscular dystrophy participants.

• What is the goal or purpose of this study? Researchers will utilize the Cooperative International Neuromuscular Research Group (CINRG) network to collect and store tissue and blood from patients with Duchenne with specific genetic mutations within the dystrophin gene that could be treated by antisense oligonucleotide (AO) drugs (exon skipping therapies).

• Who is sponsoring this study?

This study is sponsored by the National Institutes of Health (NIH)

• Who is eligible to participate in this study? Researchers are recruiting 60 males with Duchenne, age 4 years and older. Participants must have a known out-offrame deletion that could be targeted by exon skipping therapies for exons 45, 51, or 53. These include: Mutations eligible for exon 45:

Mutations eligible for exon 51:

Mutations eligible for exon 53:

• • • • • • • • •

• • • • • • • • • •

• • • • • • •

Exon 44 Exon 46 Exon 46-47 Exon 46-48 Exon 46-49 Exon 46-51 Exon 46-53 Exon 46-55 Exon 46-60

Exon 13-50 Exon 29-50 Exon 43-50 Exon 45-50 Exon 47-50 Exon 48-50 Exon 49-50 Exon 50 Exon 52 Exon 52-63

Exon 10-52 Exon 43-52 Exon 45-52 Exon 47-52 Exon 48-52 Exon 49-52 Exon 50-52

• What to I have to do if I decide to participate in this study? A blood and skin sample will be collected from each participant and will be held in a tissue bank at Carolinas Medical Center in Charlotte, NC for future Duchenne research.

• Where does this study take place?

Participants must have their blood and skin sample collected from a participating CINRG site.

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• How many visits to the study site are necessary? Only 1 visit will be needed to collect the blood and skin samples.

• Can any visits be done locally? No, they must be done at a participating CINRG center.

• Is there any funding to help pay for travel? The study does not provide any funds for travel.

• Will I get paid for participating in this study? No, you will not be paid for your participation in this study. You will not be charged for additional tests and procedures that are performed only because you are participating in this research. Your responsibility to pay for other medical treatment will not be changed by your participation in this study.

• Why should I consider participating in this study? While no personal benefit can ever be guaranteed by participation in a study, there are other benefits, including allowing you to play an active role in your own health care (or that of your child), gaining access to medical specialists that are normally not available to you or your child, and helping others by contributing to the better understanding of Duchenne.

• Where can I learn more about this study? »» You can learn more about this study at www.cinrgresearch.org and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: actively recruiting

Follistatin Gene Transfer

Follistatin Gene Transfer to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis • What stage is this research?

This Phase 1 trial is enrolling participants by invitation only.

• Where is this research being performed and who is funding this research?

This research is being led by Dr. Jerry Mendell at Nationwide Children’s Hospital Research Center in Columbus, Ohio. It is being funded by PPMD’s GIFTED Program and the The Myositis Association.

• What is the goal or purpose of this research?

»» Follistatin is a muscle growth-stimulating protein. This research is intended to build upon preliminary studies in mice with muscular dystrophy and in non-human primates which demonstrated that the follistatin gene, when injected into muscles, can cause significant increases in the size of injected muscles and improvements in the strength of injected muscles. If successful, the investigators can potentially prolong a patient’s ability to walk. »» The gene will be carried into the muscle by a virus called adeno-associated virus (AAV). This virus occurs naturally in muscle and does not cause any human disease.

the screening visit and several times throughout the study to make sure that there are no side effects from the gene injections.

• What are the future plans for this research?

If this study is successful, the investigators will expand the research to a phase 2 study and will also make plans to test it in patients with Duchenne.

• Where can I learn more about this research? »» You can learn more about this research at www.nationwidechildrens.org/center-for-gene-therapy and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• Who is eligible to participate in this study?

Again, this study is recruiting patients by invitation only. Adult male Becker patients (>18yo) with a proven mutation of the dystrophin gene and continued ambulation after age 15 years old are being recruited. Participants must have identifiable atrophy of the quadriceps muscle with muscle weakness ≥2 standard deviations below predicted using quantitative muscle testing. This study is also recruiting patients with sproadic inclusion body myositis.

• What do participants have to do in this study?

Participants with either of these diseases will have shots of the follistatin gene injected directly into their thigh muscle on one or both legs (one time only). 180 days following the gene delivery, participants will undergo testing to see if their muscle strength has improved and muscle biopsy to look closely at the muscle to see if the muscle fibers are bigger. Between the time of the gene transfer and the muscle biopsy, participants will be carefully monitored for any side effects of the treatment. This will include an MRI of the thigh muscle before treatment and at day 180 following treatment. Blood and urine tests, as well as physical examination will be done on the participants during

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CLINICAL TRIALS: actively recruiting

FOR-DMD

Finding the optimal steroid treatment for Duchenne muscular dystrophy • What stage is this research?

This study is actively recruiting participants.

• What is the goal or purpose of the FOR-DMD study?

»» This study will look at the benefits and side effects of the three most widely prescribed steroid treatments for Duchenne muscular dystrophy (Duchenne). The type of steroids commonly prescribed for Duchenne are called corticosteroids. Corticosteroids are a type of drug similar to natural hormones produced by the adrenal glands that reduce inflammation and suppress the immune response. They are often prescribed to boys with Duchenne. These steroids may have an effect on stabilizing or even improving muscle strength for a period of time but not all boys respond to treatment. The main steroid that is used is called predniboye. Deflazacort is also used in some countries. These are not “anabolic steroids” which is what athletes use illegally to build up muscle–these do not have an effect in Duchenne. Sometimes they are also referred to as ‘glucocorticoids.’ »» We will compare three different treatment groups: »» Daily predniboye »» Daily deflazacort »» Intermittent predniboye (10 days on / 10 days off). The study is randomised (your child’s treatment group will be decided randomly, as in drawing names from a hat or tossing a coin) and double-blind which means that neither participants nor their doctors will know which group the child is in (until the study is completed). »» All three steroid treatments are commonly used in boys with Duchenne and have been shown to be beneficial. Benefits include an increase in the length of time that the boys can continue to walk, reduction in the development of curvature of the spine, a longer time of adequate breathing, and possibly protection against the development of heart problems. »» However, we do not yet know which steroid treatment has the most benefit and most tolerable side effects. Therefore, this is a trial of present day steroid use which is needed because the practice of prescribing steroids varies a lot across doctors. This means that patients may not be getting the best possible treatment and management of side effects. All boys in this study will be receiving treatment with steroids and will be managed as per the recognized standards of care.

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• Who is eligible to be in this study? To be in this study your child must have a confirmed diagnosis of Duchenne by genetic test. He must be between 4 and 7 years old and NOT previously treated with steroids except by inhaler or as an ointment. 300 participants are needed, and approximately 30 have enrolled since January.

• Where will this study take place?

This study will take place in at least 40 muscle clinics in the US, Canada, UK, Germany, and Italy and other countries may also be included later. Please visit www.ClinicalTrials.gov for a complete list of all study sites. The principal investigators are Dr. R Griggs at the University of Rochester, NY and Prof. K Bushby at Newcastle University, UK.

• What will happen during the study? »» If you are interested in the study and your child appears to be eligible, he will be invited to visit the study site for a screening visit. At this appointment the study will be explained to you and your child in detail and some tests will be performed to allow the study doctors to ensure your child meets all the necessary requirements to participate in this study. After the screening period, you and your child will visit the study site at 3 months and then every 6 months after that. There will be a total of around 8-13 visits depending on when your child is enrolled. At each visit your child will be assessed to monitor benefits and side effects of corticosteroids. We hope that many children will be able to find a muscle clinic that is participating in the study reasonably close to where they live and that the study visits will take the place of their routine follow up. »» We expect your child will be in the study for 3-5 years.

• Is there any funding to help pay for travel? Not at this time. We are seeking additional support and may be able to offer travel assistance at some point during the study, but this is not guaranteed. After the screening visits, the frequency of clinic visits should not be any more than is usual for follow up in Duchenne.

• Will I get paid for participating in this study? No.


CLINICAL TRIALS: actively recruiting

• Will I have access to the drug once the study has ended? »» Yes, your doctor will discuss treatment options at the end of the study to decide the best steroid treatment plan for your child. »» The only issue is that deflazacort is not currently available in the US and we don’t know if it would be available in the US if the study showed it to be better than the other treatments. We are discussing this with the FDA. Deflazacort is already available in many countries and, in the US, it can be ordered from other countries by physician prescription.

• Who is funding this study?

This study is funded by the National Institutes of Health (NINDS).

• Where can I learn more about this study?

»» You can learn more about this study at www.for-dmd.org and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• Will participating in this study prevent my child from taking part in other clinical trials? We are aware that trials of other potential new therapies may start during the course of the study. As steroid treatment is part of the normal standard of care in Duchenne we do not believe that being in this study would prevent your child from being in another study later if there were one that he were eligible for. Moreover, although we hope that the majority of children will finish the whole trial, as with any clinical study, you are entitled to withdraw at any time if you no longer wish to participate.

• Why should I consider participating in this study? »» While no personal benefit can ever be guaranteed from being in a clinical trial, there are other benefits, including: »» Allowing you to play an active role in Duchenne research »» Access to medical specialists that might not normally be available to your child »» Access to high standard medical care and management in Duchenne »» Contributing to the better understanding of Duchenne and what the best steroid treatment is »» All participants will be getting active drug (there is no placebo group) and will be followed up and managed during the trial according to current standards of care.

• What should I do if I decide I want to take part in this study?

Please visit www.ClinicalTrials.gov for a complete list of study sites and the study coordinator at each site. Please call or email the study coordinator at the site nearest your home if you would like to participate. You can also contact the FOR-DMD US Project Manager, Kimberly Hart, at telephone 585-275-3767 or email Kim_Hart@urmc.rochester.edu.

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CLINICAL TRIALS: actively recruiting

HT-100

Safety, Tolerability, and Pharmacokinetics of Single & Multiple Doses of HT-100 in Duchenne • What stage is this research?

This trial is actively recruiting participants.

• What is the goal or purpose of this research? »» The main purpose of this study is to test the safety and tolerability of different, increasing doses of an experimental medication called HT-100 in boys and young men with Duchenne muscular dystrophy (Duchenne). The study medication, HT-100, is a medicine that may help promote healthy muscle regeneration, diminish inflammation and the resulting damage to muscle, and decrease the scar tissue that forms in the muscles of children with Duchenne. HT-100 does not appear to be mutation-specific, meaning it is potentially applicable to all boys and young men with Duchenne. »» Halo Therapeutics has an approved IND from the FDA allowing the company to conduct this research and has received Orphan Drug status for HT-100 for Duchenne.

• Who is funding this research?

The drug is being developed for Duchenne by Halo Therapeutics, LLC. This research is funded by the Nash Avery Foundation, Charley’s Fund, Parent Project Muscular Dystrophy, and 14 other Duchenne patient foundations.

• Who is eligible to participate in this trial?

This trial is open to males with Duchenne, ages 6-20 years old. Ambulatory or non-ambulatory boys can enroll, and participants may be either corticosteroid-naive or on corticosteroid therapy for at least 12 months (stable dose and regimen). Recent, substantial change in use of cardiac medications or medications affecting muscle function and/ or significantly compromised cardio-respiratory function would exclude you from this trial.

• What to I have to do if I decide to participate in this trial? »» Single and multiple ascending doses of HT-100 will be given to participants. Safety and tolerability will be assessed. Pharmacokinetic sampling, or measurements of the amount of HT-100 in the bloodstream, will also be taken. »» This initial study of safety and tolerability will be followed immediately by a 6-month, open label extension study. All boys and young men who complete the initial study will be eligible to participate in the extension study.

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• Where does this clinical trial take place? »» There are 5 sites in the US: UC-Davis in Sacramento, CA; Kennedy Krieger Institute in Baltimore, MD; Washington University School of Medicine in St. Louis, MO; Nationwide Children’s Hospital in Columbus, OH; and Cincinnati Children’s Hospital in Cincinnati, OH.

• How many visits to the study site are necessary? For the initial study, there are 9 separate visits to the study site, some of which require an overnight stay, and some of which occur over multiple days. For the extension study, there are 4 separate visits to the study site, about 1 every other month. All visits, except the visit at 6 months (which occurs over multiple days), are 1-day visits.

• Is there any funding to help pay for travel? Yes, there is some funding available to help pay for travel. In addition, Halo Therapeutics (the sponsor) is making available a travel coordinator to assist families with travel planning.

• Will I get paid for participating in this study? No, there is no stipend for participating in this study

• Why should I consider participating in this study? While no personal benefit can ever be guaranteed by participation in a clinical trial, there are other benefits, including allowing you to play an active role in the health care of your child, gaining access to medical specialists that are normally not available to your child, and helping others by contributing to the better understanding of Duchenne.

• Where can I learn more about this research?

»» You can learn more at www.halotherapeutics.com and www.ClinicalTrials.gov. »» Patients interested in participating in this trial can email Halo using this address: trialinfo@halotherapeutics.com »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: actively recruiting

ImagingDMD

Magnetic Resonance Imaging and Biomarkers for Muscular Dystrophy • What stage is this research?

This is an actively recruiting clinical trial.

• What is the goal or purpose of this study? This study focuses on developing Magnetic Resonance Imaging (MRI) as a tool to monitor disease progression in Duchenne and to serve as an outcome measure for clinical trials. The aim of the study is to determine whether noninvasive MRI outcome measures can replace muscle biopsies in evaluating the effectiveness of new treatments in future clinical trials.

• Who is funding this study?

This study is funded by the NIH – NIAMS/NINDS.

• Who is eligible to participate in this study?

To participate in this study you must be a male with Duchenne muscular dystrophy, age 5 to 14 years upon entering the study, able to walk independently for at least 100 meters (length of a football field) without assistive device and climb 4 stairs. Subjects will not be excluded based on corticosteroid treatment. Minorities with Duchenne who fit these inclusion criteria are needed in this study.

• Will I get paid for participating in this study? No, there is no stipend for participating in this study.

• Why should I consider participating in this study? While no personal benefit can ever be guaranteed by participation in a clinical trial, there are other benefits, including allowing you to play an active role in the health care of your child, gaining access to medical specialists that are normally not available to your child, and helping others by contributing to the better understanding of Duchenne.

• Where can I learn more about this study?

»» You can learn more about this study at www.ImagingDMD.org and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• What do I have to do if I decide to participate in this study? MRI and Magnetic Resonance Spectroscopy (MRS) measurements will be performed on the participants’ leg muscles, and muscle strength and functional tests such as walking and climbing 4 steps will also be performed. Additionally, a small sample of skin cells will be taken from the participants and stored in established tissue banks.

• Where does this study take place?

This study is recruiting at 3 different cities in the US: Gainesville, FL at the University of Florida; Philadelphia, PA at Children’s Hospital of Philadelphia (CHOP); and Portland, OR at the Oregon Health and Science University (OHSU) and Shiners Hospital for Children-Portland.

• How many visits to the study site are necessary? Only one visit per year after baseline measures, up to 5 years. A subgroup of participants choosing not to go on corticosteroids or those that are just initiating corticosteroid treatment may have additional visits.

• Is there any funding to help pay for travel? Yes, there is funding to cover travel costs and accommodations.

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CLINICAL TRIALS: not yet recruiting

Eteplirsen (AVI-4658) Using a Phosphorodiamidate Morpholino Oligomer – also called a PMO – to skip exon 51 and produce functional dystrophin protein • What stage is this research?

»» A Phase 2b clinical trial with eteplirsen was completed in 2012. All boys who participated in the initial 24-week placebo-controlled stage of the Phase 2b study are receiving treatment with eteplirsen in a long-term, openlabel extension study. Clinical results through 74 weeks of treatment were recently reported at the Muscular Dystrophy Association Scientific Conference in April 2013. »» While there are no eteplirsen studies actively recruiting at this time, planning for a larger confirmatory Phase 3 clinical trial of eteplirsen is underway. This study is expected to begin enrolling new patients in the first quarter of 2014. Information about the study including participating clinical sites and eligibility criteria will be posted on www.ClinicalTrials.gov as it becomes available.

• What is the goal or purpose of this research? Duchenne muscular dystrophy is caused by a genetic mutation or error in the gene that carries instructions for the essential muscle protein dystrophin. Eteplirsen uses Sarepta’s exon-skipping technology to skip exon 51 of the dystrophin gene to repair specific genetic mutations that affect approximately 13 percent of boys and young men with Duchenne. Patients eligible for treatment with eteplirsen may have a mutation comprising a deletion of exons 45-50, 47-50, 48-50, 49-50, 50 or 52. Eteplirsen is designed to restore the gene’s ability to make a shorter – but still functional – form of dystrophin. Because the absence of dystrophin is the underlying cause of Duchenne, promoting the synthesis of novel dystrophin might stabilize or significantly slow the disease process. Sarepta is also developing additional earlier-stage exon-skipping therapies utilizing the same technology as eteplirsen to address patients with Duchenne due to other genetic mutations.

• Who is sponsoring this research?

Research of eteplirsen is led and sponsored by Sarepta Therapeutics, a biotechnology company focused on the discovery and development of novel RNA-based therapeutics for rare diseases. Sarepta has partnered with the Duchenne community to advance exon-skipping technology for more than a decade, and is committed to exploring the potential of this technology to address all of the boys and young men with Duchenne who could potentially benefit from an exon-skipping therapy.

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• What are the recent results that have been reported from this research?

»» Recently reported results from the Phase 2b clinical study of eteplirsen showed statistically significant and clinically meaningful changes on measures of novel dystrophin production and walking ability. In addition, through 74 weeks of treatment, eteplirsen was well tolerated in patients with no clinically significant treatment-related adverse events, serious adverse events, hospitalizations, or study discontinuations. Overall, these data support continued development of eteplirsen. »» In the study, novel dystrophin production was assessed by muscle biopsy. After the last muscle biopsy at week 48, there was a statistically significant increase in dystrophin-positive muscle fibers to 47.0 percent of normal (p≤0.001) among the eight patients who were treated once weekly with either 30 mg/kg or 50 mg/ kg of eteplirsen. The four patients in the placebo/ delayed-treatment group, who received a placebo for 24 weeks before initiating treatment with eteplirsen at 30 mg/kg or 50 mg/kg, also demonstrated a statistically significant increase in dystrophin-positive fibers to 38.3 percent of normal (p≤0.009) at week 48, after 24 weeks of treatment. »» Clinical outcome measures including the 6-minute minute walk test continue to be evaluated in the openlabel Phase 2b extension study. Results through 74 weeks – or after nearly one and a half years of treatment – showed a continued stabilization of walking ability in patients who remained evaluable on the 6-minute walk test. Through 74 weeks, patients treated with 30 mg/ kg or 50 mg/kg showed less than a 5 percent decline (13.4 meters) in walking ability from baseline. After experiencing a substantial decline earlier in the study, patients in the placebo/delayed-treatment group also demonstrated stabilization in walking ability from week 36 through 74, the period in which meaningful levels of dystrophin were likely produced, with a less than 10 meter decline over this timeframe. Two patients in the 30 mg/kg group were excluded from the analysis because they showed signs of rapid disease progression upon enrollment in the study and lost their ability to walk by week 24.


CLINICAL TRIALS: not yet recruiting

• What steps need to be completed before moving into the next phase of clinical development?

Sarepta is currently engaged in discussions with the U.S. Food and Drug Administration (FDA) regarding the regulatory path forward for eteplirsen, including the feasibility of a New Drug Application for accelerated approval based on the Phase 2b clinical study results. In parallel, Sarepta is working to obtain feedback from the FDA on the design of the confirmatory Phase 3 clinical study of eteplirsen.

• What is your best estimate for the length of time it will take to move into the next phase? »» Sarepta expects the confirmatory Phase 3 clinical study of eteplirsen to begin patient enrollment in the first quarter of 2014. »» Based on feedback from the FDA, Sarepta expects to provide an update on the regulatory path forward for eteplirsen, including the feasibility of a potential New Drug Application for accelerated approval, later this year.

• Will the next clinical trial include study sites in the US? The confirmatory Phase 3 clinical study of eteplirsen will include clinical sites in the US. Information about participating clinical sites will be posted on www.ClinicalTrials.gov as it becomes available.

• Who would be eligible to participate in the next phase of clinical trial?

Eligibility criteria for the confirmatory Phase 3 clinical study of eteplirsen have not yet been finalized. However, the criteria are likely to be similar to the recently completed Phase 2b clinical study. That study enrolled ambulatory boys between the ages of 7 and 13 years with an out-of-frame deletion correctable by skipping exon 51, and who were on a stable dose of oral corticosteroids for at least 24 weeks. Information about eligibility criteria will be posted on www.ClinicalTrials.gov as it becomes available.

• Where can I learn more about this study? »» Information about the confirmatory Phase 3 clinical study will be posted on www.ClinicalTrials.gov at it becomes available. »» Additional information is available on Sarepta’s website at www.sareptatherapeutics.com or the DuchenneConnect website at www.DuchenneConnect.org.

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CLINICAL TRIALS: not yet recruiting

SMT C1100

A Small Molecule Utrophin Upregulator for Duchenne • What stage is this research? Our lead utrophin modulator, SMT C1100 is ready to progress into patient clinical trial having successfully completed a Phase 1 clinical trial in healthy male volunteers in 2012. A dose-finding study (Phase 1b) in Duchenne patients is expected to start in the second half of 2013, with a Phase 2 proof of concept trial to follow.

• What is the goal or purpose of this research? »» Utrophin is a naturally occurring protein that is similar to dystrophin and scientists have shown that upregulating (increasing) its production can compensate for the missing dystrophin and help to restore healthy muscle function. »» SMT C1100 is a small molecule utrophin modulator that has the potential to treat all genetic forms of Duchenne and so benefit all patients. In addition, SMT C1100 is anticipated to be complementary to other therapeutic approaches currently in development.

• Who is funding this research?

Summit is funding the program although is also seeking additional support from the Duchenne community to help accelerate the rate of development. The 2012 Phase 1 trial was supported by the Muscular Dystrophy Association, Parent Project Muscular Dystrophy, Charley’s Fund, CureDuchenne, the Foundation to Eradicate Duchenne, and the Nash Avery Foundation.

• What is the current state of this research?

»» The Phase 1 clinical trial in healthy volunteers showed SMT C1100: »» Was safe and well tolerated at all doses tested »» Achieved good bioavailability with all the volunteers who received repeat doses of SMT C1100 achieving blood plasma concentrations of the drug that are expected to confer therapeutic benefit based on the data generated in non-clinical activity studies »» Trial evaluated a new formulation of SMT C1100 that has been specifically formulated for use by a pediatric population »» Non-clinical activity data showed SMT C1100: »» Increases utrophin protein in dystrophin deficient muscle cells from Duchenne patients to levels expected to have significant therapeutic benefit »» Significantly increases the amount of utrophin in the mdx mouse model of Duchenne

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»» Improves whole muscle function in a study with an endpoint similar to the 6-minute walk test »» Reduces muscle degeneration, fibrosis, and chronic inflammation

• What steps need to be completed before recruitment can begin for the dose-finding study and the Phase 2 trial? In preparation for the patient clinical studies, drug material manufacture and long-term regulatory toxicology studies will be commissioned. Summit has selected a specialist contractor capable of manufacturing and formulating GMP grade drug material for use in the long-term toxicology studies, the patient proof of concept trials, and ultimately any potential future registration trials and market use. The Phase 1b patient clinical trial needs to confirm the drug is safe and well tolerated and achieves drug levels in boys similar to those that were seen in adults. Finally, continuing development of the biomarkers required to help demonstrate proof of concept in the Phase 2 trial is needed.

• What will the inclusion (enrollment) criteria be for the upcoming trial? Summit is currently finalizing it plans for the upcoming clinical trials and this includes deciding what the inclusion and exclusion criteria will be.

• Where will the trial take place? Will there be study sites in the US? The Phase 1b dose finding and safety trial is expected to be located in the UK. The Phase 2 trial is expected to be an international study and is likely to include sites within Europe and also the US, although these plans are still to be finalized and remain subject to review by the various regulatory authorities and other experts.

• Where can I learn more about SMT C1100?

»» You can learn more at www.summitplc.com. »» www.ClinicalTrials.gov will post the next phase of patient trials as soon as they are recruiting. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: not yet recruiting

Tadalafil

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Tadalafil for Duchenne Muscular Dystrophy • What stage is this research?

This Phase 3 clinical trial is not yet open for participant enrollment.

• What is the goal or purpose of this research?

• Where can I learn more about SMT C1100?

»» www.lilly.com and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

The main purpose of this study is to determine if tadalafil can slow the decline in walking ability of boys who have Duchenne muscular dystrophy. The study will also assess the safety of tadalafil and any side effects that might be associated with it in boys who have Duchenne. Participants will receive study treatment (tadalafil or placebo) for the first 48 weeks of the study, and can then continue into a 48-week extension period during which all participants will receive tadalafil.

• Who is the sponsor of this study?

Eli Lilly and Company (www.lilly.com) is the sponsor of this study.

• When will recruitment begin?

The estimated study start date is August 2013.

• What will the inclusion (enrollment) criteria be for the upcoming Phase 1b dose finding trial?

Participants will need to be boys with Duchenne who are between the ages of 7-14 years old and ambulatory. Participants must be on a stable corticosteroid therapy for at least 6 months prior to screening, and must have a left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiogram. Additional details regarding the inclusion and exclusion criteria are posted on www.ClinicalTrials.gov.

• Where will the trial take place? Will there be sites in the US? There will be multiple sites in the US and abroad. This list of study sites is currently being finalized. Please check www.ClinicalTrials.gov for updates.

• Why should I consider participating in this study? While no personal benefit can ever be guaranteed by participation in a clinical trial, there are other benefits, including allowing you to play an active role in the health care of your child, gaining access to medical specialists that are normally not available to your child, and helping others by contributing to the better understanding of Duchenne.

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CLINICAL TRIALS: PRE-CLINICAL

AAV-GALGT2 therapy for DMD

Development of AAV-GALGT2 gene therapy to treat Duchenne Muscular Dystrophy • What stage is this research? This research in Duchenne is pre-clinical, meaning it has not advanced to clinical trials in patients. This work, however, is in its final pre-clinical stages. INDenabling pre-clinical toxicology studies are underway to develop the drug for a future Phase 1 clinical trial in DMD patients.

• Where is this research being done and who is funding this research?

This research is being done by the Center for Gene Therapy at Nationwide Children’s Hospital. This is funded in large part by a U54 grant from the NINDS branch of the National Institutes of Health.

• What is the goal or purpose of this research? GALGT2 is an enzyme (specifically, a glycosyltransferase) that is present normally at the neuromuscular junction in adult skeletal muscles. Transgenic overexpression of GALGT2 in skeletal muscles stimulates the glycosylation of alpha-dystroglycan everywhere in muscle – not just at the neuromuscular junction – and results in the upregulation of proteins that are normally found bound to dystroglycan only at the neuromuscular junction. Some of these proteins, including utrophin, are dystrophin surrogates that can compensate for loss of dystrophin function in muscles. The goal of this research is to use an AAV gene therapy approach to stimulate the therapeutic overexpression of GALGT2 in the skeletal muscles of Duchenne patients. Such an approach would apply to all Duchenne patients, regardless of their underlying mutation.

• What is the current state of this research and what steps need to be completed before moving into a clinical trial? »» A Pre-IND meeting with the FDA has been held and IND-enabling toxicology studies are ongoing. Once these studies are completed and an IND has been filed and approved by the FDA, funding must be obtained to perform a Phase 1 clinical trial.

• What is your best estimate for the length of time it will take to move this research into clinical trials? The hope is that an IND will be filed in early 2014. If the IND is accepted by the FDA, and funding for a trial is successfully obtained, the first human trial likely would begin in the fall of 2014.

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• Where would a clinical trial take place? Nationwide Children’s Hospital in Columbus, OH.

• Who would be eligible to participate in a clinical trial? Duchenne patients aged 7 years and above.

• Where can I learn more about this research? »» http://www.nationwidechildrens.org/wellstone-center »» http://www.nationwidechildrens.org/neuromusculardisorders


CLINICAL TRIALS: PRE-CLINICAL

Biglycan

A Unique Utrophin Upregulator • What stage is this research?

This research is pre-clinical, meaning it has not advanced to clinical trials involving people yet.

• Where is this research being done and who is funding this research?

This research is taking place at Tivorsan and in the laboratory of Dr. Justin Fallon at Brown University. This work was funded by PPMD’s End Duchenne GAP program. Current funding is coming from private investors in Tivorsan, recently awarded PPMD and MDA foundation grants to Tivorsan, and an NIH grant (“UO1 mechanism”) to Dr. Fallon.

• What is the goal or purpose of this research? The goal of this research is to use a protein called recombinant human biglycan (rh-biglycan) to increase utrophin and neuronal NOS (nNOS) at the muscle cell membrane, resulting in reduced muscle damage and improved muscle function. Utrophin is a molecule that is related to dystrophin in structure and form and can “stand in” for dystrophin when present in larger than normal quantities.

• Where would a clinical trial take place? It is too early to know where a clinical trial for this research would be located. Many complex factors go into determining the right location(s) for a clinical trial.

• Who would be eligible to participate in a clinical trial? Again, it is too early to know what the inclusion criteria would be for a future clinical trial. However, TVN-102 therapy is applicable to all forms of Duchenne, regardless of the underlying mutation.

• Where can I learn more about this research? »» You can learn more about this research at www.Tivorsan.com. »» www.ClinicalTrials.gov will post all clinical trials once they are actively recruiting patients. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• What is the current state of this research? »» Independent laboratories have reproduced the beneficial effect of rh-biglycan (rhBGN) in mice that lack dystrophin. A reliable method to manufacture the protein has been established and a scalable production process is being optimized. Additional pre-clinical studies are currently in process. »» An optimized version of rhBGN has been developed and this molecule, called TVN-102, has been designated the lead clinical candidate.

• What steps need to be completed before moving into a clinical trial? »» Manufacturing of TVN-102 needs to be scaled-up to produce quantities and purity necessary for use in humans. »» Safety testing must be completed and the pharmacology properties of TVN-102 must be determined.

• What is your best estimate for the length of time it will take to move this research into clinical trials? 12-18 months.

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CLINICAL TRIALS: PRE-CLINICAL

CAT1000

Catabasis’ Lead Program for Targeting Inflammation • What stage is this research?

• Who would be eligible to participate in a clinical trial?

• Where is this research being done and who is funding this research?

• Where can I learn more about this research?

This research in Duchenne is pre-clinical, meaning it has not advanced to clinical trials involving people with Duchenne yet. However, Catabasis’ lead compound, CAT-1004, completed a Phase 1 clinical trial in early 2013.

This research is being done at Catabasis, a private, venture-backed biopharmaceutical company leveraging the therapeutic potential of omega-3 fatty acids and other clinically validated compounds to create new medicines for the treatment of inflammatory and metabolic diseases, including Duchenne. The MDA Venture Philanthropy (MVP) program recently awarded a grant to Catabasis.

• What is the goal or purpose of this research? The CAT1000 NCEs (new chemical entities) are orally available, anti-inflammatory agents developed by Catabasis to target inflammation, which has been shown to be an underlying cause of many chronic diseases. Inflammation has been shown to play a critical role in the degeneration process in Duchenne. Targeting inflammation is an approach that may increase the quality of life for patients and prolong their ambulatory period and increase lifespan.

• What is the current state of this research and what steps need to be completed before moving into a clinical trial? »» Catabasis plans to test the therapeutic potential of the CAT1000 compounds in mdx mice, as well as GRMD dogs, both animal models of Duchenne. »» Catabasis will determine whether either or both of two compounds in the CAT1000 series reduce inflammation in muscle tissue and improve muscle function. »» If favorable results are obtained, Catabasis plans to begin clinical trials in people with Duchenne.

• What is your best estimate for the length of time it will take to move this research into clinical trials? It is difficult to estimate at this time, but if studies move forward and are successful, clinical trials in patients with Duchenne could start in 1-2 years.

• Where would a clinical trial take place? It is too early to know where a clinical trial for this research would be located. Many complex factors go into determining the right location(s) for a clinical trial.

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Again, it is too early to know what the inclusion criteria would be for a future clinical trial. However, the CAT1000 NCEs are not expected to be mutation-specific, so they could potentially benefit all boys with Duchenne and Becker. »» You can learn more about this research at www.catabasispharma.com. »» www.ClinicalTrials.gov will post the clinical trial once it is actively recruiting patients. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: PRE-CLINICAL

DT-200

DT-200, a selective androgen receptor modulator (SARM) to improve muscle strength and function in Duchenne Muscular Dystrophy, and other myopathies • What stage is this research? The DT-200 development program has completed 3 initial phase 1 trials in 78 healthy adult volunteers showing the SARM is safe and well tolerated for up to 14 days treatment. Testing in Duchenne has not yet begun.

• Where is this research being done and who is funding this research? DT-200 is wholly owned by DART Therapeutics, who are leading the clinical development program. DART is currently seeking funding for the next development step, a 4-week Proof of Concept Clinical (POC) trial.

• What is the goal or purpose of this research? DT-200 is a selective androgen receptor modulator (SARM). Selective androgen receptor modulators (SARMs) have been developed to mimic the muscle building effects of androgens (testosterone), without their undesirable side effects. DART hopes that the more precise action of this drug will confer better, longer term safety and tolerability in both adult and pediatric muscle diseases compared to androgens. DT-200 is effective in multiple animal models, including mice that lack dystrophin. Importantly, compared to other SARMs in clinical development, DT-200 shows significantly greater preference for skeletal muscle. Accordingly, DART is developing DT-200 with the objective of improving muscle strength and function in both adult muscle diseases, such as Charcot Marie Tooth disease (CMT) and Facioscapulohumeral Muscular Dystrophy (FSHD), and in pediatric myopathies, such as Duchenne and Spinal Muscle Atrophy (SMA).

• What is your best estimate for the length of time it will take to move this research into clinical trials? If the POC trial in healthy adult subjects is positive, DART anticipates initiation of clinical trials in adult and pediatric muscle diseases, in the second half of 2014.

• Where would a clinical trial take place? Phase 2 trials would be initiated in both the US and Europe.

• Who would be eligible to participate in a clinical trial? Again, it is too early to know what the inclusion criteria would be for a future clinical trial.

• Where can I learn more about this research? »» You can learn more about DT-200 (and other DART initiatives) by consulting the DART website at: http://dartrx.com »» www.ClinicalTrials.gov will post all DT-200 clinical trials once they are actively recruiting subjects.

• What is the current state of this research and what steps need to be completed before moving into a clinical trial? Three phase 1 studies with DT-200 were successfully completed in Belgium and Germany, having confirmed the product is safe and well tolerated at the once daily oral dose of 0.5 mg. DART met with the UK Regulatory Agency (MHRA) in May 2013 for scientific advice and input into the design of a Proof of Concept clinical trial. DART plans to initiate this 4-week POC trial in the UK in Q4 2013 in healthy adult volunteers. The main objective of the POC trial is first to evaluate DT-200’s ability to increase mass, strength and function of healthy muscle. It is anticipated the POC trial will take approximately 9 months to complete.

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CLINICAL TRIALS: PRE-CLINICAL

Laminin-111

Laminin-111, Integrin and Utrophin as a Potential Therapy for Duchenne Muscular Dystrophy • What stage is this research?

This research is pre-clinical, meaning it has not advanced to clinical trials involving people yet.

• Where is this research being done and who is funding this research? »» LAM-111 research is currently being performed within Prothelia’s lab in Massachusetts; the University of Nevada, Reno; and Laval University in Canada. »» Prothelia’s funding has been primarily through US Government grants. Prothelia has received funding from several advocacy groups including Struggle Against Muscular Dystrophy (SAM), PPMD’s End Duchenne Grant Program, and Hope for Gus. Prothelia has no funding to continue development of LAM-111 for Duchenne and has shifted focus towards the use of LAM-111 for treatment of MDC1A.

• What is the goal or purpose of this research?

Animal data shows that human laminin-111 upregulates (increases) the molecules integrin and utrophin. Both integrin and utrophin work together to restore lost muscle cell adhesion when dystrophin is missing at the muscle membrane. This approach should help all patients regardless of their dystrophin mutation.

• What is the current state of this research?

This project is in preclinical development with demonstrated effectiveness in the mdx and dyW mouse models of Duchenne and MDC1A, respectively. Furthermore, LAM-111 has been validated as a therapy for Duchenne by two other research organizations as effective when administered systemically with no detectable toxicity. Prothelia has a comprehensive product development plan to bring human LAM-111 to clinical trials for Duchenne and MDC1A. All investment interest is focused on MDC1A, though positive clinical data for MDC1A would accelerate clinical development for Duchenne. Further studies in a more severely affected animal model of Duchenne are required to justify further development of rhLAM-111 for treatment of Duchenne.

• What steps need to be completed before moving into a clinical trial? Prothelia must construct a consistently scalable process that produces sterile human laminin-111. Prior to any approval to test human laminin-111 in clinical (human) studies, we must ensure the human laminin-111 is safe and effective in the mouse and larger animal models of muscular dystrophy.

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• What is your best estimate for the length of time it will take to move this research into clinical trials? In the absence of Duchenne-specific funding, rhLAM-111 will not enter the clinic for treatment of Duchenne.

• Where would a clinical trial take place? There are several candidate locations including hospitals in Cincinnati (OH), Boston (MA), and Rochester (NY). However, there are many complex factors that go into determining the right location/countries for a clinical trial and further determinations will be made once we approach clinical development.

• Who would be eligible to participate in a clinical trial? Children who are affected with Duchenne regardless of their mutation would be eligible. At this time we have not formulated any inclusion or exclusion criteria. As we get closer to clinical trials, researchers will target those Duchenne patients most likely to respond to therapy.

• Where can I learn more about this research?

»» www.Prothelia.com »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: PRE-CLINICAL

NBD Peptide

Using NF-kB blockers to Decrease Inflammation and Increase Regeneration in Duchenne • What stage is this research?

This research is pre-clinical, meaning it has not advanced to clinical trials involving people yet.

• Where is this research being done and who is funding this research?

This research is being done at Dr. Denis Guttridge’s laboratory at The Ohio State University in conjunction with Theralogics and various academic partners. The work is funded by the NINDS branch of the NIH.

• What is the goal or purpose of this research? The NF-kB pathway has been shown to be involved in promoting inflammation and preventing regeneration in response to the loss of dystrophin in Duchenne (prednisone is a non-specific blocker of this pathway). Dr. Guttridge’s group has used a small molecule called “NBD” to specifically block this pathway without interfering with some of the other signalling pathways that can lead to the negative side effects seen with prednisone. In mice that lack dystrophin, NBD significantly improves the function of breathing muscles and allowed the mice to balance on moving rod for longer. Also, in mice that lack dystrophin and utrophin, the drug significantly improved cardiac function.

• Where would a clinical trial take place? The Phase 1 safety clinical is planned for Nationwide Hospital, Columbus Ohio, directed by Dr. Jerry Mendell. For Phase 2, it is too early to know where a clinical will take place and much will depend on the safety profile determined in Phase 1.

• Who would be eligible to participate in a clinical trial? Again, it is too early to know what the inclusion criteria would be for a future clinical trial.

• Where can I learn more about this research? »» You can learn more about Dr. Guttridge’s research at The Ohio State University website: http://biomed.osu.edu »» www.ClinicalTrials.gov will post all clinical trials once they are actively recruiting patients. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• What is the current state of this research and what steps need to be completed before moving into a clinical trial? »» Dr. Guttridge’s laboratory has reproduced results using NBD manufactured at an academic lab and with NBD purchased from a commercial source. The group has also completed informal toxicology testing and developed preliminary data on the pharmacokenetics of the drug; studies in a large animal model are also complete and the data are undergoing analysis. »» Based on discussions with the FDA in a pre-Investigational New Drug application meeting, formal toxicology studies have been planned and the results will be used to guide the protocol for a human clinical trial. »» The group determined that the manufacture of the drug can be scaled up adequately for a large animal study.

• What is your best estimate for the length of time it will take to move this research into clinical trials? At this time, it is too early to estimate when a clinical trial in Duchenne would start. However, the preclinical studies leading up to an IND submission will start soon.

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CLINICAL TRIALS: PRE-CLINICAL

Rycal® ARM210

Using Rycal® ARM210 to Improve Muscle Strength and Function in Duchenne • What stage is this research?

This research in Duchenne is pre-clinical, meaning it has not advanced to clinical trials involving people with Duchenne yet. However, a related compound in development by ARMGO is in clinical testing now for heart failure and cardiac arrhythmias.

• Where is this research being done and who is funding this research? This research is being done by ARMGO Pharma, Inc. The Muscular Dystrophy Association recently awarded the company $1 million to develop the compound, Rycal ARM210, for Duchenne.

• What is the goal or purpose of this research? ARMGO has identified a new class of small molecule therapeutics (Rycals®) that restore the normal balance of calcium within muscle cells by correcting the activity of a type of channel called the “ryanodine receptor calcium channel complex” (RyR). In mice that lack dystrophin, Rycal ARM210 corrected a calcium leak occurring through the RyR and improved daily activity and muscle force. The degree of benefit depended on the dose of the compound administered. These studies help establish the rationale for conducting a clinical trial with this compound in Duchenne.

• What is the current state of this research and what steps need to be completed before moving into a clinical trial? Preliminary pre-clinical toxicology studies are now complete and the company has begun the formal toxicology studies required by the FDA to support advancement into human trials. Pending successful completion of pre-clinical studies, ARMGO plans to file an Investigational New Drug (IND) Application at the end of this year or early next year in preparation for beginning a human clinical trial in Duchenne.

• What is your best estimate for the length of time it will take to move this research into clinical trials? If an IND is filed by the company at the end of 2013 and is accepted by the FDA, a clinical trial could begin as early as the first quarter of 2014. Initial clinical studies in healthy volunteers to establish safety would then be followed by studies in Duchenne patients.

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• Where would a clinical trial take place? It is too early to know where a clinical trial for this research would be located. Many complex factors go into determining the right location(s) for a clinical trial.

• Who would be eligible to participate in a clinical trial? Again, it is too early to know what the inclusion criteria will be for the clinical trial.

• Where can I learn more about this research? »» You can learn more about Rycan ARM210 at ARMGO’s website (http://armgo.com/). »» www.ClinicalTrials.gov will post all clinical trials once they are actively recruiting patients. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: PRE-CLINICAL

Spironolactone

Using Aldosterone Antagonists to Improve Muscle Strength and Function in Duchenne • What stage is this research?

This research in Duchenne is pre-clinical, meaning it has not advanced to clinical trials involving people with Duchenne yet. However, spironolactone is an FDA-approved drug for high blood pressure and end-stage heart failure.

• Where is this research being done and who is funding this research?

This research is being done at Dr. Jill Rafael-Fortney’s laboratory at The Ohio State University. Parent Project Muscular Dystrophy and CureDuchenne funded initial studies, and now larger federal grants are helping the team to conduct larger studies that will provide enough critical information to design clinical trials.

• What is the goal or purpose of this research? Dr. Rafael-Fortney’s laboratory recently observed a profound improvement in a mouse model of Duchenne resulting from treatment with the FDA-approved drugs lisinopril and spironolactone. Muscle strength in skeletal muscles in limbs and those used in respiration was doubled in treated mice compared to untreated mice and function of the heart was also significantly improved. Ongoing muscle damage in skeletal muscles and heart was almost completely prevented. These studies have direct implications for designing clinical trials for the Duchenne patient population.

• What is your best estimate for the length of time it will take to move this research into clinical trials? At this time, it is too early to estimate when a clinical trial in Duchenne would start. However, the preclinical studies are scheduled to begin in July, 2013 and should be completed within 1 year.

• Where would a clinical trial take place? It is too early to know where a clinical trial for this research would be located. Many complex factors go into determining the right location(s) for a clinical trial.

• Who would be eligible to participate in a clinical trial? Again, it is too early to know what the inclusion criteria would be for a future clinical trial.

• Where can I learn more about this research? »» You can learn more about Dr. Rafael-Fortney’s research at The Ohio State University website (http://biomed.osu.edu). »» www.ClinicalTrials.gov will post all clinical trials once they are actively recruiting patients. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• What is the current state of this research and what steps need to be completed before moving into a clinical trial? »» Dr. Rafael-Fortney’s laboratory is currently trying to identify whether lisinopril and spironolactone have independent positive value for each muscle type or work best in combination; are able to halt or reverse disease at different stages of pathogenesis; and determine whether treatment of the utrophin/dystrophin-deficient Duchenne mouse model is able to extend its lifespan. »» A preclinical study with cardiologist collaborator Dr. Subha Raman is planned to begin in July, 2013, to compare the cardiac improvements in dystrophic mice with spironolactone versus eplerenone. This will be followed by a clinical trial with primary cardiac outcome measures, using whichever drug is more effective in preclinical studies. »» Additional funding is expected, which will allow the researchers to determine the efficacy of each of these drugs on limb and respiratory skeletal muscles.

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CLINICAL TRIALS: PRE-CLINICAL

Tamoxifen

Using tamoxifen to improve muscle strength in Duchenne and Becker • What stage is this research?

This research in Duchenne is pre-clinical, meaning it has not advanced to clinical trials involving people yet. Tamoxifen is the generic name for an approved drug that is used to treat estrogen-dependent breast cancer.

• Where is this research being done and who is funding this research? This research is being done at Dr. Urs Ruegg’s laboratory at the University of Geneva. Parent Project Muscular Dystrophy is helping to fund this research.

• What is the goal or purpose of this research? »» Recent data from Dr. Urs Ruegg’s laboratory has shown that tamoxifen can trigger substantial improvements in muscle strength in mice that lack dystrophin. How the drug works in the mice is not yet fully understood. The fact that very low doses in mice (threshold 0.3 mg/ kg body weight per day) are effective to improve muscle quality. Such low doses suggest that the drug interacts with a high-affinity target, which might be the one of the nuclear estrogen receptors. »» Ultimately, tamoxifen may be part of a “cocktail” along with other treatments that work together to slow or stop the loss of strength in Duchenne. It is also possible that tamoxifen could take the place of prednisone as an alternative with less side effects.

• What is the current state of this research? Drs. Ruegg and Dorchies have tested various doses of tamoxifen in both young and old mice that lack dystrophin. Benefits of treatment included lower creatine kinase levels, 40% less fibrosis (scarring) than in untreated mice, and near normal improvements in muscle strength. The mice also showed some improvement in the length of bones in the spine. Although mice are not humans and it is never entirely certain how results will translate, a robust treatment response in mice that lack dystrophin is the gold standard for moving drugs into human clinical trials for Duchenne.

• What steps need to be completed before moving into a clinical trial? While preliminary data are encouraging, we don’t yet know if tamoxifen will have the same positive effects in Duchenne and Becker. We need to understand more about how tamoxifen may work in Duchenne at the cellular level and also how it might interact with cardiac medications and

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prednisone, which are considered a part of the standard of care for Duchenne. Answers to these questions are needed to plan a human clinical trial of this drug in Duchenne.

• What is your best estimate for the length of time it will take to move this research into clinical trials? It is difficult to estimate when a clinical trial will begin recruitment, but the goal is to have tamoxifen in a clinical trial with Duchenne patients starting in early 2014.

• Where would a clinical trial take place? It is too early to know where a clinical trial for this research would be located. Many complex factors go into determining the right location(s) for a clinical trial.

• Who would be eligible to participate in a clinical trial? Again, it is too early to know what the inclusion criteria will be for the clinical trial. The improvements seen in the mice with tamoxifen are likely not dependent on any particular type of mutation in the dystrophin gene, so tamoxifen is potentially applicable to all boys and young men with Duchenne and Becker.

• Where can I learn more about this research?

»» www.ClinicalTrials.gov will post this clinical trial once it is actively recruiting patients. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: PRE-CLINICAL

Utrophin

PTC Utrophin Upregulator • What stage is this research?

This research is pre-clinical, meaning it has not advanced to clinical trials involving people yet.

• Where is this research being done and who is funding this research?

This research is being performed at PTC Therapeutics and was initiated through PPMD’s Project Catalyst program. This research has received funding from a National Institutes of Health grant to Dr. Lee Sweeney in the past; it is currently unfunded.

• Who would be eligible to participate in a clinical trial? Again, it is too early to know what the inclusion criteria would be for a future clinical trial.

• Where can I learn more about this research? »» You can learn more about this research at www.ptcbio.com. »» www.ClinicalTrials.gov will post all clinical trials once they are actively recruiting patients. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• What is the goal or purpose of this research?

The goal of this research is to identify small molecule compounds that are able to increase production of the utrophin protein. Utrophin is a kind of molecular cousin to dystrophin (the protein that is missing or altered in Duchenne and Becker), and utrophin can compensate for the lack of dystrophin when it is present in larger than normal quantities.

• What is the current state of this research? Researchers have performed studies in the mdx muscular dystrophy mouse model that demonstrate the utrophin protein is produced and that this level of utrophin protein protects muscle from injury. They are evaluating oral bioavailability in large animals and are evaluating the safety of the small molecules.

• What steps need to be completed before moving into a clinical trial? Researchers need to demonstrate efficacy in a large animal model before moving into formal toxicology studies, required by the FDA, before clinical trials can be planned.

• What is your best estimate for the length of time it will take to move this research into clinical trials? At least several years to start Phase 1 clinical trials in healthy volunteers.

• Where would a clinical trial take place? It is too early to know where a clinical trial for this research would be located. Many complex factors go into determining the right location(s) for a clinical trial.

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CLINICAL TRIALS: PRE-CLINICAL

VBP15

A Novel Delta-9,11 Glucocorticoid Analogue • What stage is this research?

This research is pre-clinical, meaning it has not advanced to clinical trials involving people yet.

• Where is this research being done and who is funding this research?

»» This research is being performed at ReveraGen Biopharma Inc. and Children’s National Medical Center. »» ReveraGen has partnered with the NIH under the Therapeutics for Rare and Neglected Disease (TRND) Program as part of an effort to facilitate drug development for rare and neglected diseases. »» VBP15 has nearly successfully completed the second round of milestone driven funding from the MDA Venture Philanthropy (MVP) program. »» Additional funding is provided by the CDMRP Department of Defense, Muscular Dystrophy Association Venture Philanthropy (MVP), Foundation to Eradicate Duchenne, and CureDuchenne.

• What is the goal or purpose of this research?

The goal of this research is to develop a drug (VBP15) that will work just as well or better than traditional glucocorticoids (prednisone, deflazacort) but with an improved safety profile compared to these ‘standard of care’ drugs. This will hopefully result in better efficacy (clinical outcomes), and better patient compliance due to improved side effect profile.

• What is the current state of this research? »» A series of different but related delta 9,11 compounds have been tested, and a lead compound selected for the best effects (VBP15 - ‘lead selection’). »» VBP15 has had many of the standard IND-enabling tests done, with the drug showing excellent profiles. VBP15 shares many ADME features (ADME – absorption, distribution, metabolism, excretion) with prednisone & other routinely utilized steroids. »» Studies in the mdx mouse have shown improvements in function equal to prednisone, yet reduced side effects. »» Testing in mouse models of other inflammatory indications has shown biological activity equal to or better than prednisone.

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• What steps need to be completed before moving into a clinical trial? We have initiated a series of IND-enabling studies that need to be completed, including toxicology in two species, formulation studies, and carcinogenicity.

• What is your best estimate for the length of time it will take to move this research into clinical trials? We anticipate that the support of the NIH TRND Program and MVP will lead to Phase 1 studies by the end of 2013.

• Where would a clinical trial take place? It is too early to know where a clinical trial for this research would be located, however current drug development plans are focusing on the US, Canada, and Australia.

• Who would be eligible to participate in a clinical trial? We anticipate Phase 1 studies to be performed in normal healthy adult volunteers. Phase 2 studies would likely be open to many Duchenne patients, although it is too early to know what the inclusion criteria would be for a future clinical trial.

• Where can I learn more about this research?

»» www.reveragen.com & www.nih.gov/trnd. »» www.ClinicalTrials.gov will post this trial once it is actively recruiting. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: Active but not recruiting

CATENA®

Phase 3 Study of Idebenone in Duchenne Muscular Dystrophy (DELOS) • What stage is this research?

This is an ongoing trial, but currently participant recruitment is on hold.

• What is the goal or purpose of this study? The purpose of this study is to assess the effectiveness of idebenone (Catena®) on pulmonary function, motor function, muscle strength, and quality of life in patients with Duchenne. The safety and tolerability of idebenone will also be assessed.

• Will there be additional clinical trials in the future, and if so, when? It is too early to know if additional trials will be required.

• Where can I learn more about this study?

»» You can learn more about this study at www.santhera. com and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• Who is funding this study?

This study is funded by Santhera Pharmaceuticals.

• Who was eligible to participate in this study?

This study is open to males with a diagnosis of Duchenne, between the ages of 10-18 years old. Both ambulatory and non-ambulatory patients are eligible. Enrollment of patients occurs in phases, depending on the use of glucocorticoids.

• What are participants doing in this study? Participants are randomized to receive either idebenone (900 mg/day) or placebo 3 times a day with meals for 52 weeks. The primary outcome measure will be percent predicted peak expiratory flow (PEF) to assess the effectiveness of idebenone in improving or delaying the loss of respiratory function in patients with Duchenne. Other respiratory endpoints, muscle strength and motor function, quality of life, and safety and tolerability will also be assessed.

• When will this study be completed?

Participants of the first cohort (steroid non-using patients) will finish the study in early 2014. Study completers may have access to the drug while data is being analyzed and before FDA approval.

• Are there any preliminary results available?

The DELOS study recently successfully passed a planned futility and safety analysis. The independent Data Safety Monitoring Board (DSMB) for DELOS informed Santhera that the study has a reasonable chance of achieving its primary endpoint for improving or delaying the loss of respiratory function in Duchenne patients not using corticosteroids, and since no safety issues were detected, recommended that the study should continue as planned.

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CLINICAL TRIALS: Active but not recruiting

Drisapersen (GSK2402968) Investigating the Efficacy, Safety, Tolerability, and Pharmacokinetics of GSK2402968 to Skip Exon 51 in Ambulatory Boys with Duchenne Muscular Dystrophy (GSK Study: DMD114876 • What stage is this research?

»» This ongoing trial is fully recruited. »» Please see www.ClinicalTrials.gov for further details.

• What is the goal or purpose of this study?

»» This phase 2 study will test an investigational drug, drisapersen, that has been designed to skip exon 51 of the dystrophin gene. The investigators will be assessing the efficacy, safety and tolerability of the drug in ambulant boys. Importantly, the study will also study the absorption and processing of the drug in their bodies. »» Duchenne muscular dystrophy (DMD) is caused by a fault in the gene that carries the instructions for the essential muscle protein called dystrophin. Molecular patches (also known as ‘antisense oligonucleotides’) are short strands of DNA that function to restore the production of dystrophin protein by a process called ‘exon skipping’. Exon skipping works by masking the faulty part of the dystrophin gene, allowing a shortened but functional dystrophin protein to be produced, as is produced by people with the milder condition Becker muscular dystrophy. »» Drisapersen is designed to mask mutations in a region of the dystrophin gene called exon 51. Approximately 13% of DMD boys have a mutation in this region and could therefore potentially be treated with drisapersen. »» This study will evaluate two doses of drisapersen in ambulant boys over 24 weeks versus placebo. The study’s post treatment period will provide information on how long the dystrophin produced stays in the body and provide information about how long an effect from the study drug is seen after study drug has been stopped. This trial is expected to provide essential information for future clinical trials in this patient group.

• Who is funding this study?

GlaxoSmithKline (GSK) is sponsoring this study (www.gsk. com). GSK has in-licensed drisapersen from the Dutch pharmaceutical company Prosensa Therapeutics who led early clinical development.

• Who is eligible to participate in this study? The study was open to boys in the United States with DMD at least 5 years old who were on steroids and could walk at least 75 meters (unassisted) and also who could rise from the floor in 15 seconds or less (unassisted). They must also have one of the mutations in the dystrophin gene that is correctable by exon 51 skipping.

• What are participants doing in this study?

»» Participants were assigned to one of three groups. The first group received up to 24 injections (one injection per week) of drisapersen under the skin at a dose of 3 mg/kg. The second group received up to 24 injections (one injection per week) of drisapersen under the skin at a dose of 6 mg/kg. The third group received up to 24 injections (one injection per week) under the skin of placebo. Placebo is an inactive substance designed to resemble the drug being tested. It is used to rule out any benefits a drug might exhibit because the recipients believe they are taking the study drug. »» Participants must return to the study site for weekly visits to include but not limited to blood and urine tests, physical examinations, and assessments of muscle strength. »» After 6 months the injections will stop. Participants will then continue to see the study doctor periodically for another 6 months.

• When will this study be completed?

The estimated completion date is November, 2013.

• Are there any preliminary results available? No, the study is still fully blinded at this time.

• Will there be an extension study and/or another clinical trial in the future, and if so, when? GSK is committed to providing boys who have completed DMD114876 with continued access to drisapersen while ensuring that appropriate safety monitoring is maintained. The primary route for boys to continue to receive drisapersen will be through the use of a treatment protocol (rather than a research protocol). The treatment protocol (DMD117402) allows for local laboratory assessments and for physicians who may be closer to the patient’s home to participate, thus potentially minimizing travel for boys and their family. The treatment protocol is currently in the startup process. Therefore, an extension protocol (DMD115501) was started at DMD114876 sites with the earliest completers. This extension protocol will not be offered to additional sites due to the proximity of the expected startup of the treatment protocol. Boys currently enrolled in the extension protocol (DMD115501) will be transitioned to the treatment protocol.

• Where can I learn more about this study?

»» Learn more about this study at www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

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CLINICAL TRIALS: Active but not recruiting

Early Treatment of Cardiomyopathy Early Treatment of Cardiomyopathy with Eplerenone in Duchenne Muscular Dystrophy • What stage is this research?

This is an ongoing trial, but is no longer recruiting participants.

• What is the goal or purpose of this study?

• Where can I learn more about this study? »» You can learn more about this study at www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

The goal of this study is to determine if eplerenone, a medicine traditionally used for high blood pressure and late-stage heart failure, can actually prevent heart muscle damage in patients with Duchenne. This team of researchers has recently made a breakthrough in a Duchenne mouse model, showing that eplerenone prevented heart muscle damage. Because of this drug’s proven safety in both children and adults, it is ready to be studied in patients with Duchenne to hopefully show, as they did in mice, that the devastating consequences of heart muscle damage can be prevented.

• Who is sponsoring this study?

This study is sponsored by The Ohio State University.

• Who was eligible to participate in this study?

Participants are patients with Duchenne, age 7 years and older, who are able to complete cardiac magnetic resonance imaging (MRI) without sedation, and have preserved left ventricular systolic function.

• What are the participants doing in this study? Participants are assigned to one of two arms, either taking the study drug or taking placebo, for 12 months. The primary outcome measure is myocardial strain, a sensitive measurement of heart function using cardiac MRI. The study takes place at two sites in Ohio (The Ohio State University in Columbus, OH and Cincinnati Children’s Hospital in Cincinnati, OH) and at Mattel Children’s Hospital/David Geffen School of Medicine at UCLA in Los Angeles, CA.

• When will this study be completed?

The estimated study completion date is March, 2015.

• Are there any preliminary results available? No, patient enrollment into the trial was just completed so there are not any preliminary results to share.

• Will there be additional clinical trials in the future, and if so, when? It is too early to know if additional trials will be required.

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CLINICAL TRIALS: Active but not recruiting

IGF-I (Increlex)

Safety and Efficacy Study of IGF-I in Duchenne Muscular Dystrophy • What stage is this research?

This trial has been completed and is no longer recruiting patients.

• What is the goal or purpose of this study?

The purpose of this study is to determine whether IGF-I (insulin-like growth factor-I) therapy, also known as Increlex, improves or preserves muscle function in Duchenne. The investigators also want to learn if IGF-I can reduce glucocorticoid side effects such as growth failure and insulin resistance.

• Who is funding this study?

This study is funded by Charley’s Fund, Nash Avery Foundation, Action Duchenne, and Tercica (subsidiary of Ipsen).

• Who is eligible to participate in this study?

Participants were males with a diagnosis of Duchenne, age 5 years or older, ambulatory, and who had been on daily glucocorticoid (prednisone or deflazacort) therapy for > 12 months.

• What were participants doing in this study? This study involved two groups. Participants in the first group received IGF-I (Increlex) once daily by subcutaneous injection every morning with breakfast for a duration of 6 months, and they also continued to take their glucocorticoid. Participants in the second group only took their glucocorticoid. The study took place at Cincinnati Children’s Hospital Medical Center.

• When will this study be completed? The clinical aspects of the study were completed at the end of 2012. Analysis of results is ongoing. The estimated completion date of the study is around June, 2013.

• Are there any preliminary results available? Not yet.

• Will there be additional clinical trials in the future, and if so, when? It is too early to know if additional trials will be required.

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• Where can I learn more about this study?

»» You can learn more about this study at www.tercica.com and www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: Active but not recruiting

REVERSE DBMD

Revatio for Heart Disease in Duchenne Muscular Dystrophy and Becker Muscular Dystrophy • What stage is this research? This trial has suspended participant enrollment, as recommended by the Data Safety and Monitoring Board (DSMB).

• Where can I learn more about this study?

»» www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.

• What is the goal or purpose of this study?

This study is being done to determine if the drug Revatio® (also known as Sildenafil) is safe and improves heart function in people with Duchenne muscular dystrophy and Becker muscular dystrophy (DBMD).

• Who is funding this study?

This study is supported by Charley’s Fund, Inc. and the Nash Avery Foundation, with help from Action Duchenne, CureDuchenne, Hope for Javier, and Zubin’s Wish.

• Who is eligible to participate in this study? This study was recruiting 30 males with DBMD, age 15 years or older. Participants must have an echocardiogram, cardiac MRI, or multi-gated acquisition (MUGA) scan that shows cardiac dysfunction with left ventricular ejection fraction (LVEF) less than or equal to 50%. In addition, participants must be on a stable dose of ACE-inhibitor or angiotensin receptor blocker (ARB) for at least 3 months.

• What are participants doing in this study?

»» For the first 6 months, half of the participants receive Revatio and half receive placebo (an inactive substance that looks like the study drug, but contains no medication). For the second 6 months of the study, all participants receive Revatio. Revatio is taken orally three times daily. All participants have cardiac MRIs performed as well as lung function tests (FVC) and strength testing. »» The study is taking place at the Kennedy Krieger Institute, Johns Hopkins School of Medicine in Baltimore, MD.

• When will this study be completed?

The estimated study completion date is August, 2014.

• Are there any preliminary results available? No, there are no preliminary results available at this time.

• Will there be additional clinical trials in the future, and if so, when? It is too early to know if additional trials will be required.

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CLINICAL TRIALS: Active but not recruiting

TADALAFIL and SILDENAFIL PDE Inhibitors in Duchenne Muscular Dystrophy (Acute Dosing Study) • What stage is this research?

This is an ongoing trial, but is no longer recruiting participants.

• What is the goal or purpose of this study?

»» This is an acute dosing study for tadalafil (Cialis) and sildenafil (Viagra or Revatio). An ongoing trial at CedarsSinai Medical Center is studying whether tadalafil or sildenafil can improve muscle blood flow during exercise in boys with Duchenne. »» These studies are intended to build on recent findings published in the journal Nature showing beneficial effects of tadalafil in mice with an animal version of Duchenne. Only two doses of tadalafil improved muscle blood flow, reduced muscle injury during exercise, and reduced fatigue after exercise.

• Who is funding this study?

This research has been funded by Parent Project Muscular Dystrophy (PPMD).

• Who is eligible to participate in this study?

Participants in this study were boys with Duchenne, between the ages of 7-15 years, still ambulatory, and without any evidence of heart failure.

• What are participants doing in this study?

This study took place at the Cedars-Sinai Medical Center in Los Angeles, CA. The initial screening visit included a medical history, physical exam, echocardiogram, and blood draw to determine eligibility for the study. Eligible boys took two different study drugs: sildenafil or tadalafil the first week, and the other drug the second week. The boys took a low dose of the study drug (sildenafil or tadalafil) for the first treatment day and then a higher dose the next day. Blood was drawn several times throughout the day on both the low dose and higher dose days. There was a one week wash-out period. The boys returned to take a low dose of the other drug for the first day of the second week, and then a higher dose the next day. A one week follow-up phone call was done to check for any adverse events after completion of the study.

• When will the study be completed?

The estimated study completion date is December, 2013.

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• Are there any preliminary results available? The results will be available soon. The researchers are currently analyzing the data.

• Will there be additional clinical trials in the future, and if so, when? A randomized, multicenter trial of PDE inhibitors is in the planning stages.

• Where can I learn more about this study? »» You can learn more about this study at www.ClinicalTrials.gov. »» Please check www.DuchenneConnect.org for updates to this FAQ sheet.


CLINICAL TRIALS: Terminated/Suspended

ACE-031 (HGT-4510)

A Therapeutic Agent under Investigation for Duchenne Muscular Dystrophy • What is the status of the program? On May 2, 2013, Shire and Acceleron announced that they have decided to discontinue development of ACE-031 for Duchenne. ACE-031 clinical trials have been on hold since February 2011. Since then, the companies have performed a number of additional non-clinical and toxicology studies, but unfortunately the findings from these studies do not support further development.

• Why were the clinical studies terminated? During the course of clinical trials in healthy adults and in boys with Duchenne, some participants experienced predominantly minor nosebleeds, gum bleeding, and/or small dilated blood vessels within the skin that resolved after ACE-031 dosing was stopped. By themselves, the minor bleeding events and dilated blood vessels were not considered to be a serious safety concern for study subjects. However, based on review of these safety data with the FDA and Health Canada, Acceleron and Shire terminated the clinical studies and performed additional animal studies to evaluate the possibility of returning to the clinic.

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חוברת המחקרים השנתית 2013