Industry Partner News: Jerry Mendell, M.D., Presented Positive Updated Results at World Muscle Society from Four Children Dosed in Sarepta's Gene Therapy Micro-dystrophin Trial for DMD

 
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Dear Duchenne Community,

At the World Muscle Society in Argentina today, Dr. Jerry Mendell of Nationwide Children’s Hospital shared additional data relating to our micro-dystrophin gene therapy program. In particular, as a follow up to his presentation of the first three patients at our R&D Day in June of this year, Dr. Mendell today shared micro-dystrophin results for the fourth patient and provided positive functional signals for all patients.

It is important to remember that while we are very encouraged by all of the results we have to date, these are early days relating to our first four patients. It is important that we quickly commence a controlled trial to confirm these results. Fueled by our preliminary data, we are moving with a sense of urgency to move to a study that, if successful, could bring this therapy to those patients who can benefit from it.

As mentioned in June, the next micro-dystrophin trial will take place in the United States, will be carried out by Nationwide Children’s Hospital, and will be limited in size. Sarepta is mapping ways to expand the gene therapy clinical program to a broader population with considerations of study inclusion and geography. We will update the community about the plans as we finalize them.

Given the volume of inquiries received about this investigational effort, we know that there is a high level of anticipation within the worldwide Duchenne community surrounding gene therapy. Physicians and advocacy groups alike have expressed hope that families will stay focused on current treatment plans and investigational options selected in consultation with their healthcare team.

Let us once again be reminded that as encouraged as we are, these are preliminary results and we must continue to follow our initial patients and commence a controlled trial. But also know this, we are investing our energy, resources and creativity to moving the development forward as fast as is possible, planning meetings with the FDA and other agencies around the world to take their input, building a compelling access and reimbursement package, and establishing sufficient manufacturing capacity to fully serve the community if our program is successful.

I will provide additional updates as the program moves forward.

Sincerely,

Douglas S. Ingram
President and Chief Executive Officer
Sarepta Therapeutics, Inc

Industry Partner News: Catabasis Pharmaceuticals Initiates Phase 3 PolarisDMD Clinical Trial for Edasalonexent in Duchenne Muscular Dystrophy

 
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Pivotal Study of Novel Inhibitor of NF-kB, a Key Driver of Skeletal Muscle Disease and Cardiomyopathy in Duchenne

CAMBRIDGE, Mass., September 25, 2018 – Catabasis Pharmaceuticals, Inc. (NASDAQ:CATB), a clinical-stage biopharmaceutical company, today announced the initiation of PolarisDMD, the Company’s Phase 3 trial for edasalonexent in Duchenne muscular dystrophy (DMD). Edasalonexent inhibits NF-kB, which is the key link between loss of dystrophin and disease pathology and plays a fundamental role in the initiation and progression of skeletal and cardiac muscle disease in DMD. The PolarisDMD trial will evaluate the efficacy and safety of edasalonexent in patients with DMD and is intended to support an application for commercial registration of edasalonexent. Top-line results from the Phase 3 PolarisDMD trial are expected in the second quarter of 2020.

 Click to read the Catabasis Quarterly for September 2018.

Click to read the Catabasis Quarterly for September 2018.

PolarisDMD clinical trial sites across the United States will open in the coming days for enrollment of the Phase 3 PolarisDMD trial, with enrollment expected to run through this year and into next year. Additional sites in Australia, Canada, Europe and Israel are also expected to open early next year. In total, the PolarisDMD trial is expected to include approximately 40 clinical trial sites globally. The trial design was informed by discussions with the U.S. Food and Drug Administration (FDA) as well as input from treating physicians, patient organizations and families of boys affected by Duchenne.

“We are very excited to initiate our Phase 3 PolarisDMD trial as we believe edasalonexent has tremendous potential to become the new standard of care for all affected by Duchenne, regardless of mutation type and from the time of diagnosis throughout their lifespan,” said Joanne Donovan, M.D., Ph.D., Chief Medical Officer of Catabasis. “Edasalonexent inhibits NF-kB, which plays a fundamental role in skeletal and cardiac muscle disease in Duchenne. In the MoveDMD trial, edasalonexent slowed disease progression and preserved muscle function.”

The Phase 3 PolarisDMD trial is a one-year, randomized, double-blind, placebo-controlled trial. Catabasis plans to enroll approximately 125 patients ages 4 to 7 (up to 8th birthday) regardless of mutation type who have not been on steroids for at least 6 months. Boys on a stable dose of eteplirsen may be eligible to enroll. The primary efficacy endpoint will be change in the North Star Ambulatory Assessment score after 12 months of treatment with edasalonexent compared to placebo. Key secondary endpoints include the age-appropriate timed function tests time to stand, 4-stair climb and 10-meter walk/run. Assessments of growth, cardiac and bone health are also included. Two boys will receive 100 mg/kg/day of edasalonexent for each boy that receives placebo and after 12 months, all boys are expected to receive edasalonexent in an open-label extension.

“We are so glad to bring edasalonexent into Phase 3 for boys affected by Duchenne that could benefit from this potential therapy,” said Richard Finkel, M.D., Chief, Division of Neurology, Department of Pediatrics at Nemours Children’s Health System and a Principal Investigator for the Phase 2 and Phase 3 trials with edasalonexent. “With the stabilization of muscle function and excellent safety profile seen with edasalonexent treatment in the MoveDMD trial, patients and families are eager for a treatment for Duchenne that has demonstrated slowed disease progression in the clinic.”

“PPMD has conducted preference studies of those impacted by Duchenne to understand what is most important for novel therapies. Families responded that their highest priority is to stop or even slow disease progression and maintain muscle function,” Pat Furlong, Founding President and Chief Executive Officer of Parent Project Muscular Dystrophy (PPMD). “We are enthusiastic to see edasalonexent, with these potential effects, entering the Phase 3 PolarisDMD trial as an oral therapy that could treat all of those affected by Duchenne.”

Edasalonexent has been shown to preserve muscle function and substantially slow DMD disease progression across all four assessments of muscle function (the North Star Ambulatory Assessment, time to stand, 4-stair climb and 10-meter walk/run) compared to control in the MoveDMD® Phase 2 trial and open-label extension. Preclinical data and clinical biomarker data from the MoveDMD Phase 2 trial suggest that edasalonexent could have potential benefits in skeletal muscle, diaphragm and heart. Edasalonexent has been well tolerated through more than 45 patient-years of treatment with no safety signals observed.

More information about the Phase 3 PolarisDMD clinical trial will be available on www.clinicaltrials.gov in the coming days or contact the Catabasis clinical team via email at DMDtrials@catabasis.com.

About Edasalonexent (CAT-1004)
Edasalonexent (CAT-1004) is an investigational oral small molecule that is being developed as a potential new standard of care for all patients affected by DMD, regardless of their underlying mutation. Edasalonexent inhibits NF-kB, which is the key link between loss of dystrophin and disease progression. NF-kB has a fundamental role in skeletal and cardiac muscle disease in DMD. Catabasis is currently enrolling the single global Phase 3 PolarisDMD trial to evaluate the efficacy and safety of edasalonexent for registration purposes. Edasalonexent continues to be dosed in an open-label extension of the MoveDMD Phase 2 clinical trial. The FDA has granted orphan drug, fast track and rare pediatric disease designations and the European Commission has granted orphan medicinal product designation to edasalonexent for the treatment of DMD. For a summary of clinical results, please visit www.catabasis.com.

About Catabasis
At Catabasis Pharmaceuticals, our mission is to bring hope and life-changing therapies to patients and their families. Our lead program is edasalonexent, an NF-kB inhibitor in development for the treatment of Duchenne muscular dystrophy. The global Phase 3 PolarisDMD trial is currently enrolling boys affected by Duchenne. For more information on edasalonexent and our Phase 3 PolarisDMD trial, please visit www.catabasis.com or www.twitter.com/catabasispharma.

Forward Looking Statements
Any statements in this press release about future expectations, plans and prospects for the Company, including statements about future clinical trial plans including, among other things, statements about the Company’s global Phase 3 PolarisDMD trial in DMD to evaluate the efficacy and safety of edasalonexent for registration purposes, and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” “may” and similar expressions, constitute forward- looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of the Company’s product candidates; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; other matters that could affect the availability or commercial potential of the Company’s product candidates; and general economic and market conditions and other factors discussed in the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018, which is on file with the Securities and Exchange Commission, and in other filings that the Company may make with the Securities and Exchange Commission in the future. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward- looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this release.

###

Investor and Media Contact
Andrea Matthews
Catabasis Pharmaceuticals, Inc.
T: (617) 349-1971
amatthews@catabasis.com



Industry Partner News: Sarepta Announces Clinical Hold Lifted for its DMD Micro-dystrophin Gene Therapy Program

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CAMBRIDGE, Mass., September 24, 2018 (GLOBE NEWSWIRE) – Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases, announced today that the Food and Drug Administration (FDA) has lifted the clinical hold for the Company’s Duchenne muscular dystrophy (DMD) micro-dystrophin gene therapy program. Sarepta previously announced on July 25, 2018, that the FDA placed the program on clinical hold due to the presence of trace amounts of DNA fragment in research-grade third-party supplied plasmid in a manufacturing lot. In response, and in collaboration with Nationwide Children’s Hospital, an action plan was developed and submitted to the FDA, including an audit of the plasmid supplier and a commitment to use GMP-s plasmid for all future production lots.

“Thanks to the diligent and rapid work of my Sarepta colleagues and Nationwide Children’s Hospital in compiling and submitting a complete response and the expeditious evaluation by the FDA in reviewing the response and removing this clinical hold, we have been able to address the clinical hold in record time and without delay to this profoundly important clinical program,” stated Doug Ingram, Sarepta’s president and chief executive officer. “Our focus now is on meeting with the Division to take guidance and gain alignment around what we hope to be our registration trial for our micro-dystrophin program and achieving our goal of commencing that trial by year-end 2018.”

About Sarepta Therapeutics

Sarepta Therapeutics is a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases. The Company is primarily focused on rapidly advancing the development of its potentially disease-modifying Duchenne muscular dystrophy (DMD) drug candidates. For more information, please visit www.sarepta.com.

Industry Partner News: Community Letter from Sarepta Regarding CHMP's Negative Opinion for Eteplirsen

Please read the following community letter from Douglas S. Ingram, President and Chief Executive Officer of Sarepta Therapeutics, Inc., regarding the Committee for Human Medicinal Products (CHMP) in Europe’s negative opinion for eteplirsen.

21 September 2018

Dear European Duchenne Community,

This morning Sarepta announced that following its request for re-examination, the Committee for Human Medicinal Products (CHMP) in Europe issued a negative opinion for eteplirsen. While we recognized the probability of success was low, we committed our full resources and energy to this re-examination because we believe that the European Duchenne community deserves access to eteplirsen.

We are grateful for your insights, contributions and thoughtful engagement during this process. We also appreciated the open additional dialogue and advice we received from the CHMP, who signaled an openness to considering a regulatory pathway that could balance the needs of patients and their families with the requirements for additional supportive data. For eteplirsen, our next step is to initiate a request for follow up scientific advice, which we plan to do in 2019.

Given our discussions and commitment to the Duchenne community, we will continue to engage the European Medicines Agency (EMA) and explore the most appropriate path forward for eteplirsen and our other investigational medicines. We will seek scientific advice for our clinical programs as we continue to advance our pipeline of Duchenne therapies, including next-generation PPMO RNA therapy and the micro-dystrophin gene therapy candidate.

Despite today’s news, we continue to believe that there is a path forward in Europe to bring new therapies that can improve the lives of individuals living with Duchenne. Sarepta will continue to sponsor clinical trials in Europe. The ESSENCE trial is still enrolling in Europe as a method to understand the safety and efficacy of golodirsen and casimersen. There is also an eteplirsen study focused on individuals with Duchenne who are 6 months-48 months old in process. We will soon be initiating our high dose eteplirsen study, as well as trials for our next generation PPMO candidates in Europe.

We look forward to continued engagement as we advance these programs together.

Sincerely,

Douglas S. Ingram
President and Chief Executive Officer
Sarepta Therapeutics, Inc

 
 

Industry Partner News: Community Letter From Genetech/Roche Regarding RG6026

Please read the following Community Letter pertaining to Roche/Genentech's RG6206 program. 

13 September 2018

Dear Duchenne community,

By now, many have heard about Pfizer’s decision to stop their clinical studies of domagrozumab in Duchenne Muscular Dystrophy. We have received questions as to whether Pfizer’s decision has an impact on our clinical development program of RG6206 in Duchenne.

RG6206 is an investigational anti-myostatin adnectin that is designed to block the activity of myostatin and is given subcutaneously (by injection under the skin). The safety and efficacy of RG6206 in ambulatory boys (6-11 years old) is being evaluated in the Phase 2/3 SPITFIRE clinical study (www.clinicaltrials.gov reference NCT03039686, Roche study WN40227). Enrollment in the SPITFIRE clinical study is ongoing globally, and there are no planned changes to the study or its timelines as a result of Pfizer’s recent decision.

When evaluating investigational therapies, individual clinical studies are designed to address questions of safety and/or efficacy in a way that is specific and unique to the investigational molecule being studied. This means that studies with different study designs cannot be easily or directly compared. As such, it is not possible to draw comparisons or conclusions about RG6206 based on studies of other molecules with different study designs.

We are very grateful and appreciate the continuous partnership of the Duchenne community and would like to extend our thanks to all study participants and their families.

If you have questions:

  • Regarding your ongoing participation in the SPITFIRE study, or if you are in the screening phase, please contact your study physician.

  • If you are not in the SPITFIRE study, but have questions about RG6206, please contact me at elena.zhuravleva.ez1@roche.com.

Warm regards,

Elena Zhuravleva, MD, PhD on behalf of the Roche Duchenne team
Patient Partnership Director, Rare Disease, Roche, Switzerland

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Industry Partner News: Pfizer Announces Decision to Discontinue Domagrozumab Clinical Studies

Today, Pfizer announced the disappointing news that it is discontinuing its clinical studies of Domagrozumab. Please read their letter and press release below for more information.

Dear Jett Foundation,

It is with profound disappointment that we announce our decision to discontinue the
clinical studies evaluating domagrozumab for the treatment of Duchenne muscular
dystrophy (DMD). The two ongoing clinical trials include; a Phase 2 safety and efficacy
study (B5161002) and an open-label extension study (B5161004). The decision comes
following completion of the primary analysis. The primary analysis was based on a
statistical test which compared the difference in the time to climb 4 standard stairs
(known as the 4 Stair Climb) after 1 year of treatment with domagrozumab as compared
to placebo treated subjects. This analysis showed no statistical difference between these
two groups at the one year period. Evaluation of the totality of evidence, including
secondary endpoints, also did not support a significant treatment effect. It is important
to note that the studies were not discontinued for safety reasons.

The discontinued Phase 2 double-blind, placebo-controlled, multicenter, clinical trial
investigated the efficacy and safety of domagrozumab, administered in monthly IV doses,
in 121 boys aged 6 to 15 with DMD, regardless of underlying mutation. It was designed as
a two-year, placebo-controlled study (with the above noted primary analysis performed
after one year); all subjects used background corticosteroid management. The primary
efficacy endpoint was mean change from baseline in 4 Stair Climb (in seconds). Secondary
endpoints included evaluation of the change from baseline of participants on other
functional tests, including forced vital capacity, Northstar Ambulatory Assessment, the
six-minute walk test, muscle strength, range of motion, and Performance of Upper Limb
(PUL). For more information, please visit www.clinicaltrials.gov (NCT02310763).

We expect that this news will deeply disappoint the many families living with DMD who
directly participated in the study, as well as all of the families living with DMD hoping for
therapies that will alter the trajectory of this devastating disease. In recognition of the
continued burden of unmet needs in DMD, Pfizer continues to advance research and
clinical development efforts focused on DMD, including our investigational mini-
dystrophin gene therapy program. In addition, we are involved in efforts focused on
optimizing drug development for DMD. We intend to share data from the phase 2 clinical
study of domagrozumab with the DMD community in order to contribute to the body of
scientific knowledge which may enable the development of new therapies for patients.

In terms of next steps:

  • All clinical sites participating in the domagrozumab DMD studies have been provided with instructions for actions to take with enrolled participants. 

  • Patients and caregivers who have questions regarding their study participation should speak with their study physician for more information. 

  • Pfizer will share additional information about these results with the community when we are able.

We recognize the commitment that the DMD community has provided to these studies
and to our research and development efforts. It is with heartfelt gratitude that we
extend our sincerest ‘thank you’ to all the boys and families who expressed interest in the
study, underwent screening for the study, and to those ultimately participating in the
study. We are also grateful to the advocacy associations and advocates who provided the
tools and support needed for families to engage in clinical research and who continue to
care for the Duchenne community, and to the clinical research sites and staff who
collaborated with us on this important research.

Kind regards,
Michael Binks, MD
Shannon Marraffino
Katherine Beaverson
Rare Disease Research Unit
Pfizer Inc.

PRESS RELEASE

Pfizer Terminates Domagrozumab (PF-06252616) Clinical Studies for the Treatment of Duchenne Muscular Dystrophy

NEW YORK, NY, August 30, 2018 - Pfizer Inc. (NYSE: PFE) announced today that it is
terminating two ongoing clinical studies evaluating domagrozumab (PF-06252616) for the treatment of Duchenne muscular dystrophy (DMD): a Phase 2 safety and efficacy study
(B5161002) and an open-label extension study (B5161004). The Phase 2 study (B5161002), did
not meet its primary efficacy endpoint, which was to demonstrate a difference in the mean
change from baseline in 4 Stair Climb (in seconds) following one year of treatment with
domagrozumab as compared to placebo in patients with DMD. Further evaluation of the totality of evidence including secondary endpoints did not support a significant treatment effect. The
decision comes after a thorough review of data available at the time of the primary analysis,
which evaluated all study participants after one year of treatment, as well as those participants
who were in the trial beyond one year. The studies were not terminated for safety reasons. Pfizer
will continue to review the data to better understand any insights they may provide, and will share results with the scientific and patient community.

“We are disappointed by these results and while we are not progressing with the studies, the
data will contribute to a greater understanding of this disease and we will evaluate the total
data set to see if there is a place for this medicine in muscular diseases,” said Seng Cheng,
PhD, Senior Vice President and Chief Scientific Officer, Pfizer Rare Disease Research Unit.
“We are extremely grateful to all those involved with this trial, especially the boys who
participated, and their families.”

Pfizer is continuing research in DMD and rare neuromuscular diseases, with the goal of bringing
therapies to patients with unmet needs. The company’s continued partnership with advocacy
associations and the community is critical to finding innovative therapies for these diseases.
Pfizer has one ongoing clinical trial in DMD with a gene therapy, PF-06939926, which is an
investigational, recombinant AAV9 capsid carrying a truncated or shortened version of the human
dystrophin gene (mini-dystrophin) under the control of a human muscle specific promotor. 1

About the Domagrozumab Clinical Studies 1
The Phase 2 double-blind, placebo-controlled, multicenter clinical trial investigated the efficacy
and safety of domagrozumab, administered in monthly IV doses, in 121 boys aged 6 to 15 with
DMD, regardless of underlying mutation. It was designed as a two-year, placebo-controlled study
(with the primary analysis after one year); all subjects used background corticosteroid therapy.
The open-label extension study was designed to evaluate long-term safety and efficacy of
domagrozumab.

About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a rare, serious, debilitating childhood genetic disease
characterized by progressive muscle degeneration and weakness and significantly shortened life
expectancy. It is the most common form of muscular dystrophy worldwide and primarily affects
boys, with incidence of 1 in every 3500 to 5000 live male births each year. 2 , 3 Children with DMD typically present with signs of weakness, including late walking, trouble getting up, and difficulty running or climbing stairs, usually manifesting in early childhood between the ages of 1 and 4 years. 4 The progressive muscle degeneration leads to a loss of the ability to walk in the early teenage years, on average. Weakness of respiratory muscles ultimately leads to use of mechanical ventilatory support, and weakness in cardiac muscle involvement results in cardiomyopathy.


Pfizer Rare Disease
Rare disease includes some of the most serious of all illnesses and impacts millions of patients
worldwide, 5 representing an opportunity to apply our knowledge and expertise to help make a
significant impact on addressing unmet medical needs. 1 The Pfizer focus on rare disease builds
on more than two decades of experience, a dedicated research unit focusing on rare disease,
and a global portfolio of multiple medicines within a number of disease areas of focus, including
hematology, neuromuscular, and inherited metabolic disorders. Error! Bookmark not defined.

Pfizer Rare Disease combines pioneering science and deep understanding of how diseases
work with insights from innovative strategic collaborations with academic researchers, patients,
and other companies to deliver transformative treatments and solutions. We innovate every day
leveraging our global footprint to accelerate the development and delivery of groundbreaking
medicines and the hope of cures.

Click here to learn more about our Rare Disease portfolio and how we empower patients,
engage communities in our clinical development programs, and support programs that heighten
disease awareness.

Working together for a healthier world ®
At Pfizer, we apply science and our global resources to bring therapies to people that extend and
significantly improve their lives. We strive to set the standard for quality, safety and value in the
discovery, development and manufacture of health care products. Our global portfolio includes
medicines and vaccines as well as many of the world's best-known consumer health care
products. Every day, Pfizer colleagues work across developed and emerging markets to advance
wellness, prevention, treatments and cures that challenge the most feared diseases of our time.
Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com . In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and
@Pfizer_News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer .

Industry Partner News: Wave Life Sciences Receives US Orphan Drug and Rare Pediatric Disease Designations for WVE-210201

CAMBRIDGE, Mass., Aug. 16, 2018 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (NASDAQ:WVE), a biotechnology company focused on delivering transformational therapies for patients with serious, genetically-defined diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted both orphan drug designation and rare pediatric disease designation for WVE-210201 for the treatment of Duchenne muscular dystrophy (DMD). The European Commission previously granted orphan drug designation for WVE-210201 in July 2018.  

"Our team is motivated by a sense of urgency and compassion for the patients, families and caregivers affected by Duchenne muscular dystrophy and other serious, life-threatening conditions with high areas of unmet need," said Michael Panzara, MD, MPH, Neurology Franchise Lead of Wave Life Sciences. "We are very pleased to receive these two important designations from the FDA and believe they further reinforce the potential of WVE-210201 to help boys suffering from DMD."

The Orphan Drug Act provides for economic incentives to encourage the development of drugs intended to treat, diagnose or prevent rare diseases and conditions affecting fewer than 200,000 people in the United States. In determining orphan drug designation, the FDA's Office of Orphan Products Development evaluates preclinical and clinical data to identify products as promising for rare disease. If market approval is granted by the FDA for WVE-210201 for the treatment of DMD, orphan drug designation would entitle Wave to seven years of market exclusivity in the United States. Additional incentives may include tax credits related to clinical trial expenses, exemption from prescription drug user fees and FDA assistance in clinical trial design.

Rare pediatric disease designation by the FDA is granted in the case of serious or life-threatening diseases affecting fewer than 200,000 people in the United States in which the serious or life-threatening manifestations are primarily in individuals 18 years of age and younger. The designation provides regulatory incentives for companies to develop and market therapies that treat these conditions. The sponsor of a drug for a rare pediatric disease may be eligible for a priority review voucher upon approval of the drug that can be used to obtain a priority review of a subsequent marketing application.

"These designations from U.S. regulators represent the significant progress being made by Wave Life Sciences and our community is grateful to Wave for their ongoing commitment to the Duchenne muscular dystrophy community," said Pat Furlong, founding President and CEO of Parent Project Muscular Dystrophy. "We look forward to their exon 51 skipping program advancing and Wave's other initiatives in DMD."

WVE-210201 is currently being studied in an ongoing global, multicenter, double-blind, placebo-controlled Phase 1 clinical trial designed to evaluate the safety, tolerability and plasma concentrations of single ascending doses of WVE-210201 administered intravenously in DMD patients with gene mutations amenable to exon 51 skipping. The trial is expected to enroll up to 40 patients, including ambulatory and non-ambulatory patients, between the ages of 5 and 18 years of age. As patients complete the Phase 1 trial, they have the option to enroll in an ongoing open label extension study in which they receive continued treatment with WVE-210201.

About Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic neuromuscular disorder caused predominantly by out-of-frame deletions in the dystrophin gene, resulting in absent or defective dystrophin protein. Dystrophin protein is needed for normal muscle maintenance and operation. Because of the genetic mutations in DMD, the body cannot produce functional dystrophin, which results in progressive and irreversible loss of muscle function, including the heart and lungs. Globally, DMD affects approximately one in 5,000 newborn boys.

About WVE-210201

WVE-210201 is an investigational stereopure oligonucleotide that has been shown to induce skipping of exon 51 of dystrophin pre-mRNA in preclinical studies and is intended for the treatment of Duchenne muscular dystrophy (DMD). Approximately 13% of DMD patients have genetic mutations that are amenable to treatment with exon 51 skipping therapy. Exon-skipping technology has the potential to induce cellular machinery to ‘skip over' a targeted exon and restore the reading frame, resulting in the production of internally truncated, but functional, dystrophin protein. Wave preclinical in vitro experiments using gymnotic delivery (free uptake) of WVE-210201 in DMD patient-derived myoblasts demonstrated efficient exon 51 skipping and dystrophin protein restoration. Preclinical Western blot studies of WVE-210201 demonstrated 52% dystrophin protein restoration as compared with normal skeletal muscle tissue lysates.

About Wave Life Sciences

Wave Life Sciences is a biotechnology company focused on delivering transformational therapies for patients with serious, genetically-defined diseases. Its chemistry platform enables the creation of highly specific, well characterized oligonucleotides designed to deliver superior efficacy and safety across multiple therapeutic modalities. The company's pipeline is initially focused on neurological disorders and extends across several other therapeutic areas. For more information, please visit www.wavelifesciences.com.

Industry Partner News: Sarepta Therapeutics Announces that Phase 1/2a Duchenne Muscular Dystrophy (DMD) MicroDystrophin Gene Therapy Trial Placed on Clinical Hold

-- Out-of-specification lot resulted from the presence of trace levels of DNA fragment in research-grade . . raw material plasmid sourced from third-party manufacturer --

-- Fragment fully characterized; preliminary testing and analysis indicates no safety signals --

-- Subject to FDA review of a corrective action plan, which will include the use of GMP-s plasmid for all . . . future production lots --

-- Clinical timeline to commence dosing of patients in pivotal trial by year-end 2018 remains on track --

-- Sarepta to host conference call on Wednesday, July 25, 2018 at 5:00 p.m. ET --

CAMBRIDGE, Mass., July 25, 2018 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases, has been notified by the Research Institute at Nationwide Children’s Hospital (the Research Institute) that they have received a letter from the Food and Drug Administration (FDA) on July 24, 2018, stating that their Phase 1/2a Duchenne Muscular Dystrophy (DMD) Micro-Dystrophin Gene Therapy Trial has been placed on clinical hold due to the presence of a trace amount of DNA fragment in research-grade third-party supplied plasmid. Preliminary in-vivo testing performed by the Research Institute indicates that the trace fragment does not result in protein expression and is quickly cleared.

The Research Institute, working with Sarepta, has developed their action plan with immediate plans to submit for review by the FDA, which will include the use of GMP-s plasmid for the program. Subject to the FDA’s acceptance of the action plan, Sarepta does not anticipate any material delay in dosing patients as originally planned by year-end 2018.

“Patient safety is our top priority at Sarepta as we know it is for Nationwide Children’s Research Institute,” stated Doug Ingram, Sarepta’s president and chief executive officer. “We intend to rapidly respond to the FDA’s clinical hold letter, including a commitment to the Agency to only use GMP-s plasmid. Independently, we will also request a meeting with the Agency to discuss the micro-dystrophin program with the goal of commencing a pivotal trial by year-end 2018.”

Sarepta will host a conference call today, Wednesday, July 25, 2018 at 5:00 p.m. ET. The conference call may be accessed by dialing 844-534-7313 for domestic callers and +1-574-990-1451 for international callers. The passcode for the call is 8689739. Please specify to the operator that you would like to join the "Sarepta Conference Call." The conference call will be webcast live under the investor relations section of Sarepta's website at www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

About Sarepta Therapeutics

Sarepta Therapeutics is a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases. The Company is primarily focused on rapidly advancing the development of its potentially disease-modifying Duchenne muscular dystrophy (DMD) drug candidates. For more information, please visit www.sarepta.com.

For more information, visit sareptatherapeutics.com 

Industry Partner News: PTC Therapeutics Announces Positive Data from its Translarna™ Phase II Clinical Trial in Children as Young as Two Years with Nonsense Mutation Duchenne Muscular Dystrophy

SOUTH PLAINFIELD, N.J., July 9, 2018 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ:PTCT) today announced the presentation of data from the Translarna (ataluren) Phase II Study 030 demonstrating that the safety and pharmacokinetic profile of Translarna in children from two to five years with nonsense mutation Duchenne muscular dystrophy (nmDMD) was consistent with that for older children.1  Importantly, the data also showed that treatment with Translarna resulted in improvements in timed function tests and the North Star Ambulatory Assessment from baseline at weeks 28 and 52, with mean changes showing as much as a 25 percent improvement after one year.1 The data at 28 weeks formed the basis of the recent positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) to expand the current indication of Translarna to include nmDMD ambulatory children from two to five years of age.2  The data was presented at the International Congress on Neuromuscular Diseases in Vienna.

Translarna is the only approved treatment to address the underlying cause of nmDMD, a rare, genetic, muscle-wasting disease,1 and is currently licensed in Europe for ambulatory patients aged five years and older.3

"We are excited to demonstrate that Translarna showed an improvement over one year of treatment in patients with nonsense mutation Duchenne as young as two years of age," stated Stuart W. Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics, Inc. "Irreversible muscle damage starts before the age of five. Early intervention is critical to maintain muscle function and delay disease progression."

An interim analysis of Study 030 demonstrated that at week 28, the safety and pharmacokinetic profile for Translarna in children aged two to five years is consistent with that for older children.1 Clinical benefits were also observed at 28 weeks with Translarna, with decreases versus baseline in the time to run/walk 10 meters, climb four stairs, and stand from lying face up (supine).1 The most common adverse events included pyrexia, ear infection, and nasopharyngitis.1

Study 030 evaluated changes in timed function tests (TFTs) and the 3-part, 8-part and full (16) items North Star Ambulatory Assessment (NSAA) scales, adopted for children under five years of age (N=12).1 Results summarized in the table below.

About Study 0301

Study 030 was an open-label, Phase 2 study designed to evaluate the safety and pharmacokinetics (PK) of ataluren (10, 10, and 20 mg/kg) in patients aged ≥2 to <5 years with nmDMD. The study includes a 4-week treatment period, a 48-week extension period, and a 4-week follow-up period. Secondary objectives in Study 030 evaluated changes in timed function tests (TFTs) and the total, 3-part,8-part and full (16) items North Star Ambulatory Assessment (NSAA) scales, adapted for children <5 years of age. All patients were male (N=14) with genotypic confirmation of nmDMD. Two patients were excluded from the current analysis: one patient did not have reported functional assessment at Week 28; and one patient did not have baseline measurement all for post-line evaluations, resulting in N=12. Seven out of the fourteen patients in the safety population (50%) reported ≥1 treatment-emergent adverse event (TEAE) during the extension phase, all of which were deemed unrelated to the study drug; there were no serious TEAEs or discontinuations due to a TEAE. Pyrexia, ear infection, and nasopharyngitis were the most common TEAEs, each occurring in 2 patients (14.3%).

About ataluren (Translarna™)

Ataluren, discovered and developed by PTC Therapeutics, Inc., is a protein restoration therapy designed to enable the formation of a functioning protein in patients with genetic disorders caused by a nonsense mutation. A nonsense mutation is an alteration in the genetic code that prematurely halts the synthesis of an essential protein. The resulting disorder is determined by which protein cannot be expressed in its entirety and is no longer functional, such as dystrophin in Duchenne muscular dystrophy. Translarna, tradename of ataluren, is licensed in the European Economic Area for the treatment of nonsense mutation Duchenne muscular dystrophy in ambulatory patients aged five years and older. Ataluren is an investigational new drug in the United States. The development of ataluren has been supported by grants from the Muscular Dystrophy Association; FDA's Office of Orphan Products Development; National Center for Research Resources; National Heart, Lung, and Blood Institute; and Parent Project Muscular Dystrophy.

About Duchenne Muscular Dystrophy

Primarily affecting males, Duchenne muscular dystrophy (DMD) is a rare and fatal genetic disorder that results in progressive muscle weakness from early childhood and leads to premature death in the mid-twenties due to heart and respiratory failure. It is a progressive muscle disorder caused by the lack of functional dystrophin protein. Dystrophin is critical to the structural stability of all muscles, including skeletal, diaphragm, and heart muscles. Patients with Duchenne can lose the ability to walk as early as age ten, followed by loss of the use of their arms. Duchenne patients subsequently experience life-threatening lung complications, requiring the need for ventilation support, and heart complications in their late teens and twenties. More information on the signs and symptoms of Duchenne can be found at: www.duchenneandyou.com

About PTC Therapeutics, Inc.

PTC is a science-led, global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. Founded 20 years ago, PTC Therapeutics has successfully launched two rare disorder products and has a global commercial footprint. This success is the foundation that drives investment in a robust pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need.

Industry Partner News: Catabasis announces plans for edasalonexent Phase 3 POLARIS DMD trial and newsletter

-- Global Phase 3 POLARIS DMD Trial Expected to Initiate in the Second Half of 2018 and Enroll Approximately 125 Patients --

-- Phase 2 MoveDMD® Trial and Open-Label Extension Showed Substantially Slowed Duchenne Disease Progression in Patients Treated with Edasalonexent --

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jul. 9, 2018-- Catabasis Pharmaceuticals, Inc. (NASDAQ:CATB), a clinical-stage biopharmaceutical company, today announced plans for the Phase 3 POLARIS DMD trial with edasalonexent in patients with Duchenne muscular dystrophy (DMD). Catabasis plans to initiate the global POLARIS DMD trial in the second half of 2018 with top-line results expected in the second quarter of 2020.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180709005089/en/

The POLARIS DMD trial will evaluate the efficacy and safety of edasalonexent in patients with DMD and is intended to support an application for commercial registration of edasalonexent. The trial design was informed by discussions with the U.S. Food and Drug Administration (FDA) as well as input from treating physicians and families of boys affected by Duchenne.

The randomized, double-blind, placebo-controlled POLARIS DMD trial has many key elements in common with the Phase 2 MoveDMD® trial, including the patient population and functional endpoints. Catabasis anticipates enrolling approximately 125 patients between the ages of 4 and 7 regardless of mutation type who have not been on steroids for at least 6 months. Boys on a stable dose of eteplirsen may be eligible to enroll. The primary efficacy endpoint will be change in the North Star Ambulatory Assessment score after 12 months of treatment with edasalonexent compared to placebo. Key secondary endpoints are planned to include the age-appropriate timed function tests time to stand, 4-stair climb and 10-meter walk/run. Assessments of growth, cardiac and bone health are also planned to be included. Two boys will receive edasalonexent for every boy that receives placebo and after 12 months, all boys are expected to receive edasalonexent in an open-label extension.

“We have designed a robust study with POLARIS DMD to evaluate edasalonexent as a potential new treatment for Duchenne. We have benefited from input from many people that are part of the Duchenne community and we are well underway with our preparations to begin the trial,” said Joanne Donovan, M.D., Ph.D., Chief Medical Officer of Catabasis. “We are very excited to advance edasalonexent through this potentially last phase of clinical development with the hope of providing a new treatment option to all boys affected by this disease. We believe that edasalonexent has great potential as a therapy to be taken on its own as well as in combination with other treatments.”

Edasalonexent is a potential oral foundational therapy that is being developed for all patients affected by DMD. Edasalonexent is being developed for use as monotherapy and in possible combination with dystrophin upregulation therapies. Edasalonexent has been shown to preserve muscle function and substantially slow Duchenne disease progression in the MoveDMD Phase 2 trial and open-label extension. Preclinical data and clinical biomarker data from the MoveDMD Phase 2 trial suggest that edasalonexent could have potential benefits in skeletal muscle, diaphragm and heart. Edasalonexent has been safe and well tolerated through more than 45 patient-years of treatment.

About Edasalonexent (CAT-1004)
Edasalonexent (CAT-1004) is an investigational oral small molecule that is being developed as a potential disease-modifying therapy for all patients affected by DMD, regardless of their underlying mutation. Edasalonexent inhibits NF-kB, a protein that is activated in DMD and drives inflammation, fibrosis and muscle degeneration and suppresses muscle regeneration. Edasalonexent continues to be dosed in an open-label extension of the MoveDMD Phase 2 clinical trial, and Catabasis is preparing to initiate a single global Phase 3 trial in the second half of 2018 to evaluate the efficacy and safety of edasalonexent for registration purposes. The FDA has granted orphan drug, fast track and rare pediatric disease designations and the European Commission has granted orphan medicinal product designation to edasalonexent for the treatment of DMD. For a summary of clinical results reported to-date, please visit www.catabasis.com.

About Catabasis
At Catabasis Pharmaceuticals, our mission is to bring hope and life-changing therapies to patients and their families. Our lead program is edasalonexent, an NF-kB inhibitor in development for the treatment of Duchenne muscular dystrophy. Edasalonexent was designed using our SMART (Safely Metabolized And Rationally Targeted) Linker drug discovery platform that enables us to engineer molecules that simultaneously modulate multiple targets in a disease. For more information on edasalonexent or our drug discovery platform, please visit www.catabasis.com.

Forward Looking Statements
Any statements in this press release about future expectations, plans and prospects for the Company, including statements about future clinical trial plans including, among other things, statements about the Company’s plans to commence a single global Phase 3 trial in DMD to evaluate the efficacy and safety of edasalonexent for registration purposes, and other statements containing the words “believes,” “anticipates,” “plans,” “expects,” “may” and similar expressions, constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of the Company’s product candidates; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; the Company’s ability to obtain financing on acceptable terms and in a timely manner to fund the Company’s planned Phase 3 trial of edasalonexent in DMD for registration purposes; availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; other matters that could affect the availability or commercial potential of the Company’s product candidates; and general economic and market conditions and other factors discussed in the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2018, which is on file with the Securities and Exchange Commission, and in other filings that the Company may make with the Securities and Exchange Commission in the future. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date of this press release. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this release.

Industry Partner News: Summit Announces PhaseOut DMD Did Not Meet Primary Endpoint

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To the DMD community,

After reviewing the top-line results of PhaseOut DMD, we have made the difficult decision to discontinue the development of ezutromid.

We recognize that this decision will be disappointing for the Duchenne community, but the data from PhaseOut DMD were clear that ezutromid, while well-tolerated, did not provide a benefit to patients with DMD.

These results are not what we had hoped for, and certainly not what we had expected based on the encouraging interim results from PhaseOut DMD. But, they provide a clear answer to the important scientific question of ezutromid’s effect in DMD. The results provided no evidence that ezutromid is having a meaningful effect on slowing DMD progression. We therefore cannot support further development of ezutromid. We are now working with our clinical trial investigators to bring the PhaseOut DMD clinical trial and associated extension phase to a close. Patients in PhaseOut DMD should contact their study doctors for more information.

We sincerely thank the patients, families and clinical trial sites who have been involved in all of our clinical trials of ezutromid. We plan to explore ways that the information gathered as part of PhaseOut DMD can be made available to support other research activities in DMD for the benefit of the entire community.

We are also grateful for the support that we’ve had from patient organizations worldwide in the development of ezutromid.

We believe that the future of Duchenne research is bright. There are numerous clinical trials and research studies taking place in this field, and there is hope on the horizon for all those living with DMD.

If you have further questions, please contact Michelle Avery, PhD, our Director of Patient Engagement, at michelle.avery@summitplc.com.

Sincerely,
Glyn Edwards, CEO of Summit

FAQs

1.       What do these data mean? We designed PhaseOut DMD to answer if ezutromid is safe and efficacious in patients with DMD. Unfortunately, the results are quite clear that ezutromid is not having a clinical benefit for patients with DMD. It does continue to be well-tolerated, but given the lack of evidence we’ve seen, we have decided to discontinue its development.

2.       Will patients in PhaseOut DMD be allowed to continue to receive ezutromid? We are working with our clinical trial investigators to bring the trial and extension phase to a close, including any patients who have been enrolled into the additional cohort of the trial that was opened in March 2018. We have taken this difficult decision as the data were clear that patients in PhaseOut DMD were not benefitting from ezutromid treatment.

3.       Are you continuing to work on future generation compounds? While we still believe utrophin modulation could have a place in the treatment of DMD and other dystrophinopathies, our focus will be on the development of our new mechanism antibiotic pipeline.

To read the full press release, please visit Summit's website here.

Industry Partner News: Sarepta Announces that Jerry Mendell, M.D. Presented Positive Preliminary Results from the First Children Dosed in Gene Therapy Micro-dystrophin Trial to Treat DMD Patients

dinarudick.bostonglobe

Dear Duchenne Community,

Today Sarepta Therapeutics held its first ever Research and Development Day, an opportunity to gain insight into Sarepta’s pipeline, its collaborations, and its progress toward its mission of bringing a better life to those living with Duchenne muscular dystrophy, Limb-girdle muscular dystrophy and other rare diseases.

Multiple speakers shared information regarding their work in Duchenne muscular dystrophy today. From these presentations a notion of Sarepta’s full body of work is emerging. The good news is that we are making progress toward our goal of developing therapeutic options for 100% of the individuals with Duchenne. Speakers included (in order of appearance):

  • Doug Ingram, President & Chief Executive Officer, Sarepta Therapeutics
  • Gilmore O’Neill, M.B., M.M.SC., Chief Medical Officer, Sarepta Therapeutics
  • Kevin M. Flanigan, M.D., Director, Center for Gene Therapy, Nationwide Children’s Hospital
  • Serge Braun, Pharm.D., Ph.D., Chief Scientific Officer, AFM-Téléthon; Director Neuromuscular Strategy, Genethon; President, Genosafe SAS; Member, French National Academy of Pharmacy
  • Jerry R. Mendell, M.D., Curran-Peters Chair of Pediatric Research, Center for Gene Therapy, Nationwide Children’s Hospital
  • Louise Rodino-Klapac, Ph.D., Vice President, Gene Therapy, Sarepta Therapeutics; Chief Scientific Officer, Myonexus Therapeutics
  • Charles A. Gersbach, Ph.D., Associate Professor of Biomedical Engineering, Director, Center for Biomolecular and Tissue Engineering, Duke University
  • Gunnar J. Hanson, Ph.D., Senior Director, Research Chemistry, Sarepta Therapeutics
  • Marco Passini, Ph.D., Senior Director, Biology, Sarepta Therapeutics

Notably, Drs. Jerry Mendell and Louise Rodino-Klapac presented positive preliminary results from the first three children dosed in the Phase 1/2a gene therapy micro-dystrophin trial to treat patients with Duchenne muscular dystrophy. Dr. Mendell shared the following:

  • Biopsies performed at Day 90 showed robust micro-dystrophin expression in muscle measured by all methods and observed in all three patients
  • Significant decrease in levels of serum creatine kinase (CK), an enzyme biomarker strongly associated with muscle damage caused by Duchenne muscular dystrophy
  • No serious adverse events (SAEs) observed

We should remember that these are preliminary results involving three patients; much more work
remains to be done. Nevertheless, this data is encouraging and gives us confidence that we are on the right track. 

Regarding the micro-dystrophin gene therapy program, we want to pause and acknowledge every person who has helped to bring this work forward including Dr. Jerry Mendell, Dr. Louise Rodino-Klapac, Pat Furlong, and Parent Project Muscular Dystrophy, who from the earliest days supported this work. We also want to thank the individuals with Duchenne and their families who participated in our clinical trials. Their courage and dedication benefits all living with Duchenne.

Great science is born from great questions, and we know that this community has enormous insight to share. If you have questions related to today’s news, please reach out to your advocacy partners. We will be offering a conference call with them in the near future to discuss community questions. Advocacy groups are instrumental in helping digest movement and change, and they can be a fantastic conduit for ongoing conversation with the community. If you would like to receive future updates from Sarepta, please register on www.duchenne.com/connect.

Thank you to the community for allowing us to engage in this fight with you. We are humbled and inspired by your spirit daily and will remain dedicated to finding meaningful solutions.

Sincerely,

Douglas S. Ingram
President & Chief Executive Officer
Sarepta Therapeutics, Inc.

To read Sarepta's full Press Release, please click here.

Industry Partner News: Activities to Resume Enrollment in Solid's IGNITE DMD Phase I/II Clinical Trial are Underway

CAMBRIDGE, Mass., June 18, 2018 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (NASDAQ:SLDB) today announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on IGNITE DMD, the Company’s Phase I/II clinical trial for its investigational microdystrophin gene transfer, SGT-001, for the treatment of Duchenne muscular dystrophy (DMD). In its letter, the FDA acknowledged that the Company satisfactorily addressed all clinical hold questions. Solid has begun activities to resume the clinical trial and plans to reinitiate enrollment as quickly as possible.

“We believe SGT-001 has the potential to offer significant benefit to patients with DMD, regardless of their age or stage of disease,” said Ilan Ganot, Founder and Chief Executive Officer of Solid Biosciences. “We are pleased to have been able to provide the FDA with a comprehensive response resulting in the removal of the clinical hold so we can continue development of this important potential treatment.”

As previously disclosed, the FDA placed a clinical hold on IGNITE DMD following the Company’s report of a Serious Adverse Event (SAE) in the first patient dosed with SGT-001. The event was characterized by a decrease in platelet count followed by a reduction in red blood cell count, transient renal impairment and evidence of complement activation. There were no signs of bleeding or clotting abnormalities and no laboratory evidence of liver dysfunction. The patient received standard medical care, a modified steroid regimen and a limited course of eculizumab for the observed complement activation. He remained clinically stable and generally asymptomatic throughout the event, which fully resolved.

“Gene therapy has the potential to dramatically change the course of DMD and may offer long-term benefit for those who suffer from this devastating disease,” said Barry Byrne, M.D., Ph.D., Director, University of Florida Powell Gene Therapy Center and Professor, Pediatrics and Molecular Genetics & Microbiology at the University of Florida College of Medicine. "After a thorough analysis of the clinical and laboratory data for the patient, I am confident the event was easily monitored and medically manageable. Our patient quickly returned to his normal activities and planned study assessments. We look forward to continuing the IGNITE DMD study and providing additional children and adolescents with this promising investigational therapy.” 

In connection with the lifting of the clinical hold, Solid has made changes to the IGNITE DMD protocol, including the addition of IV glucocorticoids in the initial weeks post administration of SGT-001 and enhanced monitoring measures that include a panel for complement activation. The amended protocol also specifies that eculizumab will be available as a treatment option if complement activation is observed.

The Company plans to enroll and dose several children prior to dosing additional adolescents. In addition, Solid now has the choice to obtain the intermediate muscle biopsy at 45 days post administration of SGT-001 to collect additional information about the time course of microdystrophin expression.

As a result of the clinical hold, Solid now expects to report initial data from a pre-specified interim analysis of IGNITE DMD in the second half of 2019.

Conference Call
Solid's management team will host a conference call and webcast at 8:30 a.m. ET today to discuss the lifting of the clinical hold. The conference call can be accessed by dialing +1 866 763 0341 for domestic callers and +1 703 871 3818 for international callers. The passcode for the call is 8892798. A live webcast of the conference call can also be accessed through the "Investors" tab on the Solid Biosciences website at www.solidbio.com. A webcast replay will be available online after the call.

About SGT-001
Solid’s lead candidate, SGT-001, is a novel adeno-associated viral (AAV) vector-mediated gene transfer under investigation for its ability to address the underlying genetic cause of Duchenne muscular dystrophy (DMD), mutations in the dystrophin gene that result in the absence or near-absence of dystrophin protein. SGT-001 is a systemically administered candidate that delivers a synthetic dystrophin transgene, called microdystrophin, to the body. This microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins, including neuronal nitric oxide synthase (nNOS). SGT-001 utilizes AAV9, which has an affinity for muscle and is currently being evaluated in multiple clinical programs in other indications. Data from Solid’s preclinical program suggest that SGT-001 has the potential to slow or stop the progression of DMD, regardless of genetic mutation or disease stage.

SGT-001 is based on pioneering research in dystrophin biology by Dr. Jeffrey Chamberlain of the University of Washington and Dr. Dongsheng Duan of the University of Missouri. SGT-001 has been granted Rare Pediatric Disease Designation, or RPDD, in the United States and Orphan Drug Designations in both the United States and the European Union.

About Solid Biosciences
Solid Biosciences is a life science company focused solely on finding meaningful therapies for Duchenne muscular dystrophy (DMD). Founded by those touched by the disease, Solid is a center of excellence for DMD, bringing together experts in science, technology and care to drive forward a portfolio of candidates that have life-changing potential. Currently, Solid is progressing programs across four scientific platforms: Corrective Therapies, Disease-Modifying Therapies, Disease Understanding and Assistive Devices. For more information, please visit www.solidbio.com.

Industry Partner News: Sarepta Therapeutics Announces First Quarter 2018 Financial Results and Recent Corporate Developments

-- First quarter 2017 EXONDYS 51® (eteplirsen) total net revenues of $64.6 million --

-- Sarepta signs exclusive partnership and buy-out option with Myonexus Therapeutics; pipeline expands from 16 to 21 programs --

-- Company announces date of first R&D day, at which clinical data from gene therapy micro-dystrophin program will be announced --

-- Company receives negative trend vote following its CHMP oral explanation; will request re-examination and Scientific Advisory Group to be convened --

CAMBRIDGE, Mass., May 03, 2018 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases, today reported financial results for the three months ended March 31, 2018.

“In the first quarter, we continued our successful launch of EXONDYS 51 and advanced our pipeline to bring life-enhancing therapies to those suffering from rare disease around the world,” said Doug Ingram, Sarepta’s president and chief executive officer. “We accelerated our gene therapy and RNA platform, and in that regard are excited to announce that our first R&D day will take place on June 19 to showcase the breadth, depth and progress of our pipeline. Significantly, at this event we will report preliminary safety and gene expression data from at least two patients from our micro-dystrophin gene therapy trial underway with Nationwide Children’s Hospital.”

Mr. Ingram continued, “Aligned with our stated goal of leveraging our expertise beyond DMD, we announced today a collaboration with Myonexus Therapeutics for the development of five potentially transformative gene therapies to treat a debilitating set of diseases, all under the umbrella of Limb-girdle muscular dystrophy. Through this collaboration, we have expanded our pipeline to 21 therapies in development. Our confidence in the Myonexus collaboration comes from the similarities between the Myonexus and Sarepta approaches to gene therapy.  Both are seeking to treat rare neuromuscular disease through the AAVrh.74 vector; and both rely upon the unparalleled expertise of Dr. Louise Rodino-Klapac in developing and executing gene therapy constructs. This partnership with Myonexus enables us to expand our efforts beyond DMD while maintaining our unwavering commitment to those suffering from DMD.” 

Mr. Ingram concluded, “Unfortunately, in addition to our successes in the first quarter, we also have had a delay in our effort to bring eteplirsen to patients in Europe who could potentially benefit from it. I could not be prouder of our Sarepta team and the team of experts who spoke on behalf of eteplirsen at the CHMP oral explanation last week. The rigorous work that was done to prepare for the hearing only strengthened our resolve that eteplirsen should urgently be made available to those waiting in Europe. Unfortunately, the CHMP’s trend vote was negative. Based on discussions with CHMP representatives, it is our understanding that the CHMP did not conclude that eteplirsen is ineffective for exon 51 amenable patients, but rather that Sarepta has not yet met the regulatory threshold for conditional approval, in part due to the use of external controls as comparators in the studies. Sarepta plans to file for re-examination and will request that a Scientific Advisory Group (SAG), which is made up of DMD and neuromuscular specialists, be convened to provide expert guidance and insight into, among other things, the validity of the external controls used and the importance of slowing pulmonary decline in patients with DMD.”

Financial Results

For the first quarter of 2018, on a GAAP basis, Sarepta reported a net loss of $35.4 million, or $0.55 per basic and diluted share, compared to net income of $84.1 million reported for the same period of 2017, or $1.53 per basic share and $1.50 per diluted share. On a non-GAAP basis, the net loss for the first quarter of 2018 was $17.9 million, or $0.28 per share, compared to a net loss of $31.4 million for the same period of 2017, or $0.57 per share.

Net Revenues

For the three months ended March 31, 2018, the Company recorded net product revenues of $64.6 million, compared to net revenues of $16.3 millionfor first quarter of 2017. The increase primarily reflects increasing demand for EXONDYS 51 in the U.S.

Cost and Operating Expenses

Cost of sales (excluding amortization of in-licensed rights)

For the three months ended March 31, 2018, cost of sales (excluding amortization of in-licensed rights) was $5.6 million, compared to $0.2 millionfor the same period of 2017. The increase primarily reflects royalty payments to BioMarin Pharmaceuticals (BioMarin) as a result of the execution of the settlement and license agreements with BioMarin in July 2017 as well as higher inventory costs related to increasing demand for EXONDYS 51 during 2018. Prior to the approval of EXONDYS 51, the Company expensed related manufacturing and material costs as research and development expenses.

Research and development

Research and development expenses were $46.2 million for the first quarter of 2018, compared to $29.1 million for the same period of 2017, an increase of $17.1 million. The increase in research and development expenses primarily reflects the following:

  • $4.4 million increase in clinical and manufacturing expenses primarily due to increased patient enrollment in the Company’s ongoing clinical trials in golodirsen and casimersen, as well as a ramp-up of manufacturing activities for the Company’s PPMO platform. These increases were partially offset by a ramp-down of clinical trials in eteplirsen primarily because the PROMOVI trial has been fully enrolled;
     
  • $3.2 million increase in collaboration cost sharing with Summit on its utrophin platform;
     
  • $2.7 million increase in compensation and other personnel expenses primarily due to a net increase in headcount;
     
  • $2.4 million increase in professional services primarily due to an expansion of the Company’s research and development pipeline; and
     
  • $1.6 million increase in preclinical expenses primarily due to the continuing ramp-up of toxicology studies in the Company’s PPMO platform as well as golodirsen and casimersen.

Non-GAAP research and development expenses were $43.3 million for the first quarter of 2018, compared to $26.7 million for the same period of 2017, an increase of $16.6 million.

Selling, general and administration

Selling general and administrative expenses were $43.3 million for the first quarter of 2018, compared to $26.2 million for the same period of 2017, an increase of $17.1 million. The increase in selling, general and administrative expenses primarily reflects the following:

  • $6.4 million increase in professional services primarily due to continuing global expansion as well as preparation for a potential product launch in the EU should the Company’s Marketing Authorization Application be approved by the European Medicines Agency;
     
  • $5.3 million increase in compensation and other personnel expenses primarily due to a net increase in headcount; and
     
  • $4.6 million increase in stock-based compensation primarily due to the impact of revising the forfeiture rate assumption for officers and Board of Directors as well as an increase in stock price.

Non-GAAP selling, general and administrative expenses were $33.7 million for the first quarter of 2018, compared to $21.1 million for the same period of 2017, an increase of $12.6 million.

Amortization of in-licensed rights

Amortization of in-licensed rights was $0.2 million during the first quarter of 2018, compared to less than $0.1 million for the same period of 2017. The increase was primarily due to the BioMarin transactions that occurred in July 2017.

Other (loss) Income

Gain from sale of Priority Review Voucher

In connection with the completion of the sale of the Priority Review Voucher (PRV) in March 2017, the Company recorded a gain of $125.0 from sale of the PRV in the first quarter of 2017. There was no similar activity in the first quarter of 2018.

Interest (expense) income and other, net

For the three months ended March 31, 2018 and 2017, the Company recorded $4.5 million interest expense and other, net and $0.3 interest income and other, net, respectively.  The period over period unfavorable change primarily reflects the interest expense accrued on the Company’s debt facilities partially offset by interest income from higher balances of cash, cash equivalents and investments.

Cash, Cash Equivalents, Restricted Cash and Investments

The Company had $1.0 billion in cash, cash equivalents, restricted cash and investments as of March 31, 2018 compared to $1.1 billion as of December 31, 2017. The decrease is primarily driven by the use of cash to fund the Company’s ongoing operations during the first quarter of 2018.

Use of Non-GAAP Measures

In addition to the GAAP financial measures set forth in this press release, the Company has included certain non-GAAP measurements. The non-GAAP loss is defined by the Company as GAAP net loss excluding interest expense/(income), income tax expense/(benefit), depreciation and amortization expense, stock-based compensation expense, restructuring expense and other items. Non-GAAP research and development expenses are defined by the Company as GAAP research and development expenses excluding depreciation and amortization expense, stock-based compensation expense, restructuring expense and other items. Non-GAAP selling, general and administrative expenses are defined by the Company as GAAP selling, general and administrative expenses excluding depreciation and amortization expense, stock-based compensation expense, restructuring expense and other items.

1. Interest, tax, depreciation and amortization

Interest income and expense amounts can vary substantially from period to period due to changes in cash and debt balances and interest rates driven by market conditions outside of the Company’s operations.  Tax amounts can vary substantially from period to period due to tax adjustments that are not directly related to underlying operating performance. Depreciation expense can vary substantially from period to period as the purchases of property and equipment may vary significantly from period to period and without any direct correlation to the Company’s operating performance. Amortization expense associated with in-licensed rights as well as patent costs are amortized over a period of several years after acquisition or patent application or renewal and generally cannot be changed or influenced by management.

2. Stock-based compensation expenses

Stock-based compensation expenses represent non-cash charges related to equity awards granted by Sarepta. Although these are recurring charges to operations, management believes the measurement of these amounts can vary substantially from period to period and depend significantly on factors that are not a direct consequence of operating performance that is within management's control. Therefore, management believes that excluding these charges facilitates comparisons of the Company’s operational performance in different periods.

3. Restructuring expenses

The Company believes that adjusting for these items more closely represents the Company’s ongoing operating performance and financial results.

4. Other items

The Company evaluates other items of expense and income on an individual basis. It takes into consideration quantitative and qualitative characteristics of each item, including (a) nature, (b) whether the items relates to the Company’s ongoing business operations, and (c) whether the Company expects the items to continue on a regular basis. These other items include the aforementioned gain from the sale of the Company’s PRV.

The Company uses these non-GAAP measures as key performance measures for the purpose of evaluating operational performance and cash requirements internally. The Company also believes these non-GAAP measures increase comparability of period-to-period results and are useful to investors as they provide a similar basis for evaluating the Company’s performance as is applied by management. These non-GAAP measures are not intended to be considered in isolation or to replace the presentation of the Company’s financial results in accordance with GAAP. Use of the terms non-GAAP research and development expenses, non-GAAP selling, general and administrative expenses, non-GAAP other income adjustments, non-GAAP income tax expense, non-GAAP net loss, and non-GAAP basic and diluted net loss per share may differ from similar measures reported by other companies, which may limit comparability, and are not based on any comprehensive set of accounting rules or principles. All relevant non-GAAP measures are reconciled from their respective GAAP measures in the attached table "Reconciliation of GAAP to Non-GAAP Net Loss.”

First Quarter and Recent Corporate Developments

  • Golodirsen (SRP-4053): Based on Sarepta’s Type C meeting with the FDA’s Division of Neurology Products to solicit the Division's guidance on the development pathway for golodirsen, the Company remains on track to complete a rolling NDA submission by year-end 2018, seeking accelerated approval based on an increase in dystrophin protein as a surrogate endpoint.
  • Myonexus Therapeutics Partnership: Sarepta and Myonexus Therapeutics entered into a partnership to advance multiple gene therapies for various forms of Limb-girdle muscular dystrophies (LGMDs). The lead program, MYO-101, has generated encouraging pre-clinical safety and efficacy data utilizing the AAVrh.74 vector system, the same vector used in the micro-dystrophin gene therapy program Sarepta is developing with Nationwide Children’s Hospital. A Phase 1/2a study of MYO-101 is scheduled to begin in mid-2018. The companies plan to report on 60-day biopsy data in late-2018 or early 2019. Additionally, Myonexus is advancing MYO-102 for LGMD2D, MYO-103 for LGMD2C, MYO-201 for LGMD2B, and MYO-301 for LGMD2L. Under the terms of the agreement, Sarepta will make an upfront payment of $60 million and additional development-related milestone payments to purchase an exclusive option to acquire Myonexus at a pre-negotiated, fixed price with sales-related contingent payments. If all development-related milestone payments are met, Sarepta will make payments of up to $45 million over an approximately two-year evaluation period. Sarepta has the option to purchase Myonexus at any time, including upon review of proof-of-concept data.
  • Sarepta R&D Day (Tuesday, June 19, 2018): Sarepta management, along with several key-opinion leaders, will provide an in-depth look into the Company’s pipeline programs across several modalities, included RNA-targeted therapies, gene therapy and gene editing. Of particular note, we look forward to presenting our micro-dystrophin expression data from at least two patients enrolled in the Phase 1/2a gene therapy clinical trial underway with Drs. Jerry Mendell and Louise Rodino-Klapac of Nationwide Children’s Hospital. To date, the Company has enrolled four patients in this study and no significant adverse events have been reported. In addition, Dr. Rodino-Klapac, who is also chief scientific officer and co-founder of Myonexus, will present data from Myonexus’ entire LGMD program. For all to access, Sarepta’s R&D day will be webcast live under the investor relations section of the Company’s website at: www.sarepta.com and will be archived there following the event for 90 days.

Conference Call

The Company will be hosting a conference call at 4:30 p.m. Eastern Time, to discuss these financial results and provide a corporate update. The conference call may be accessed by dialing 844-534-7313 for domestic callers and +1-574-990-1451 for international callers. The passcode for the call is 2798939. Please specify to the operator that you would like to join the "Sarepta First Quarter 2018 Earnings Call”. The conference call will be webcast live under the investor relations section of Sarepta's website at www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

About EXONDYS 51

EXONDYS 51 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to skip exon 51 of the dystrophin gene. EXONDYS 51 is designed to bind to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 51 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

Important Safety Information About EXONDYS 51

Hypersensitivity reactions, including rash and urticaria, pyrexia, flushing, cough, dyspnea, bronchospasm, and hypotension, have occurred in patients who were treated with EXONDYS 51. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion or interrupting the EXONDYS 51 therapy.

Adverse reactions in DMD patients (N=8) treated with EXONDYS 51 30 or 50 mg/kg/week by intravenous (IV) infusion with an incidence of at least 25% more than placebo (N=4) (Study 1, 24 weeks) were (EXONDYS 51, placebo): balance disorder (38%, 0%), vomiting (38%, 0%) and contact dermatitis (25%, 0%). The most common adverse reactions were balance disorder and vomiting. Because of the small numbers of patients, these represent crude frequencies that may not reflect the frequencies observed in practice. The 50 mg/kg once weekly dosing regimen of EXONDYS 51 is not recommended.

In the 88 patients who received ≥30 mg/kg/week of EXONDYS 51 for up to 208 weeks in clinical studies, the following events were reported in ≥10% of patients and occurred more frequently than on the same dose in Study 1: vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

For further information, please see the full Prescribing Information.

About Sarepta Therapeutics

Sarepta Therapeutics is a commercial-stage biopharmaceutical company focused on the discovery and development of precision genetic medicine to treat rare neuromuscular diseases. The Company is primarily focused on rapidly advancing the development of its potentially disease-modifying DMD drug candidates. For more information, please visit www.sarepta.com.

Industry Partner News: Capricor Launches HOPE-2 Clinical Trial of CAP-1002 in Duchenne Muscular Dystrophy

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UC Davis Medical Center First Site in Nation To Enroll and Treat Participants

LOS ANGELES – April 30, 2018 – Capricor Therapeutics (NASDAQ: CAPR) today announced it has initiated the HOPE-2 clinical trial at UC Davis Medical Center. The trial will test the safety and efficacy of Capricor’s novel cellular therapy, CAP-1002, in boys and young men with Duchenne muscular dystrophy, a devastating and fatal genetic disorder with limited treatment options and no cure.

Up to 84 boys and young men with Duchenne muscular dystrophy will be enrolled in HOPE-2, a Phase 2, randomized, double-blind, placebo-controlled trial that will test CAP-1002 in participants with advanced stages of Duchenne muscular dystrophy. The medical center in Sacramento is the first site in the nation to begin enrolling and treating participants. Approximately 12-15 investigative sites are expected to participate in the trial.

“We are very pleased to begin this important clinical trial of CAP-1002,” said Craig McDonald, M.D., the national principal investigator for the HOPE-2 clinical trial and UC Davis professor and chair of its Department of Physical Medicine and Rehabilitation. “The HOPE-2 trial will study whether CAP-1002 can maintain or improve cardiac and skeletal muscle function. Because many of the participants are non-ambulatory, the study will focus primarily on the impact on arm mobility.”

Linda Marbán, Ph.D., Capricor president and chief executive officer, said CAP-1002 is one of the very few clinical initiatives to focus on helping boys and young men whose ability to walk has been seriously impaired by the loss of muscle function that occurs as Duchenne muscular dystrophy progresses.

“We are thrilled to begin enrolling participants in HOPE-2 because we have seen the potential for improvements in muscle function in both pre-clinical studies and in our earlier HOPE-Duchenne trial,” she said. “We have also been granted the RMAT and orphan disease designations by the U.S. Food and Drug Administration (FDA). These designations will enable us to work closely with the FDA in finalizing the regulatory approval pathway for CAP-1002 and to receive expedited FDA reviews. We are hopeful that HOPE-2 may potentially be a registration trial.”

Dr. Marbán said CAP-1002 could be an important tool in the toolbox to treat Duchenne muscular dystrophy.

“While gene and other therapies have the potential to restore dystrophin expression and sustain muscle function, there will still be significant inflammation and fibrosis which can offset the restorative effects,” she said. “CAP-1002 may work synergistically with the emerging disease-modifying therapies to control those additional pathological aspects of Duchenne muscular dystrophy because CAP-1002’s primary mechanism of action is immunomodulatory, meaning it can help balance inflammation in this chronic inflammatory disease.”

Capricor’s previous clinical trial, the HOPE-Duchenne trial, evaluated the safety and efficacy of a single dose of CAP-1002 in boys and young men with heart disease related to Duchenne muscular dystrophy. It found CAP-1002 was generally safe, well tolerated and demonstrated significant and sustained signals of improvement in cardiac and skeletal muscle function.

Participants in the HOPE-2 trial will be randomized to receive either placebo or CAP-1002, delivered intravenously every three months for a total of four administrations. Participants will be followed for a one-year period following randomization. An open label extension is planned if trial evidence suggests an appropriate risk/benefit profile of CAP-1002. For more information, please visitwww.HOPE2Trial.com.

For more information, please visit Capricor's website.