EPI743

Edison Pharmaceuticals EPI-743 Clinical Trial Information

Update: December 2012

CURRENTLY RECRUITING CHILDREN WITH LEIGH SYNDROME FOR EPI-743 TRIAL

If your child or patient is between the ages of 1-12 and has been diagnosed with Leigh Syndrome (Leighs Disease), please consider joining the EPI-743 clinical trial. CONTACT THE EPI-743 HOTLINE FOR MORE INFORMATION 1-800-243-0254

We are actively recruiting children ages 1-12 years with Leigh syndrome for a trial of EPI-743. This is a randomized, double-blinded, and placebo-controlled trial using a novel drug, alpha-trocotrienol quinone (EPI-743). During the first six months of the trial children are randomized to receive the active agent or placebo. During the next six months, those on placebo are randomized to one of two dosages of the active agent (and those on the active agent remain on the active agent). Neither the patient nor doctor will know during the first six months if the child is on EPI0743 or a placebo. A computer performs the randomization.

The Italian experience in children with genetically confirmed Leigh syndrome treated in an open label study is published and you can the basic information about this study at this web site: http://www.ncbi.nlm.nih.gov/pubmed/23010433 Improvement in function was noted in 10 consecutive patients.

We are looking for candidates that can travel to one of the four centers. All study expenses are covered. We ask that you consider this trial. If you have any questions please feel free to contact any of us.

The major eligibility requirements include:
-Age 1-12 years

-Clinical diagnosis of Leigh Syndrome

-Confirmed Genetic mutation known to cause Leigh Syndrome

-MRI confirms Leigh syndrome

-Progression within the last 12 months but stable respiratory status and never trached

Full information about this trial with institutional contact information, inclusion and exclusion criteria as well as outcome measures is available at: http://clinicaltrials.gov/ct2/show/NCT01721733?term=EPI-743&rank=2

Sincerely yours,

Bruce H. Cohen (Akron Children's Hospital)

Greg Enns (Lucille Packard Children's Hospital - Stanford)

Fernado Scaglia (Texas Children's Hospital -Baylor)

Russ Saneto (Seattle Children's Hospital)

Contact us via the EPI-743 hotline 800-243-0254

LISTEN TO THE RECORDING OF THE OCTOBER 5th LIVE TELECONFERENCE with Dr. Guy Miller, Edison Pharma, and Dr. Greg Enns, Stanford University

Summary from the October 5^{th 2012} EPI-743 Joint Teleconference (UMDF & MitoAction)

Presented by Guy Miller, MD, PhD, CEO of Edison Pharmaceuticals & Greg Enns, MD, Lucille Packard Children's Hospital at Stanford University

Introduction In September (2012), Edison Pharmaceuticals announced positive results of their Phase 2A clinical trial of EPI-743 for children with Leigh syndrome conducted in Rome, Italy. All children treated showed reversal of disease progression. Following this unprecedented news, the results were published online in the September 10, 2012, publication of the Molecular Genetics and Metabolism journal. At the same time, Edison announced that EPI-743 had received orphan drug status from the European Medicines Agency (the European regulatory agency akin to the FDA in the United States).

Background Generally, several studies are required before a drug can be approved by the US or European regulatory agencies for public availability: Phase 1 (initial phase to test for safety); Phase 2A (to demonstrate in an unequivocal manner that the drug meets a specific threshold for efficacy and safety); Phase 2B (a double-blind trial with control group); and Phase 3 (a broader group sample).

For the EPI-743 Phase 2A trial, ten (10) children in Rome, Italy with Leigh syndrome were treated for 180 days. All ten subjects responded favorably. After 90 days all subjects demonstrated arrest and reversal of the disease; after 180 days the reversal persisted in all but one subject. In this one patient, treatment was discontinued by the choice of the patient’s parents and the patient reverted to his original status. All patients also had a normalization of disease-relevant biomarkers. An extension phase of this trial that includes the original 10 enrolled patients is ongoing. Based on the findings of this Phase 2A trial, Edison Pharmaceuticals plans to conduct a Phase 2B trial—the next step in the process for drug approval. The trial will enroll 30 (or more) children at four different sites in the US. In the Phase 2B trial, children will randomly be placed into one of two groups. One group will receive EPI-743 for 6 months; the other group will receive a placebo for 6 months. Importantly, parents, patients, and physicians are blinded, meaning they do not know which children are receiving EPI-743 and which are receiving placebo. Following six months, all children in the placebo group will receive EPI-743 for six months. The children who received EPI-743 initially will continue to receive EPI-743 for six additional months.

To determine the effectiveness of EPI-743 as compared to placebo, the following will be measured:

disease progression based on the Newcastle Pediatric Mitochondrial Disease Scale
neurologic and neuromuscular function
respiratory function
quality of life
number of hospitalizations and admissions to the intensive care unit

Brain imaging, including MRI's, will also be obtained to study response to therapy. Safety will be followed using laboratory studies and electrocardiograms.

While EPI-743 has been well tolerated and shown to be safe and effective in the children treated to date, surveillance continues. Worldwide there have been over 125 patients (children and adults) who have been treated with EPI-743 with only one serious side effect possibly related to EPI-743.

Phase 2B Trial Criteria for participation in the Phase 2B EPI-743 trial will be posted on clinicaltrials.gov and are briefly as follows:

Age between 1 and 12 years;
MRI findings consistent with Leigh syndrome
Moderate degree of disease severity based on Newcastle score with evidence of disease progression in the past year;
Parental consent;
Access to a treatment center (Akron Children’s Hospital, Ohio; Lucille Packard Children’s Hospital, California; Baylor University, Texas; Seattle Children’s Hospital, Seattle, WA)
- Note: Travel funds are being established to assist patients and families

Complete details, including full exclusion and inclusion criteria may be found at www.clinicaltrials.gov

Children enrolled in the trial are not allowed to take Coenzyme Q10, vitamin E, alpha lipoic acid and/or vitamin C within two weeks prior to enrollment and for the duration of trial. In addition, potential enrollees must not be allergic to sesame oil. Children with end-stage kidney disease, severe liver disease or who are ventilator dependent are excluded from this trial at this time.

What can parents and patients do?

Adult patients, parents of affected children and families are encouraged to:

a) Enroll in the North American Mitochondrial Disease Registry http://rarediseasesnetwork.epi.usf.edu/NAMDC/register/index.htm ;

b) Contact a participating site (listed below) if your child has Leigh Syndrome;

c) Share the information from www.clinicaltrials.gov and related EPI-743 publication abstracts from www.pubmed.gov with your physician.

MitoAction, UMDF, Edison Pharmaceuticals and physicians around the world stress the value of participating in the NAMDC registry. As protocols become available for additional trials for EPI-743 (or other new treatments), those who are on the registry are likely to be the first to be able to enter the trials. Patient databases and registries follow strict patient privacy guidelines and are offered at no cost to the patient. Likewise, for patients who qualify and enroll in an EPI-743 trial, there is no cost to the patient.

The Future Adult patients and children with other mitochondrial disorders are encouraged to participate by taking the action steps outlined above. It is our collective hope that by galvanizing the mitochondrial disease community, we can assist in enrollment of at least 30 children with Leigh syndrome by January 2013; consequently, we remain optimistic that additional trials and options for more patients will become available in late 2013. The success of EPI-743 brings hope to the entire Mito community!

Additional Information about Participating Centers:

AKRON CHILDREN’S HOSPITAL

Investigator: Bruce Cohen, MD, FAAN
Director of Pediatric Neurology; Professor of Pediatrics
1 Perkins Square
Akron, OH 44308-1062

Site Coordinator: Hilary Wolf
Phone: 330-543-3193
Fax: 330-543-3166
Email: hwolf@chmca.org
Hospital Study Line: 330-543-5012 (Voicemail, will be transferred to Hilary on the next business day.)

Hospital Information:
One Perkins Square
Akron, Ohio 44308
Website : www.akronchildrens.org

LUCILE PACKARD CHILDREN’S HOSPITAL -STANFORD

Investigator: Gregory M. Enns, MB ChB
Associate Professor and Director of Biochemical and Genetics Program
Phone: (650) 498-5798
Greg.enns@stanford.edu

Site Coordinator: Katherine Connors, MPH
Sr. Clinical Research Coordinator
Spectrum Child Health - Genetics
Stanford University School of Medicine
300 Pasteur Drive, H-315 (Rm A071)
Stanford, CA 94305-5208
Tel: 650-736-8166
Fax: 650-498-4555
kconnors@stanford.edu

BAYLOR COLLEGE OF MEDICINE

Investigator: Fernando Scaglia, M.D.
Department of Molecular and Human Genetics
Phone: (832) 822-4280
E-mail: fscaglia@bcm.edu

Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030

Site Coordinator:

Catherine Loffredo, BSN, RN, CCRP

Research Nurse

Department of Molecular and Human Genetics

Baylor College of Medicine

Texas Children's Hospital

6701 Fannin CC 1560

Houston, TX 77030

email: catherine.loffredo@bcm.edu

832-822-4276 (office)

832-825-1515 (fax)

Seattle Children’s Hospital

Investigator: Russell Saneto, DO, PhD
Professor, Neurology
Seattle Children’s Hospital
4800 Sandpoint Way NE, MS B 5552
Seattle, WA 98105
Email: russ.saneto@seattlechildrens.org

Site Coordinator:
Laurie Guidry, RNC, BSN
Research Nurse Coordinator, Dept. of Neurology
Seattle Children's Hospital
4800 Sandpoint Way NE, MS B 5552
Seattle, WA 98105
Email: laurie.guidry@seattlechildrens.org
(Phone) 206-987-0058

For more information:
www.edisonpharma.com

www.umdf.org/epi743

www.mitoaction.org/epi743

About Dr. Greg Enns:

Dr. Enns is an Associate Professor of Pediatrics and has been Director of the Biochemical Genetics Program at Stanford University since 1998. He was trained in clinical genetics and clinical biochemical genetics at the University of California, San Francisco, graduating from the program in 1998. Dr. Enns has also directed the California Department of Health Services Newborn Screening Area Service Center for Northern California since 2003. He is on the Board of Directors of the Society for Inherited Metabolic Disease and the Scientific and Medical Advisory Board of the United Mitochondrial Disease Foundation. As a clinician, he cares for patients who have a broad range of metabolic disorders and focuses on diagnosing and managing those with mitochondrial disorders, urea cycle defects, aminoacidemias, organic acidemias, and lysosomal storage disorders. His current research involves the development of a panel of sensitive blood biomarkers of redox imbalance, using tandem mass spectrometry and Hi-D FACS, so that patients who have mitochondrial dysfunction can be detected and monitored non-invasively. He is most interested in developing clinical trials for patients with metabolic disorders, and has a particular interest in novel therapeutics for mitochondrial disease.

About Dr. Guy Miller:

Guy Miller, MD, PhD is the founder of Edison and has served as Chairman and Chief Executive Officer of its Board since the company's inception in 2005. Prior to this, he founded Galileo Pharmaceuticals, a biopharmaceutical company, and was its Chairman and CEO from 1995-2005.

Dr. Miller holds an MD from the Medical College of Pennsylvania and a PhD in chemistry from the University of Virginia. He completed his surgical internship at the University of Chicago, and a residency in anesthesiology and critical care medicine at Johns Hopkins. Dr. Miller completed a fellowship in multidisciplinary critical care medicine at Johns Hopkins, where he was on the faculty as an Assistant Professor until 1996. He is currently an attending physician in medical-surgical critical care medicine at Stanford University-PAVAMC.

He also serves as Executive Chairman of Ampere Life Sciences, a spinout of Edison focused on antioxidants and consumer products.

About Edison Pharma:

Edison Pharmaceuticals, Inc. was founded with one goal: to develop a clinically meaningful treatment for inherited mitochondrial disease. Mitochondrial disease is most often diagnosed in childhood, is highly debilitating and often results in early death. When mitochondrial disease progresses to adulthood, it is significantly disabling and also life-shortening.

The term inherited mitochondrial disease actually represents a family of diseases. While they are known by a variety of names, they share a common feature--a defect in how energy is made and regulated. Today there are over 2,000 known genetic defects that cause mitochondrial disease. There are no approved drugs to treat mitochondrial disease.

In 2005 patient families, physicians, scientists, and foundations joined together around a single mission: to build a company that would translate promising laboratory findings into clinically meaningful drugs. Since the beginning of operations in late 2006 Edison has placed three new drugs into clinical development. EPI-743 is now in phase 2B/3 pivotal clinical trials for inherited mitochondrial disease. EPI-A0001 has now recently completed a phase 2A study in the mitochondrial disease Friedreich's ataxia where it has improved neurological outcome measures.

To accomplish its mission, Edison built a discovery and translational research platform that centers on the regulation of energy metabolism, and its clinical measurement. The company holds over 100 patents that span cell biology, chemistry, and methods for drug discovery.

Edison Pharmaceuticals, Inc. is headquartered in Mountain View, California and has European offices in The Netherlands. In Mountain View, the company occupies 15,000 square feet of state-of-the-art research and development space.