FMM Case for Giving

Hope Flies速 Campaign For The Cures

CASE for GIVING 1

A cure for mitochondrial disease could impact cures for Autism, Alzheimer’s, Parkinson’s, Muscular Dystrophy and More Mitochondrial Dysfunction Mitochondrial dysfunction is a central element of familiar diseases.

Studies indicate the ones represented by circles closest to the center are more influenced.

The Facts: • Mitochondria, the body’s cellular “power plants”, produce the body’s essential energy. When they don’t­—there is a “power failure.”

• 1 in 2,500 are affected by mitochondrial disease.

• Mitochondrial disease is more common than childhood cancer.

• The disease can appear at any age, infancy to adulthood.

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• If you know someone with Alzheimer’s, Parkinson’s, or Autism, then you are connected to mitochondrial disease.

Mitochondrial disease can appear at any age, infancy to childhood.

It is more common than childhood cancer.

Become Part of a Common Solution…Help our Hope Fly! The unifying thread of the mitochondria gives hope for collective answers and treatments for millions of people Hope and positivity are the sources for reigniting the energy for people with mitochondrial disease. With hope comes promise of a brighter future for those suffering from mitochondrial disease and many related diseases Hope…for a Center of Excellence for adult and pediatric patients with multiple specialists and doctors, aligned in terms of diagnosis, treatments and follow up Hope…for partnerships and collaboration among philanthropy, medical communities, pharmaceutical and bio tech industries Hope…for research and drug therapies connecting related diseases with common causes Hope…for increased awareness so that doctors, teachers and the publicat-large understand the disease for accurate diagnoses, care and consideration To turn these hopes into reality, the Foundation for Mitochondrial Medicine is launching a $5 million Hope Flies® Campaign for the Cures.

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Our Path Forward Today, the Foundation for Mitochondrial Medicine has a unique opportunity to lead the way in bringing to the forefront collaboration and effective treatments for mitochondrial dysfunction across multiple diseases.

Alzheimer’s, Parkinson’s, Autism, Epilepsy, Diabetes, Lou Gehrig’s (ALS), Chronic Fatigue, Huntington’s and others all have something in common— problems with mitochondria. The list of known diseases and conditions with mitochondrial dysfunction is long—and growing longer.

As scientists have learned more about the mitochondria’s role in health and disease, they have concluded that mitochondrial dysfunction is at the root of diseases and conditions that affect the young and old, in ways that can range from subtle to devastating. Mitochondrial dysfunction is even responsible for the aging process itself.

FMM Strategic Direction

Awareness ing the Cures Fund

Clinic

Center of ExcellenceMultidisciplinary Coordinated Care

Partnerships and Alliances

s Fund i n g t h e C u re 4

• Medical Institutions • Related Disease Groups • Bio Tech Companies • Pharma • Angel Venture Groups

Laboratory

Diagnostics, Research, and Therapeutics Leverage of mitochondrial dysfunction across multiple disease state

are affected by mitochondrial disease The Hope Flies® Campaign for the Cures The Hope Flies Campaign for the Cures will ensure long-term sustainability for the Foundation for Mitochondrial Medicine’s mission to accelerate the development of the most promising treatments and cures for the many, many forms of mitochondrial disease.

Our strategic direction combines a dedicated focus on our three priorities with an emphasis on treatments in both the clinic and laboratory. It is through partnerships and collaboration that treatments can be attained for multiple diseases caused by mitochondrial problems.

Our priorities are three-fold: 1. raising awareness for mitochondrial disease 2. fueling connections and partnerships with related diseases 3. funding treatments and cures

Hope Flies® Campaign For The Cures Plan Elements A. FMM Program and Clinic for Mitochondrial Medicine at UAB

$1.25 million

B. Partnerships and Joint Venture Drug Discovery Programs

$1.375 million

C. Awareness Programs, Scientific Summit and Hope Flies Health Series

$1.25 million

D. FMM Programs, Events, Operations

$1.125 million

Total

$5 million

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The Foundation for Mitochondrial Medicine Clinical Program at UAB The Foundation for Mitochondrial Medicine, The University of Alabama at Birmingham and Seahorse Bioscience have embarked upon creation of the first academic medical institution-biotech industry-philanthropic partnership for mitochondrial clinical care and research advancements.

The Foundation for Mitochondrial Medicine Clinical Program at UAB will: • Respond to the unmet clinical, diagnostic and therapeutic needs of the patient community impacted by mitochondrial disorders; • Leverage UAB mitochondrial research in the field of translational bioenergetics; • Address the growing scientific and clinical market of testing instruments for the fields of metabolomics and bioenergetics;

FOUNDATION FOR MITOCHONDRIAL MEDICINE CLINICAL PROGRAM AT UAB

NEUROLOGY; NEUROMUSCULAR

GASTROENTEROLOGY

A multi-disciplinary program where pediatric and adult patients can be diagnosed, treated and regularly evaluated; where care is coordinated, PAIN MANAGEMENT; learnings are shared and collaboration is fostered for longer-term FMM ClINIC ANESTHESIOLOGY translational research outputs

AT UAB

DIAGNOSTICS

Physical Therapy; Occupational Therapy; Dietician

GENETICIST

BLOOD TESTS AND TISSUE SAMPLES

Clinical Research Laboratory

DISEASE MONITORING

NEW TREATMENTS

SEAHORSE BIOSCIENCE SUPPORT

Grace Elva Martin

Nurse Navigator 1. Liase with multiple specialists to form a comprehensive view of the patient (initially 120 patient encounters, annualized) 2. Centralize reporting for testing and samples (population science) to create grants / reports

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3. Provide support and information sharing for the patient community with website FAQ responses leveraging FMM and content partners

The Foundation for Mitochondrial Medicine Clinical Program at UAB Two components will be developed in parallel: 1. a multi-disciplinary clinic for adult and pediatric mitochondrial patients 2. a CLIA* certified mitochondrial clinical laboratory with new state-of-the art blood tests, including a Bioenergetics Health Index (BHI), to measure mitochondrial function *Clinical Laboratory Improvement Amendments—Congressional quality standards

The expected outcome is to have an integrated clinic that serves the patients’ needs and provides the clinical testing protocols for diagnosing and monitoring therapeutic interventions for mitochondrial dysfunction.

The clinic: • A monthly multi-disciplinary clinic to evaluate and care for adult and pediatric patients staffed by specialist physicians (adult and pediatric neurologist, geneticist, coordinated consultations from a pain management specialist and gastroenterologist, among others as relevant), a nurse navigator, physical therapist, occupational therapist and dietitian.

• The Nurse Navigator will play a key role with objectives to: coordinate, schedule and manage patient care; liaise with the multiple specialists to form a comprehensive view and treatment plan for the patient; hold monthly case management discussions with clinic staff to highlight shared learnings and important observations impacting the various functional areas; centralize reporting for Bioenergetics Health Index testing and other tests.

The CLIA laboratory: • Develop state-of-the-art non-invasive blood tests for bioenergetic health from the research of the UAB Mitochondrial Medicine Laboratories.

• The BHI blood tests measuring mitochondrial function will be a better method of diagnosing mitochondrial disease (serving as a surrogate for the traditional muscle biopsy), and will also help monitor the stability of a patient over time as well as measure efficacy of therapeutics to improve patients’ lives.

• The BHI blood tests measuring mitochondrial function can also be applied to patients with Parkinson’s, Alzheimer’s and other related diseases, where mitochondrial dysfunction is a key contributor.

• Additionally, obtain CLIA certification for standard tests using the Seahorse platform technology and validate new approaches with current diagnostics.

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Part B. Partnerships And Joint Venture Drug Discovery Projects Mitochondrial dysfunction underlies many different diseases. Novel therapies that can correct defects in mitochondrial functioning have the potential to impact different diseases—from early childhood genetic diseases to late life neurodegenerative diseases. FMM builds partnerships with like-minded, research-focused related disease organization, such as the Alzheimer’s Drug Discovery Foundation and the Michael J. Fox Foundation for Parkinson’s Research, to jointly fund research projects.

ROADMAP TO DRUG DEVELOPMENT Drug development for mitochondrial disease has only just begun (see light blue area on chart).

The road to successful new drugs and drug therapies is riddled with incredible successes and forgotten failures. Recent studies estimate an average timeline to bring a drug to market is 13 years and $1B. And each new drug leads us to a cure.

75% of the costs of drug development are associated with compounds failing in early stage development. Additionally, 90% of new drugs fail in Phase 2 and 3.

Phase 1 The drug is tested for safety, dosage and side effects in a small group of volunteers.

Initial studies determine the metabolic and pharmacologic effects and side effects associated with increasing doses.

1-3 years / $100m+

1 year

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Preclinical Research Pharmacodynamics, pharmacokinetics, ADME, and toxicity testing 1-2 years / $100m+

Preclinical Development 1-2 years / $100m+

Feasibility Study regulatory review financial review data review equipment review database development 6 months / $1m+

Today, venture philanthropy is playing an important role in drug discovery.

Funding to support and catalyze research through the risky early stages of the pre-clinical drug discovery and development process that are typically not supported by VC’s or big pharma companies is an important mechanism to increasing the potential pipeline for discovery. These types of joint venture research/drug discovery projects ranging in size of $100,000-$200,000 per project, per year meet the goals of increasing the number of therapeutic prospects for treatments and cures. Moreover, by co-funding projects with partnering philanthropies, dollars are maximized.

$800M -$1B

Phase 2 Expands the study to a larger group of people.

1-3 years / $150m+

Phase 3 Expands the study to an even larger group of people to confirm effectiveness, evaluate the overall benefit and, risk relationship.

Data is collected, analyzed, then submitted to the FDA for review. Drug can be perscribed.

1-3 years / $150m+

Phase 4 These studies are done after the drug has been licensed and marketed.

Post-marketing studies to delineate additional information including the drug’s risks and benefits are colected and analyzed.

1-3 years / $100m+

Feasibility Studies KEY Significant activity* *See Detail: The Foundation’s Bypass No activity

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Recent FMM Research Projects Include:

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Project Description

FMM Investment

Recipient

Outcome

Novel Research for MitochondrialDirected Therapies to Address Alzheimer’s and Mitochondrial Disease

$100,000

Dr. James Bennett, VA Commonwealth University

rhTFAM, a new drug, was injected intravenously and helped to stimulate the generation of new mitochondria, referred to as “mitochondria biogenesis” in Alzheimer’s affected mouse models.

New Small Molecule Development for Treatment of Mitochondrial Dysfunction

$50,000

Dr. Jan Smeitink, Resulted in testing of 5 new drug Khondrion, The compounds and an subsequent Netherlands award of 5M Euros; which led to a total compound library of 300 and 1 drug submitted for toxicology testing.

MitochondriaTargeted Therapeutic Discovery Project to Treat Parkinson’s and Mitochondrial Disease

$50,000

Dr. Wolfdieter Springer, Mayo Clinic, Jacksonville, FL

fMRI Study on Cognitive Fatigue in children with mitochondrial disease and Autism

$10,000

Partner: Alzheimer’s Drug Discovery Foundation, NY

Partner: Michael J. Fox Foundation for Parkinson’s Research, NY

Study of the parkin protein, a common cause of early-onset Parkinson’s disease has revealed an important role for the protein in maintaining healthy mitochondria. Drug compounds have been identified that activate parkin to help cells get rid of dysfunctional, unhealthy mitochondria.

Dr. Robin Morris, Georgia State Univ. and GaTech, Center for Advanced Brain Imaging, Atlanta, GA

Through the use of functional MRI imaging, children with mitochondrial disease and children with Autism have been studied to understand the diverse developmental outcomes caused by cognitive fatigue.

H O PE FLI ES

H

ea

lth S eries

Keynote speaker for our inaugural Hope Flies® Health Series, actress and autism and Parkinson’s advocate, Holly Robinson Peete, shared her journey with her father’s Parkinson’s and her son’s autism and how she has become an advocate on behalf of her family and how others can do the same.

Part C: Scientific Summit And Hope Flies® Health Series Information dissemination among the scientific community and the various patient constituencies of mitochondrial disease and related diseases is an important tenet of FMM’s strategy. FMM programmatically seeks to bring together thought leaders in the research, clinical and pharmaceutical fields to convene and collaborate by focusing on the common thread of mitochondrial dysfunction among all areas of interest: 1. FMM Mitochondrial Medicine Scientific Summit—a scientific gathering to bring together a leading group of clinicians, drug developers/bio companies and research scientists of major related disease areas (Alzheimer’s, Parkinson’s, chronic fatigue, etc.) for exploration of the linkage and opportunities presented by mitochondrial dysfunction in order to accelerate treatment for common diseases where mitochondrial dysfunction is an important cause.

2. Hope Flies® Health Series—both in webinar and live program forms, the Hope Flies® Health Series highlights the latest research, links among related diseases, current disease management suggestions and most importantly, hope for the future. Additionally, these programs present a platform for further partnering and collaboration opportunities.

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Part D. FMM Awareness, Events And Operations Hope Flies® is our signature awareness and fundraising program brand dedicated to celebrating hope and raising both awareness and funds for the most promising mitochondrial disease treatments. Our events are held in various locations around the country and come in different shapes and sizes. From galas like Hope Flies Catch the Cure, to 5K walks such as the Walk for Abby, established by the Sauerhoefer Family of Broad Brook, CT, penny wars, wine tastings and Major League Baseball games, constituents across the country have gotten involved in a variety of FMM events.

Additional retail partners have joined with FMM to host Partners for the Cures charity events at their locations and for their customers, including: Hublot, Neiman Marcus, Saks 5thAvenue, Your Pie, J. McLaughlin, Kaycee Hughes, Rebecca Taylor, David Yurman and others. All of these programs continue to be both an important source of friendraising, fundraising and fun-raising to tell the FMM story.

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Complications at birth of pneumonia and feeding difficulties, were soon followed by seizures and developmental delays. Although Abby can’t walk, sit up or speak and her only means of nourishment is through a feeding tube, her fighting spirit and the light in her eyes melt hearts all around her. Abby’s Family

© Lisa Martin Photography

Please Join Us! We encourage you to aim high as you consider your support for the Foundation for Mitochondrial Medicine. Your gift will provide the structure for FMM to lead the way: • improving lives for those suffering with mitochondrial disease and related diseases • empowering tomorrow’s leaders and change agents • advancing research that makes a difference.

Hope Flies® Campaign For The Cures A. FMM Program and Clinic for Mitochondrial Medicine at UAB

$1.25 million

B. Partnerships and Joint Venture Drug Discovery Programs

$1.375 million

C. Scientific Summit, Awareness Programs and Hope Flies Health Series

$1.25 million

D. FMM Programs, Events, Operations

$1.125 million

Total

$5 million

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Background What is Mitochondrial Disease?

It’s an energy production problem. Almost all cells in the body have mitochondria, which are “tiny power plants” that produce a body’s essential energy. Mitochondrial disease occurs when the power plants in cells don’t function properly. Brain, heart and muscle are primarily affected in varying degrees.

Mitochondrial disease means waking up feeling like you’ve run a marathon in your sleep Mitochondrial disease means people can one day keep up with their peers ‘going full speed,’ and then the next day they crash and burn and need twice as long as others to recover and recuperate Mitochondrial disease means children may not walk, talk or feed themselves like typically developing children Mitochondrial disease means some lives don’t last as long as they should because this disease robbed them of quality and years

The disease is a thief that steals your chance for a normal life. It has caused so much pain and heartache from being misunderstood and misdiagnosed. I live with nausea, vomiting, headaches, abdominal pain, and fatigue everyday. I hope and dream that a cure is found in the near future.

I pray I will be able to have the energy and good health to enjoy my life. Desmond

It took two and a half years and 13 doctors to get diagnosed. I have been a chronic pain patient for almost 9 years, and I experience a wide range of symptoms such as tremors, nausea, and weakness.

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Amanda

I awake every day feeling as if I’ve run a marathon in my sleep. My hope each day is to slow the process of how the mitochondrial disorder is affecting my body. Jason A favorite song came on the radio, and for about 45 seconds I forgot. I forgot about the therapy appointments and neurologist visits.

I forgot about the MRI’s, blood draws, and the muscle biopsy. I forgot about the insurance billing and the school meetings. I forgot that my son spends his days fighting gravity. He has a startle reflex that will bring him to the floor, and he cannot walk unassisted. But in the 46th second, I remembered...that with all of this worry, we have never been so blessed.

Drew’s Family

How Common is Mitochondrial Dysfunction?

If you know a person with Parkinson’s disease, diabetes, Alzheimer’s, ALS, chronic fatigue, you have encountered mitochondrial dysfunction.

If you have met a child with autism, Asperger’s syndrome, or epilepsy, mitochondrial dysfunction may be already affecting their developing brains.

In addition to extending the span of healthy lives, reducing the economic impact of these diseases is extremely necessary.

Recognizing and treating mitochondrial dysfunction now is essential!

1 in 2,500 are affected by mitochondrial disease

1 in 68 children are affected by autism 1 in 85 are affected by Alzheimer’s 1 in 500 are affected by Parkinson’s 1 in 50,000 are affected by ALS (Lou Gehrig’s Disease)

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From birth I wasn’t developing like my twin brother. Doctors thought it was Autism or Cerebral Palsy. I live with mitochondrial disease.

Grace, on cover

Foundation for Mitochondrial Medicine 1266 W. Paces Ferry Rd. Suite 301 Atlanta, GA 30327 Phone: 888-448-1495 Online Giving at: www.hopeflies.org/donate

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