Power of the Rare Disease Community - FARA Story What Friedreichs - PowerPoint PPT Presentation

PKU Conference Salt Lake City July 11, 2014 Power of the Rare Disease Community - FARA Story

What Friedreich’s Ataxia (FA) is NOT! Few years ago at benefit concert in Phoenix (Martina • McBride), at open bar in the arena prior to the show, having a drink with a couple who asked me why I was there. Explained that the organization I represented – the • Friedreich’s Ataxia Research Alliance – was one of the beneficiaries of the concert. Thought I explained, too, over the half hour we shared • a couple of drinks from the open bar, what our organization was trying to accomplish but, when the chimes sounded for us to go to our seats and I handed them my FARA card, the wife said to me, “thank you for giving us your card which has your organization’s name written out. All this time, I thought you were saying, ‘Free Drinks and a Taxi.’”

What is Friedreich’s Ataxia (FA)? Ataxia – Greek “incoordination”, a symptom of many • disorders Nikolaus Friedreich – identified it in 1863 • Like PKU, rare, hereditary, autosomal recessive, no • difference between male/female, no carrier symptoms ~ 1 in 40,000 - 50,000 in populations of European origin • vs. ~ 1 in 10,000 – 20,000 PKU ~ 1 in 90 - 100 are carriers vs. ~ 1 in 50 PKU • Estimate ~ 5,000 American patients vs ~ 14,500 PKU • 1 in 4 chance for each offspring of two carriers • FA is life-shortening, neuromuscular disorder usually • diagnosed in childhood (5-15 yrs); causes loss of coordination and strength in the arms and legs; diminished vision, hearing and speech; scoliosis, diabetes; full-time wheel-chair use by the mid teens or twenties; life-threatening heart condition; currently no treatment. Death in early adulthood.

Personal Intro to FA & FARA • In 1997, our middle son Keith, then 11, after a couple of years puzzling over the cause of some physical awkwardness and incoordination, diagnosed with FA. • My wife Raychel and I met at the family computer that evening and web-searched FA. Found plenty of bad news: • - Keith’s FA would be relentlessly degenerative. He would get very sick very fast. Predicted to experience all the above symptoms & likely to die young. - No treatment, no clinical trials - Very little research; no organization devoted to supporting the research solely for FA. - Isolated patients (~ 5,000 U.S., ~ 15,000 world), no contact, no hope, no help. - Other two boys – clear & carrier – (Keith asked about dying young).

FA and FARA – Getting Started • But, one piece of good news – the FA gene had been identified one year earlier. • We believed that, if we established an organization devoted entirely to supporting FA research and could raise sufficient resources and awareness, we could make a real difference. Met the NINDS/NIH Program Director and asked for her help. • Assembled three leading FA scientists, six other FA parents and one adult patient to form FARA in September 1998. • Mission – to marshal and focus the resources and relationships needed to cure FA. Initial goals: - Grow the field to I.D. and begin to fill research gaps - Collaborate and cooperate not confront and compete - Among patient families, establish hope, community and commitment to replace hopelessness, isolation and helplessness.

How is FARA Funded? • 501 (c)(3), not membership org. • First year (1998-99), raised $100,000 – individual donations, letter-writing campaigns, small fundraising activities, NIH workshop grant (R-13) for world’s first FA scientific conf. • Doubled that in year two and again in subsequent years until began to raise several million per year via growing number of grassroots events around country (walks, runs, golf, dinners/auctions, etc.), two signature events (Ride Ataxia and Energy Ball) and increasing gift size. • Now, world’s largest funder of FA research; raised $4.5M last year; have devoted about $30M to FA research and leveraged about $20M from public-private partners.

How has FARA Evolved … • Staff – 1998-2006, all volunteer, no full-time staff, paid own expenses for travel, pubs, etc. • Staff – 2006-present, grown slowly to 6 FTE, 2 PT scientific directors, 1 PT consultant . • Board of Directors – All 11 of the originals, except 3 who have passed away, still with us; have added scientists, several with pharma leadership experience, a dean, several with big business experience, 2 adult patients. No splintering. While maintaining focus on mission and goals? • Mission remains to marshal and focus the resources and relationships needed to cure FA. Initial goals: - Grow the field to I.D. and begin to fill research gaps - Collaborate and cooperate not confront and compete - Among patient families, establish hope, community and commitment to replace hopelessness, isolation and helplessness.

Growing the Field… • Assemble investigators; insist on & support collaboration - 1999, held world’s first FA scientific conference: 80 scientists (65 + 15); zero pharmas; one other NPO – collaboration began - 2003, 100 scientists fm 12 countries, 4 pharmas, 4 other NPOs - 2006, turned away 30 scientists to hold to 150, 6 pharmas funding the conference, 6 other advocacy orgs co-funding – all w/R-13 - 2011, turned away many to hold to 200 scientists, dozen pharmas, 10 other advocacy orgs - 2015 - London

Identifying, Filling the Gaps • Scientific Advisory Board & Scientific Review Committee assess gaps and outline projects that would help fill them. • FARA awards research grants: -- initially seed grants, now $100K - $250K, one much higher -- initially 24/7/365, now 3 annual cycles plus 4 special grants -- most investigator initiated, some RFPs -- translational tools – assays, animal/cell models, biorepositories -- Recently established Center of Excellence to increase research there and help provide guidance globally -- support clinical network of 11 sites (9 U.S., 1 CA, 1 Australia), collaborate with similar Euro network. -- 10-year natural history study, clinical outcome measures, progress toward biomarkers, clinical trials, clinical care, clinical care guidelines -- Patient registry – largest in the world -- Natural History & Registry are vital – game changers

Collaboration & Partnership • Collaboration, Collaboration, Collaboration – cannot do it alone - Public/Private partnership – Joint Venture Philanthropy (JVP) NIH -- NIH – program directors, Council, advocacy for, 2-way commo -- FDA – pt. focused initiative, mtgs (pre-pre IND to AdCom), Pt. Rep -- Congress- testified, rpt lang., w/them vs to them rising tide… -- Other NPOs – w/ and w/o overlap, NORD, Research!America, Alliance for a Stronger FDA -- Industry – grown from zero to > 2 doz. Active partners - JVPs -- Scientists -- Patients & Families – TRUST – eager to participate, all in. “If you are interested in FA research and we are not collaborating with you, it means we have not found you, but we will.” Ripple effect: “Friedreich's ataxia now joins a growing list of degenerative disorders, such as Parkinson's disease, in which free radicals have been implicated. As with progress in many rare diseases, what we discover about cellular changes and therapeutic approaches in Friedreich's ataxia may lead us to important insights about more common disorders.” (Harold Varmus - 1998)

Collaboration & Partnership w/ Industry Approved Pre-Clinical with Compounds Therapy: STATegics Biomarin HDACi Companies In Clinical Trials or planned for 2014 Bioblast Edison: EPI 743 RaNa Shire OX-1 Stealth Peptides Retrotrope: dPUFA/RT001 AAVLIFE Horizon (Vidara) Interferon Gamma Chondrial Therapeutics Nicotinamide Target end 2014 Ixchel Reata RT 408, Target Q4 2014 Raptor RP-103, Target Q4 2014 FA Program, no compounds Agilis/Intrexon Pfizer Novartis Voyager Venture Capital Firms Development Firms SR One (Glaxo) Cydan MedImmune Ventures (AstraZeneca) Velocity Pharma Companies with Interest but Third Rock Ventures (PE) no program JAFCO (PE) Biogen/IDEC Griffin Securities (Investment bank) Trevi Therapeutics Fidelity Ventures (VC arm of Fidelity) Genzyme NPH Ventures (Mitsubishi) Mitokine/Astellas Atlas Ventures (PE) Dimension Therapeutics NEA Ventures (PE) Velocity Pharma Versant Ventures (PE) Cydan

FA Treatment Pipeline - 1998 1 Clinical Trial (stopped) Available to Patients 3 Potential Treatment Approaches (ideas) Phase III (Definitive Trial) Phase II (Human Safety and Efficacy Trial) Phase I (Human Safety Trial) Santhera Iron Chelator Pre-Clinical Idebenone (Testing in Laboratory) Research (Finding Potential Therapies/Drugs) Decrease Oxidative Decrease Increase Stress Iron Frataxin and/or Increase Toxicity Expression Mitochondrial Function (Compounds)

FA Treatment Pipeline - 2004 1 Clinical Trial Available to Patients 3 Potential Treatments/Approaches Phase III (Definitive Trial) Phase II Santhera (Human Safety and Efficacy Trial) Idebenone Phase I (Human Safety Trial) Iron Chelator Pre-Clinical Edison (Testing in Laboratory) Research A0001 (Finding Potential Therapies/Drugs) Decrease Oxidative Decrease Increase Stress Iron Frataxin and/or Increase Toxicity Expression Mitochondrial Function (Compounds)