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

• rganization 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.

• 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).

Personal Intro to FA & FARA

• 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.

FA and FARA – Getting Started

• 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 is FARA Funded?

• Staff – 1998-2006, all volunteer, no full-time staff, paid
• wn 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.

How has FARA Evolved …

• 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

• ther advocacy orgs co-funding – all w/R-13
• 2011, turned away many to hold to 200

scientists, dozen pharmas, 10 other advocacy

• rgs
• 2015 - London

Growing the Field…

• 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

Identifying, Filling the Gaps

• Collaboration, Collaboration, Collaboration – cannot do it alone
• Public/Private partnership – Joint Venture Philanthropy (JVP)
• - 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

NIH

Companies In Clinical Trials or planned for 2014

Edison: EPI 743 Shire OX-1 Retrotrope: dPUFA/RT001 Horizon (Vidara) Interferon Gamma Nicotinamide Target end 2014 Reata RT 408, Target Q4 2014 Raptor RP-103, Target Q4 2014

Venture Capital Firms Development Firms

SR One (Glaxo) Cydan MedImmune Ventures (AstraZeneca) Velocity Pharma Third Rock Ventures (PE) JAFCO (PE) Griffin Securities (Investment bank) Fidelity Ventures (VC arm of Fidelity) NPH Ventures (Mitsubishi) Atlas Ventures (PE) NEA Ventures (PE) Versant Ventures (PE)

Companies with Interest but no program

Biogen/IDEC Trevi Therapeutics Genzyme Mitokine/Astellas Dimension Therapeutics Velocity Pharma Cydan

Pre-Clinical with Compounds

STATegics Biomarin HDACi Bioblast RaNa Stealth Peptides AAVLIFE Chondrial Therapeutics Ixchel

Approved Therapy:

Collaboration & Partnership w/ Industry

FA Program, no compounds

Agilis/Intrexon Pfizer Novartis Voyager

Research

(Finding Potential Therapies/Drugs)

Pre-Clinical

(Testing in Laboratory)

Phase I

(Human Safety Trial)

Phase II

(Human Safety and Efficacy Trial)

Phase III

(Definitive Trial)

Available to Patients

Decrease Oxidative Stress and/or Increase Mitochondrial Function Decrease Iron Toxicity Increase Frataxin Expression (Compounds) Idebenone Iron Chelator

Santhera

1 Clinical Trial (stopped) 3 Potential Treatment Approaches (ideas)

FA Treatment Pipeline - 1998

Research

(Finding Potential Therapies/Drugs)

Pre-Clinical

(Testing in Laboratory)

Phase I

(Human Safety Trial)

Phase II

(Human Safety and Efficacy Trial)

Phase III

(Definitive Trial)

Available to Patients

Decrease Oxidative Stress and/or Increase Mitochondrial Function Decrease Iron Toxicity Increase Frataxin Expression (Compounds) Idebenone Iron Chelator

Santhera Edison

1 Clinical Trial 3 Potential Treatments/Approaches

A0001

FA Treatment Pipeline - 2004

Conclusions

• Have changed the landscape from isolated patients

with no hope, first to a team and now a global FA family – FA research is now a family affair and our family is not only hopeful but confident.

• From no clinical trials to eight trials currently with

more to begin later this year.

• These trials are not competing one with another –

aimed at different mechanisms of damage and therapeutic action. They are not shots in the dark; they are high-percentage, well-executed shots on goal. Some will find the back of the net and, we are confident, will result in a cocktail therapy (with that, I will offer free drinks and a taxi).

Conclusions

• Data should be available by later this summer; FARA will go

to FDA with the company. IF NDA is submitted, should have FDA decision by 1st Quarter 2015.

• When we obtain our first approved treatment, will be back

in front of the HHS newborn screening committee so FA can join PKU on NBS panels so we can treat current FA patients, begin treating infants before damage is done, postpone symptoms to provide time for treatments two and three; eliminate FA in the next generation. Would still be born with the mutation, but would not suffer symptoms – live normal healthy lives.

• Raychel and I lost our son, Keith, to the congestive heart

failure of FA four and a half years ago. Just before he died, thanked us; said he knew we would keep going until we get it, not in time for him but for some of his friends. We WILL keep going until we get it. And, it will be because we did it together.

17 Evan Luebbe and Tiki Barber Keith Andrus Samantha and Alexandria Bode with Mary Stuart Masterson

Acting alone, there is very little we can accomplish. Acting together, there is very little we will NOT accomplish!