1. THE NEXT ALS BREAKTHROUGH COULD BE YOURS
Prize4Life: on the road to finding a cure
to ALS disease
Presentation to MIT Enterprise Forum Israel
Nov. 2012
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2. What is ALS (Lou Gehrig’s disease)?
 A neurodegenerative disease, Amyotrophic
lateral sclerosis (ALS) is also referred to as
‘motor neurone disease‘
 Rapid and progressive paralysis of unknown
cause, 100% lethal
 Death within 2-5 years from diagnosis
(respiratory failure)
 First clinically identified in 1869--over 140
years ago
 Only existing FDA-approved treatment
prolongs life by 2-3 months
 Affects both men and women primarily in mid-
life but can strike at any adult age (including
rarely in teenagers)
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3. ALS presents a clear unmet medical need
No • No disease modifying therapies available
treatment
• ALS strikes as many people as Multiple Sclerosis, and more people than
Need
Fit with Huntington’s Disease, but because ALS is so rapidly fatal, at any given time
increasing
Teva there are fewer people alive with ALS
• Orphan disease with estimated 30,000 individuals affected in the U.S. at
any given time and 600,000 worldwide
• In the industrialized world, more than one in 500 people die of ALS
• With aging, prevalence of ALS- and associated costs- are likely to increase
• Disease cost is extremely high for patients and families – financial and
High cost emotional burden
• $160,000/year for in-home treatment; US$430,000/year for
institution-based treatment
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4. So what’s holding us back?
The challenges facing ALS are typical of those in the broader neuro space
Drug development  The brain is hard to access
 High fail rate
is hard  Expensive
 Complex and unpredictable regulatory environment
 Hard to cross the “Valley of Death”
 The nervous system is REALLY complex
Fit with Teva
Basic research  Animal models have not yet led to treatments
is hard  Multiple levels of analysis difficult to integrate
Incentives are  Publish or perish
 Incentives for data sharing often lacking
misaligned  Few data standards
 Clinical research viewed as less attractive than basic research
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5. Due to these challenges, innovation in basic research
often isn’t translated into direct patients’ benefit
Research – Development - Access:
Universities/ “Valley Health Systems
Research of Biotech – Hospitals
Institutions Death” Pharma Health Services
“Valley of Death” = gap between academic research and industry
involvement
Without industry commitment, basic research does not get
translated into tangible results for patients
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6. The drug discovery gap: valley of death
Basic Research
• Academic researchers Academia
have typically focused on Disease Mechanism
understanding biological
fundamentals and
Target Identification
disease mechanisms
• Industry focus is now on Assay Development
the later stages of drug
development Valley of Death Screening
• This gap is particularly Lead Optimization
worrisome in the context
of ALS and other Preclinical Development
neurodegenerative
disorders Clinical Trials
Industry
Submission/ Approval
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7. Prize4Life: an organization with the sole purpose
of being terminated
 Prize4Life is an innovative, results-oriented 501(c)(3) not-for-
profit organization focusing exclusively on ALS
 Founded by a group of Harvard Business School students in
2006 after one of their classmates—Avichai (Avi) Kremer—
was diagnosed with ALS at the age of 29
 Prize4Life has embraced the Incentive Prize Model to change
the landscape for ALS research
 We are small but have grown quickly from 2 staff (2007), to
our current staff of 6 (2012). P4L has raised +$9M for ALS
since 2005
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8. From the get-go, Prize4Life’s mission statement was
developed to be both inspirational and pragmatic
Mission Statement
To accelerate the discovery of treatments and a
cure for ALS by using powerful incentives to
attract new people and drive innovation
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9. Prize4Life’s approach: how can we make ALS
breakthroughs more likely
 Triple mission
 Accelerate existing efforts in ALS research
o Create new tools
o Promote new collaborations
 Bring new ideas and new minds into the field
 Complement existing funding models
o Draw attention to ALS research
o Raise funding from previously untapped sources
 Leverage is our operating principle
 Inclusive approach
 All of Prize4Life’s programs are designed to accelerate ALS
therapy development across the board and are open to all
(“lift all boats”, “we don’t bet on one horse, we focus on
improving the entire track”)
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10. Over the years, Prize4Life has been launching incentive
prizes and spearheaded several infrastructure program
Ongoing
Incentive Prize Programs
 $1M ALS Biomarker Prize (2011 Awarded)
 $1M ALS Treatment Prize
 ALS Mouse Colony
 ALS Mouse Manual
 ALS Prediction Prize (algorithm/”big data” challenge,
awarded November 13, 2012(!))
Infrastructure Programs
 PRO-ACT Database
 ALS Forum Portal
 ALSGene Database
 Alzforum Science Writer Collaboration
 Bi-weekly E-Newsletter
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11. Prize4Life: focus on current programmatic portfolio
• $1M ALS Treatment Prize; Re-launched June 2012
Pre clinical
• Supported by the ALSGene, The ALS forum and the ALS mouse colony.
science
• Allows P4L to understand, define, engage and incentivize the ALS preclinical community
and to bridge between the ALS research community and relevant industry
• PRO-ACT Database: Over 8,500+ records of patients from 20+ clinical trials from Teva,
PRO ACT Sanofi Aventis, Novartis, Regeneron and NEALS; to be launched early 2013
database
• ALS Prediction Prize; Launched July 2012 and won Nov. 2012. Attracted over 750 solvers;
Can reduce clinical trials variability by up to ~25%.
• Allows P4L to support finding biomarkers, progression algorithms, stratification for
personal medicine, stratification of drug responses and more
Promoting • Avichai Kremer awarded 2012 Prime Minister award for innovation and
research entrepreneurship in a non profit
funding • Avichai has been involved in fostering ALS research such as through ISF
• Prize4Life is developing advocacy efforts regarding an Israeli “Orphan Disease Act” and
efforts to promote foreign investment in Israeli orphan disease R&D.
• Allows P4L to support funding and remove barriers for R&D of orphan diseases
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12. Prize4Life is constantly monitoring global ALS research so it
can develop the best programs to accelerate research
Drug and Biotech
companies
currently
investing in ALS
R&D
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13. What is an incentive prize?
What is an incentive prize Benefits of an incentive prize
• An effective form of crowd- • Democratic funding model which does not
sourcing/open innovation pre-select a winner/idea based on any
• Crowd-funding particular criteria (anyone can compete)
• Open source movement unlike other up-front funding models,
which are often predicated on prior results
• A results-based reward for a very or pedigree or networks
specific pre-determined need (not a
recognition prize like the Nobel Prizes) • Attracts new minds, new media, and new
money
• An example of “pull” funding vs. “push”
(upfront) funding (e.g. grant or contract) • Encourages outside-of-the-box thinking
• A mechanism to create excitement, • Complimentary to existing funding models
momentum, competition, and attention
• Results focused (you get what you want
• Prize purses can range from 0 to or you don’t pay)
millions of dollars
• Efficient from a funder/donor perspective
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14. Large incentive prizes throughout history
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15. The incentive prize model has grown exponentially over
the last fifteen years
Aggregate prize purse, prizes over $100,000 Large prize purses by sector
18% CAGR
18% CAGR
Source: Set of 219 prizes worth >$100,000 from “And the Winner Is …”, McKinsey, 2009
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16. History of the ALS biomarker prize challenge
 Prize4Life launched the $1,000,000 ALS Biomarker Prize in
November 2006
 Challenge was for an ALS Biomarker capable of reducing the cost of
ALS clinical trials by 50% or greater
 Five $15,000 “idea prizes” awarded in May 2007 to researchers who
submitted theoretical solutions to finding a biomarker including:
o Plant biologist
o Chemist
o Dermatologist
o Small biotech
o Anonymous solver
 54 teams from 18 different countries around the world actively
competed
 27 of these teams initiated interdisciplinary collaborations
 65% of teams competing for the prize came from a discipline other
than ALS (new minds!)
 60% of teams competing for the prize came from academia and
40% from other domains (industry, gov’t, individuals)
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17. History of the ALS biomarker prize challenge – cont’d
 ALS Biomarker Prize closed in November 2008
 12 submissions received from 7 countries
 In 2009 Prize4Life awarded $100,000 in Progress Prizes to two teams
for a:
o Novel skin-based biomarker
o Novel electrophysiological based biomarker
 Relaunched the $1,000,000 Prize4Life ALS Biomarker Prize in May
2009
 Over 1000 potential teams viewed the prize criteria
 Received 4 submissions within the first year
 Submissions vetted by Prize4Life’s SAB, expert biostatisticians, and
several additional outside experts
 One submission was deemed to have met all 5 basic requirements and
5/7 desirable features
 ALS Biomarker identified and $1M Prize Challenge officially awarded in
February, 2011
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18. Pooled Resource Open-Access ALS Clinical Trials
(PRO-ACT) Project: Prediction Prize >> Won yesterday!!
ALS Prediction Prize Overview
 The ALS Prediction Prize was designed to capitalize on the creation of the PRO-ACT
Database and attract widespread attention to the database (and ALS) from various
quantitative communities (statisticians, computer scientists, bioinformatics
specialists, computational neuroscientists, etc.). The 50K prizes were given for the
best prediction algorithm(s) enabling prediction of the degree of change in a
patient’s disease status over the following year (with an ultimate goal of improving
ALS clinical trials).
Prize Details:
 The algorithm needs to predict a patient’s individual progression, using data only
from the first three months of clinical data collection
 The prize was launched on July 15th in collaboration with IBM’s DREAM Project
(Dialogue for Reverse Engineering Assessments and Methods) and using the
InnoCentive platform
 Three winners announced Nov. 13 out of ~1040 solvers registered for the
competition and 25 unique solvers who have submitted an algorithm for testing
and ranking on a leaderboard
 Active solvers currently competing from AMIA, IBM, Microsoft, Google, MIT,
Stanford, Princeton, and many other leading institutions around the world
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19. Key lessons learned
 There are multiple kinds of crowdsourcing; prizes are just one
example
 Crowdsourcing can be used successfully to address complex
biological questions/problems but it isn’t easy
 It is ok to increment a challenge/divide a problem into intermediate
steps and milestones
 Defining and articulating your goal/question/challenge carefully is
key
 Lower barriers to entry whenever possible (to maximize the benefits
of using the incentive prize model you want a large diverse pool of
solvers)
 Marketing
 IP policy
 Access to resources
 Maintain momentum (especially for large/multi-year challenges)
 Big and small incentives can both work (depends on the complexity
and resource requirements of the desired solution)
 The “community” formed by crowdsourcing competitions is typically
ephemeral but ties to the challenge/problem, as well as to the entity
posting the challenge, can be lasting
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