1. A Third-Party Model for Expanded Access Programs 1. We can deliver large EAPs, far in advance of FDA approval. 2. We can do it in today’s regulatory environment. The ALS Emergency Treatment Fund. Jess Rabourn www.ALSETF.org February 27 th, 2014. Washington DC. Hosted by EveryLife Foundation for Rare Diseases

2. ALS-ETF Aligning the interests of current patients, industry, and regulators Patients Regulators Drug Companies

3. Experience, focused in Expanded Access Programs Medical Advisers Richard Bedlack, MD, PhD Richard Barohn, MD Terry Heiman-Patterson, MD Gerard Kennealy, MD Lynn Klein, RN CRO Network Cato Research Kaizen Research INC Research ICON plc Business Advisory Clinical Operations Manufacturing Control Regulatory Affairs Biostatistics Legal / Liability Science Advisory DeNovo Biomarkers UCSF Jackson Labs Iron Horse Diagnostics

4. Perceived Challenges: Possibility of adverse events impacting regulatory filing Regulatory policies that restrict access to these drugs Risk of impairing enrollment in trials Drain of internal company resources Different EAP regulations offshore Possible impact on reimbursement once drug is launched Perceived Benefits: Fulfillment of unmet patient needs (NEED for OPTIONS) Collection of additional “real-world” data outside of the clinical trial setting Development of network of physicians educated on the proper use of the drug Generation of data on drug usage patterns to help forecast demand Establishment of KOL relationships prior to launch Source: 2008-2009 Survey conducted by IDIS via Pharmaceutical Executive Decision factors for EAP sponsors

5. Commercial Risks Additional Regulatory Risks Medical Monitoring Concerns Expense Address Patients’ Immediate Treatment Need Economic Reward Do the factors balance?

6. Big Regulatory Risk Uncontrollable Costs Uncertain Economic Reward Q: Do the factors balance? A: Depends on the company’s situation For lean companies in poorly understood diseases…………..

7. Regulatory Negotiation, representing patients’ needs first, then company’s –Advocate EAP launch early in development cycle –Cost recovery –Clear agreement on findings of AEs –Our own meetings with review division Charitable Resources –Project financing –In-kind, pro-bono, at-cost services Clinic Relationships –ALSETF providing a service to participating clinics, not the other way around –Cost partnership; no profit margin 501c3 Public Charity. Intrinsic alignment with patients  Allows for:

8. The evolution of expanded access business models? No EAP. Fail Traditional EAP. Not meaningful in size. No NPO engagement. Expensive. Nonprofit 3 rd party sponsor. Multi-stakeholder involvement. Little to no cost to drug company

9. How can more EAPs be done at meaningful size? 1.Our target community is dying patients who have no access to clinical trials. 1.Fail enrollment criteria 2.Cannot come frequently to clinic 3.Trial is closed / over-enrolled. Tens of thousands unable to participate in research.

10. Cost Recovery = Scalability These organizations launched scalable humanitarian platforms. Others help in expanding the reach. (individuals, Oxfam, UNICEF)

11. Is this the best we can do? 1. Cost recovery -  Expandable Access Program 2. EAP sponsored by 3rd party non-profit partner 3. Managed regulatory risk 4. Minimal cost to drug company

12. LEARNING FROM PATIENTS!

13. *Learning from Patients*: Responder Profiling and Marker Discovery

14. Large EAPs can enable discovery of subgroup markers for more targeted trials, companion diagnostics, swifter marketing approval, and more personalized clinical care. ALIGNMENT OF INTERESTS Patients / Drug Companies / Regulators (and Researchers & Clinics, too) =

15. 1.FDA cannot offer access programs. IND sponsors do. 2.FDA policies already permit what we want to do. 3.A nonprofit 3 rd party can make EAP feasible. 4.Early, Expandable EAP for meaningful impact 5.Learning From Patients 6.Not just for ALS! Franchise this to other diseases. SUMMARY