Suzanne M. Sensabaugh, MS, MBA Orphan Drugs Suzanne M. Sensabaugh, MS, MBA smsensabaugh@hw-fda.com

Panacea Pharmaceuticals, Inc. Suzanne Sensabaugh, MS, MBA Former FDA: Reviewer of hundreds of industry submissions. Committee member who drafted FDA Guidelines: Received numerous awards. Former industry: Drafted submissions for FDA review. Since 2009, assisted in the development of over 120 drugs. 2

Panacea Pharmaceuticals, Inc. Introduction 21 CFR 316 Encourage and facilitate the development of drugs for rare diseases or conditions Affects less than 200,000 persons in the US or Can affect more than 200,000 persons in the US, but for which there is no reasonable expectation that the cost of developing and making available in the US a drug for such a disease or condition will be recovered from sales in the US Application submitted for Orphan Drug designation The Office of Orphan Products Development administers the program Involved in the identification of orphan products and the facilitation of their development CDER and CBER provide scientific and medical review Safety and efficacy established through adequate and well-controlled studies 3

Incentives for Orphan Drug development Panacea Pharmaceuticals, Inc. Incentives for Orphan Drug development 7-years of marketing exclusivity once approved FDA will not approve a marketing application for the same drug Begins on date of approval Only to the indication for which the drug has been approved Another application could be approved for the same drug in a different indication Tax credits for clinical research to generate data required for marketing approval Formal protocol assistance Research grants Clinical trials are awarded grants from $200,00 (Phase 1) to $350,000 (Phase 2 and 3) per year in total costs for up to 3 years. Agency provides written recommendations on the preclinical and clinical investigations Usually decreased development time 4

Clinical superiority Same drug for same indication as a previously designated product must demonstrate clinical superiority Significant therapeutic advantage over and above that provided by an approved Orphan Drug Demonstrated in one or more of the following ways Greater effectiveness as assessed by an effect on a clinically meaningful endpoint in adequate and well-controlled trials Greater safety in a substantial portion of the target population Demonstration that the drug makes a major contribution to patient care 5

Panacea Pharmaceuticals, Inc. Any questions? smsensabaugh@hw-fda.com 6