Industry Perspective: Expanded Access Programs Barbara Klencke, M. D. Senior Vice President, Development Onyx Pharmaceuticals, an Amgen Subsidiary Introduction: Your 2 decades of patient care experience Medical oncologist at UCSF Firsthand experience treating patients who have run out of treatment options and the impact on families Industry experience Strong interest in advances that have potential to transform lives of patients with cancer

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Approved medicines Clinical Trials Expanded Access Types of Access Regulatory approval provides broadest access Clinical Trials Evaluation of safety and efficacy of medicines to support approvals Expanded Access Single patient and treatment protocols Primary goal: access Ultimate goal: to provide broadest access possible to all patients who could benefit from a medicine Fastest way to provide broadest access: through approval mechanism, so robust regulatory strategy needs to be priority FDA has programs/pathways in place to accelerate regulatory process for important new medicines Breakthrough therapy designation Accelerated approval pathways Surrogate endpoints Importance of partnering with FDA, Advocating w/ FDA for early approvals Clinical trials: Awareness, i.e., Clinicaltrials.gov Patient groups: Advocate w/ companies to perform clinical trials that enroll patients with the greatest unmet needs Expanded Access: Can provide patients with access to a medicine w/ a proven benefit/risk profile, while regulatory strategy in place Single patient programs Clinical trials with primary goal, or primary endpoint, of access

Goals of Expanded Access/Compassionate Use Provide seriously ill patients, who have no other treatment options, access to investigational new drugs that are not yet approved, based on a request from the treating physician Set context: Ultimate goal: to provide broadest access possible to all patients who could benefit from a medicine Fastest way to provide broadest access: through approval mechanism, so robust regulatory strategy needs to be priority Role of Expanded Access: Can provide patients with access to a medicine w/ a proven benefit/risk profile, generally once regulatory strategy is clear

1 2 Expanded Access Unapproved Therapies Approved Therapies Access to a product not yet approved anywhere in the world, in any indication Access in a region beyond where a product is currently approved Access for an unapproved indication Various models for expanded access

Expanded Access Considerations Sufficient Benefit/Risk Data Sufficient clinical evidence of safety and effectiveness established Defined Approval Pathway Medicine is under active development in the indication Regulatory strategy determined and underway Program Viability Sufficient medicine to ensure adequate supply for clinical trials Sufficient staff to support program Regulatory mechanism in the region to support expanded access Patient Need The patient has a serious/ life threatening disease or condition No comparable or satisfactory alternative therapy Discuss four considerations for expanded access programs

Case Study: Partnering for Patient Access Collaboration with Multiple Myeloma Research Foundation Patient access prior to FDA accelerated approval Access for more than 300 patients CMAP: example of successful expanded access program Multiple myeloma: rare blood cancer, new treatments needed Carfilzomib Myeloma Access Program (CMAP) established to bring carfilzomib to patients who had exhausted available treatment options Keys to success Program launched in 2011 after benefit/risk profile for carfilzomib understood, US regulatory process defined and underway Partnership with Multiple Myeloma Research Foundation (MMRF) advocacy group which simultaneously advocated w FDA for Accelerated Approval of Carfilzomib Results More than 300 patients received carfilzomib through CMAP before cafilzomib achieved US accelerated approval in 2012 Onyx provided patient support and service program to help patients transition from CMAP clinical trial to commercial Kyprolis, once approved

Shared goal: Broad patient access to important medicines Next Steps Shared goal: Broad patient access to important medicines Consider all types of access: Rapid regulatory approval of safe, effective new medicines Clinical trials Expanded Access Partnership and support of FDA, clinical trials In summary, patients, regulators and companies share a common interest in bringing important new medicines to the patients that need them the most once sufficient evidence of safety and effectiveness is established Informed patients and patient advocacy groups can influence the process through partnership and support of FDA and the regulatory process, and through participation in important clinical trials.