Strategic Plan Session A Primer on Drug Discovery

Answer Six “Simple” Questions Can you find it ? Do you own it ? Can you make it ? Is it safe ? Does it work ? Can you sell it ?

TARGET VALIDATION In vitro Assay RAPID SCREENING LEAD MOLECULE PROFILING Pharmacology & Biology Medicinal Chemistry DEVELOPMENT TRACK CANDIDATES TARGET IDENTIFICATION Pilot Toxicology Drug Metabolism Formulation Process Chemistry Ancillary Pharmacology Patents Phase IPhase IIPhase III IND Application to FDA PRECLINICAL DEVELOPMENT DISCOVERY RESEARCH PIVITOL CLINICAL TRIALS NDA Application to FDA Safety Efficacy COMPOUND SCREENING & OPTIMIZATION Drug Discovery & Development

TARGET VALIDATION In vitro Assay TARGET IDENTIFICATION DISCOVERY RESEARCH CML Target = BCR/ABL Kinase Drug Discovery & Development Produces BCR/ABL Kinase

TARGET VALIDATION In vitro Assay RAPID SCREENING LEAD MOLECULE PROFILING Pharmacology & Biology Medicinal Chemistry DEVELOPMENT TRACK CANDIDATES TARGET IDENTIFICATION DISCOVERY RESEARCH COMPOUND SCREENING & OPTIMIZATION Drug Discovery & Development Imatinib Mesylate (Gleevec)

TARGET VALIDATION In vitro Assay RAPID SCREENING LEAD MOLECULE PROFILING Pharmacology & Biology Medicinal Chemistry DEVELOPMENT TRACK CANDIDATES TARGET IDENTIFICATION Pilot Toxicology Drug Metabolism Formulation Process Chemistry Ancillary Pharmacology Patents Phase IPhase IIPhase III IND Application to FDA PRECLINICAL DEVELOPMENT DISCOVERY RESEARCH PIVITOL CLINICAL TRIALS NDA Application to FDA Safety Efficacy COMPOUND SCREENING & OPTIMIZATION Drug Discovery & Development

To Take Home 7 – 10 years: Average time to develop a drug $800 million: Average investment in a successful drug development program 51: Number of blood cancer drugs from large Pharma currently in clinical trials 1 in 10: Average success rate for new drugs entering clinical trials

Concert/Collaboration Goals:  Actively seek collaborations across the spectrum of non-profit, biotechnology, pharmaceutical, government and patient advocacy organizations. “Develop productive collaborations that result in effective treatments and improved healthcare accessibility for blood cancer patients”  Initiate a new Therapy Acceleration Program that facilitates our patients’ abilities to cope with all aspects of their illness and that brings new opportunities for therapies, fund-raising and advocacy.

 Broaden and increase fundraising opportunities  Accelerated development of drugs for hematological malignancies  Enhanced delivery of drugs to patients  Increased the patient’s ability to make medically-based decisions  Greatly improved visibility for the Society Outcomes of the New Mission: “More Therapies to Patients, Faster”

Strategy for Accelerating Therapies for Hematological Malignancies Patient Accessibility Program Patient Ambassadors Clinical Trials Consortium Synergistic Collaborations Drug Development Program Biotechnology Accelerator Academic Concierge Fundraising and LLS Visibility

Ave. 10 – 15 Yrs. ~ $1.2 Billion Drug Development Activities: Career Development Program Translational Research Program GAP LLS Drug Development Program SCOR

Accelerating The Process: Moving specific therapies to clinic faster Biotechnology Accelerator Academic Concierge Drug Development Activities: Bottleneck LLS Drug Development Program

The Need: Therapy Development in both early-phase biotechnology companies and academic institutions have common problems:  Both have molecules and/or diagnostics with wide oncological applications that can be applied to hematological malignancies.  Both need support at critical early drug development phases (the bottleneck).  Both must meet FDA regulatory requirements and approval. LLS Drug Development Program

The Solution: Biotechnology Accelerator: Moving specific therapies to the patient faster.  Identify viable companies and fund valid compounds  A company’s funding is therapy based; thus fund case by case  Continued funding is milestone based  Expected % success rate  Agreements crafted to provide down-stream revenue  Mitigate risk by appropriate LLS oversight (new committee) LLS Drug Development Program

The Solution: Academic Concierge: Facilitates specific therapies reaching the patient faster.  Provide information and funding for specific gap-bridging studies  Broker access to private sector; both biotech and Pharma  Help with FDA application and/or compliance issues  Agreements crafted to provide down-stream revenue  Mitigate risk by appropriate LLS oversight LLS Drug Development Program

Biotechnology Compounds: Does the Need exist ?  Human Genome Sciences: Has therapies for Blood Malignancies that are not being pursued due to budget  ProNAi: Therapy for indolent Non-Hodgkin’s Lymphoma  SuperGen: Larger markets are in the solid tumors; can’t do the hematological malignancies. Has therapies LLS Drug Development Program

 Hagop Kantarjian, M.D. (MD Anderson): Definite need; many compounds stuck in Laboratories  Beverly Mitchell, M.D. (Stanford): Need is there, but LLS must carefully vet set up and use of funds  LLS SCORE Principle Investigators: Many of their programs have developed to the point of needing this type of help LLS Drug Development Program Academic Investigators: Does the Need exist ?

The need: Accelerated Access to Care Patient Ambassadors Clinical Trials Consortium Synergistic Collaborations LLS Patient Accessibility Program The Need. There is a critical, unmet need among our patients to make sure that they make the best medically-based decisions regarding their therapies, participate in clinical trials and receive the best possible care.

The Solution: Patient Ambassadors:  Provide patients with medically-based information regarding treatment, clinical trial participation and palliative care.  Clinically-trained individuals that serve as medical intervention specialists that help solve medical problems of our patients  Typically function in the critical time period between diagnosis and chronic care.  Medically-trained physician extenders: e.g., oncological nurses, nurse-practitioners, or physician assistants.  Function at Regional or, in certain instances, at the Chapter level. LLS Patient Accessibility Program

The Solution: Clinical Trials Consortium:  Many clinical investigators have difficulties in accruing enough patients to carry out a given trial.  Patients need and want to be involved in clinical trials.  Clinical Trials Consortium is a LLS-sponsored network of disease-specific trials sites.  Central trials office would provide help in trial-design, oversight, FDA filings, etc. LLS Patient Accessibility Program

The Solution: Synergistic Collaborations:  Example: a possible joint effort between the LLS and the National Marrow Donor Program (NMDP) to promote cord blood transplants.  Opportunities exist both now and in the future to interact with other non-profit organizations, government, and patient-advocacy groups.  LLS will actively continue this process and explore new opportunities. LLS Patient Accessibility Program

Measurements of Success  Number of therapies program has moved forward to clinical trials  Number of therapies successfully completing clinical trials  Amount of revenue produced by program  Number of patients utilizing Patent Ambassadors  LLS mediated Increases in patient accrual to clinical trials  Measurable advances resulting from Synergistic Collaborations Return on Investment

Revenue Generation SourceProgram Program Revenue: Drug Development Major Donors, Foundations Patient Accessibility Major Donors, Foundations, Pharmaceutical Biotechnology Academic Concierge Share in Profits Royalties

 Program strategically enters new territory to accelerate new therapies and to improve patient healthcare access and wellbeing.  It allows the LLS to effectively bridge a critical gap in drug research & development. THE RESULT: more lives saved, a better quality of life for patients, increased visibility and more revenue to further support our mission.  Addresses our patients’ needs utilizing a broad spectrum of new collaborative partners. Therapy Acceleration Program: A Quantum Leap

Climbing the Mountain: “Curing Leukemia, Lymphoma, and Multiple Myeloma”

George Dahlman James Davis, J.D., Ph.D. Louis DeGennaro, Ph.D. (Co-Chair) Alan Gewirtz, M.D. Michael Long, Ph.D. (Chairman) James Manuso, Ph.D. W. Stratford May, M.D., Ph.D. James Nangle Lisa Owens Michele Wong (Co-Chair) Concert Collaborations Plan Development Team

Paul CienkeJim McKinnis Brian DrukerBob Rollwagen Tom BehanTom Zak Richard KrumviedaDeborah Nix Jon LowellKen Tirino Claude EdkinsJohn Walter Marshall LichtmanStephanie Paul Concert Collaborations Resource Team