A Tough Pill to Swallow - Illustrated Guide to Drug Discovery

A TOUGH PILL TO SWALLOW illustrated guide to drug discovery by: JP SCIENCE MARKETING PROPRIETARY PATENT PROFIT POTENTIAL 20 o/o %24 YEARS INCENTIVES FOR INNOVATION Companies weigh profit potential vs risk factors. Immediate and long-term incentives help to spur innovation. START JAN пом FEB background RESEARCH MAR 20M APR disease components RESEARCH FOR UNDERSTANDING MAY 30M TAGC ATCG JUN DISCOVERY & IDENTIFICATION SEQUENCING GENE STRUCTURAL ANALYSIS BIOLOGICAL ACTIVITY SIGNALING PATHWAYS 40M JUL AUG the complete picture O PUTTING IT ALL TOGETHER SOM SEP INDUSTRY ост 60M NOV GOVERNMENT ACADEMIA 70M UNDERSTAND THE CONDITION YEAR Collaboration in research by industry, academia, & government provides the basis for drug discovery strategies. FEB 8OM MAR APR choose a MAY TARGET $100M JUN targetable biomolecules JUL 4 CLASSES oo0o PROTEINS POLY SACCHARIDES NUCLEIC ACIDS LIPIDS desirable characteristics d WHAT MAKES A GOOD TARGET NOV OFF CRITICAL TO DISEASE UNIQUE BINDING SITE ACCESSIBLE BY A DRUG MODIFIABLE ACTIVITY usually proteins in a complex pathway FEB MAR APR MAY JUN 170 DIS ASE JUL CONFIRM ROLE IN DISEASE AUG 180 The target is validated (shown to be critical to the disease) by research, and screening assays are developed. SEP OCT NOV $200M generate YEARS LEADS 210 FEB MAR pharmaceutical agents INCREASINGLY MORE BIOLOGICS ARE BEING DEVELOPED APR MAY CHEMICAL BIOLOGICAL JUN drug design methods: biopharmaceuticals/biologics: (3D models to fit target) Direct Nucleic acids (DNA, RNA) (mimic target binders) Indirect Proteins (enzymes, antibodies) Microorganism (virus, bacteria) Cell therapy (stem cells) Tissue therapy (transplant) JUL types of bonds: (reversible) lonic, Hydrogen (irreversible) Covalent AUG CHOOSE THE RIGHT APPROACH SEP Type of lead developed depends on the unique characteristics of the target. Not all targets can be reached with a pill. OCT NOV target YEARS DISCOVER POTENTIAL LEADS FEB Safe molecules that modify the target are found via nature, 3D modeling, high- throughput screening, & biotechnology. MAR APR MAY target $300M JUN JUL 2.0 OPTIMIZE WITH ANALOGUES Variations of 'hits' are tested for improved strength and specificity of interaction with the target. AUG OCT only in NOV 10,000 YEARS SCREENED MOLECULES will survive to become an FDA-approved DRUG FEB MAR APR pre-clinical TESTING JUN pharmacokinetics WHAT THE BODY DOES TO A MOLECULE AUG SEP ABSORPTION DISTRIBUTION METABOLISM EXCRETION OCT OPTIMIZE PHARMACOKINETICS 390 Leads are tested in animals & modified for optimal absorption, distribution, metabolism, and excretion properties. NOV $400M pharmacodynamics YEARS WHAT A MOLECULE DOES TO THE BODY FEB EFFICACY DOSAGE SAFETY SIDE EFFECTS MAR SAFETY+PHARMACODYNAMICS Efficacy, dosing, and negative effects are tested. Strict safety requirements must be met before testing in humans. APR MAY 430 1. 250 JUN only in JUL 440 AUG TESTED LEADS SEP will survive to become an FDA-approved DRUG OCT 460 NOV YEARS 470 IND IND APPLICATION Investigation New Drug application is filed with the FDA, outlining drug safety, known risks, and plans for clinical trials. INVESTIGATIONAL FEB do APPLICATION MAR FDA REQUIREMENTS BEFORE HUMAN TESTING MAY JUN $500M clinical tri als PHASE 1&II JUL AUG healthy volunteers SEP 20-100 OCT PHARMACO- KINETICS SAFETY NOV T PHASE I CLINICAL TRIALS Pharmacokinetics and safety data are collected from a small group of healthy volunteers. YEARS diseased patients 540 FEB 100-500 MAR EFFICACY DOSAGE SAFETY SIDE EFFECTS PHASE II CLINICAL TRIALS APR Efficacy, dosage, safety, and side effects are measured in diseased patients. Sometimes combined with Phase I. MAY JUN JUL AUG clinical tr ials PHASE III SEP OCT 590 healthy & diseased volunteers NOV $600M YEARS EFFICACY SAFETY FEB 610 COMPARISON SIDE EFFECTS MAR 1000-5000 620 II PHASE III CLINICAL TRIALS APR Large, time-consuming, expensive trials determine efficacy, safety, side effects, & comparison to existing treatments. MAY 630 JUN JUL only in 640 AUG CLINICALLY-TESTED SEP DRUG CANDIDATES 650 will survive FDA approval ост and hit the MARKET NOV 660 10 YEARS FEB NDA NEW DRUG APPLICATION All data, research, information, and manufacturing & labeling plans are compiled and submitted to the FDA. NEW DREG 680 APPLICATION MAR 100,000 pages APR FDA REQUIREMENTS BEFORE PUBLIC RELEASE JUN $700M JUL fda APPROVAL AUG SEP 720 ост what they're looking for NOV BENEFITS/RISKS LABEL QUALITY 11 3 possible outcomes YEARS APPROVED NEEDS WORK DENIED FEB BENEFIT VS RISK ANALYSIS MAR The FDA weighs the benefits & risks, determines appropriate label content, and approves manufacturing plans. 750 APR MAY 760 JUN JUL pre-market SCALE-UP AUG SEP small to large-scale MANUFACTURING CHALLENGES ост $4 790 NOV EFFICIENCY COST QUALITY SAFETY ENVIRONMENT CONSTRUCTION OF FACILITIES $800M 12 Each drug has unique production & safety concerns, often requiring con- struction of new equipment & facilities. YEARS FEB MAR APR 820 product MAY LAUNCH 830 JUN marketing and distribution JUL MAKING SALES & IMPROVING LIVES ilıl AUG BRANDING ADVERTISING PRESS ENDORSEMENTS DISTRIBUTION SEP 850 SALES! OCT After spending staggering amounts on R&D, an even greater amount is required to reach those who need it. NOV post-market surveillance 13 YEARS SUBGROUPS SAFETY FEB 880 MAR LONG-TERM SIDE EFFECTS APR JV PHASE IV CLINICAL TRIALS Sometimes required by the FDA to measure long-term safety and effects on subgroups of patients. 890 MAY JUN $900M top 5 worst drug recalls YEARS ON MARKET: SIGNIFICANT LOSSES: AUG SEP $21 BILLION IN LEGAL FEES FEN-PHEN 24 TUMORS IN CHILDREN 100,000 DEATHS WORLDWIDE $6 BILLION IN LEGAL FEES DES 37 OCT BAYCOL 4. VIOXX NOV $2 BILLION IN LEGAL FEES BEXTRA 14 > DRUG RECALLS & LAWSUITS Even after clinical trials & years on the market, unforeseen long-term side effects can be devastating. YEARS 940 FEB MAR APR total MAY INVESTMENT $ JUN 15 $1 JUL AUG YEARS BILLION SEP [avg. 10 to 20 years] [avg. 0.5 to 2.0 billion ] OCT YEAR $80OM 540OM $60OM $10OM HYEARS NOV $700M 20OM $300M $900M 11 $500M 14 VEANS 15 $1Billion YEARS FINIS H AN INVESTMENT OF THIS MAGNITUDE DESERVES ONLY THE BEST. SCIENTIFIC MARKETING materials WRITTEN & DESIGNED by JP SHOW. and TELL. O JP SCIENCE MARKETING PRESENTATION References biectpd kodureaef ahiaimnih gowpstmed/1222 en wikipedia.org/wik/Dreg distevery readcabe.com/artides/10.10/rd2 made by: JP SCIENCE MARKETING ADVERTISING Copyright o 2014 JP Science Marketing LLC jpsciencemarketing.com TAX CREDITS GRANTS BRAND