<ul><li>Successful New Drug Development for Small Companies </li></ul>
Not to know is bad; not to wish to know is worse  (African proverb)
Spend Your Project $$Wisely
New Drug Development is Risky Business Source: PhRMA Pharmaceutical Industry Profile 2006
Pitfalls:   Why Drugs Fail to Reach Patients <ul><li>Toxicity </li></ul><ul><li>PK / Formulation </li></ul><ul><li>Clinica...
Further Observations <ul><li>First-in-Class compounds have a high attrition rate </li></ul><ul><li>Large companies still s...
<ul><li>Understand your drug </li></ul><ul><ul><li>Strengths / Weaknesses </li></ul></ul><ul><ul><li>Knowledge gaps </li><...
<ul><li>Learn from competitor drugs </li></ul><ul><ul><li>Strengths / Weaknesses </li></ul></ul><ul><ul><li>Knowledge gaps...
<ul><li>1. Demonstrated Preclinical Efficacy </li></ul><ul><ul><li>validated model? (biomarker predictive of clinical effi...
The person who knows everything has a lot to learn (anonymous)
Recommendations for Small Companies <ul><li>Learn from “first in class” compounds </li></ul><ul><li>Get earlier and better...
Advice for Business People Interested in Advancing Medicine <ul><ul><li>Finding an effective new drug treatment is a  Mara...
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Successful New Drug Development Strategies for Small Companies

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  • Successful New Drug Development Strategies for Small Companies

    1. 1. <ul><li>Successful New Drug Development for Small Companies </li></ul>
    2. 2. Not to know is bad; not to wish to know is worse (African proverb)
    3. 3. Spend Your Project $$Wisely
    4. 4. New Drug Development is Risky Business Source: PhRMA Pharmaceutical Industry Profile 2006
    5. 5. Pitfalls: Why Drugs Fail to Reach Patients <ul><li>Toxicity </li></ul><ul><li>PK / Formulation </li></ul><ul><li>Clinical Safety </li></ul><ul><li>Efficacy </li></ul><ul><li>Funding </li></ul><ul><li>What does this refer to? </li></ul><ul><li>Preclinical or long-term tox </li></ul><ul><li>Drug interaction, CYP induction, variable PK </li></ul><ul><li>Low incidence adverse events most difficult </li></ul><ul><li>More novel target, less known here </li></ul><ul><li>Low projected sales, high COGs, indication determined “non-strategic”, multiple compounds with same target </li></ul><ul><li>When? </li></ul><ul><li>Early or late (carc studies) </li></ul><ul><li>Usually in Phase 1 </li></ul><ul><li>Anytime Phase 1  </li></ul><ul><li>Anytime Phase 1  More novel target, higher risk </li></ul><ul><li>Anytime – Phase 3 funding a real issue for small companies </li></ul>
    6. 6. Further Observations <ul><li>First-in-Class compounds have a high attrition rate </li></ul><ul><li>Large companies still structured to focus on compounds with high commercial potential </li></ul><ul><ul><li>~25% of post IND program terminations for low commercial value/portfolio reasons </li></ul></ul><ul><ul><li>Undertreated diseases: HIV-AIDS in Africa, Malaria, TB, Lupus, Childhood genetic diseases </li></ul></ul><ul><li>Trends </li></ul><ul><ul><li>Dose selection will remain the single most important scientific decision to be made </li></ul></ul><ul><ul><li>Drug delivery nanotechnologies creating a new paradigm for development – miRNA, oncology, neurology </li></ul></ul>
    7. 7. <ul><li>Understand your drug </li></ul><ul><ul><li>Strengths / Weaknesses </li></ul></ul><ul><ul><li>Knowledge gaps </li></ul></ul>Step 1
    8. 8. <ul><li>Learn from competitor drugs </li></ul><ul><ul><li>Strengths / Weaknesses </li></ul></ul><ul><ul><li>Knowledge gaps </li></ul></ul><ul><li>Have we / others been this way before? </li></ul><ul><ul><ul><li>If yes, what worked, what didn’t? </li></ul></ul></ul>Step 2
    9. 9. <ul><li>1. Demonstrated Preclinical Efficacy </li></ul><ul><ul><li>validated model? (biomarker predictive of clinical efficacy?) </li></ul></ul><ul><ul><li>validated target? </li></ul></ul><ul><ul><li>Sufficient animal model exploration? </li></ul></ul><ul><li>2. Favorable MAP profile </li></ul><ul><ul><li>CYP450 substrate / inhibition profile </li></ul></ul><ul><ul><li>active metabolites / enantiomers? </li></ul></ul><ul><ul><li>Allometric scaling </li></ul></ul><ul><ul><li>CYP induction signal (PXR, HHA)? </li></ul></ul><ul><ul><li>dose proportional PK? </li></ul></ul><ul><ul><li>Toxicokinetics for preclinical tox </li></ul></ul><ul><li>3. Formulation / Drug solubility </li></ul><ul><ul><li>Any limits to ability to evaluate preclinical toxicology across the intended tox dose range via the intended route of admin in humans? </li></ul></ul>Practice Rigorous Dose Selection Science Early <ul><li>4. Select preliminary Phase I dose range and doses for IND tox studies </li></ul><ul><li>5. IND tox studies </li></ul><ul><ul><li>Are MTD and dose-limiting toxicities sufficiently characterized in rodent and non-rodent species? </li></ul></ul><ul><ul><li>Selectivity - any unwanted secondary pharmacology? </li></ul></ul><ul><ul><ul><li>If metabolism-related, would potential for tox increase in man due to drug-drug interactions? </li></ul></ul></ul><ul><ul><ul><li>Species sensitivity? </li></ul></ul></ul><ul><ul><ul><li>Chemotype or target-related specific toxicities? class liabilities? </li></ul></ul></ul><ul><ul><ul><li>Nature of toxicity vs. target patient population evaluated (risk/benefit) </li></ul></ul></ul><ul><ul><li>Safety/exposure multiples support Phase-I dose range as is? Pre-IND meeting needed? </li></ul></ul><ul><li>6. Finalize Phase I dose range </li></ul>          
    10. 10. The person who knows everything has a lot to learn (anonymous)
    11. 11. Recommendations for Small Companies <ul><li>Learn from “first in class” compounds </li></ul><ul><li>Get earlier and better patient and standard of care information </li></ul><ul><li>Critically evaluate all the data to understand what safety and efficacy biomarkers may be predictive – what are not </li></ul><ul><li>Focus clinical development plan on efficacy biomarkers with real potential, not exploratory </li></ul><ul><li>Utilize a rigorous approach for dose selection that provides a defendable risk-benefit for the patient </li></ul><ul><li>If the efficacy-safety problem warrants it, consider partnerships with drug delivery technology company </li></ul>
    12. 12. Advice for Business People Interested in Advancing Medicine <ul><ul><li>Finding an effective new drug treatment is a Marathon not a Mile run! </li></ul></ul><ul><ul><li>Don’t oversell the science until it is proven! </li></ul></ul>

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