Department of Medicine Infectious Diseases Yale...Peter Gareiss, PhD Yale / Biology Yulia...

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Cure by design Choukri Ben Mamoun [email protected] Department of Medicine Infectious Diseases Yale

Transcript of Department of Medicine Infectious Diseases Yale...Peter Gareiss, PhD Yale / Biology Yulia...

  • Cure by design

    Choukri Ben [email protected]

    Department of MedicineInfectious Diseases

    Yale

  • Develop a breakthrough therapy for radical cure of fungal infections

    Safe

    Radical cure

    Potent

    ELIV5’S MISSIONCure by design

  • William HungerfordYale / Chemistry

    Choukri Ben MamounFounder and CEOYale

    Peter Gareiss, PhDYale / Biology

    Yulia Surovsteva, PhDYale / Biology

    Marwan Azar, MDYale, Consultant

    Jose Thekkiniath, PhDYale / Scientific Manager

    ELIV5 TEAM

  • Cure by design

    PROBLEM & OPPORTUNITY

    Fungal Infections1.5 million deaths worldwide

    97,000 deaths in USCandida and Aspergillus

    Pulmonary Aspergillosis

    HighMedium

    Very High

    Low

  • Cure by design

    GLOBAL ANTIFUNGAL MARKET>$12B IN 2018 $19.3B by 2023

    Major Players

    Abbott LaboratoriesPfizerMerck

    Arbor Pharma, IncBaxter

    Astella Pharma IncBayer Healthcare

    Azoles42%

    Echinochandins33%

    Polyenes9%

    Allyamines6%

    Pyrimdines4%

    Others6%

    www.marketresearchfuture.com; www.grandviewresearch.com

  • HIGH MORTALITY RATES DESPITE THERAPY

    Fungal Disease Estimated Cases/year

    Estimated Mortality Rates (% of infected)

    Cryptococcus infections > 1,000,000 20 – 70%Candidiasis >400,000 10 - 75%Aspergillosis >200,000 30 – 95%Pneumocystis Pneumonia >400,000 20 – 80%Mucormycosis >11,000 30 - 90%

    Pianalto and Asplaugh, J. Fungi 2016

    Cure by design

  • VOL. CLXVIII . . . No. 58,289 + © 2019 The New York Times Company NEW YORK, SATURDAY, APRIL 6, 2019

    Late EditionToday, clouds and fog giving way tosome sunshine, milder, high 66. To-night, partly cloudy, low 49. Tomor-row, sunshine mixing with clouds,high 65. Weather map is on Page C8.

    $3.00

    FUNGAL INFECTIONS KILL MORE PEOPLE THAN TB AND MALARIACure by design

  • Cure by designUNIQUE TARGET AND MODE OF ACTION

    Pantothenate CoA

    EliV5Inhibitors

    PanK PPCS PPCDC PPAT DPCK

  • Cure by design

    FIRST-IN-CLASS INHIBITORS IDENTIFIED

    131,334 Compounds

    (+ 25,000 ongoing)

    25 Hits

    50 Analogs

    Actives

    3 Chemotypes3 Singletons

  • Cure by design

    TECHNOLOGY & PRODUCTS STRENGTHS

    Hit

    Prop

    ertie

    s

    Highly selective

    Excellent safety profile

    Novel compounds (IP: competitive advantage)

    CompoundEC50 (µM) LD50 (µM)

    AspergillusPanK

    Human PanK3 HeLa

    YU182690 (Chemotype 1: PT) 0.74 >50 >50

    YU253854 (Chemotype 2: NP) 8.6 >100 >100

    YU196223 (Chemotype 3: SA) 3.6 >100 >100

    -7 -6 -5 -4

    -5 0

    0

    5 0

    1 0 0

    Y U 2 5 3 8 5 4N itr ile

    lo g [ ] , MPe

    rce

    nt

    Inh

    ibit

    ion

    A .fu m . P a n K

    h u P a n K 3 Y U 2 5 3 8 5 4

    AfPanKHuPanK3

  • Cure by design ELIV5 1-2 PUNCH STRATEGY

    Pantothenate CoA Ergosterol

    • Azoles (Voriconazole)• Polyenes (Ampho-B)• Allylamines (Terbinafine)• Morpholines (Amorolfine)

    EliV5Inhibitors

  • 1-2 PUNCH STRATEGY FOR RADICAL CURE

    PanK100% active

    20

    40

    60

    80

    100

    No drug

    AmphoB(1 µg/ml)

    No drug

    AmphoB(1 µg/ml)

    Wild type PanK mutant

    % G

    row

    th

    PanKactivity

    100%

    8%

    100%

    8%

    AmphoB

    -

    -

    +

    +

    Cell numbers106 105 104 103 102 10

    PanKactivity

    100%

    8%

    100%

    8%

    AmphoB

    -

    -

    +

    +

    Cell numbers106 105 104 103 102 10

    Cure by design

    PanK8% active

    20

    40

    60

    80

    100

    No drug

    AmphoB(1 µg/ml)

    No drug

    AmphoB(1 µg/ml)

    Wild type PanK mutant

    % G

    row

    th

    PanKactivity

    100%

    8%

    100%

    8%

    AmphoB

    -

    -

    +

    +

    Cell numbers106 105 104 103 102 10

    PanKactivity

    100%

    8%

    100%

    8%

    AmphoB

    -

    -

    +

    +

    Cell numbers106 105 104 103 102 10

    Ampho-B (µg/ml)a

    -Pan

    Am

    (µg/

    ml)

    Synergy between a-PanAm and Ampho-B

  • Seed $430K

    Lead Identification

    ASK $1.8MDrug

    OptimizationIn vitroEfficacy Pharmacology

    In vivoEfficacy

    Cure by designUSE OF FUNDS

    Clinical CandidatesPhase I

  • Cure by design

    SUMMARY

    Novel inhibitors

    Novel mode of action

    Novel strategy for radical cure

    Competitive advantage

    (IP to 2039)

    ELIV5 TECHNOLOGY AND COMPETITIVE ADVANTAGE

    ASK$1.8M

    MilestoneIdentify clinical

    candidates

    GoalTherapy for radical cure

  • Cure by design

    STRATEGIC PLANNING

    2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027

    Pre-clinical Launch

    PITCH$438,870

    STTR+SBIR

    Private ($1.8M) Acquisition / IPO

    Strategic partner/Joint Venture

    Alli

    ance

    s / p

    artn

    ersh

    ips

    Clinical