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Cure by design
Choukri Ben [email protected]
Department of MedicineInfectious Diseases
Yale
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Develop a breakthrough therapy for radical cure of fungal infections
Safe
Radical cure
Potent
ELIV5’S MISSIONCure by design
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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
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Cure by design
PROBLEM & OPPORTUNITY
Fungal Infections1.5 million deaths worldwide
97,000 deaths in USCandida and Aspergillus
Pulmonary Aspergillosis
HighMedium
Very High
Low
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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
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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
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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
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Cure by designUNIQUE TARGET AND MODE OF ACTION
Pantothenate CoA
EliV5Inhibitors
PanK PPCS PPCDC PPAT DPCK
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Cure by design
FIRST-IN-CLASS INHIBITORS IDENTIFIED
131,334 Compounds
(+ 25,000 ongoing)
25 Hits
50 Analogs
Actives
3 Chemotypes3 Singletons
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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
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Cure by design ELIV5 1-2 PUNCH STRATEGY
Pantothenate CoA Ergosterol
• Azoles (Voriconazole)• Polyenes (Ampho-B)• Allylamines (Terbinafine)• Morpholines (Amorolfine)
EliV5Inhibitors
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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
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Seed $430K
Lead Identification
ASK $1.8MDrug
OptimizationIn vitroEfficacy Pharmacology
In vivoEfficacy
Cure by designUSE OF FUNDS
Clinical CandidatesPhase I
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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
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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
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