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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