Unlocking protein production with translational - read-through for rare genetic diseases - Eloxx Pharmaceuticals
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Unlocking protein production with translational
read-through for rare genetic diseases
Investor Presentation July 2018
Forward-Looking Statements
Certain statements included in this presentation are forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. These include statements of management’s intentions, belief, plans and future
expectations and, therefore, you are cautioned not to place undue reliance on them. Such forward-looking statements
involve risks and uncertainties and actual results could differ materially from any forward-looking statements expressed or
implied herein.
The risks and uncertainties that could result in actual results to differ materially from those forward-looking statements
expressed or implied herein include, but are not limited to: the Company's ability to continue as a going concern; the ability
of the Company to consummate additional financings; the development of the Company's technology; the approval of the
Company's patent applications; the Company's ability to successfully defend its intellectual property or obtain the
necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company's
research and development programs and collaborations; the success of the Company's license agreements; the timing
and success of the Company's preliminary studies, preclinical research, clinical trials and related regulatory filings; if
approved, the acceptance by the market of the Company's products; and the continued quotation of the Company's
common stock on the over-the-counter securities market, as well as other factors expressed from time to time in the
Company’s 10-K, 10-Qs and other filings with the SEC. The forward-looking statements contained herein are made only
as of the date of this presentation, and the Company undertakes no obligation to publicly update such forward-
looking statements to reflect subsequent events or circumstances.
2
Eloxx Pharmaceuticals Highlights
Leading Read Clinical stage biopharmaceutical company developing novel small molecule
Through medicines designed to treat genetic diseases by restoring the production of
Company proteins from genes with nonsense mutations
Experienced Management team with established track record of successful product
Management development and commercialization
Strong Clinical On track for mid 2018 IND (FDA) and CTA (Belgium) submission to support
Focus initiation of Phase 2 studies in Cystinosis and Cystic Fibrosis in 2018. Phase 1
SAD complete, MAD ongoing. Pediatric Orphan Opportunity.
Diversified Global rights for library of novel molecules that address the
Development aminoglycoside/ribosome binding site. Anticipate advancing second
Portfolio compound to IND enabling studies in 2018.
Financially Cash of $18.3 million as of March 31, 2018; No debt
Sound Extensive IP portfolio; Composition of matter thru 2031
April 30, 2018 closing of public offering of 5.9 million shares, net proceeds
$53.4 million
Trading as ELOX (Nasdaq)
3
Key Scientific Highlights
• Key positive organoid data in Cystic Fibrosis
• Heterozygous and homozygous CFTR mutations
• Key positive model data in Cystinosis
• Reduction of kidney cystine levels
• On track for completion of Phase 1 studies
• SAD completed
• MAD enrolling
• Initiation of Phase 2 studies in Cystic Fibrosis and
Cystinosis (4Q’18)
• Participation at Key Scientific Conferences
• 2 ELX-02 Abstracts presented at European Cystic Fibrosis
Society Meeting in June, including late breaker in organoids
• Eloxx to nominate second novel molecule for development
in rare/ultra-rare orphan disease
4
Highly Experienced US Leadership Team
Robert Ward Pedro Huertas, MD, PhD Gregory Weaver
CHAIRMAN AND CEO CMO CFO
John van Duzer, PhD Barbara Ryan Neal Sharpe, PhD
VP CMC INVESTOR RELATIONS VP TRANSLATIONAL SCIENCE
5
The Promise of Read-Through
Aminoglycosides' tolerability
profile historically limited
suitability for read-through
Cystic Cystinosis
Fibrosis treatment of serious
genetic diseases
>1,800 Aminoglycosides first
Genetic showed read-through activity
diseases MPS I Rett Duchenne
in nonsense mediated
involve Syndrome Syndrome Muscular
Dystrophy
diseases
nonsense
mutations • In every genetic disease a subset of patients Advances in our
have nonsense mutations that impair the
production of essential proteins
understanding
• Translational read through is directed at
of translational
restoring the production of full length proteins read-through enables
by overcoming the premature stop codon and
nonsense mediated decay
design of novel
small molecules
6
Target Profile for Read-Through
Eloxx read-through program is pursuing product candidates with the
following characteristics:
Activity independent of gene size or Molecular scaffold Active at all three
complexity of genetic disorder with defined premature stop
ribosomal effect codons
Reduces rate Restores protein Acceptable Suitable
of nonsense production to tolerability profile for chronic
mediated decay a clinically administration
significant level
7
Aminoglycoside Ribosomal Interaction
• Well defined molecular interaction with helix 44
• Role in stabilization of tRNA binding at Site A
• Optimizing scaffold by altering interaction with
prokaryotic and mitochondrial ribosomes
• Defined tissue penetration and tolerability profile for
read-through applications
Aminoglycoside activity observed on single pre-translocation ribosome complexes. Feldman, MB;
Terry DS; Altman RB; Blanchard SC. Nature Chemical Biology volume6, pages54–62 (2010)
8
ERSGs Enable Translation Across Premature Stop
Codons
mRNA
“Off” State “On” State
A1755
Cognate tRNA
A1754
mRNA
Non-cognate tRNA
Discovery of ELX-02
• Novel compounds derived from
aminoglycoside scaffold
• Screened for read-through activity on
known disease related nonsense
mutations
• Reduced mitochondrial inhibition
(range 12-140X)
• Reduced prokaryotic ribosomal
inhibition
Increased Selectivity towards Cytoplasmic versus Mitochondrial Ribosome Confers Improved Efficiency of Synthetic
Aminoglycosides in Fixing Damaged Genes: A Strategy for Treatment of Genetic Diseases Caused by Nonsense Mutation.
Kandasamy, K; Atia-Gilkin D; et al. J Med Chem (2012) 55(23):10630-10643
10ELX-02 Preclinical Development
CTA (EU) & IND (US) Enabling Studies
• Functional and anatomic hearing studies
– No observation of ototoxicity
• Histopathology and functional renal studies
– Data to date suggest improved NOAEL margin
– Currently anticipate dosing without adjustment for renal impairment
• Submitted CTA for Cystic Fibrosis in May
• On track for mid-year submission of IND for Cystinosis
Initiated regulatory pre-IND review of CMC to support planned
clinical program
11ELX-02 Clinical Development – Phase 1 Studies
CLINICALTRIALS.GOV CLINICALTRIALS.GOV
Identifier: NCT03292302 Identifier: NCT03309605
A Phase 1a, Randomized, Double-blinded, A Phase 1, Randomized,
Placebo-Controlled, Single Dose Escalation Double-Blinded, Placebo-Controlled, Third
Study to Evaluate the Safety, Tolerability, Party Open, Multiple Dose Escalation,
and Pharmacokinetics of ELX-02 in Healthy Single Center Study to Evaluate the Safety,
Adult Volunteers Tolerability and Pharmacokinetics of
Subcutaneously Administered ELX-02 in
Independent Consecutive
COMPLETED Cohorts of Healthy Subjects ONGOING
Planned Enrollment: 45
TO DATE:
• No SAE Observed
• No renal or otoacoustic SAE
• Generally well tolerated
12Our Current Development Pipeline
2017 2018 2019 2020
ELX-02 Phase 1a SAD Phase 1b MAD
Cystic Submission
Fibrosis CTA (Belgium) Phase 2*
IND (FDA)
Cystinosis
ELX Library Candidate
Preclinical Mutational Profiling
Compounds Nomination
ELX-02 and the ELX Library Compounds are investigational agents and have not been approved for use by any regulatory agency
*Subject to Regulatory Review of CTA and IND respectively
13Cystic Fibrosis Development Program
• Systemic rare disease
• Caused by mutations in transmembrane
conductance regulator (CFTR)
– Chloride channel
• Mutations lead to dysregulation in multiple
organ systems
• Current standard of care based on molecular
chaperones for trafficking and conformation
– Target Class II – Class V CFTR Defects
– No currently approved drugs for Class I CFTR Defects
• Currently available data for our investigational drug,
ELX-02, suggests the potential for:
– Active for both homozygous and heterozygous
Class I nonsense mutations
Zoltan Bozoky et al. PNAS
– Increase translational read-through 2013;110:47:E4427-E4436
– Improve chloride currents in HBEs and organoids
– Demonstrate synergy with correctors and
potentiators in heterozygous population
14Cystic Fibrosis: CFTR Molecular Defect
• Premature stop codons or
nonsense mutations are Class I
• Estimated that 22% of patients
have Class I mutations on one or
both CFTR alleles
• The G542X nonsense mutation
occurs in 5% of CF patient
population
• Eloxx’s development path for
read-through therapeutics will be
focused on the patient subset
with diagnosed nonsense
mutations
Novel personalized therapies for cystic fibrosis: Treating the basic defect in all
patients. Journal of Internal Medicine 277(2) · September 2014
15Goals of Cystic Fibrosis Personalized
Medicine Approach
Development path focused on individual’s genetic background
(ie, CFTR mutation)
WITHOUT PERSONALIZED MEDICINE: WITH PERSONALIZED MEDICINE:
Some Benefit, Some Do NOT Each Patient Receives the Correct
BENEFIT Medicine for Them THERAPY
NO BENEFIT THERAPY
BIOMARKER
PATIENTS THERAPY PATIENTS
DIAGNOSTICS
EACH PATIENT BENEFITS
FROM INDIVIDUALIZED
ADVERSE TREATMENT
EFFECTS THERAPY
Today most patients have genetic sequence data that could enable
personalized treatment
16Organoids For Cystic Fibrosis Screening
A CF assay on cystic fibrosis patient organoids
Healthy CFTR activation: CF mutated CFTR activation:
Swelling of Organoids No-Swelling of Organoids
17
11/13/2017 | ConfidentialOrganoids Pre-clinical Patient Stratification
Potential Use To Define Clinical Trial Populations
A CF swelling assay on cystic fibrosis patient organoids
Patient Organoid without drug treatment: Patient Organoid with drug treatment:
No Swelling of Organoids Swelling of Organoids
18
11/13/2017 | ConfidentialHeterozygous nonsense mutations
First investigational read-through agent to demonstrate in vitro activity in organoid cultures
4-points dose titration of ELX-02 compound at 5µM Forskolin after 48h incubation in absence or
presence of VX-770 in F508del/G542X organoid cultures. Combination VX-809/VX-770 was
performed as control.
19Homozygote nonsense mutations
First investigational read-through agent to demonstrate in vitro activity in organoid cultures
F 5 0 8 d e l/R 1 1 6 2 X -A
• Early-stage data involve key homozygous
G542X/G542X
200
0 u g /m l
nonsense mutations 190
200
1 2 .5 u g /m l
2 5 u g /m l
– G542X prevalence estimated at 5% of CF population
180
5 0 u g /m l
170 180
– W1282X prevalence est. at 4% of CF population
1 0 0 u g /m l
O r g a n o id s S w e llin g
(N o r m a lis e d A r e a )
160
O r g a n o id s S w e llin g
160
• This testing in a limited number of in vitro
150
140
organoid cultures suggests organoid response to
140
130
increasing exposure to our drug candidate ELX-02 120 120
– Dose-proportional response 110
100
100
– Pronounced swelling 90
0 20 40 60 80 100 120
T im e p o in t ( m in )
0 20 40 60 80 100 120
• Organoid responses are considered important tim e p o in t
contributor to clinical trial design 200
W1282X/W1282X-A
– High unmet medical need population
180
– Demonstrate potential for clinical response
O r g a n o id s S w e llin g
160
• Data to be submitted for scientific presentation
140
– Additional homozygous and heterozygous
response data 120
– Evaluation of in vitro response in organoid cultures in 100
combinations with correctors and/or potentiators 0 20 40 60 80 100 120
T im e p o in t ( m in )
20FIS Response Correlates Strongly with mRNA Levels in
G542X/X CFTR Organoids
6000
AUC accumulative swelling
G542X/G542X
5000
(t=120min)
4000
G542X/ΔF508
3000
2000 G542X/W1282X
R² = 0.9811
1000
0
1 1.5 2 2.5 3 3.5 4
Elevation of CFTR mRNA after treatment with ELX-02
(normalized to GAPDH)Cystic Fibrosis Phase 2
• Clinical Trial Application (CTA) Submitted in Belgium
• Protocol Assigned “High Priority” for EU Cystic Fibrosis
Clinical Trial Network
• 24 Patients, 3 Cohorts Dose Escalation
• Primary Endpoint: Sweat Chloride, Nasal Potential
Difference
• Key Secondary Endpoint: FEV1
• G542X homo/heterozygous genotypes (~ 5%)
• On track for FPFV in 4Q2018
22ELX-02 Cystic Fibrosis Next Steps
Jan 2018 Pre-CTA (Belgium) Regulatory Meeting
CTA (Belgium) Submitted
Targeting 4Q 2018 for FPFV Phase 2 Study
23Cystinosis Development Program
• Ultra-rare lysosomal storage disease
• Caused by mutations in cystinosin (CTNS)
– Cysteine efflux channel
• Cystine lysosomal accumulation causes manifestations of disease
• The current standard of care, Cysteamine acts within the
lysosome to convert cystine into forms which can exit the
lysosome via cysteine transport pathways.
• W138X most common nonsense mutation is estimated to
represent 1/3 of patient population
• Currently available data on our investigational drug candidate,
ELX-02, suggest the potential to:
– Increase translational read-through
– Reduce NMD
– Restore CTNS mRNA to near normal levels
– Lower cystine accumulation in vitro and in vivo
24ELX-02 Preclinical Cystinosis
In vitro model
indicates ELX-02
reduces nonsense
mediated decay
(NMD)
in vitro model
CTNSW138X/W138X
fibroblasts
In vitro model
indicates ELX-02
restores Cystinosin
transporter function
25ELX-02 Animal Model Cystinosis
21 Days of Biweekly
ELX-02 Administration
Significantly Reduced
Kidney Cystine Levels
Dr Paul Goodyer
McGill University
CTNSY226X/Y226X knock-in
26ELX-02 Cystinosis Next Steps
Dec 2017 Pre-IND FDA (Written Response)
On track for mid-2018 IND Submission in US
Targeting 4Q2018 for FPFV Phase 2 Study
27Financial Summary
• $18.3 million cash as of March 31, 2018
• No debt
• Funded through 2020 and completion of Phase 2 trials in
cystic fibrosis and cystinosis
• Completed public offering of 5,899,500 shares of common
stock at a price of $9.75 per share on April 30, 2018, net
proceeds of $53.4 million
• Shares outstanding totaled 33.4 million as of 4/30/18
• Traded Nasdaq: ELOX
28Eloxx Pharmaceuticals Highlights
• Key positive organoid data in Cystic Fibrosis
• Heterozygous and homozygous CFTR mutations
• Key positive model data in Cystinosis
• Reduction of kidney cystine levels
• On track for completion of Phase 1 studies
• SAD completed
• MAD enrolling
• Initiation of Phase 2 studies in Cystic Fibrosis and
Cystinosis (4 Q)
• Participation at Key Scientific Conferences
• 2 ELX-02 Abstracts presented at European Cystic Fibrosis
Society Meeting in June, including late breaker in organoids
• Eloxx to nominate second novel molecule for development
in rare/ultra-rare orphan disease
29Thank you. Investor Presentation July 2018
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