Pioneering Next-Gen Precision Medicine Approaches in ALS and Other Neurodegenerative Diseases - December 2021
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Pioneering Next-Gen Precision Medicine Approaches in ALS and Other Neurodegenerative Diseases December 2021
Legal Disclaimer This presentation contains forward-looking statements based on current expectations that involve a number of risks and uncertainties. All opinions, forecasts, projections, future plans, or other statements, other than statements of historical fact, are forward-looking statements and include words or phrases such as “believes,” “will,” “expects,” “anticipates,” “intends,” “estimates,” “our view,” “we see,” “would” and words and phrases of similar import. The forward looking statements in this presentation are also forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and involve substantial risks and uncertainties. We can give no assurance that such expectations will prove to have been correct. Actual results could differ materially as a result of a variety of risks and uncertainties, many of which are outside of the control of management. CONFIDENTIAL & PROPRIETARY 2
New insights into human genetics and stem cell
technology provide genetically-validated targets for
ALS and other neurodegenerative diseases
Next-gen, precision medicine approaches using
biomarkers for patient selection, target engagement
and efficacy
First-in-class and Best-in-class programs for ALS and
other neurodegenerative diseases
• 2 programs projected to be in the clinic in 2022
2 Proprietary platforms to enable additional therapies
• Only company with comprehensive TDP-43 platform
• Novel FlexASO platform for splice modulator targets
World-class leadership in place for execution
Why QurAlis Can Succeed in ALS & Other Neurodegenerative Diseases
● Past companies applied ● QurAlis is applying precision oncology-like approaches in
“one-drug fits all” approach neuroscience
● Lacked understanding of ● QurAlis’ unique understanding of disease and biomarkers lead to
“disease-drivers” identification of sub-groups of patients for the right therapy
Applying Precision Medicine Approaches Initially in ALS
TBK1 SOD1 Understand
C9orf72 Sporadic Genetic Drivers in
8% Sub-Forms of ALS
Others 80% Kv7 TDP-43
8% GoF
Design
Precision Medicines
& Biomarkers
ALS
Patients STMN2
Future
Programs
Deliver
Precision Therapies
to Patients
CONFIDENTIAL & PROPRIETARY 4
QurAlis’ Comprehensive Approach to Tackling ALS
Kevin Chris
Kevin Clifford Sandy Angela Merit Leonard
Michelle Hagen Sudhir Manuel Dan
Matthew Brian
CONFIDENTIAL & PROPRIETARY 5
QurAlis at a Glance
Founded in 2016 Multi-Billion Dollar Commercial $47 Million
• By internationally recognized team of Opportunity • Series A financing in 2020
neurodegenerative biologists in Success in ALS is predicted to create • Led by Polaris Partners, Mission BioCaptial,
collaboration with Harvard/Eggan Lab analogous market opportunity as MS INKEF Capital, DDF and Droia Ventures
2 Proprietary Platforms* ALS: ~2 in 100,000 Patents
• QR43TM: Proprietary TDP-43 platform • Most common form of motor neuron • Strong IP Positions
• FlexASOTM: Proprietary Anti-Sense Oligo- disease • Multiple patent families filed
nucleotide splice modulator platform
FTD: ~3.5 in 100,000 • NCE market exclusivity
Deep Pipeline of Antisense • 2nd most common form of dementia
& Small Molecule Programs Award Winning
• With diverse MOA 2 Programs projected to be in the • 2020 Fierce 15 Awardee
• Centered on TDP-43 clinic in 2022 • NEVY 2020 Winner
• Amgen and Pfizer Golden Ticket
2 Proprietary platforms* and unique biomarkers enable us to understand, identify and
deliver next-generation precision medicines to patients with neurodegenerative diseases
CONFIDENTIAL & PROPRIETARY 6
Pioneers with Unrelenting Commitment to Patients
Kasper Roet, Ph.D. Dan Elbaum, Ph.D. Vikas Sharma, Ph.D. Angela Genge, Hagen Cramer, Sandy Hinckley, Talia Ben
CEO CSO CBO MD FRCP Ph.D. Ph.D. Sasson-Gordis,
CMO CPO Head of Biology MBA, LLB
COS
Harvard Medical Retrophin BioXcel Tx Montreal Wave Life Sanford Burnham Anti-Defamation
School Neurological Hospital Sciences Prebys Medical League
Pfizer, Amgen, MacroGenics
Discovery Institute
Harvard Stem Cell Vertex, Critical Montreal Avecia Attorney at law, Yigal
Rexahn
Institute Therapeutics, Neurological Institute Neurocore LLC Arnon & Co
Girindus
FoldRx, MedImmune
Johnson & Johnson McGill University CIRM Law Clerk Supreme
(Astrazeneca)
Ra Pharmaceuticals Court of Israel
Founder of Netfase
CHOP, Bradley
Pharma
CONFIDENTIAL & PROPRIETARY 7
Exceptional Scientific and Clinical Advisory Board Members
C
A Ammar Al-Chalabi Jinsy Andrews Merit Cudkowicz Dame Pamela J. Shaw Philip Van Damme Leonard van den Berg
B MB, ChB, Ph.D. M.D., MSc M.D., MSc DBE, MBBS, M.D.,
FRCP, FMedSci, FAAN,
M.D., Ph.D. M.D., Ph.D.
FANA, FAAS
S
A Clifford Woolf Kevin Eggan Matthew Kiernan Bernhardt Trout Brian Wainger Christopher Shaw Sudhir Agrawal Michelle Hastings
B M.D., Ph.D. Ph.D. M.D., Ph.D. Ph.D. M.D., Ph.D. M.D., Ph.D. Ph.D. Ph.D.
CONFIDENTIAL & PROPRIETARY 8
Supported and Recognized by Investors, Pharma and Industry
INVESTORS
Sanford Biosciences
AWARDS
PARTNER
Raised $47M Series A
CONFIDENTIAL & PROPRIETARY 9
Genetics of ALS Uncovers Major Disease Drivers Linked to TDP-43
STMN2
Only company with multiple programs against TDP-43 pathology affecting
~90% ALS, ~50% FTD, ~30% AD and ~7% PD
CONFIDENTIAL & PROPRIETARY 10QurAlis’ Advantage - Two Proprietary Platforms
QR43 PlatformTM: Proprietary & Investigative TDP- FlexASOTM: Proprietary Anti-Sense Oligonucleotide
43 Platform Splice Modulator Platform
Attributes Traditional ASO FlexASO
Stem cell In vitro Size
model neuronal
Efficacy
systems functional
readouts Safety
CMC
Known for spinal Similar or better
Distribution cord and frontal (experiments
TDP-43 loss Clinical cortex ongoing)
of function TDP-43
animal model biomarkers May overcome modality-specific, dose-limiting
The only company with a toxicities observed with “traditional ASO”
TDP-43 LoF animal
model
CONFIDENTIAL & PROPRIETARY 11Pipeline Targeting Major Disease Drivers in Patients
Program Population Modality MOA Indication Preclinical IND/FPI
QRL-201 STMN2 ALS
Excitatory
QRL-101 (Kv7)
ALS
QRL-203 STMN2 FTD
QRL-202 TDP-43 GoF ALS/FTD
Splice
QRL-204 Modulation
Not Disclosed
Additional indications and programs under consideration
CONFIDENTIAL & PROPRIETARY 12QRL-201 STMN2 Program
QRL-201 Program Overview
Candidate ● First-in-Class ASO against STMN2 pathology
Function/MoA ● Restoration of protein activity
Patient Selection ● STMN2 biomarker (30-90% of ALS patients*)
Indications ● Reduce ALS disease progression
Development ● IND-enabling studies on-going
& Status ● CTA/IND to be filed mid 2022
● Precision medicine approach
Commercial &
● Superior to standard-of-care (Rilutek** and Radicava***)
Regulatory Adv
● Increases probability of success
Rights ● QurAlis retains global rights
*Majority of ALS and FTD patients and 30-50% of AD patients; **Rilutek: can cause liver damage; only ~30% of patients use Rilutek ***Radicava: 6 month regimen of intravenous treatment
CONFIDENTIAL & PROPRIETARY 14QRL-201
STMN2 Levels Are Consistently Decreased In Sporadic ALS Patients
STMN2 levels are consistently decreased in Loss of TDP-43 from the nucleus (ALS
sporadic ALS patients hallmark) leads to loss of STATHMIN-2
Eggan Lab
Truncated STATHMIN-2 mRNA abundant TDP-43 loss causes loss of axon repair
in sporadic ALS spinal cord and brain Rescue by restoring STATHMIN-2 levels
Cleveland Lab
CONFIDENTIAL & PROPRIETARY 15
Nat. Neurosci. Feb 2019QRL-201
STMN2: A Genetic Target For The Sporadic ALS Population
QurAlis Therapeutic Strategy
In ALS motor neurons TDP-43 control of Loss of full Axonal degeneration
TDP-43 leaves the nucleus cryptic exon splicing lost length STATHMIN-2 and impaired repair
Rabin et al., 2009
QurAlis niche TDP-43 regulation Cryptic splicing-ASO Rescue of axonal
of STATHMIN-2 approach to restore stability and repair
STATHMIN-2
Nat. Neurosci. Feb 2019, Eggan ALS One 2020, Li et al., 2009, Morii et al., 2006, Shin et al., 2012, Shin et al., 2014, Xu et al., 2010,
CONFIDENTIAL & PROPRIETARY 16QRL-201
QRL-201 Protects Human Motor Neurons Against Neurodegeneration
QRL-201 Protects Human
TDP-43 Toxicity in
Motor Neurons from
Market
Human Motor Neurons
TDP-43 Toxicity Opportunity
● ~90% of ALS & ~50%
FTD patients
● Genetic target for sporadic
ALS and FTD with additional
opportunities in AD and PD
● Patients are selected by
biomarker
● Target engagement
Neurons degenerate Neurons protected measured by biomarker
CONFIDENTIAL & PROPRIETARY 17QRL-101 Excitotoxicity Program
QRL-101 Program Overview
Candidate ● Potential best-in-class Kv7 opener
Function/MoA ● Reduction of hyperexcitability through K+ channels
Patient Selection ● Excitability biomarker* (50% of ALS patients)
Indications ● Reduce ALS disease progression
Development ● IND-enabling studies ongoing
& Status ● CTA/IND to be filed mid 2022
● Wider therapeutic window
Commercial &
● Superior to standard-of-care (Rilutek** and Radicava***)
Regulatory Adv
● Potential to reduce disease progression
Rights ● QurAlis retains global rights
*Excitability biomarker: strength duration time constant **Rilutek: can cause liver damage; only ~30% of patients use Rilutek ***Radicava: 6 month regimen of intravenous treatment
CONFIDENTIAL & PROPRIETARY 19QRL-101
Kv7 is a Clinically Validated Target in ALS
● EFFICACY
● Retigabine trial in 65 patients showed Kv7 opener can lead to clinical benefits
Significant dose dependent effects on biomarkers that predict patient survival
Significant correlation between effect size on excitability biomarker and efficacy biomarker CMAP
ADVERSE EVENT: 97% Participants in the retigabine trial reported at least one adverse event
● Fatigue, dizziness and somnolence were major adverse events
● Retigabine caused blue discoloration of eyes and skin
● Retigabine interacts with the GABAa receptor
● Lack of selectivity for many Kv7 family members
A More Selective Kv7.2/7.3 Opener is Needed to Decrease AE Rates
*Wainger BJ, Macklin EA, Vucic S, et al. Effect of Ezogabine on Cortical and Spinal Motor Neuron Excitability in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Neurol.
2021;78(2):186–196. doi:10.1001/jamaneurol.2020.4300
CONFIDENTIAL & PROPRIETARY 20QRL-101
QRL-101 is More Potent and Selective than Previously Marketed Retigabine
● Retigabine has a problematic adverse event profile in the clinic due to lack of selectivity
● QRL-101 in preclinical studies has demonstrated lack of same liabilities as retigabine
● QRL-101 IND enabling studies ongoing
Side Effects (AE Profile)
Efficacy
Fatigue/ Somnolence Dizziness Urinary Retention Pigmentation
GABAa Compound
REM/
Test Kv7.2/7.3 activity receptor activity/ Rotarod Bladder strip test specific
non-REM sleep
binding photo-reactivity
Liability Liability Liability
Retigabine EC50=1.2uM +++ (10mg/ kg) (10mg/ kg) (1uM)
Liability
QRL-101 EC50=0.06uM -- No Liability No Liability No Liability No Liability
CONFIDENTIAL & PROPRIETARY 21QRL-101
QRL-101: A Potent & Validated Therapeutic in Development for ALS Patients
● A first in class precision therapy to treat hyperexcitability-
induced disease progression
● 50% of ALS Patients provides a large market opportunity
● Kv7.2/7.3 is a clinically validated target
● QRL-101:
▪ Highly potent and selective
▪ Favorable side effect profile
▪ Target engagement and patient selection biomarkers
established
▪ IND-enabling studies ongoing; IND filing mid 2022
CONFIDENTIAL & PROPRIETARY 22QurAlis Growth Strategy Beyond ALS
Combinations
New Indications/Targets
● Next generation ASOs
FlexASO Platform
● Bio-superiors
Additional ● FTD
Indications ● AD
ALS ● Sub-forms of the disease
CONFIDENTIAL & PROPRIETARY 23New insights into human genetics and stem cell
technology provide genetically-validated targets for
ALS and other neurodegenerative diseases
Next-gen, precision medicine approaches using
biomarkers for patient selection, target engagement
and efficacy
First-in-class and Best-in-class programs for ALS and
other neurodegenerative diseases
• 2 programs projected to be in the clinic in 2022
2 Proprietary platforms to enable additional therapies
• Only company with comprehensive TDP-43 platform
• Novel FlexASO platform for splice modulator targets
World-class leadership in place for executionFor more information, contact: Kasper Roet Kasper.Roet@QurAlis.com
You can also read
