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Liminal BioSciences Inc. (NASDAQ: LMNL, TSX:LMNL)
Corporate Presentation – November 2019
© 2019 Liminal BioSciences Inc.
Forward Looking Statement
This presentation contains forward-looking statements about Liminal BioSciences’ objectives, strategies and businesses that involve risks and uncertainties. These statements are “forward-looking” because
they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Forward looking statements are subject to a number of risks, uncertainties and
assumptions. Moreover, Liminal BioSciences operates in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for Liminal BioSciences' management
to predict all risks, nor can Liminal BioSciences assess the impact of all factors on its business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from
those contained in any forward looking statements it may make. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect
our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to statements concerning the outcome or success of Liminal BioSciences'
clinical trials, its ability to successfully gain regulatory approvals and commercialize products, its ability to successfully advance its pipeline of product candidates, the potential benefits of strategic
collaboration agreements and its ability to enter into strategic arrangements or collaborations, the rate and degree of market acceptance of its products, its ability to develop sales and marketing
capabilities, the closing of the share purchase agreement for the divestment of Prometic Bioseparations Ltd., the availability of funds and resources to pursue R&D projects, the ability of Liminal to take
advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of
the risks that could cause actual events or results to materially differ from our current expectations in the Annual Information Form for the year ended December 31, 2018, under the heading “Risk
Factors”. As a result, we cannot guarantee that any forward-looking statement will materialize. Although Liminal BioSciences believes that the expectations reflected in the forward looking statements are
reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward looking statements will be achieved or occur. Moreover, except
as required by law, neither Liminal BioSciences nor any other person assumes responsibility for the accuracy and completeness of the forward looking statements. Forward looking statements in this
presentation represent Liminal BioSciences' views only as of the date of this presentation. We assume no obligation to update or review any forward-looking statement even if new information becomes
available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. All amounts are in Canadian dollars unless indicated otherwise.
Copyright notice
The information contained in this presentation (including names, images, logos and descriptions portraying Liminal BioSciences’ products and/or services) is the property of Liminal BioSciences Inc., of its
divisions and / or of its subsidiaries (“Liminal”) and is protected by copyright, patent and trademark law and / or other intellectual property rights. Neither this presentation nor any part may be
reproduced or transmitted in any form or by any means, electronic or mechanical, including printing and photocopying, or by any information storage or retrieval system without prior permission in writing
from Liminal.
Disclaimer
Liminal reserves the right to make improvements, corrections and/or changes to this presentation at any time.
Safe Harbour
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© 2019 Liminal BioSciences Inc.
• Trading commenced on the Nasdaq Global Market on Nov 18, 2019 (cross-listed on TSX)
• 25 year old biotech undergoing significant strategic transformation to simplify operations, achieve financial stability
and focus R&D on small molecule therapeutics
• Filing of amended BLA expected in 1H-2020 for Ryplazim™ for treatment of congenital plasminogen deficiency
• Current R&D focus on novel targets for treatment of serious fibrosis in respiratory, liver and kidney disease with
expected expansion of R&D portfolio through collaboration, in-licensing and acquisition
• Current financial position : USD$ 85 MM in new equity financing in Q2-2019, pending sale of PBL division to KKR
and expected Ryplazim™ marketing partnership
• Supportive majority stockholder in Thomvest, a private investment affiliate of the Thomson family
• 350 employees located in Canada, USA and UK
Investment Highlights: LMNL
Liminal BioSciences Inc.
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© 2019 Liminal BioSciences Inc.
Priority focus on rare and orphan
diseases
Initiate Phase 2 and 3 clinical
studies for PBI-4050 in 2020
Add to our current talent hubs in
Canada, USA and UK
Drive preclinical and clinical development of
multiple compounds in specific indications of
interest in fibrosis in respiratory, liver and
kidney diseases
Opportunistic partnering and
divestiture for other products and
businesses outside of small
molecule therapeutics
Our Focus
Expand our research engine beyond
FFAR’s through licensing, acquisition
and early-stage research
collaborations
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© 2019 Liminal BioSciences Inc.
2019
New capital structure
and infusion of new
equity capital of USD
85 MM, since April
2019
Recent Achievements
2019 2019 2019
Revitalized leadership
at board and leadership
team with additions
ongoing
Rebranding and name
change to signify new
direction
NASDAQ listingPending sale of
Bioseparations
business to KKR
2019
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© 2019 Liminal BioSciences Inc.
Anticipated Major Milestones
1H-2020
Expected filing of amended BLA
with FDA for Ryplazim™ (priority
review)
2022-2023
Expected completion of registration
studies to support filings for PBI-
4050 for ALMS in in global markets
2019
Expected commercial partnership
for Ryplazim™
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© 2019 Liminal BioSciences Inc.
• Sale of Bioseparations business (PBL) located in Isle-of-Man announced in Nov 2019 with closing expected in Q4-2019
• PBL has a 30 year track record in affinity chromatography contract services to global speciality pharma and biotech companies
• Annual revenue run-rate of approx. GBP16 MM with current breakeven profitability
• Total transaction value of up to GBP 45 MM
• Upfront payment expected on closing of approx. GBP 32 MM
• Remaining contingent payments of GBP 13 MM based on future sales performance of business
• Liminal to continue as a customer of PBL for materials required for Ryplazim™ manufacturing process
Divestiture of Bioseparations business to KKR
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© 2019 Liminal BioSciences Inc.
• Expected filing of amended BLA with FDA, in H1-2020, for approval of Ryplazim™ for congenital plasminogen deficiency
• Filing expected to be under priority review with PDUFA date in 2020
• European filing for Ryplazim™ to be commenced after expected US approval and launch
• Ongoing discussions to establish global commercial partnership for Ryplazim™ for launch in major markets
• Liminal will continue to manufacture Ryplazim™ and supply commercial partner for global sales from internal production facility
and contract manufacturing organizations in North America
Expected Marketing Partnership for Ryplazim™
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© 2019 Liminal BioSciences Inc.
Anti-Fibrotic Small Molecule Therapeutics
PBI-4050 and PBI-4547
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© 2019 Liminal BioSciences Inc.
PBI-4050 Phase 2 in ALMS completed with demonstrated impact on fibrosis in
multiple organ systems.
PBI-4050 Phase 3 expected to begin in 2020 to treat Alström Syndrome
(ALMS)
• Liver
• Renal
• Respiratory Disease
Therapeutic Targets
Building a Portfolio of Novel Antifibrotics
Additional clinical studies for respiratory indications to be commenced in 2020
supported by existing preclinical and clinical data
PBI-4050 Phase 2 Respiratory Indications in 2020
The study has been suspended while the pharmacokinetic (“PK”) data for the
first three cohorts is obtained and reviewed. No safety issues or severe adverse
effects were observed in first three cohorts.
PBI-4547 Phase 1 in healthy volunteers commenced H2-2019
Additional clinical studies to explore potential in anti-fibrotic indications
in kidney disease with a new drug compound to be selected
Additional clinical studies to be underway in 2020 and 2021
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© 2019 Liminal BioSciences Inc.
• Free fatty acids (FFA’s) traditionally viewed as nutrients and metabolic substrates
• Deorphanization of several G protein coupled receptors (GPCR’s) during the 2000’s led to evidence of a role for FFA’s in
important signalling pathways primarily in metabolic disorders
• GPCR’s activated by FFA’s are categorized by ligand profile, long, medium or short-chain fatty acids (LCFA’s, MCFA’s or SCFA’s)
• FFAR1 (or GPR40) and FFAR (or GPR120) are two important targets as receptors for MCFA’s and LCFA’s
• GPR84 is a related receptor for MCFA’s with a role in the regulation of inflammation
• Liminal research has focused on mechanisms involving these three GPCR’s, compounds with multi-targeting effect and roles in
inflammation, metabolic disease and fibrosis
• Discovery engine has generated over 3,000 proprietary compounds with multi-target effect against FFAR’s
• Robust activity in broad panel of in vivo disease models confirmed for over 30 compounds
• Therapeutic areas of focus: system fibrosis conditions, respiratory disease, kidney disease and liver disease
Fatty Acids and Free Fatty Acid Receptor Family
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© 2019 Liminal BioSciences Inc.
Demonstrated across multiple disease models in
preclinical studies:
• Chronic kidney disease (CKD);
• Diabetic kidney disease (DKD);
• Lung fibrosis, liver fibrosis;
• Heart fibrosis, Crohn’s disease, scleroderma and osteoporosis.
Evaluated in over 250 subjects,
dosed up to 1,200 mg daily, in 8
clinical studies
Composition of matter patent
coverage in major markets until at
least 2030
3-pentylbenzeneacetic acid sodium salt with a
molecular weight of 228.3, derived from a
structure-activity study of sodium decanoate, a
salt of the naturally-occurring medium-chain fatty
acid, decanoic acid
Profile well-established in [Phase 1
and 2] clinical studies; most
adverse events reported were mild
and discontinuations from clinical
studies to date have been rare
Designed to reduce fibrosis via
regulation of macrophages,
fibroblasts/myofibroblasts, and epithelial
cells
PBI-4050: An Anti-inflammatory And Anti-Fibrotic Agent
PBI-4050
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© 2019 Liminal BioSciences Inc.
Lead Indication for PBI-4050: Alström Syndrome (ALMS)
Progressive and severe fibrosis
affecting heart, kidney, lungs
and liver
ALMS patient life expectancy
rarely exceeds 50 years of age
Early onset obesity with
severe insulin resistance
Rare autosomal recessive
mutations in ALMS1 gene,
expressed in metabolic tissues
and in ciliated tissues
Fibroblasts with ALMS1
mutations are resistant to
apoptosis and secrete high
levels of extracellular matrix
Childhood onset with visual
dysfunction and hearing loss
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© 2019 Liminal BioSciences Inc.
Transforming ALMS Patient Care
No FDA or EMA approved treatments for ALMS patients
FDA granted both orphan drug designation and rare paediatric disease designation, EMA granted orphan drug status and UK MHRA granted Promising Innovative Medicine (PIM) status for PBI-4050 in ALMS. Further potential to expand
clinical program to other rare diseases similar to ALMS
PBI-4050 is a potential first-in-class therapy to reduce fibrosis in ALMS
patients
ALMS patients showed a dramatic impact on
fibrosis in multiple organ systems in Ph II
study
Phase 3 clinical study expected to begin in
2020
1200Affected individuals
have been identified
worldwide
*Estimates have ranged from 1 in 10,000 to less than 1 in 1,000,000 individuals in the general population
12 2020 1st
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© 2019 Liminal BioSciences Inc.
Study design Key Inclusion Criteria
Single-centre trial evaluating the safety and tolerabilityof multiple oral doses of 800 mg PBI-4050
18 subjects were planned for enrolment (E); 12 subjects enrolled
After 24 weeks, subjects were eligible for a 36/48 week extension period
24 weeks
PBI-4050 (800 mg od)*Screening period
• Documented diagnosis of Alström syndrome, confirmed by genetic testing
• Age ≥ 16 years
• Subjects on diabetes treatment have stable background therapy for at least 1 month
• Metabolic syndromeDiagnosis of ALMS
Key Exclusion Criteria
E
• Uncontrolled hypertension with BP > 170/100 mmHg
• AST/ALT level ≥ 5 × upper limit of normal (ULN)
Completed Phase 2, Open-Label Study In Subjects With Alström Syndrome (University Hospital of Birmingham, UK : National Center of Excellence for ALMS)
Ph II Trial Design Summary
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© 2019 Liminal BioSciences Inc.
Endpoints (cont.)Primary endpoints
• Adipose tissue biopsy (Fat biopsy)
• Liver stiffness(transient elastography, FibroScan)
• Liver MRI to assess liver fibrosis and fat content
• Cardiac MRI to assess cardiac fibrosis
• Hyperinsulinaemic-euglycaemic clamp (endogenous glucose, insulin, lipid dynamics)
• 4-point glucose profile(insulin-dependent subjects)
• Safety and tolerability
• Adverse Events (AEs)
• Clinical laboratory tests
• Vital signs
• Physical exam
• Electrocardiogram
Secondary endpoints
• Diabetic/Metabolic Syndrome parameters
• Inflammatory/obesity markers in blood and urine
• Antidiabetic dosage changes
Exploratory endpoints
Clinical Trial Endpoints
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© 2019 Liminal BioSciences Inc.
Reduction of Liver Stiffness in ALMS SubjectsFibroScan score reduced or stabilized in 10 out of 11 evaluable patients
Fatty Liver
Mild FibrosisF1
Significant Fibrosis
F2
Severe FibrosisF3
CirrhosisF4
FibroscanScore
2.5
7
9.5
12.5
17.1
7.8
5.0
12.4
21.1
9.9
8.1
8.8
Fibroscan Score
Baseline
Last available measurement
13.1
5.1
12.2
10.4
5.55.1
4.6
6.1 6.0
6.6
7.5
8.6
7.67.4
Note: No baseline Fibroscan data available for one patient 17
© 2019 Liminal BioSciences Inc.
Rollover Study Underway
Ongoing:
Open-Label Rollover Study of PBI-4050 in Subjects with Alström Syndrome at the specialist patient
management center in Birmingham (UK)
• Primary objectives: long term safety & tolerability
• Secondary objectives: effect on metabolic syndrome parameters & liver stiffness using FibroScan
• Up to 96 weeks of treatment
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© 2019 Liminal BioSciences Inc.
Changes In Cardiac T1 Observed Before And After Treatment
*Richard Steeds et al manuscript in preparation
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© 2019 Liminal BioSciences Inc.
Several FDA Type C meetings held in
2018 and 2019; final meetings with
FDA and EMA scheduled in Q1-2020
Clinical study protocol to be finalized
after final comments from FDA/EMA,
including primary endpoints as
agreed with FDA/EMA
Investigators selected in North
America and Europe, and patient
identification for study underway
Enrolment goal of approximately 45
ALMS subjects, 30 adults and 15
paediatric, treated with 1200 mg of
PBI-4050 dosed once daily
Working with well-established
international ALMS patient advocacy
organizations to assist in conduct of
study
Principal Investigator: Dr. Clair
Francomano, University of Indiana
Investigator: Dr. Tarekegn Hiwot,
University Hospital Birmingham, UK
Investigator: Dr. Pietro Maffei, Padua
Hospital, Italy
PBI-4050 ALMS Phase 3 Clinical Study Update
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© 2019 Liminal BioSciences Inc.
Phase 1 clinical study of PBI-4547
commenced
Mechanism of action includes
GPR120 agonist in addition to being
GPR84 antagonist and GPR40
agonist
Phase 1 clinical study paused after
third dose cohort to study PK results
Second clinical candidate developed as an
analogue of PBI-4050
GPR120 agonists shown to improve
insulin sensitivity
Pre-clinical studies show that PBI-
4547 could be a potential treatment
for NASH with an effect on both
liver fibrosis and metabolic disease
in patients
PBI-4547: A Differentiated Mechanism for Treating Liver Fibrosis
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© 2019 Liminal BioSciences Inc.
Metabolic Reprogramming MoA: PBI-4547 Designed to Promote -Oxidation and Mitochondrial Uncoupling
Fatty Acid Fatty Acyl-CoA
CPT2
Pyruvate
MPC
Pyruvate
Fatty Acyl-CoA
Fatty Acidβ-Oxidation
Acetyl CoA
TCACycle NADH
FADH2
PDH
GlucoseOxidation
H+
H+
H+
H+
ADP ATP
ATPase II
H+
H+I
III
IV
H+
ACC MCD
Acetyl CoA
Malonyl CoA
UNCHANGED
Fatty Acid
UPREGULATED
CD36
CPT1
HADHA
PDK4
AMPK ACOX
UCP
Fatty acid
-oxidation
Energy
expenditure/ browning
Glucose
oxidation
PBI-4547:• Reduced insulin resistance
in HFD mice• Observed to promote fatty
acid β-oxidation in liver from high-fat diet mice, resulting in reduced steatosis
• Restored WAT homeostasis by reducing inflammation and fibrosis
• Increased Ucp1 expression in WAT and Ucp2/3 in liver, promoting mitochondrial proton leak and increasing overall energy expenditure
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© 2019 Liminal BioSciences Inc.
In relevant animal models, PBI-4547 effects included:
• Metabolic regulation
• Improved lipid and glucose metabolism
• Increased fatty acid oxidation/ mitochondrial effects
• Anti-inflammatory activity
• Reduction of inflammatory cytokines
• Anti-fibrotic activity
• Reduction of stellate cell proliferation and activation
• Reduction of pro-fibrotic cytokines (CTGF, TGFβ, IL-6 and others)
• Reduction of fibrotic markers (collagen, α-SMA and others)
• Promotes matrix re-modelling and tissue regeneration
NASH is a multi-faceted disease including metabolic dysregulation, chronic inflammation and fibrosis;
PBI-4547 displayed activity against each of these aspects in preclinical studies
Overview of PBI-4547 Pre-clinical Evidence: NASH
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© 2019 Liminal BioSciences Inc.
High-fat diet model: PBI-4547
improved glucose metabolism and
insulin resistance, and reduced liver
damage:
• Improved glucose metabolism by reducing insulin resistance and preserving beta-cell function
• Reduced hepatic steatosis and ballooning
• Reduced serum triglycerides and increased adiponectin* levels
• Regulated pro-inflammatory / fibrosis gene expression in liver and adipose tissues
NASH / Metabolic Syndrome
Obese mouse model (ob/ob) : PBI-
4547 reversed diabetes and metabolic
syndrome through regulation of lipid/
glucose metabolism, beta-oxidation
and fibrosis in liver and white adipose
tissue:
• Reduced blood glucose, cholesterol and triglyceride levels
• Reduced pro-inflammatory / pro-fibrotic markers in liver
• Reduced adipocyte size and level of fibrosis in white adipose tissue
• Increased serum adiponectin levels
NASH / Metabolic Syndrome
• CCL4 liver fibrosis mouse model:
PBI-4547 reduced the collagen
content / level of liver fibrosis
• Upper bile duct ligation model: PBI-
4547 reduces the collagen content/
level of liver fibrosis
Liver Fibrosis
Summary of Key Pre-clinical Studies: NASH / Liver Fibrosis
*Adiponectin is produced by adipose cells. It helps to regulate glucose and lipid metabolism, improves insulin sensitivity and it also has anti-inflammatory effects. Levels of adiponectin are inversely correlated with the presence and severity of metabolic diseases / dysfunction
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© 2019 Liminal BioSciences Inc.
Results available to date demonstrate
that GPR84 has a crucial role in the
effect of PBI-4547 on:
• Glucose metabolism and insulin-sensitization
• Lipid metabolism
• Liver cell ballooning
• However, the effect of PBI-4547 on adiponectin levels is independent of GPR84
Knockout mouse studies with PBI-4547 are underway to elucidate the relative roles of GPR40, GPR84 & GPR120
GPR40 knockout studies are still
underway
GPR120 knockout mice showed
significantly increased TGF-β mRNA and
collagen type1α mRNA in the liver
compared to wild-type mice (i.e. had
more severe liver fibrosis)
Evidence for GPR84 / GPR40 Receptor Engagement
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© 2019 Liminal BioSciences Inc.
2020 to 2022
Dr. Stephen Harrison advising on
future clinical studies planned for
PBI-4547
Phase 2b in NASH and/or an
additional liver fibrosis indication
Multiple ascending doses in healthy
volunteers and patients with NAFLD
or NASH
Phase 2a in NASH and an additional
liver fibrosis indication
Anticipated Future Clinical Studies with PBI-4547
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© 2019 Liminal BioSciences Inc.
• Novel biological target with differentiated mechanism of action versus other current drugs under development
• Substantial preclinical data potentially supports the treatment of patients with conditions relating to metabolism disorders,
inflammation and liver fibrosis
• Presentations given at AASLD in November of preclinical data for PBI-4547
• Broad mechanism of action against multiple targets may be well-suited for NASH patients
• Combination studies with newly approved agents possible in future
• Other patient populations with liver fibrosis beyond NASH under consideration for future clinical study
• PBI-4547 selected specifically for development in liver disease due to presumed mechanism of action
• Strong IP protection on PBI-4547 and other back-up compounds
Summary of PBI-4547 in NASH and Liver Fibrosis
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© 2019 Liminal BioSciences Inc.
• Expansion to study current novel pathway in FFAR’s and compounds in serious fibrosis in kidney disease (PBI-4610 and other
potential drug candidates)
• Novel targets and novel pathways beyond FFAR biology
• Novel technologies to expand current drug discovery engine
• Potential cquisition of clinical-stage compounds in current therapeutic areas of focus
Anticipated Expansion of R&D Portfolio
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© 2019 Liminal BioSciences Inc.
Potential for first-in-class therapy for
PBI-4050 in ALMS and multiple
opportunities for expansion and
growth in respiratory disease and
systemic fibrosis
Late-stage pipeline with potential best-in-class drugs for fibrosis in treatment of liver, renal and respiratory diseases
Exceptional leadership team and
board, with support from existing
institutional investors
Clinical development plans ready to
execute, with milestones expected
over next 12-36 months
Ryplazim™ partnerships and strategic
divestiture of PBL expected to
strengthen balance sheet in 2019 and
2020
Investment Summary
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© 2019 Liminal BioSciences Inc.
What we do today, will change lives tomorrow.
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