liminal biosciences inc. corporate presentation november …...the information contained in this...

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.

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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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• 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.

3


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

4


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

5


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™

6


• 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

7


• 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™

8


Anti-Fibrotic Small Molecule Therapeutics

PBI-4050 and PBI-4547

9


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

10


• 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

11


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

12


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

13


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

14


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

15


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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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


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

18


Changes In Cardiac T1 Observed Before And After Treatment

*Richard Steeds et al manuscript in preparation

19


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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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

21


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

22


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

23


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

24


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

25


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

26


• 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

27


• 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

28


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

29


What we do today, will change lives tomorrow.

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