Corporate Presentation August 2020
Transcript of Corporate Presentation August 2020
© 2020 Liminal BioSciences Inc.
This presentation contains forward-looking statements about Liminal BioSciences’ objectives, strategies and businesses that involve risks and uncertainties.
Forward‐looking information includes statements concerning, among other things, statements with respect to the timing of any planned Biologics License Application
resubmission for Ryplazim® plasminogen (human) or Ryplazim®, the development of R&D programs, the timing of initiation of clinical trials, the exploration of potential
alternatives for the future commercialization of Ryplazim®, if approved, including through a third-party marketing collaboration, and the potential commercial launch of
Ryplazim®, if approved, and the impact of COVID-19 on our business.
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.
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, Liminal BioSciences’ ability to develop, manufacture, and
successfully commercialize value-added pharmaceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of
clinical studies, the ability of Liminal BioSciences’ 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 these risks, uncertainties and other risks that could cause actual events or results to materially differ from our current
expectations in the Company’s U.S. Securities and Exchange Commission and Canadian Securities Commission filings and reports, including in the Annual Report on Form
20-F for the year ended December 31, 2019, the 6-K containing our results for the quarter ended March 31 and June 30, 2020 and future filings and reports by the
Company, from time to time. As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update 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.
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 BioSciences’ reserves the right to make improvements, corrections and/or changes to this presentation at any time
Safe Harbour
© 2020 Liminal BioSciences Inc.
• Management team and key advisors with a track record of successful development and business strategies assumed control in 2019 after a shareholder re-organization
• Following an extensive review and investment cycle, clinical candidates are ready to move forward
• Committed shareholder backing from Thomvest and Consonance Capital
New management and scientific teams
set the stage for long term value creation
• Deep domain expertise in small molecule drug development, biology of fibrosis and GPCRs
• Lead small molecule candidate, fezagepras, with an intriguing pre-clinical activity and tolerability profile
• Broadening pre-clinical R&D pipeline focused on novel biologic pathways
• Filing of BLA anticipated in Q3-2020 with US commercial launch to follow if approved by FDA
• Foreign market access strategy under development
• Initial patient population addressable with a targeted commercial infrastructure and potential for broadening commercial opportunity with new indications
• BLA approval to potentially trigger a priority review voucher (PRV)
Liminal BioSciences at a Glance
3
Development pipeline led by
fezagepras
BLA-ready plasminogen deficiency
therapy, Ryplazim®
© 2020 Liminal BioSciences Inc.
Product Pipeline
4
Selective OXER1 Antagonist
Selective GPR84 Antagonist
Fezagepras (PBI-4050)
Plasma Segment:
Therapeutic Indication Preclinical Phase I Phase II Phase IIIProgram Status
BLA resubmission Q3-2020Expected PDUFA in Q1-2021
In H2-2020 higher dose in healthy volunteers followed by high triglyceride patients
Phase 2 clinical trials for fezagepras in selected fibrosis indications expected to be initiated after multiple ascending dose study (MAD) study
NDA/BLA
Congenital Deficiency
Additional MAD
Liver:
NASH
Lung:
IPF
Kidney:
Alström Syndrome
Respiratory / GI
Fibrosis Lead candidate nomination H2-2020
Expected nomination of preclinical product candidate for OXER 1 antagonist program in H2-2021
Ryplazim®
Small Molecule Segment:
CKD
© 2020 Liminal BioSciences Inc.
Most fibrotic diseases are progressive and fatal with few treatment options available
Pulmonary fibrosis, renal fibrosis and NASH are well known examples of fibrotic diseases
Fibrosis can occur in many organs as a result of formation of excess fibrous connective tissue due to chronic disease
Our novel biology focused on targeting PPARs, FFARs and related GPCRs to halt the progression of, or reverse, fibrosis
Fibrosis: Significant Unmet Needs in Multiple Therapeutic Areas
Fibrosis
5
*Fezagepras, previously referred to as PBI-4050
Fibrosis is an aberrant response of the body
to tissue injury, but its causes aren’t fully
understood
Fibrotic disease is driven by both metabolic and inflammatory processes and is very complex. We believe this complexity will likely lead to the need for multi-targeted therapy
© 2020 Liminal BioSciences Inc.
Pre-clinical and preliminary, open-
label human data suggestive of
anti-fibrotic activity in multiple
organs provides future development
rationale
Dosed daily for up to 12 weeks up to
1,200mg
Orphan drug designation for two
indications (IPF and Alström
Syndrome)
Evaluated in over 250 individuals
(166 patients) in 8 clinical studies
Fezagepras
Anti-inflammatory and
anti-fibrotic small
molecule
Reduces fibrosis via regulation of
macrophages, fibroblasts/
myofibroblasts and epithelial cells
Fezagepras Profile: A Well-Tolerated, Novel, Oral Anti-Fibrotic Agent
7
© 2020 Liminal BioSciences Inc.
Both play a role in
the pathogenesis of
NAFLD and NASH
PPARa appears to
modulate lipids;
FFAR1 appears to
modulate glucose
To date, empirical
evidence consistent
with presumed
mechanism
Both have a well
understood impact on
metabolic control, but
act through distinct
pathways
Presumed Mechanism of Action for Fezagepras
Activates both PPARa
and FFAR1 (GPR40)
8
© 2020 Liminal BioSciences Inc.
FFAR1 (GPR40) Agonists: An Emerging Class for T2DM
9
• FFAR1 (GPR40) is a well-validated target for the treatment of Type 2 Diabetes
• Strong clinical evidence that GPR40 agonists can improve glucose control, without the risk of hypoglycemia
• Liver toxicity led to the discontinuation the most advanced clinical-stage product (TAK-875)
• Recent studies confirmed toxicity related to unique structure of TAK-875 not GPR40 MOA
• Numerous programs are underway to optimize drug design and reduce the risk of toxicity
• Eli Lilly, BMS, Amgen, J&J and Merck are among the companies working on next-generation GPR40 agonists
• At least 10 programs are in the pre-clinical phase or Phase 1 safety studies
• Below are two GPR40 agonists as disclosed currently in clinical development:
Stage of Development
Company Drug Indication Target
Phase 1 Hyundai Pharma HOB-047 T2D Dual GPR40 & GPR119 agonist
Phase 1Scohia Pharma
(Takeda)SCO-267 T2D / Obesity GPR40 full agonist
© 2020 Liminal BioSciences Inc.10
PPAR Alpha as an Anti-fibrosis Target
• PPARa is a ligand-activated nuclear receptor
• Enriched in tissues with high fatty acid oxidation (FAO) rates such as liver, heart, skeletal muscle and brown adipose tissue
• Expressed in intestine, vascular endothelium, smooth muscle and immune cells such as monocytes, macrophages and lymphocytes
• Transcriptional regulator of genes involved in peroxisomal and mitochondrial B-oxidation and FA transport
• Negatively regulates pro-inflammatory and acute phase response signalling pathways
© 2020 Liminal BioSciences Inc.11
PPAR Agonists and Fibrosis: An Evolving Landscape
PPAR agonism has long been a well-validated target for the treatment of metabolic disease with a strong rationale in fibrotic disease, however, clinical success has proven elusive
• Traditional PPARa agonists do not appear to create a therapeutic effect on fibrosis
• Traditional PPARg agonists have shown some efficacy, but with a troublesome toxicity profile
• Finding the correct dose is paramount to drug activity
Updated research has improved the understanding of the class and newer modalities of PPAR activation which appear to have a differentiated impact on the target and have shown more promise in early stage development for fibrotic disease
PPARa PPARd PPARg
Pemafibrate (Kowa Pharma) x
Lanifibranor (Inventiva Pharma) x x x
Elafibranor (Genfit) x x
Seladelpar (CymaBay) x
Bezafibrate (Intercept) x
© 2020 Liminal BioSciences Inc.
• Bleomycin-induced lung fibrosis (Liminal)
• Comparison with pirfenidone
• Comparison with nintedanib
• TGFβ-induced lung fibrosis (Kolb / McMaster U.)
• Acute Lung Injury post pancreatitis (Liminal)
• IPF patients fibroblasts (McMaster – Liminal)
Lung models
• CCL4 induced liver fibrosis (Liminal)
• CCL4 induced hepatocarcinoma (Liminal)
• High-fat diet mice (Liminal)
• Liver steatosis in db/db eNOS-/- mice
(Vanderbilt)
• Upper Bile duct ligation Rat (Liminal)
Liver models
• 5/6 nephrectomised rats – CKD ESRD (Liminal)
• db/db uninephrectomized mice (Liminal)
• db/db eNOS-/- mice (Vanderbilt)
• Doxorubicin-induced nephrotoxicity mice (Liminal)
• Adenine model in -/- animals (U of Ottawa)
• UUO – ischemia models (Liminal)
Kidney models
• FBN-1 mice scleroderma model (Vanderbilt)
Skin models
• Suprarenal banding of aorta (MHI)
• Myocardial infarction rat model (MHI)
Heart models
• Type-1 Non-Obese diabetic mice (NOD)
(Liminal)
• db/db eNOS-/- mice (Vanderbilt)
Pancreas models:
Fezagepras: Anti-fibrotic Activity in Six Different Organ Systems
12
PBI-4050 has been tested in >30 animal models and in vitro experiments on human / patient cells; it has shown pre-clinical activity in all of the key models listed below:
*MHI = Montreal Heart Institute
© 2020 Liminal BioSciences Inc.
Effect on Liver Stiffness in Patients with Alström Syndrome
13
Results shown are from an open-label, single-centre study; FibroScan® is a measure of liver stiffness, a surrogate for liver fibrosis
© 2020 Liminal BioSciences Inc.14
Effect on IPF from Open-label Study
Pulmonary
Function Test
FEZAGEPRAS(N = 9)
FEZAGEPRAS +NINTEDANIB
(N = 16)
FEZAGEPRAS +PIRFENIDONE
(N = 15)
TOTAL(N = 40)
FVC (mL)
Mean change (±
SD) at Week 12
-12.2
(137.09)
1.875
(127.6)
-102
(137.80)
-40.3
(138.96)
95% confidence
interval
-117.60,
93.157
-66.121,
69.871
-178.31,
-25.69
-84.692,
4.192
• Though a small sample size (N=9) Fezagepras monotherapy showed an effect at 12 weeks.
• Combination results were mixed, but Fezagepras + Nintedanib did show improved lung function over baseline at 12 weeks.
• Tolerability acceptable.
© 2020 Liminal BioSciences Inc.
We plan to initiate a Phase 1 clinical trial
in 2H 2020 to evaluate multiple ascending
doses of fezagepras in normal healthy
volunteers and in Q1 2021 in patients (T2DM
with high TG's)
Long-term repeat dose toxicity animal studies of
fezagepras suggests maximum daily dosing of 2,400
mg in humans; BID dosing also to be studied
Dose dependent responses in our preclinical studies
suggest higher doses than previously studied to date
could lead to increased efficacy in human trials
The optimal dose and dosing regimen of fezagepras
is expected to be further evaluated in Phase 2
clinical trials in selected fibrosis indications to be
initiated in 2021
Finding the optimal dose of fezagepras will be a
large factor in clinical success due to the
complexity of fibrosis. Recent clinical experience of
competing compounds has reinforced this point.
Data and biomarkers (TG's, fgf21, HbA1c, etc.)
will help define dose levels and regimen for any
future clinical trials evaluating fezagepras
Determining the Optimal Dose for Fezagepras
15
© 2020 Liminal BioSciences Inc.
• Reduced steatosis, ballooning and
total NAFLD score in High Fat Diet
models of metabolic syndrome
• Reduced liver stiffness scores in 10
out of 11 human subjects, as
measured by FibroScan® in an
open label Phase 2 study in Alström
Syndrome
Liver Fibrosis
• Improved Lung Function in
Bleomycin and TGF-b induced
models of Pulmonary Fibrosis
• Held lung function as measured by
FVC to a small decline at 12 weeks
(=12.2 ml) in 9 patients
monotherapy arm of Phase 2 open
label study in IPF
Respiratory Fibrosis
• Reduced tubulointerstitial fibrosis
levels and Increased renal function
and reduced anemia in adenine
induced model of kidney fibrosis
• Drug concentration levels quickly
returned to normal in both single
and multiple dose administrations
in patients with stable renal
impairment
Renal Fibrosis
Fezagepras: One Candidate, Many Possibilities
16
Phase 1 multiple ascending dose ranging study to determine next steps in 3 key areas with phase 2 well-controlled, randomized clinical studies in selected fibrosis indications expected in 2021. Existing pre-clinical and/or clinical data have shown:
© 2020 Liminal BioSciences Inc.
Plasminogen Overview
18
A naturally occurring enzyme, plasminogen plays a role in many complex biological processes regarding the regulation of plasma proteins
Amongst the areas where plasminogen plays a role are the lysis of blood clots and the wound healing process (fibrinolysis)
Our primary focus has been on Type 1 congenital plasminogen deficiency (C-PLGD) with the development of Ryplazim®, however, we believe plasminogen’s broad role could create additional therapeutic opportunities in the future
Other potential therapeutic applications based on both fundamental biology and our pre-clinical findings are:
• Hereditary angioedema with a plasminogen gene mutation• Complex wound healing, including in a post-radiation therapy setting• Idiopathic pulmonary fibrosis, including acute exacerbations
© 2020 Liminal BioSciences Inc.
Potentially eligible for Priority Review
Voucher (PRV) if approved
Attractive initial launch
opportunity either for Liminal
or a collaboration partner
Potential for growth through
additional clinical indications and
foreign markets
Potentially first FDA-approved
treatment for plasminogen deficiency, a
rare congenital disorder
BLA to be re-submitted in Q3-2020
following efforts to address CMC
issues raised in initial CRL in 2018
Achieved both co-primary
endpoints in pivotal Phase
2/3 trial
Ryplazim® Plasminogen Replacement Therapy
19
© 2020 Liminal BioSciences Inc.
Type 1 Congenital Plasminogen Deficiency (C-PLGD): A Rare Genetic Disease with Potentially Devastating Effects
Inadequate plasminogen activity levels result in fibrinous lesions on mucous membranes.
• These lesions vary from patient to patient in terms of size, location, and clinical consequences.
• They may initially develop and/or recur at any age.
Potential life-altering consequences of C-PLGD include
• Vision loss
• Airway obstruction
• Hydrocephalus
• Infertility
• Impaired postsurgical wound healing
20
© 2020 Liminal BioSciences Inc.
Current Treatment Options are not FDA Approved
21
• No FDA-approved treatments or standardized treatment guidelines
• No current options treat the underlying systemic plasminogen deficiency
• Fresh frozen plasma may be used, but durability of relief is uncertain
• Surgical removal of growths is also an option but comes with associated risks
and offers only temporary relief
• Topical eyedrops for ligneous conjunctivitis have no confirmed efficacy
• Teams of specialists (paediatricians, ophthalmologists, hematologists, dental
specialists, pulmonologists) may be necessary to manage C-PLGD
© 2020 Liminal BioSciences Inc.
Patients in the US remained on
treatment beyond 48 weeks and were
moved to a compassionate access
program
Dosing of 6.6 mg/kg via IV infusion for
10 to 30 minutes every 2 to 4 days for
48 weeks of treatment
Primary endpoints:
(1) increase of individual trough
plasminogen activity by at least
an absolute 10% from baseline
through 12 weeks of therapy; and
(2) 50% resolution of lesions in 50%
of patients after 48 weeks of
therapy
Two clinical sites: Indiana Hemophilia
and Thrombosis Center and Oslo
University Hospital
Evaluate PK, efficacy and safety of
Ryplazim® in 15 pediatric and adult
subjects with hypoplasminogenemia
Ryplazim® Pivotal Phase 2/3 Study Design
22
Safety
• Most AE’s were characterized as mild
• Most frequent AE’s were nasopharyngitis, headache and GI related
• No deaths or SAE’s
• No drug-related AE’s that caused study discontinuation
Ryplazim® Pivotal Phase 2/3 Study Summary Results
Efficacy
• Achieved primary endpoint to improve trough plasminogen by greater than 10%
• All patients achieved this level of trough plasminogen improvement
• Ryplazim® treatment resolved all lesions in all 15 patients treated for 48 weeks.
• 73% of patients had a significant resolution of lesions after 12 weeks of treatment
• US patients have remained on Ryplazim® compassionate use study since 2018
23
© 2020 Liminal BioSciences Inc.
U.S. launch initially where
literature suggests
prevalence of between 500-
1000 patients1
Traditional orphan indication sized
salesforce to target universe of
treating haematologists and
ophthalmologists
Work with payors to secure
reimbursement consistent with
patient benefit as an orphan
disease
Initial group of patients well
identified via clinical trial and
compassionate use conversion
along with IMS code
Efforts to support patient
registry and patient advocacy
groups ongoing
Potential for future growth from
additional indications (HAE, IPF and
wound care) and ex-U.S. launches (10
to 15X > US market)
Ryplazim®(plasminogen) Commercial Plans
24
1Literature indicates 1.6 birth/million incidence rate or 500 in the US. Proprietary internal Liminal estimates suggest 1000 patients
© 2020 Liminal BioSciences Inc.
GPR84 is a pro-inflammatory target primarily expressed on cells associated with the immune system and its expression levels increase significantly during periods of inflammatory stress
Developing a selective GPR84 antagonist would build on Liminal’s in-house expertise in novel biology targets
GPR84 antagonist could be used in combination therapy with either internal or external agents
GPR84 Antagonist Discovery Program
GLPG1205, currently in Phase 2 for IPF, is the only other GPR84 antagonist in development to our knowledge
26
© 2020 Liminal BioSciences Inc.27
GPR84: Role in Fibrosis and Metabolic Diseases
• GPR84 expression is not restricted to cells in the immune system
• Also expressed in brain, heart, muscle, colon, thymus, spleen, kidney, liver,
intestine, placenta and lung
• Liminal has shown that GPR84-deficient mice develop reduced fibrosis in a model of
kidney fibrosis (adenine-induced chronic kidney disease)
• GPR84 may also be a mediator of the relationship between inflammation, obesity
and diabetes
• Rodent models have shown that GPR84 expression is up-regulated in adipocytes in
response to TNF-α released from infiltrating macrophages
• In the presence of TNF-α, medium chain fatty acids down-regulate adiponectin
mRNA expression in 3T3-L1 adipocytes
• Adiponectin is a key adipokine that has insulin sensitizing effects and directly
enhances fatty acid oxidation
© 2020 Liminal BioSciences Inc.28
Liminal: Key GPR84 Preclinical Studies
Liminal’s research has shown that:
• GPR84-deficient mice develop reduced fibrosis in a model of kidney fibrosis
(adenine-induced chronic kidney disease)
• GPR84 mRNA is overexpressed in various acute and chronic kidney models such as:
• 5/6-nephrectomy (Nx)-induced chronic kidney disease
• Doxorubicin (DOX)-induced nephropathy
• Adenine-induced tubulointerstitial injury
• GPR84 expression is increased in murine macrophages following inflammatory
stimuli
Eosinophils are major effector cells in the immune system
• Part of the innate immune system
• When activated, they release a cocktail of cytotoxic proteins and cytokines from the eosinophilic granules
Eosinophils have a key role in Type 2 inflammation-driven diseases
• May help to regulate the type of immune response generated
• Cytokines such as IL-4, IL-13 and IL-25 are found within eosinophilic granules
• Direct the response to be Th2–polarised
• Th2-polarised responses are linked with asthma and other allergic and inflammatory diseases
• Activated eosinophils also release lipid mediators that can cause airway smooth muscle contraction and contribute to airway hyper-responsiveness
• Aberrantly-activated eosinophils are known to be present in patients with severe asthma and other eosinophil-related diseases
Summary of Opportunity in Eosinophilic-Driven Diseases
29
Potential Indications in Eosinophilic-Driven Diseases:
Respiratory and Inflammatory Disease:
• Severe eosinophilic asthma
• COPD
• Hypereosinophilic syndrome (HES)
• Nasal polyposis
• Atopic dermatitis
• Chronic spontaneous urticaria
Gastrointestinal Disease:
• Eosinophilic gastritis
• Eosinophilic esophagitis (EoE)
• Eosinophilic gastroenteritis
© 2020 Liminal BioSciences Inc.30
Novel Pathway: OXER1 for 5-oxo-ETE
• 5-oxo-ETE is one of the metabolites generated via 5-LO metabolism of AA
• 5-oxo-ETE is a potent pro-inflammatory mediator; a powerful eosinophil chemoattractant
• Also aids eosinophil migration out of blood vessels and into the surrounding tissues
• Produced by several activated immune cell types and by damaged structural cells
• Also produced by activated eosinophils; acts in an autocrine fashion to sustain their own activation
• Its receptor is known as the OXE receptor (OXER1)
• OXER1 is also expressed on neutrophils, macrophages & basophils, but to a lesser extent
• Series of highly potent synthetic antagonists for the OXER1 with activity in non-human primates
• Multiple potential clinical indications to explore, including orphan diseases
*Blattermann et al
© 2020 Liminal BioSciences Inc.
Kenneth Galbraith, Chief Executive Officer
Murielle Lortie, Chief Financial Officer
Moira Daniels, Head of Regulatory Affairs and Quality Assurance
Management Team and Key Advisors
32
Dr. Gary Bridger, Board Member and Strategic Scientific Adviser
Dr. Jeffrey Smith, Strategic Medical Adviser
Mr. Galbraith well-known member of the life sciences community with over 30 years of experience acting as an executive, director, investor and advisor to companies in the biotechnology, medical device, pharmaceutical and healthcare sectors. Mr. Galbraith has served at the leadership and board level for many organisations within the healthcare industry including Macrogenics (MGNX), Profound (PROF), AnorMED, QLT Inc., Zymeworks, Angiotech Pharmaceuticals (ANPI), Aquinox (AQXP), Alder Pharmaceuticals (ALDR), Tekmira (TKMR) and Celator Pharma (CPXX).
Dr. Bridger has extensive experience in leading research and development through to commercialisation. Dr. Bridger previously served as Executive Vice President of Research and Development at Xenon Pharmaceuticals Inc., Senior Vice President of Research and Development of Genzyme Corporation and co-founded AnorMED Inc., eventually acquired by Genzyme.
Moira brings significant experience in product development and regulatory affairs as well as change management within the industry. Prior to joining Liminal, Moira was VP at UCB Pharma, PAREXEL and AstraZeneca holding senior positions in Regulatory Affairs and leading trade association teams on key policy topics at an international level. Moira has worked successfully in different therapeutic areas securing regulatory approvals globally.
Dr. Smith has held many senior positions within the pharmaceutical industry, most recently, Managing Director of Alder Biopharmaceuticals Inc. Dublin, Ireland and before that Senior Vice President, Translational Medicine at Alder Biopharmaceuticals Inc, Seattle. Dr. Smith was responsible for the clinical development (phase I - III) of eptinezumab (anti-CGRP antibody for migraine) and clazakizumab (anti -IL-6 antibody for rheumatoid arthritis and cancer cachexia). Dr. Smith was also a founder of Alder Biopharmaceutcials Inc.
Murielle brings a vast amount of experience in finance and corporate strategy. Prior to joining Liminal Murielle was employedas Vice President & Chief Financial Officer at Pharmascience Inc. Previous to this, Murielle has held senior positions in finance at Bristol Myers Squibb including Vice-President of Finance and Global Director of Finance.
© 2020 Liminal BioSciences Inc.
As of June 30th, 2020 (in Canadian $):
• Cash balances of $26.0M
• $10M in debt (due 2024) and unutilized $29M line of credit with Thomvest
• Potential proceeds from sale of Priority Review Voucher (PRV) if Ryplazim® is
approved and PRV is granted
• Potential collaborations being explored for both Ryplazim®, if approved, and
fezagepras
• Common shares of 23.4M with additional 2.4M options and warrants outstanding
• Thomvest currently owns 72% (65.5% fully-diluted) of common shares
Financial Position
33
© 2020 Liminal BioSciences Inc.
• Joined with other leading plasma companies to form the CoVIg-19 Plasma Alliance
• Utilizing our plasma collection network to collect plasma from convalescent donors who have
recovered from COVID-19 for use in clinical studies by third parties
• Evaluating internal and external research regarding the use of plasminogen replacement therapy to
treat serious COVID-19 infected patients
• Evaluating other products, assets and infrastructure that may be useful in fight against COVID-19
• Protective measures in place for our employees, patients, donors and our communities
Liminal Response to COVID-19 Pandemic
34
© 2020 Liminal BioSciences Inc.
Anticipated Key Milestones
• Expected resubmission of BLA for Ryplazim® in Q3-2020
• Anticipated initiation of Phase 1 multiple ascending dose study (MAD) for fezagepras in H2-2020
• Expected nomination of preclinical product candidate for GPR84 antagonist program in H2-2020
• Pending FDA approval, expected PDUFA date for Ryplazim® in Q1-2021
• Potential monetization of PRV, if granted by FDA on successful Ryplazim® BLA approval, in 2021
• Phase 2 clinical trials for fezagepras in selected fibrosis indications expected to be initiated after MAD study
• US launch of Ryplazim®, if approved, in 2021
• Expected nomination of preclinical product candidate for OXER1 antagonist program in H2-2021
• Anticipated initiation of additional clinical studies for Ryplazim® in H2-2021
• Potential marketing collaborations and patient access for Ryplazim® in selected ex-US markets in 2021 and 2022 pending FDA approval
35
© 2020 Liminal BioSciences Inc.
Liminal BioSciences Summary
• Corporate re-organization and investment cycle has set the stage for maximizing the value of the
clinical portfolio
• Novel, oral small-molecule, fezagepras has pre-clinical and early open-label clinical data
potentially indicative of anti-fibrotic activity in multiple organ systems
• Fezagepras tolerability profile allowing for the exploration of increased dosage levels and
alternate dosing regimens in dose ranging study planned
• Broadening R&D portfolio focused on novel biologic pathways
• BLA filing expected in Q3-2020 for plasma-based therapeutic, Ryplazim® for treatment of
congenital plasminogen deficiency; a rare genetic disorder
• Potential collaborations being explored for both Ryplazim® and fezagepras
36
© 2020 Liminal BioSciences Inc.
Effect on Bleomycin Mouse Models of Lung Fibrosis
• Fezagepras reduced histological lesions of lung fibrosis in a dose-dependent manner
• Fezagepras (200 mg/kg) significantlydecreased (p ≤ 0.05) the mRNA expression of CTGF, collagen 1 and IL-23p19
38
© 2020 Liminal BioSciences Inc.
Effect on High Fat Diet Models of MetabolicDisease
Liver Histology
40
© 2020 Liminal BioSciences Inc.
Effect on Adenine-fed Models of Kidney Disease
Ad
en
ine +
Veh
icle
Ad
en
ine +
PB
I
0
2
4
6
8
T u b u lo in te rs titia l fib ro s is %
Fib
ro
tic
are
a
(%)
<0.0001
41
© 2020 Liminal BioSciences Inc.
Clinical Data: Effect on Cardiac Fibrosis in Patients with Alström Syndrome
43
Measured by cardiac MRI T1-Mapping
Intervention group results are from an open-label, single-centre study, ‘control’ group is an untreated cohort of patients followed over time, not a placebo-treated group
© 2020 Liminal BioSciences Inc.44
Treatment with PBI-4050 led to a reduction in the level of 5 different biomarkers, all related to kidney injury
Kidney Injury Biomarkers% Change
Week 24 / Baseline
P value
N=12
KIM-1 ↓ 33% 0.02
Clusterin ↓ 34% 0.03
Cystatin C ↓ 25% 0.01
MCP-1 ↓ 15% 0.03
Osteopontin ↓ 18% 0.03
Biomarkers tested in urine samples
Alström Syndrome: Reduction in Biomarkers of Kidney Injury
© 2020 Liminal BioSciences Inc.46
Ryplazim® Pivotal Phase 2/3 Efficacy Results
Subject
Population
Overall Clinical Success a
(%) Based on All Lesions
(Number of Subjects)
Overall Clinical Successa (%)
Based on Visible Lesions
(Number of Subjects)
Overall Clinical Success a (%)
Based on Measurable Lesions
(Number of Subjects)
Pediatric b 100% (3/3) 100% (2/2) 100% (2/2)
Adult 100% (8/8) 86% (6/7) 100% (4/4)
Combined 100% (11/11) 89% (8/9) 100% (6/6)
aOverall clinical success is defined as 50% of subjects with visible or other measurable lesions achieving at least 50% improvement in lesion number/size orfunctionality impact from baseline.bPediatric is defined as subjects < 18 years of age at baseline.
Subject
Population
Time to Lesion Resolution
Based on All Lesions
Resolved
Time to Lesion Resolution
Based on Visible Lesions
Resolved
Time to Lesion Resolution
Based on Measurable Lesions
Resolved
Pediatric a 12 weeks 8 weeks 8 weeks
Adult 8 weeks 6 weeks 6 weeks
Combined 8 weeks 8 weeks 8 weeks
a Pediatric is defined as subjects < 18 years of age at baseline.
Overall Clinical Success at Week 48
© 2020 Liminal BioSciences Inc.
Ryplazim® Impact on Plasminogen Trough Activity Levels and Safety Profile
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Safety
• Plasminogen (Human) Intravenous at a dose of 6.6 mg/kg administered E2D to E5D for 48 weeks and E1D to E7D for up to 124 weeks was well tolerated in pediatric and adult subjects with congenital plasminogen deficiency.
• Most AE’s were characterized as mild
• Most frequent AE’s were nasopharyngitis, headache and GI related
• No Deaths or SAE’s
• No drug related AE’s that caused study discontinuation
• No Immunogenicity