R&D Day

Unlocking the Value of Voclosporin

October 20, 2017
 Forward Looking Statements
Certain of the statements made in this presentation may constitute forward-looking information within the meaning of applicable Canadian securities law
and forward-looking statements within the meaning of applicable U.S. securities law. These forward-looking statements or information include, but are
not limited to statements or information with respect to the projected worth of the lupus nephritis (LN) market, that voclosporin is potentially a best-in-
class calcineurin-inhibitor (CNI) with robust intellectual property exclusivity and the likelihood of data exclusivity in major markets, the expectation that
voclosporin will be the only CNI with a label for LN, the expected progress of the AURORA study; the anticipated commercial potential of voclosporin for
the treatment of LN, Nephrotic Syndrome, FSGS, Dry Eye and other Autoimmune diseases; and anticipated interactions with the US Food and Drug
Administration, including potential dates for submission and approval of marketing applications, and product label . When used in these marketing
materials, the words anticipate, will, believe, estimate, expect, intend, target, plan, goals, objectives, may and other similar words
and expressions, identify forward-looking statements or information.
We have made numerous assumptions about the forward-looking statements and information contained herein, including among other things,
assumptions about: the market value for the LN program; that another company will not create a substantial competitive product for Aurinias LN
business without violating Aurinias intellectual property rights; and the size of the LN market. Even though the management of Aurinia believes that the
assumptions made and the expectations represented by such statements or information are reasonable, there can be no assurance that the forward-
looking information will prove to be accurate.
Forward-looking information by their nature are based on assumptions and involve known and unknown risks, uncertainties and other factors which may
cause the actual results, performance or achievements of Aurinia to be materially different from any future results, performance or achievements
expressed or implied by such forward-looking information. Should one or more of these risks and uncertainties materialize, or should underlying
assumptions prove incorrect, actual results may vary materially from those described in forward-looking statements or information. Such risks,
uncertainties and other factors include, among others, the following: the market for the LN business may not be as estimated; and competitors may arise
with similar products.
Although we have attempted to identify factors that would cause actual actions, events or results to differ materially from those described in forward-
looking statements and information, there may be other factors that cause actual results, performances, achievements or events to not be as anticipated,
estimated or intended. Also many of the factors are beyond our control. There can be no assurance that forward-looking statements or information will
prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. Accordingly you should not
place undue reliance on forward-looking statements or information.
Except as required by law, Aurinia will not update forward-looking information. All forward-looking information contained in this presentation is qualified
by this cautionary statement. Additional information related to Aurinia, including a detailed list of the risks and uncertainties affecting Aurinia and its
business can be found in Aurinias most recent Annual Information Form available by accessing the Canadian Securities Administrators System for
Electronic Document Analysis and Retrieval (SEDAR) website at www.sedar.com or the U.S. Securities and Exchange Commissions Electronic Document
Gathering and Retrieval System (EDGAR) website at www.sec.gov/edgar.

2
 Building the Franchise
Richard M. Glickman
Chief Executive Officer & Chairman of the Board

www.auriniapharma.com
Agenda
Topic Speaker
1 Welcome Celia Economides, VP, Corporate & Public Affairs

2 Corporate Strategy & Vision Richard Glickman, Chief Executive Officer

3 Lupus Nephritis (LN) Program Update Neil Solomons, MD, Chief Medical Officer

LN: Commercial Opportunity & Brad Dickerson, Global Commercial Lead

4 Intellectual Property Michael Martin, Chief Operating Officer

5 Voclosporin Background & Differentiation Robert Huizinga, EVP Corporate Development

Robert Huizinga, EVP Corporate Development

6 Expanding Our Renal Franchise James Tumlin, MD, Director, GA Nephrology Center for
Glomerular Diseases
New Product: VOS (voclosporin ophthalmic solution) Joseph Tauber, MD, Tauber Eye Institute
7 Keratoconjuctivitis Sicca (Dry Eye Syndrome) Michael Martin, Chief Operating Officer

8 Q&A All

9 Closing Remarks Richard Glickman, Chief Executive Officer

4
HQ: Victoria, British Columbia, Canada and Fort
Washington, PA

NASDAQ: AUPH
TSX. AUP

Founded by former members of

the Aspreva Pharmaceuticals team

Patient-focused late clinical stage

biopharmaceutical company

Targeting patient populations for which there is a

high unmet medical need

Highly experienced team with 30 full-time employees

5
Management Team

Richard M. Glickman, L.L.D. (Hon) Rashieda Gluck

Chief Executive Officer & Chairman Vice President, Clinical Operations
of the Board

Robert Huizinga
Executive Vice President,
Corporate Development

Neil Solomons, M.D. Celia Economides

Chief Medical Officer Vice President, Corporate &
Public Affairs
Erik R. Eglite, D.P.M. J.D., M.B.A
Senior Vice President, GC & Chief
Compliance Officer

Dennis Bourgeault Bradley J. Dickerson

Chief Financial Officer Global Commercial Lead

Lawrence (Larry) D. Mandt

Vice President, Quality &
Regulatory Affairs

Michael Martin Simrat Randhawa, M.D., M.B.A.

Chief Operating Officer Vice President, Medical Affairs

6
Our mission is to develop and deliver treatments to people living with
debilitating diseases.
5-Year Vision
Global Biopharma Company
Focused Renal / Autoimmune Franchise
Commercialization Capacity

Core Values

Patient-Centric Quality Passion Integrity

Aurinia Cultural Hallmarks

Accountable Trustworthy Entrepreneurial Collaborative Nimble

7
Corporate History of Aurinia

Late clinical
stage company
in Phase 3
IP consolidated
under one Well-capitalized
entity and
Vifor retains LN private-held
expertise creates Building
Aurinia &
Galenica Aurinia publicly held
Commercial
integrates spin-out and Isotechnika competencies
Aspreva into licenses VCS in merge to
Aspreva
Vifor Pharma; lupus & publicly-held Pipeline
Acquired by
proteinuric Aurinia expansion
Galenica for CellCept (MMF)
kidney disease
>$1B established as
from Isotechnika
new Standard of
Care for LN

8
Building Our Business: Strategic Goals

Execution of our Leverage our core Maximize the Long-Term:

AURORA Phase 3 capabilities and value of Leverage our renal
study without expertise to voclosporin & autoimmune
compromise improve the expertise to
current treatment acquire, develop
paradigm for lupus and commercialize
nephritis (LN) potential products

9
Lupus Nephritis Program Update
Neil Solomons, M.D.
Chief Medical Officer

www.auriniapharma.com
VoclosporinPotential to Address LN Critical Need

LN Critical Need Voclosporin

(based on AURA-LV Phase 2b 48-week results)

Control of Active Disease

Rapid Disease Control

Lower Steroid Burden

Convenient Treatment Regimen

Of note, voclosporin is an investigational drug and is NOT currently approved as safe or effective by
any regulatory agency for any use. 11
Components of NDA Submission for VCS

NON-CLINICAL
(2H 2018)

PK / PD Pharmacology

Toxicology Drug Metabolism

CMC
(1H 2019)
Drug Product
Drug Substance Drug Product Validation
Manufacture Scaled Up
Manufacture Scaled Up
Drug Product Expiry > 2 yrs & Validated Final Packaging Configuration

CLINICAL
(1H 2020)
Safety Efficacy
Kidney Transplant Lupus Nephritis AURA-LV AURION

Uveitis Psoriasis AURORA DDI

12
Voclosporin LN Clinical Program

Statistically significant higher CR, PR, time to CR/PR, UPCR

reduction & SLEDAI at 24 & 48 weeks; Achieved highest
AURA-LV remission rates of any global LN study at 48 weeks
(Phase 2b) AE, SAEs & overall trial mortality consistent with other
global LN trials

AURION UPCR at week 8 is highly predictive of renal response at

24 & 48 weeks
(Proof of
Renal function remains stable and inflammatory markers
Concept) continue to normalize

Double-blind placebo controlled study to demonstrate

that VCS added to SoC can increase overall renal response
AURORA rates in the presence of extremely low steroids;
(Phase 3) 2-year Extension Study
Primary endpoint: Renal response (or CR) at 52 weeks

Healthy volunteers (US or Canada)

Drug-Drug
2 weeks of treatment (14 days MMF, 7 days VCS)
Interaction (DDI)
Assessments: Bloodwork, PK sampling, and other
Study (Phase 1) assessments at various timepoints

13
 AURORA Study Design: Phase 3 Mimics AURA-LV Phase 2b
52-week global, double-blind, placebo-controlled study to evaluate whether
voclosporin added to SoC can increase overall renal response rates in the presence of
low steroids.
Primary endpoint: Renal response (or CR) at 52-weeks data expected late 2019
Secondary endpoint Primary endpoint
24 weeks 52 weeks

2-Year Extension Study

1:1 Randomization

VOCLOSPORIN 23.7 mg bid

MMF 2 g + oral corticosteroids

N= 324

Treatment arm

PLACEBO

MMF 2 g + oral corticosteroids

Control arm

20-25 mg/daily Rapid steroid taper

15-20 mg/daily

10-15 mg/daily

5 mg/daily

2.5 mg/daily
Week 2 4 6 8 16 24 52

14
 AURORA Phase 3 Study Status

Number of sites initiated

21 out of 29
38 USA /
Canada 21 APAC
MAJORITY
Countries
have sites
43 Europe 11 LATAM
of US sites activated
initiated.

Investigator Meetings Completed

Miami, FL, USA Madrid, Spain Bangkok, Thailand Osaka, Japan

Panama City, Panama Cape Town, South Africa Belgrade, Serbia

Upcoming Investigator Meetings

Sao Paolo, Brazil

15
 Clinical & Regulatory Timelines

1H 2018 2H 2018 1H 2019 2H 2019 1H 2020 2H 2020 1H 2021

AURORA
AURORA
DDI Study Recruitment
Data
Complete

AURORA Extension Study

Rolling NDA Submission Projected

FDA
Non-Clinical Section CMC Section Clinical Section AdCom

Potential
Approval

TARGET
LAUNCH

16
Commercial Strategy
Bradley Dickerson
Global Commercial Lead

www.auriniapharma.com
Ideal Commercial Opportunity

Additive vs.
Established community
Displacement

Reimbursement Established
Reimbursement for value Underdeveloped market
for value market

Aurinia & Voclosporin

&
VOCLOSPORIN

Limited Costly disease

Limited competition Costly disease burden
competition burden

18
US Lupus and Lupus Nephritis Population

Estimated Diagnosed Population

~300,000

~200,000

20%

Non-renal SLE Lupus Nephritis

* Data on file from Aurinia internal market research (epidemiology papers, physician market research and medical claims review)

19
 Getting Disease into Remission Quickly Is Key

Destructive Cycle of LN Outcomes Based on Response*

100%
INDUCTION 8%
90%

80%
IVC or MMF
with high 70% 57%
dose
steroids 60%
87%
FLARE REMISSION 50%
92%
40%
MMF or
30%
AZA steroid
steroid taper 20%
43%
taper
MAINTENANCE 10%
13%
0%
Remission Responder Non-Responder

Not on Dialysis @ 10 years On Dialysis at 10 years

*Chen et al. Clin J. Am Soc Neph. 2008: Response = 50% reduction in proteinuria Remission = Proteinuria <.33g/24hrs

20
 Cost Burden of Lupus Nephritis

Average Annual Cost of Illness per Patient by Condition*

$0 $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000

Asthma
Hypertension
Diabetes
COPD
Bipolar Disorder
Heart Disease
Rheumatoid Arthritis
Ulcerative Colitis
Crohns Disease
SLE (no nephritis)
Lupus Nephritis

Medical Costs Absence Costs Short Term Disability

* Carls G, et al. J Occup Environ Med. 2009;51:66-79. 21

Dollars Cant Capture the Patient Experience
Recent patient feedback from Lupus Patient Focused Drug Development
meeting with FDA confirms desire for better QOL and less steroids.

Cardiovascular Osteoporosis
Issues and Fractures

Steroid
Burden

Glaucoma
Infections and Cataracts

Emotional Issues http://www.lupuspfdd.org

22
Claims Data Tells Us When & How Patients Seek Care Today

Hydroxychloroquine
Rx Prednisone
Mycophenolate

Outpatient Hospital
Facilities Physician Office
Inpatient Hospital

Rheumatology
Providers Nephrology
Acute Care Hospital

Males: 15%
Demographics Females: 85%

Claims leveraged the the MarketScan Research Databases [1] supplied by Truven Health Analytics. The databases contain cleaned,
anonymized insurance claims data from multiple major healthcare insurers.
23
 Minimal Branded Competition at Launch
2017 2018 2019 2020 2021 2022 2023 2024 2025 2026+

Market Adoption
Lupus
Nephritis* Voclosporin
Aurinia

Phase I Phase II Phase III

Ninlaro BI 655064 Voclosporin
Takeda Boehringer Ingelheim Aurinia
OMS 721 Abatacept
Omeros BMS
Anifrolumab Belimumab
AstraZeneca GSK
Obinutuzumab
Roche

* Estimates are based on Aurinia competitive intelligence monitoring

24
Current Therapies Are Expensive

Product Strength Unit Dosing Cost Range

WAC (1 year of therapy)

Not approved for the treatment of Lupus Nephritis

Arm 1: 80 U biw, subQ, for 3
$174,634
months. Optionally additional 3
to
months of 80 U biw if a patient
$349,267
has PR
HP Acthar 80 unit/mL $7,276.401 Arm 2: 80 U qod, subQ, for 1
month, then 80 U biw, subQ, for 2 $225,568
months. Optionally additional 3 to
months of 80 U biw if a patient $400,202
has PR

1,000 mg IV on days 1, 15, 168,

Rituxan 10 mg/mL $86.861 $34,744
182

10 mg/kg IV administered on Days

1
Benlysta 400mg/ml $1,662.02 0, 14, 28, and then every 28 days $37,185
thereafter

WAC = wholesale acquisition cost as of 10/5/2017

WAC represents the manufacturers published catalog or list price for a drug product to wholesalers and may not represent actual transactional prices.
Source: AnalySource - Reprinted with permission by First Databank, Inc. All rights reserved. (2017) 25
1 Dosing source for agents: Clinicaltrials.gov
 Ideal Commercial Opportunity

Building Relationships Additive vs.

Positioning Product
Established community
Displacement

Reimbursement Established
Reimbursement for value Underdeveloped market
for Value Market

Aurinia & Voclosporin

&
VOCLOSPORIN

Pricing Assessment Limited Costly Disease Identifying Targets

Limited competition Costly disease burden
Competition Burden

26
Engaging with Key Stakeholders to Build Relationships

27
 Working to Confirm Most Important Targets

Rheumatology
Physician Universe* Nephrology
~14,000

Treater (~85%)
Treaters** Non-Treater (~15%)
~11,900

80% 20%
Patient Concentration*** (40% of Treaters) (60% of Treaters)
~4,800 ~7,100

* AAMC 2015 Medical Specialties (https://www.aamc.org/data/workforce/reports/457712/2016-specialty-databook.html

** Data on file from Aurinia internal market research
*** Data on file from Aurinia internal market research

28
Gated Commercial Hiring upon Key Inflection Points

Ongoing Phase 3 Phase 3 Data FDA Approval

(Additional Commercial Leadership)

Payer Awareness

Corporate
Market Access Accounts

Distribution
Leadership Marketing
Patient Support

Commercial Analytics / Market

Operations Research

Sales Leadership Sales Team

Prepare ahead of inflection points to quickly onboard new resources.

29
Market Opportunity

Initial estimates of voclosporin peak sales potential

in Lupus Nephritis yield global opportunity of

$1.4 billion +

30
IP in Lupus Nephritis
Michael Martin
Chief Operating Officer

www.auriniapharma.com
Voclosporin Has a Robust IP Portfolio

Current Patent Portfolio

Patent Term Adjustments

Patent Term Extensions

Regulatory Data Exclusivity

Exclusivity Period for

voclosporin Composition
of Matter

32
Hatch-Waxman Review: Drug Price Competition & Patent
Term Restoration Act Public Law 98-417
Allows protection for drug innovators while facilitating and providing
incentives for companies to file ANDAs.

Market/Data Exclusivity Patent Term Extension (PTE)*

5 years for a New Chemical Entity Life of patents extended by portion

(NCE) of time the drug is under regulatory
by FDA

Independent of patent rights Calculated by time elapsed between

date of initial IND filing divided by 2
to a max of 5 years provided
Begins upon FDA Drug Approval extension does not exceed 14 years
on-market drug exclusivity

*The European Union has a similar program, but the PTE is called Supplementary Protection Certificates (SPC)

33
Patent Protection of the Voclosporin Product

Composition of Matter

Compound Patent Isomeric Mixtures Synthesis Patent Formulation Patent

Compound Isomeric Mixtures Synthesis Formulation

34
 Composition of Matter Patent Coverage
2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031
October April
USA 2027 2028
Isomeric Patents Patent Term Extension Pediatric
Extension
(Trans Formulation) (5 years) (6 months)

PTE/SPC can only

EUROPE be tagged onto one
patent
Isomeric Patents Supplementary Protection Patent Pediatric
Extension
(Trans Formulation) (5 years) (6 months)

TARGET
LAUNCH

35
 Data Exclusivity Expectations for VCS in Ex-US Markets
2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032

NCE - DATA EXCLUSIVITY EMA (EU)

10 years

NCE - DATA EXCLUSIVITY PMDA (Japan)

8 years from approval
NCE - DATA EXCLUSIVITY CFDA (China)
6 years

TARGET
LAUNCH

Voclosporin will be considered a New Chemical Entity (NCE) across global markets
This allows for significant Data Exclusivity across various global markets.
NCE Data Exclusivity is the strongest type of protection 3rd party challenges
are extremely rare.

36
Pursuing Avenues to Expand the VCS Patent Portfolio

Use patent strategy Manufacturing patent strategy

Development of Use Patents driven Development of Manufacturing
by AURA-LV Phase 2b Data Patents driven by 15 years of
manufacturing know-how

AURA-LV Data

Learnings on how to Complex Manufacture

use VCS in LN of API

Utility Inventions Trade Secrets

Potential VCS Potential

USE Patents Manufacturing Patents

37
Composition of Matter & Data Exclusivity Provide Robust
Protection in Key Global Markets

Japan:
United States: CoM Patent 2028*^
CoM Patent 2028*^ Data Exclusivity 8
Data Exclusivity 5 years years from approval
from approval

European Union:
CoM Patent 2028*^ China+:
Data Exclusivity 10 CoM Patent 2028*^
years from approval Data Exclusivity 6
years from approval

*Includes PTE in the US and SPCs in the European Union

^Includes an expected 6 month pediatric exclusivity
+Territory currently licensed to 3SBio

38
Voclosporin The Next Generation
Calcineurin Inhibitor (CNI)
Robert Huizinga
Executive Vice President, Corporate Development

www.auriniapharma.com
Voclosporin Introduction

Predictable concentration effect

and tight PK/PD relationship
Voclosporin (VCS) is a novel CNI that may
offer a number of advantages over the Lower rates of diabetes versus
legacy CNI options (cyclosporine A (CsA) tacrolimus
and tacrolimus).

Improved lipid profile vs CsA

Calcineurin inhibitors (CNIs) have

demonstrated efficacy for a number of
conditions, including transplant patients,
lupus nephritis (LN) patients,
keratoconjunctivitis sicca (dry eye) and other
autoimmune diseases; however side effects
exist which can limit their long-term use.

MTT, multi-targeted therapy; LN, lupus nephritis; CNI, calcineurin inhibitor; MMF, mycophenolate mofetil; PK/PD, pharmacokinetics/pharmacodynamics. 40
 Calcineurin Binding Occurs Through Latch Region of VCS

voclosporin

Latch Region

Kuglstatter A, et al. Acta Crystallogr D Biol Crystallogr. 2011;67(Pt 2):119-123. Calcineurin

41
 The Activity of VCS in Renal Disease Involves 2 Separate
Mechanisms
1 2
Potential disease-modifying
Inhibition of calcineurin
podocyte stabilization, which
reduced cytokine activation
protects against proteinuria

voclosporin voclosporin
Actin
cytoskeleton

APC

Cytoplasm
T cell
receptor

Dephosphorylated
Calcineurin synaptopodin breaks
up and destabilizes the
Nucleus actin cytoskeleton of
IL-2 the podocyte
Cell-
INF-gamma mediated
TNF-alpha immune
response

Tissue Glomerular basement membrane

damage

LN, lupus nephritis; NFAT, nuclear factor of activated T cells; APC, antigen-presenting cell;
IL, interleukin; INF, interferon; TNF, tumor necrosis factor.

42
 Voclosporin Key Benefits 1,2,3

Increased potency Limited inter & intra

vs. cyclosporine A, patient variability
allowing lower dosing potentially eliminating
requirements1 therapeutic drug
monitoring 1,3

VOCLOSPORIN

Better lipid profile Better glucose profile

than CsA 1 vs. tacrolimus 2

1.Aurinia Data on file

2.Busque S, et al. Am J Transplant. 2011;11(12):2675-2684 & AURA LV Data
3.AURA-LV Data on file

43
 Predictable Concentration Effect: No TDM

Predictable Based on current data on VCS,

Tight PK/PD relationship vs
concentration-effect therapeutic drug monitoring
other CNIs1-3
relationship (TDM) is not required

Tacrolimus Cyclosporine A voclosporin

100 100 100
90
80
75 75
70
60

%CNI
%CNI

%CNI
50 50 50
40
30
25 25 r = 0.8
20 r = 0.5 r = 0.7
10
0 0 0
0 10 20 30 40 50 60 0 250 500 750 1,000 1,250 1,500 0 100 200 300 400 500 600 700 800 900
Concentration Concentration Concentration
(ng/mL) (ng/mL) (ng/mL)

Poor relationship with Variable and impaired Only CNI with predictable
calcineurin activity ability to achieve max concentration-effect
Lower signal calcineurin inhibition relationship (PK/PD)
More noise Less noise
Higher signal
PK/PD, pharmacokinetics/pharmacodynamics; CNI, calcineurin inhibitor. 3. Mayo PR, et al. J Clin Pharmacol. 2013;53(8):819-826.
1. Data on file. 44
2. Ling SY, et al. J Clin Pharmacol. 2013;53(12):1303-1312.
 Voclosporin Better Lipid Profile at Therapeutic Doses1

Patients on cyclosporine A demonstrate a Voclosporin is associated with lower

marked increase in total cholesterol compared levels of hypertriglyceridemia, even at
with those on voclosporin2 higher doses2

Cholesterol levels with CNI treatment Hypertriglyceridemia levels with CNI treatment
Total cholesterol (Study ISA05-25) %PASI versus % patients with high TG
Mean 95% CI
6.5 VCS 50 VCS
Drug therapy ends
CsA CsA
Mean Total Cholesterol

40

% Patients with de novo

6.0

Hypertriglyceridemia
30
5.5
20

5.0
10

4.5 0
10 0 10 20 30 40 50 60 70 80 40 50 60 70 80 90 100
Week %PASI

CNI, calcineurin inhibitor; PASI, psoriasis area and severity index; CI, confidence interval; TG, triglycerides; VCS, voclosporin; CsA, cyclosporine A.
1. Kockx M, et al. 2012, ISBN: 978-953-51-0773-6, InTech, DOI: 10.5772/47866. Available from: http://www.intechopen.com/books/lipoproteins-role-in-health-and-diseases/cyclosporin-a-induced-
hyperlipidemia.
2. Data on file.

45
 Across Study Comparisons of Hba1c of VCS & TAC in
Longer-Term Autoimmune Diseases
Long-Term CNI use in
Autoimmune Diseases
HbA1C > 6.5%
25

% of Patients with HbA1 >6.5%

20 *LONG-TERM TACROLIMUS USE IN RA:
At some point during the study192
15 patients experienced and elevated
HbA1C >.065 (>6.5%)
10

0 ^AURA-LV voclosporin Safety Data Set,

Long-term HbA1C at 48 weeks 1.49% of patients in LD-
VCS had a HbA1C > 6.5%
Voclosporin in LN
Tacrolimus in RA

Glucose Intolerance and Diabetes is a well characterized side-effect of tacrolimus; in AURA-

LV, voclosporin had no signficiant impact on glucose elevations and diabetes compared to
control
*Yocum et al., Safety of tacrolimus in patients with rheumatoid arthritis: long-term experience., Rheumatology 2004; 43:992-99
^52 week AURA-LV data set Aurinia data on file

46
 Functional Differences Lead to Lower Rates of NODAT

Tacrolimus voclosporin
NFATc signaling appears to play a
key role in regulating glucose and
insulin homeostasis1-4.
Cyclophilin
T cell
receptor
Tacrolimus and voclosporin
inhibit calcineurin and prevent FKBP
Calcineurin

NFATc activation through Inactive NFATc

PO43-

Nucleus
different mechanisms4,5.
Active NFATc

Higher rates of diabetes have

been shown with tacrolimus than IL-2 Cell-mediated
with voclosporin5. IFN-gamma
TNF-alpha
immune
response

FKBP, FK506 binding protein; NFATc, nuclear factor of activated T cells, cytoplasmic; IL, 3. Yang TTC, et al. Mol Cell Biol. 2006;26(20):7372-7387.
interleukin; IFN, interferon; TNF, tumor necrosis factor. 4. Heit JJ, et al. Nature. 2006;443(7109):345-349.
1. Auer VJ, et al. Clin Exp Immunol. 2012;170(2):238-247. 5. Busque S, et al. Am J Transplant. 2011;11(12):2675-2684.
2. Pereira MJ, et al. J Clin Endocrinol Metab. 2014;99(10):E1885-E1894.

47
Expanding the Renal Franchise
Robert Huizinga
Executive Vice President, Corporate Development

www.auriniapharma.com
Why Are We Looking Beyond LN?

A number of Reduction in Legacy CNIs are Voclosporin may

renal diseases proteinuria effective in have a number
are characterized correlates with reducing of advantages
by proteinuria. long-term proteinuria in over legacy CNIs.
outcomes for renal diseases.
renal diseases.

MAXIMIZE VOCLOSPORINS VALUE

49
 Indication Approach:
VCS New Indications Must Fulfill These Four Criteria

Strategic Clinical
Indications with high disease Validated highly objective
morbidity and/or mortality endpoints
Limited treatment options Biologic plausibility based on
available product and disease
characteristics
Treated by specialty physicians
Small patient enrollment
Aligned with corporate focus required

Regulatory Commercial
Potential for a straightforward Clearly defined patient
regulatory pathway population
Potential for expedited Limited approved competition
regulatory review programs Specialty pricing
Strengthen IP / Data exclusivity

50
Voclosporin Differentiation in Novel Indications

The attributes demonstrated by voclosporin in prior indications (LN, Renal Tx, PsO)
studied should apply to new indications

The advantage of a CNI with an improved PK-PD relationship should allow for:

Decreased inter and intra-patient Decreased drug exposure in patients

variability of VCS equaling less off-target toxicities

We believe this allows for VCS to exhibit an improvement in

adverse events compared to the legacy CNIs

51
 Potential Future Uses and Indications for VCS
(US Patient Estimates)

AURA data
Existing Level of Evidence That CNIs Are Effective

Renal Transplant Confirmatory

AURORA in process
AURA
~40,000 SLEDAI Data
FSGS/MCD LN
de novo/year

~60,000 ~200,000 SLE

IgA
Nephropathy

~ 150,000
Systemic Sclerosis

~500,000 (including LN)

Orphan Non - Orphan

~75,000
Diseases Diseases

Increasing Disease Prevalence (US)

52
Better Diagnosis Leads to Increased Prevalence1

1. Sim et.al. Am. J. Kid. Dis. pages 1-12 April 2016

53
~50% of NS Patients Have FSGS or MCD on Biopsy

NephCure Registry 2017

29%

41% FSGS
MCD
NS (Not Biopsied)

1% 13% Membranous
16% Other

54
The Opportunity in Nephrotic Syndrome

Focal Segmental Glomerulonephritis (FSGS)

FSGS prevalence is between 80,000-

5,400-9,500 patients are diagnosed 100,000 patients globally
with FSGS every year. ~40,000 patients in the U.S. with
similar prevalence in EU.

Minimal Change Disease (MCD)

MCD is a major cause of nephrotic

1,000 patients are diagnosed with syndrome in both children and adults.
MCD every year. MCD accounts for 50,000 of NS cases.

MCD and FSGS are often considered together because both are PODOCYTOPATHIES.

55
Nephrotic Syndrome: Focal Segmental
Glomerulosclerosis and Minimal
Change Disease

James A. Tumlin MD
Professor Medicine/Nephrology
Director GA Nephrology Center for
Glomerular Diseases

Founder NephroNet Clinical

Trials Consortium

56
 I am an investigator in the AURA, AURORA
studies

I am a consultant to Aurinia Pharmaceuticals

 Clinical Case of Severe
Nephrotic Syndrome
HPI: 17 yo African American male is referred
to the GA Center for Glomerular Diseases
after he was put on medical leave from his
High School Basketball team due to
swollen legs.

Blood Pressure: 190/115 mm Hg

Lungs Clear
Heart Regular rate rhythm-no murmors
Legs Marked edema
 Clinical Case of Severe
Nephrotic Syndrome

Laboratory Data:
BUN-21 Cr-2.4 Hgb 9.1

Total Cholesterol 656 Hct-26.7

Triglycerides-980 Albumin 1.8

Urine protein/24 hours: 23,700mg

 Clinical Case of Severe
Nephrotic Syndrome-Pedal Edema
A Renal Biopsy
was performed
 Focal Segmental Glomerulosclerosis
Not Otherwise Specified (NOS)

Bowmans Focal area

Capsule of Hyalinosis

Adhesion of
Glomerular
Open-normal
Tuft to
Capillary loops
Bowmans
Capsule
 Clinical Case of Severe
Nephrotic Syndrome

HPI; One week after seeing you in the clinic,

the patient returned to the Basketball team.
He collapsed 20 minutes into a practice game
but was successfully revived and transported
to a local ED

A Diagnostic procedure was performed.

Fatal Saddle Pulmonary Embolus
 What is Nephrotic Syndrome?
Nephrotic Proteinuria large amounts of protein in the urine
syndrome is a Hyperlipidemia higher than normal fat and
collection of cholesterol levels in the blood
symptoms that Edema, or swelling, usually in the legs, feet, or
indicate kidney ankles and less often in the hands or face
damage Hypoalbuminemia low levels of albumin in the
blood

65
 Classic FSGS
Pathologic Features
Segmental occlusion glomerular
capillaries by accumulation of
extra cellular matrix proteins

Peripheral lesions associated

younger age

Hyalinosis: accumulation of
eosinophilic, trichrome-red
staining amorphous material
beneath basement membrane

Proximal tubular foam cells

intracellular protein droplets

Seminars Nephrology 23(2) 117-134, 2003

66
 Distribution of FSGS and Other Glomerular
Diseases Among ESRD Populations: Highest in
African American Population1

1. Kitiyakara et.al. Am. J. Kid. Dis. 44(5), 815-825, 2004

67
 Like LN, Early Clinical Response is Critical to
Maintaining Long-Term Kidney Health
Rapid control & reduction of proteinuria increases kidney survival1

1. Cattran et.al J. Am. Soc. Nephrol. 16:1061-1068, 2005

68
Why is FSGS referred to as
a Podocytopathy and why
do these patients spill so
much protein?
 Podocytes Dysfunctional in FSGS:
Central Mechanism for Proteinuria

Normal Podocytes: Dome-Like

Foot Plate Processes Intertwined

FSGS Podocytes: Rounded

Loss of Foot Plate processes

70
Podocyte Injury: Multiple Pathways Contributing
to Cell Injury & Apoptotic Cell Death

Altered Ang- II-Aldo

Hemodynamics Induced Podocyte
Increased Apoptosis/Detachment
Transglomerular
Pressures

Loss of Capillary Ang-II-Aldo

Anionic Charge: Induced
Heparin SO4 ROS Injury
Podocalyxin

Reduced
TGF-b Induced Hyperglycemia Production
Podocyte Podocyte
Apoptosis/Detachment
RAGE Receptor VEGF-A
ROS Injury
What is Consequence of
Podocyte Damage or
Depletion?
 Podocyte depletion correlates
with Glomerulosclerosis

Wharram B L et al. JASN 2005;16:2941-2952

 Calcineurin Induced Dephosphorization of
Synaptopodin Destabilizes Podocyte Cytoskeleton

Early Detachment Full Detachment

Albumin a3-Integrin
a3-Integrin a3-Integrin
a3-Integrin

Endothelial cells Endothelial cells Endothelial cells

Focal Sclerotic Lesions
 Sequential Development of Synechiae
& Segmental sclerosis

Kriz et al Kidney Int 1998

 Podocyte Depletion Directly Correlates
with Development of Glomerulosclerosis
Normal 28% Loss
Glomerulus Podocytes

Absence of Early Sclerotic

pink Sclerotic Lesion
Lesions

55% Loss 93% Loss

Podocytes Podocytes

Advanced
Sclerotic Total Glomerular
Lesion Collapse

Wharram B L et al. JASN 2005;16:2941-2952

 Small Increases in Podocyte Number May
Prevent/ Reverse Scarring1

1. Shankland SJ et al. Curr Opin Nephrol Hypertens. 2017 May;26(3):154-164 78

 What is the current
standard of care treatment
of FSGS with nephrotic
syndrome?
Glucocorticoids

80
 KDIGO Treatment Recommendations
Idiopathic Focal Segmental Glomerulosclerosis

Initial treatment of FSGS

Immunosuppressive therapy only in patients with
clinically relevant nephrotic syndrome.
Corticosteroids 1 mg/kg (maximum 80 mg) daily or
alternate-day X 16 weeks until complete remission
has been achieved
Corticosteroid taper slowly over 6 months after
achieving complete remission.

Calcineurin Inhibitors first-line therapy for patients

with relative contraindications or intolerance to
steroids
 Efficacy of Prolonged Steroid Therapy
in Adult Primary FSGS

50%

44% 44% 45% 45%

42

33%
32%

26%

17%
12%
10%

Korbet J. Am. Soc. Nephrol. 9:1333 1998

 Efficacy of Prolonged Steroid Therapy
in Idiopathic Adult FSGS

Total
52.0%

Complete
36.0% Recurrence
32.0%

Partial
16.0% 14.2%

7.1% 7.1%

Ponticelli et.al. Am. J. Kid. Dis Vol 34(4) 618-625,1999

Calcineurin Inhibitors

84
 Long Term Cyclosporine Therapy for Steroid
Resistant Nephrotic Syndrome: Histologic Changes
CsA Toxicity: 17% at 14 months
FSGS
100% IgM
93%
Complete
85%
MCGN
Time to 66%
Response
58 Days

Partial
13%

Gregory et.al. J. Am. Soc. Nephrol. 7:543-549, 1996

 Legacy CNIs Demonstrate Efficacy in
Pediatric Steroid-Resistant Nephrotic Syndrome
70% overall response rate at 6 months (complete + partial remission)

70% Response Rate for both CNI at 6 Months

Choudry et.al. Am J Kidney Dis 53:760-769. 2009

 Summary
FSGS and MCD are common biopsy findings
when a patient presents with proteinuria
Both are podocytopathies
Higher incidence amongst minority
populations

Rapid control of proteinuria is key to long term

renal survival

Without adequate control, recurrence of

proteinuria is common over 24 weeks which
could eventually lead to ESRD

Stabilizing the podocyte is a key element in

treating patients 87
87
 Side Effects of Nephrotic
Syndrome Treatment
Corticosteroids Weight Gain; Steroids induced
Diabetes Mellitus; Avascular necrosis of
the Femoral Head; Steroid-Osteoporosis
Cataracts; Steroid induced Myopathy
Calcineurin Inhibitors: Acute renal failure, Tremor
Hypomagnesemia; Hyperkalemia, CKD
Interstitial Fibrosis, Peripheral Neuropathy
Insulin Dependent Diabetes
Cyclophosphamide: Bone Marrow failure, Viral &
systemic fungal infections, Sepsis, Anemia
Rituximab: Anaphylactic Shock; Low Platelets
88
What are some Clinical
Complications of
Calcineurin Inhibitors?
CNI Exhibit Both Acute and
Chronic Nephrotoxicity
Insulin Dependent
Diabetes

91
DIRECT Trial: New Onset Diabetes or Glucose
Intolerance Following Renal Transplant1
New Onset Post-Transplant Diabetes: CsA-26.0%

P=0.046
New Onset Post-Transplant Diabetes: TAC-33.6%

1. Vincenti et.al. American Journal of Transplantation 2007; 7: 15061514

92
 What are some Clinical
Benefits of Calcineurin
Inhibitors in the Kidney?
Stabilizing Podocyte
Cell Cytoskeleton
Stabilization of Synaptopodin and Podocyte
Cytoskeleton: Role of Calcineurin?
Podocyte Detachment
& Effacement Restored
a
a
TRPC-6 TRPC-6

Ca++ Albuminuria Ca++

Blocked
PO4
PO4

PO4
PO4
Synaptopodin Synaptopodin

a3-Integrin b1-Integrin a3-Integrin b1-Integrin

Endothelial cells Endothelial cells Endothelial cells

 Synaptopodin and Cell Cytoskeleton
Directs Substrates of Calcineurin1

Intact Glomeruli

Cultured Podocytes

1. Mundell & Riser Nature Medicine, Vol-14(9), 931-938, 2008

 Inhibition of Calcineurin Blocks
LPS-Induced Proteinuria1

LPS induced proteinuria

1. Faul et.al Nature Medicine Vol-14 (9), 931-938), 2008. 97

 Tacrolimus Accelerates Apoptosis Human b
Islet Cells Transplanted into Murine Hosts1

Low Power
Islet Transplant

High Power
Islet Transplant

1. Johnson et.al. Cell Transplantation Vol 18: 833845, 2009

98
 Differences in the Incidence of Diabetes
May Reflect Differential NFATc Signalling
After long-term treatment with
Tacrolimus Voclosporin
cyclosporine A or tacrolimus,
decreased insulin synthesis and
secretion by pancreatic cells and
increased
Cyclophilin
T cell
cell apoptosis have been observed1 receptor

Cyclosporine A and tacrolimus have

also been found to inhibit the uptake of FKBP
Calcineurin
glucose in peripheral tissues2 PO43-
Inactive NFATc

NFATc signaling appears to play a key Nucleus

Active NFATc
role in the regulation of glucose and
insulin homeostasis3,4 Cell-mediated
immune
response
Tacrolimus and Voclosporin both inhibit
calcineurin and prevent the activation of IL-2
NFATc and subsequent signaling, but IFN-gamma
TNF-alpha
through different mechanisms4,5

1. Auer VJ, et al. Clin Exp Immunol. 2012;170(2):238-247. 5. Busque S, et al. Am J Transplant. 2011;11(12):2675-2684.
2. Pereira MJ, et al. J Clin Endocrinol Metab. 2014 Jul 8. [Epub ahead of print]
3. Yang TTC, et al. Mol Cell Biol. 2006;26(20):7372-7387..
4. Heit JJ, et al. Nature. 2006;443:345-349.
 Blocking Podocyte
Detachment and Apotosis
Calcineurin: Role Apoptosis

101
 Voclosporin: Benefits
Increased potency vs. cyclosporine A,
allowing lower dosing requirements 1

Limited inter & intra patient variability

potentially eliminating therapeutic drug
monitoring 1,3

Better lipid profile than CsA 1

Better glucose profile vs. tacrolimus 2

1.Aurinia Data on file 3.AURA-LV Data on file
2.Busque S, et al. Am J
Transplant.2011;11(12):2675-2684 &
102
AURA LV Data
What are some other
side-effect profiles of
the Legacy CNIs?

103
 Tacrolimus Induced Inhibition of Collecting Duct
NaK-ATPase Activity: Contribution to Clinical Hyperkalemia

Control Tacroli mus

20
N a-K -A TP A cti vi ty (pmol es/ mm/ mi n)

NaCl
Cotransporter
Na+ Cl-

10
NaKATPase

0 Reduced K+
0.5 1.5 3.0 6.0 Excretion
Tacroli mus Concentrati on (ng/ml)

Lea et.al. Kidney International, Vol. 46 (1994), pp. 647652 104

 Absence of Hyperkalemia Following
Prolonged (48 wk) Course of Voclosporin
Potassium Stays Within Normal Range

Tumlin et.al. Presented EDTA Meeting Madrid Spain, June 2017 105
 Renal Function Following Prolonged (48
wk) Course of Voclosporin
eGFR remains stable over time

Tumlin et.al. Presented EDTA Meeting Madrid Spain, June 2017 106
 Summary
Nephrotic Syndrome remains an important unmet need

Early proteinuria reduction is associated with improved long-

term renal outcomes

Integrity of the podocyte is key feature of disease progression

While suggested guidelines exists, no approved therapies for

FSGS and MCD

Therapies used in clinical practice aim to elicit response for

patients, but side effects exist

Based on its differentiating characteristics, Voclosporin may

have the potential to address unmet need

107
107
Clinical Strategy for Nephrotic
Syndrome
Robert Huizinga
Executive Vice President, Corporate Development

www.auriniapharma.com
 VCS Acts Rapidly in Proteinuric Kidney Disease (Based
On LN Data)

AURA-LV: Change in UPCR (Mean) over Time

7

5
UPCR (mg/mg)

3 Placebo
2

1
VCS p<0.001
0
Baseline Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 Week 20 Week 24
Visit
Source: Table 14.2.19

109
 FSGS/MCD Clinical Strategy Timeline
Execute a Proof of Concept (PoC) study while conducting Regulatory interactions and
preparing for a global Phase 3 study.

1H 2018 2H 2018 Q1 2019

Submit IND; Initiate & Complete Proof of Concept Study

Establish Approval Pathway

Initiate Phase
3 Program

110
 FSGS/MCD Proof of Concept Study Design

6 months
Interim data Interim data Interim data
Primary
readout readout readout
Endpoint

N=~20 VOCLOSPORIN 23.7 mg bid

Q3 2018 2H 2018 2H 2018 Q1 2019

KEY INCLUSION CRITERIA PRIMARY OUTCOME MEASURE

The proportion of subjects achieving complete

Biopsy proven FSGS or MCD
or partial remission at 6 months.

CR is defined as: Urinary

Proteinuria of 3 mg/mg
protein/creatinine ratio of 0.5 mg/mg

PR is defined as 50% reduction in Urinary

Corticosteroid-Free protein/creatinine ratio

111
 Indication Approach:
FSGS & MCD Meet Our Strategic Criteria

Strategic Clinical
Indications with high disease Validated highly objective
morbidity and/or mortality endpoints
Limited treatment options Biologic plausibility based on
available product and disease
characteristics
Treated by specialty physicians
Small patient enrollment
Aligned with corporate focus required

Regulatory Commercial
Potential for a straightforward Clearly defined patient
regulatory pathway population
Potential for expedited Limited approved competition
regulatory review programs Specialty pricing
Strengthen IP/Data exclusivity

112
 Minimal Branded Competition at Projected Launch

2017 2018 2019 2020 2021 2022 2023 2024 2025 2026+

Lupus Voclosporin
Aurinia
Nephritis*

Nephrotic Voclosporin
Aurinia
Syndrome*

Pre-Clinical/Phase I Phase II Phase III

CCX 140 Acthar Gel Abatacept
ChemoCentryx Mallinckrodt BMS

Sparsentan Bleselumab
Retrophin Astellas

* Estimates are based on Aurinia competitive intelligence monitoring

113
The Opportunity in Expanding the Franchise

Strong Dual Differentiated Highly Aurinia has

biologic complementary in key safety clinically internal
plausibility in mechanism aspects vs. relevant infrastructure
FSGS and of action. legacy CNIs at development and can
MCD given likely targeted approach with leverage LN
similar VCS doses. focus on expertise to
endpoint to efficacy with expand the
LN. no steroids. renal
franchise.

114
New Product Development
Voclosporin Ophthalmic Solution (VOS)

www.auriniapharma.com
 Voclosporin Ophthalmic Solution (VOS): A New Product

1. Unique aqueous, preservative free

nanomicellar solution
voclosporin 0.2%.

2. To be used in the treatment of Dry Eye

Syndrome, impacting >20 million
patients in the United States.

3. Additional animal safety toxicology

studies planned. Studies already
completed in rabbit and dog models.

4. Additional human clinical trials planned.

Single Phase 1 study already completed.

5. IP to ~2031

1. www.webmd.com/eye-health/ss/slideshow-dry-eyes

116
 Dry Eye Syndrome

Joseph Tauber, M.D.

Tauber Eye Center
Kansas City, MO
 Financial Disclosure

I have no financial interest in any of the products discussed. I have been paid to be an
investigator in clinical trials, member of Advisory Boards and have received honoraria for
lecturing as part of the Speakers Bureau for:

Shire Parion Novaliq

Alcon / Novartis Santen EyeGate

Bausch & Lomb Senju Aldeyra

Allergan Kala Tear Film Innovations

Novaliq Sun Tear Solutions

118
 Harvard Medical School 1982

Internal Medicine and Ophthalmology Residences

Double Fellowship training at MEEI

Ocular Immunology, Corneal and External Disease

Past Clinical Professor at University of Missouri / Kansas City, and University of Kansas

Founded Tauber Eye Center 2003

Principal Investigator in over 100 multicenter clinical trials, wrote Restasis protocols, lead PI on Xiidra

Numerous Medical and Scientific Advisory Boards

Allergan, Alcon, Bausch & Lomb, Inspire, Resolvyxx, ElevenBio, Eyegate, ISTA, SARcode, SHIRE, Kala

Active referral practice for complex ocular surface disease problems

4500 dry eye patients under my care

119
The eye surface requires lubrication to
adequately perform its primary functions
of:

1. Barrier protection
2. Visual function

120
 TFOS DEWS II Revised Definition

Dry eye is a multifactorial disease of the ocular

surface characterized by a loss of homeostasis of the
tear film, and accompanied by ocular symptoms, in
which tear film instability and hyperosmolarity, ocular
surface inflammation and damage, and neurosensory
abnormalities play etiological roles.

121
What Does a Dry Eye Patient Look Like?

Blurred vision, eyestrain, CL intolerance

Burning, stinging, scratchy discomfort
Itching, eye discharge
Lost work productivity
2 to 4 or more MD visits annually
Dependent on eyedrops
Graded as equally impacting as moderate
angina

122
 Prevalence of Dry Eye
Involved in 40% of Eye Care Visits

Women:
4% @ 40 15% @ 65

Men:
4% @ 50 7.7% @ 80+

1/10 dry eye pts has Sjogrens Syndr.

1.3 M Rheum. Arthritis (CDC, 2008)
37% of diabetics
(Canadian Dry Eye Epidem. Study)

Worldwide distribution:
US 5.8%
Market Scope. 2010 Comprehensive Report on The Global Dry Eye Products Market.
Western Europe 8%
China 21%
India 12%
123
 The Dry Eye Market

Global 68MM people, 26 MM moderate to severe

US 26MM people, 7 MM moderate to severe
At the manufacturer level:
2016 ~$3.4B annual, Restasis ~ $1.4B, lubricants $540M
Estimated $4.5B in 2021
At the provider level:
Revenues from dry eye procedures growing 37% annually reaching
$427M in 2021

124
 Economics of Dry Eye (Ophthalmic Practice)

Four visits, diagnostics, tears, scrubs

net ~$600
Four visits, diagnostics, tears, scrubs and plugs
net ~$950
Six visits, diagnostics, tears, scrubs, plugs and LipiView / LipiFlow
net ~$1100
Six visits, diagnostics, tears, scrubs, plugs, LipiView / LipiFlow and amnion
net ~$2600
Six visits, diagnostics, tears, scrubs, plugs, LipiView / LipiFlow and two amnion
net ~$4100
Potential revenue from 500 dry eye patients per year.$2,050,000

125
 Patient Cost of Treating
Moderate to Severe Dry Eye Symptoms

126
 Dry Eye Is an Inflammatory Disease
CD4+ T Cell Infiltration
MHC Class II Upregulation

ICAM-1 Upregulation

CHRONIC Antigen
INFLAMMATION Presentation
T Cell Homing to the
Ocular Surface
T Cell Activation

Stern, Pflugfelder, Niederkorn

127
 ABCs of First Line Treatment

InDoctor Speak
Supplementation Stimulation Retention

In Patients Terms
Add Tears Stimulate Block tears
More Tears from leaving

NB Only 1/3 of these strategies reduces inflammation

128
 Cyclosporine for Dry Eye

immunomodulator, not Lacrimal Glands:

Inflammation Interrupted Secretomotor
immunosuppressive T-cell activation Nerve Impulses
Cytokine secretion
into tears

Tears Inflame Ocular Surface

Cytokines
Disrupt Neural Arc

prevents T cell activation, normalizes apoptosis

BID use - 15% of patients incr Schirmer by 10mm, 59% by 4mm
BID use - corneal staining improves 25-30%
BID use goblet cell density increases 190% (mucin production)
15% of patients cannot tolerate burning and stinging

129
Blocks ICAM-1/LFA-1 Interaction and Inhibits T Cell
Recruitment, Activation, and Cytokine Release

Perez VL et al. Ocul Surf. 2016;14(2):207-215.

(2) Interaction between

(1) Lifitegrast binds
LFA-1 and ICAM-1 is
to LFA-1
blocked

mAPC: mature antigen presenting cells

130
 LFA-1 Mediates T Cell Functions

LFA-1 binding to ICAM regulates T-cell trafficking, activation and inflammation

Lifitegrast blockade Cyclosporine

Rolling Adhesion Infiltration Proliferation Inflammation

LFA-1
BLOOD VESSEL

ICAM Epithelium, Endothelium

Cytokine Cytokine
Induced Release

Inflammation

131
 Unmet Needs in Dry Eye

Cure is rare or non-existent

Control of symptoms is inadequate with currently available Rx
Disease incidence may be growing, independent of improved diagnosis
Aging population, increasing incidence with age, menopause
Growth of prostaglandin / other eye drop Rx for glaucoma
Increasing patient demand for better control of symptoms
Growth of premium IOL cataract surgery, with increased insistence on
high grade vision after more expensive surgery

132
Clinician Concerns with Currently Available
Pharmaceuticals for Dry Eye

Restasis Xiidra
15% intolerance 15% intolerance, sometimes severe
High cost High cost, espec. Medicare Part D
Onset 2-4 months Onset 2 8 weeks
Rare WOW response 20% WOW response
Lack of clinical trial evidence for 5-10% blurred vision, 5% dysgeusia
symptoms, stain Weak clinical trial evidence for
Multidose bottle = $$$$ signs
Vials contain 3-5 gtt each

133
Dry Eye What Measures Improvement?

Sometimes the questions are

complicated
and the answers are simple
Dr. Seuss

SYMPTOMS

134
Dry Eye Therapeutics Regulatory Issues

A symptom and a sign

Relevant to disease (not merely anesthetic effect)
Reproduced in 2 studies
Signs: Tear production (Schirmer), corneal staining, conjunctival staining,
Alternative signs acceptable as proxy (validated correlation)
Tear cytokines, tear osmolarity
Complete clearing of corneal staining (Inspire - diquafasol clinical trials)
Acceptable to submit four studies (2) symptom and (2) sign and not
two co-primary endpoint studies

135
Clinical Trial Metrics - Symptoms
CATEGORICAL SCALES 0 - 3

Dryness None, mild, moderate severe

Pain, soreness None, mild, moderate severe
Burning None, mild, moderate severe
Sandiness, grittiness None, mild, moderate severe
Blurred vision None, mild, moderate severe
Discharge None, mild, moderate severe
Itching None, mild, moderate severe

VISUAL ANALOGUE SCALES

0 100

VISUAL ANALOGUE SCALES WITH ANCHORS

0 50 100

136
Clinical Trial Metrics Signs
Grading Schemes for Staining

Oxford 0-3, entire cornea

Fluorescein
cornea NEI 0-4, 5 zones

Modified 0-4, 5 zones

NEI micro, macropunctate

ORA proprietary system

Lissamine Green of conj/cornea zones
conjunctiva

Degree of staining increases over time (1-2-3-4 min)

- only recent trials have specified time in grading method

137
Measurement of Tear Production - Schirmers
Test

Sensitivity / specificity ~ 65%

Numerous methodologic
variations:
With / without anesthetic
Blot fornix before testing?
Measures production of tears Open or closed eyes during test?
by absorption into dry filter
paper placed over eyelid
margin for 5 minutes

138
Dry Eye Development Many Failures, Some
Success

SYMPTOMS SIGNS

Cyclosorine / Restasis positive positive (categorized Schirmer)

Diquafasol FAILED positive
Rebamipide FAILED FAILED
Hyaluronidase tears positive FAILED
Androgen Tears FAILED FAILED
Bromfenac FAILED positive
Ecabet sodium FAILED FAILED
Lifitegrast / Xiidra positive positive

139
 OCULAR SURFACE DISEASE Rx ALGORITHM

Tear Underproduction Lid Disease

Supplement Stimulate Retain
Posterior Anterior

Uncontrolled Controlled Lid Hygiene Soaks / Scrubs

Higher viscosity Tears Oral Rx (macrolides)

Demodex
P.F. Tears OM-3 supplements
Vitamin A
Xiidra & Restasis
MG Duct Probing
Serum Tears
Anti-keratin Rx
Secretagogue (oral, SL)
(Vitamin A, scraping)
Clinical Trials
Lipiflow

140
Why are Calcineurin Inhibitors Valuable in Dry
Eye Treatment?

Inhibition of T cell activation

Anti-apoptotic effect on T cells and epithelial cells
Goblet cell regrowth / regeneration

How Could Topical Ophthalmic Calcineurin Inhibitors be

Improved?

Improved tolerance as topical eyedrop

Improved efficacy re: symptoms and staining
Improved onset of action more wow effect, better compliance

141
What ocular clinical indications would merit
investigation for an compound that was shown to be
an effective inhibitor of T cell activation?

Dry Eye

Eyelid margin disease, keratitis

Ocular Surface Disease

Uveitis, scleritis, post-surgical

inflammation, infection-related
inflammation (adjunctive) Ocular Inflammatory Disease

ARMD, Glaucoma Inflammation-initiated Disease

142
 Closing Thoughts

Believe those who

Treatment of Dry seek the truth, doubt
Eye Is an Art those who find it.
Andre Gide

Even a clock that

does not work is Thank you for your
right twice a day. attention.
Polish proverb

143
Introduction to Voclosporin
Ophthalmic Solution (VOS)
Michael Martin
Chief Operating Officer

www.auriniapharma.com
Risk Mitigated Approach

DES Prevalence in the US >20M patients, with vast majority undiagnosed.

Opportunity for improved treatments exists.

Since the launch of Xiidra,
Restasis (topical CNI) approved in 2002
the growth rate of Restasis has increased
approaching $2B in sales annually
(19% vs. 2015)

IMS data & market research suggests that topical CNI will remain a mainstay of DES
treatment (as monotherapy or polytherapy).

145
Restasis (CsA) Was 1st Rx Approved for DES in the US
Unmet Need Remains High
UNMET NEED: RESTASIS Sales (IMS) 2012-2016
Label: 2000
Indication for treatment of a sign only: increased
1800
tear production
Onset of effect: 1600

Millions
Increased tear production observed after 3- 6 1400
months of treatment
1200
Efficacy:
1000
{responder analysis}: 15%-20% of patients in
clinical trial setting, 5% placebo (label) 800
Market Research showed slightly higher perceived 600
clinical efficacy in practice (~25%)
400
Adverse effects:
17% of patients experience ocular burning (per 200
label) 0
Dosing: BID 2012 2013 2014 2015 2016

Treatment success:
High drop-out rates 277 million units in the United States for
Market Research showed 70% drop-out by end of the Restasis in 2016 (MAT)
1st year
Sales growth was ~19% over 2015 despite
Xiidra launch in July of 2016 (MAT)

146
Perceived Significant Unmet Medical Need Remains for
the Treatment of DES Despite Approved Products*
PRODUCT ATTRIBUTE
Efficacy for all DES agents is poor, although
there are no H2H comparisons, only about
Efficacy 20-30% of patients respond to therapy

Restasis: 3-6 months

Onset of Xiidra: ~2 weeks in some patients
Action

Restasis label 17% have irritation

Tolerability Xiidra label. 5-25% have irritation upon application

Dosing Restasis and Xiidra are twice daily

Regimen
Poor Level of Attainment Good

Restasis Xiidra
*based on Aurinia market research; H2H comparisons have not been completed

A high level of medical need exists very few aspects of treatment

are deemed as acceptable.

147
CNI Inhibition Is a Validated Mechanism for the Treatment
of Ocular Surface Diseases
Cyclosporin A .05% in the US (DES)/Allergan
Calcineurin is a
Cyclosporin A .1% in Japan (Spring Catarhh)
validated target for
Cyclosporin A .1% in EU(DES with Keratitis)/Santen
chronic ocular
Cyclosporin A .1% in EU (V.Keratoconjunctivitis)/Santen
surface diseases. Tacrolimus .1% in Japan (Allergic Conjunctivitis)/Sanju

MARKET RESEARCH QUESTION:

Will Calcineurin Inhibitors Always Have a Place in Dry Eye Symptom Therapy?

Restasis works for some/many patients/history

Dont Know 10% of efficacy (8)*
MOA makes sense for DED/impacts
Yes
inflammation (7)
We want several options for these patients (5)
Safe to use (2)

90% Insurance plans prefer one or the other (1)

More concentrated form coming soon (1)
Nothing is that much better than Restasis (1)
90%

148
Why Voclosporin Ophthalmic
Solution (VOS)?

www.auriniapharma.com
 VOS Is a Unique Formulation

A clear, aqueous, preservative free

nanomicellar solution, containing 0.2%
voclosporin
Self assembling nanomicelles, ~12.5
nm in size
Two surfactants used: Vitamin E TPGS,
Octoxynol-40

Contains a 4x higher concentration of

active ingredient than Restasis (0.2%
vs. 0.05%) (and twice the
concentration of Santens formulation)
Restasis is an emulsion and can only
hold 0.05% of drug in the emulsion

Preparation of final formulation well

characterized (IP to ~2031)

150
 VOS Has Robust Tox and Safety Package
Oral Voclosporin (LN Program):
SAFETY AND TOXICOLOGY:
Current toxicology package supporting the
oral formulation
Voclosporin Ophthalmic Solution:
SAFETY AND TOXICOLOGY:
VOS Ophthalmic Ocular Safety and pK work
in rabbits and dogs

EFFICACY:
Current clinical package supporting the oral
formulation multiple indications including
LN
EFFICACY:
VOS Efficacy Studies in DES dogs (Proof
of Principles)
HUMAN Phase 1 Dose Escalation Study
VOS Efficacy Study vs. Standard of Care
in DES dogs (MAH under MTA)

VOS has a robust safety and EXTERNAL VOS VALIDATION:

toxicology package that Merck Animal Health Licensing deal
should support further for animal use
clinical advancement.
151
Promising VOS Efficacy Seen in Early Canine Studies
Dogs with naturally occurring model of immune-mediated KCS were switched
from Optimmune to VOS.
STT maintained at normal levels entire 30 days

SCHIRMER TEAR TEST (N=6)

25.0
Schirmer Tear Test Values (mm/min)

20.0 VOS .2%

15.0
Normal STT in Dogs >15mm/min

10.0
Discontinuation of
Optimmune (2% CsA)
5.0 initiation of VOS .2%
Expected STT value
without therapy

0.0
Baseline Day 7 Day 14 Day 28

152
VOS Has the Potential for Improved Dosing vs. Restasis
Ocular pK in animals supports QD dosing of VOS 0.2%.
Tissue levels after single dose in NZW rabbits over 24 hours
All tissues above therapeutic target concentration at 24 hours

Tissue Levels After Single Dose in NZW Rabbits

VCS Concentration in
Conjunctiva

VCS Concentration in
Cornea

Therapeutic concentration
of CsA (50-300ng/g) in
Conjunctiva & Cornea*

*R.L. Kaswan., Intraocular penetration of topically applied cyclosporine, Transplantation Proceedings, vol 20, no. 2, supplement, pp. 650-655, 1988
153
 VOS Tolerability in Healthy Volunteers Similar to Placebo
Phase 1 dose escalation study to assess the safety and tolerability
of VOS in health volunteers.
30 healthy patients, placebo vs. 2 doses VOS, over an 8 hour period four applications per
eye

Foreign Body Sensation Ocular Dryness Burning or Pain

10 10 10
9 9 9
8 8 8
7 7 7
6 6 6
5 5 5
4 4 4
3 3 3
2 2 2
1 1 1
0 0 0
None Mild Moderate None Mild Moderate None Mild Moderate
Placebo VOS .02% VOS .2% Placebo VOS .02% VOS .2% Placebo VOS .02% VOS .2%

Lemp, M.A., Beckman, R., Weiss, S., Originally published by Lux BioSciences
154
VOS Tolerability in Healthy Volunteers Similar to Placebo
Phase 1 dose escalation trial, 30 healthy patients, placebo or
2 doses VOS, over an 8 hour period four applications per eye

Visual Fluctuation with

Photo-Phobia Blink
10 10
9 9
8 8
7 7
6 6
5 5
4 4
3 3
2 2
1 1
0 0
None Mild Moderate None Mild Moderate
Placebo VOS .02% VOS .2% Placebo VOS .02% VOS .2%

Lemp, M.A., Beckman, R., Weiss, S., Originally published by Lux BioSciences
155
 VOS Also Has the Potential for Improved Onset of Action
Cohort 3 of Phase 1 safety and tolerability study: Promising early improvements in Signs and
Symptoms in 2 weeks.
OSDI scores were improved in all subjects at all time points while on drug
Phase 1 data (Cohort 3): 5 patients with DES dosed BID for 14 days
(Sign) (Symptom)
Schirmers I-test at Mean Change in OSDI & Symptom Subscales
Screening and Day 14
Tear Production Increase Reduction in Score from Baseline
+31% + 68% - 32% - 48% - 27% - 15%
9 90

0=No Disability, 100=Complete Disability

8 80
mm/5 Minutes

7 70
6 60
5 50
4 40
3 30
2 20
1 10
0 0
Left Eye Right Eye OSDI Total Score Vision Related Ocular Symtom Environmental
Function Subscale Subscale Triggers Subscale
Screening Day 14 Baseline Day 14
Lemp, M.A., Beckman, R., Weiss, S.,
Originally published by Lux BioSciences 156
VOS Clinical Development Strategy
Phase 2a Randomized Active-Controlled Parallel-group study of the Ocular
Tolerability of VOS in DES patients*
2-4 week Primary &
Q2 2018 Secondary endpoints

VOS .2%
N = ~50
Restasis .05%
2H 2018

KEY INCLUSION CRITERIA OUTCOME MEASURES

Have a hx of DES in one or both eyes
Primary: Ocular tolerability vs. Restasis
supported by a previous clinical diagnosis

A symptom score of 30 on a VAS (1-100) Secondary: Adverse Events

An anesthetized Schirmer score of 5 and

10/5min
Evidence of ocular surface staining
(fluorescein staining of at least 3 (0-15))
Secondary: OSDI, SANDE, VAS (dryness)
Secondary: Corneal Staining, Conjunctival
Staining, Schirmer test
*Subject to FDA discussions
157
 Planned VOS Development Activities and Timelines

Q4 2017 Q1 2018 Q2 2018 Q3 2018 Q4 2018 Q1 2019 Q1 2019

FDA IND
MEETING OPEN

Clinical Trial
1 Supply

2 Phase 2a:
Clinical Supply Comparative
Available Tolerability H2H
vs. Restasis

Phase 2b:
CLINICAL STUDY or Asset Monetization

158
VOS: Potential to Be a Low Risk, High Reward Project

Voclosporin Ophthalmic Solution (VOS) incorporates

a unique & patented nanomicellar formulation system with potential clinical
advantages vs. Restasis.

VOS is ~4 times more potent than CsA and

VOS achieved high concentrations in the
VOS has a 4-fold higher concentration of API
target tissues of the eye (Rabbit model
per drop than Restasis
preclinical data)
(clear solution vs. microemulsion)

VOS has demonstrated excellent tolerability

VOS has the potential to be dosed once
in a H2H preclinical comparison to Restasis
daily with a rapid onset of action (Rabbit
& in a Phase 1 study irritation equivalent to
study)
placebo

VOS has the potential to be a well differentiated and best in class CNI for the
treatment of Dry Eye Syndrome

159
 Wrap-Up
Richard Glickman
Chief Executive Officer

www.auriniapharma.com
Summary

Current clinical Aggressively NS significant New product to

program is on pursuing opportunity to develop and
track and additional IP and create value monetize
actively putting extend runway
together NDA

INDICATION EXPANSION & NEW PRODUCT DEVELOPMENT ARE WITHIN

CURRENT FINANCIAL RESOURCES

161
 Milestones

1H 2018 2H 2018 1H 2019 2H 2019 1H 2020 2H 2020 1H 2021

AURORA
Initiate Phase 3 AURORA Phase 3
DDI Study (LN) Recruitment
Program in NS Data (LN)
Complete

AURORA TARGET LN
Initiate NS Proof NS Final Proof of
of Concept
Extension Study
Concept Data
LAUNCH
Begins NS data readouts
DDI study
Initiate VOS NS Interim Data
Phase 2a Readouts

VOS Phase 2a
data

Submit IND for Rolling NDA (LN)

Rolling NDA NDA final Potential FDA
Nephrotic Initiated:
(LN):CMC submission (LN) Adcom (LN)
Syndrome (NS) Non-Clinical

FDA Meeting on Potential

VOS approval (LN)

162
Q&A Session

#1203-4464 Markham Street Victoria BC V8Z 7X8

www.auriniapharma.com