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HBV Remains
a Formidable
Challenge
Despite decades of ongoing effort,
the current standard of care is still
unable to provide a functional cure
for HBV infection
Achieving this for the vast majority of HBV patients is the key unmet
need and aspiration of the marketplace
2
Deeply
Experienced,
Results-
Driven
Leadership
ABEL DE LA
ROSA, PHDChairman I Senior Scientific &
Strategic Advisor
Coinventor of ATI-2173
Cofounder
PHARMASSET
• SVP Business Development
& Scientific Affairs
• Executive team member that
helped build company from
$30MM valuation through
development of Sofosbuvir for
HCV, IPO, and $11B acquisition
by Gilead
EMORY UNIVERSITY—
DRIVE
•Chief Scientific Officer
• Visible Genetics
GREG MAYESChief Executive Officer
ENGAGE THERAPEUTICS
• Founder and CEO
• $40MM raised, acquired by
UCB in 2020 for $270MM
following positive phase 2b
study
ADVAXIS
IMMUNOTHERAPIES
•Chief Scientific Officer
• Visible Genetics
VP,PRODUCT
DEVELOPMENT
• Acquired by Bayer
IMCLONE SYSTEMS
• VP, General Counsel, and
Chief Compliance Officer
• Acquired by Eli Lilly for $6.5B
DOUG MAYERS, MDChief Medical Officer
Cofounder
IDENIX
•Chief Medical Officer
• Acquired by Merck for $3.9B
COCRYSTAL PHARMA, INC.
•Chief Medical Officer
• NASDAQ: COCP
BOEHRINGER INGELHEIM
• Therapeutic Area Head and
International Vice President of
Virology
TAMRA ADAMSChief Financial Officer
ACCOUNTING CONCEPTS
• Founder
• Consulting CFO for Engage
Therapeutics until sale to UCB
GOLDMAN SACHS
• Senior Accounting Officer
ERNST & YOUNG
• Senior Auditor
Board of Directors
Benjamin Rovinski David Canner Iyona Rajkomar Patrick Higgins Scott Morenstein
3
ANTIOS Investment Highlights
Clinical-stage biopharma company focused on innovative therapies to treat and cure hepatitis B
• 250MM to 300MM individuals infected with chronic HBV worldwide require lifelong therapy; larger market than
hepatitis C and HIV combined
Accomplished leadership team: Cofounder helped build Pharmasset’s curative hepatitis C franchise
Lead drug candidate ATI-2173 has potential to become the cornerstone of curative, once-daily HBV therapy
• ATI-2173 is the only active site polymerase inhibitor nucleotide (ASPIN) in development
• ASPIN mechanism is complementary to all other approaches—potential to completely shut down viral
replication and cure hepatitis B
Phase 2 program informed by compelling phase 1b proof-of-concept data
• Efficacy—Potent, “next-generation ASPIN” antiviral activity confirmed, sustained beyond treatment cessation
• Safety—ATI-2173 liver-targeted active metabolite; finite duration of treatment; well tolerated
Solid interest from investor group with relevant experience
• Investors include RA Capital, Adage, Pontifax, and Aisling
• Regular phase 2 data readouts expected through 2022
4
Our Vision Is
a World
Liberated
From the
Burden of HBV
ATI-2173
THE CORNERSTONE OF CUREBecoming the critical component for achieving functional cure
for nearly all people living with hepatitis B
• The first stone set, serving as
a reference for all others
• Cornerstones serve as the
guiding light that determines
the position or direction of
everything that follows
6
Chronic HBV is a Greater Global Burden Than HCV
and HIV Combined
End-stage liver disease
(~20% of patients)
Death (~900K annually)
Source: WHO; CDC; ClearView Analysis.
Globally, 250MM to 300MM
adults have chronic HBV
1.0MM 1.8MM 77MM
Failure to successfully manage HBV leads to:
Low worldwide treatment rates
represent an opportunity-35% -35% -10%
7
Development of hepatocellular
carcinoma in ~50% of patients
Source: Tang, LSY, et al.2018 JAMA
Viable
Solutions
Promise
Substantial
Rewards
Source: WHO; CDC; ClearView Analysis.
Market Research Suggests >$9 Billion
Cumulative ATI-2173 Sales Potential
From US, China and EU
Base Case Cumulative Sales for ATI-2173
(2026-2042, US, EU3, China)
0 1 2 3 4 5 6 7 8 9
HBV
Revenue ($B)
$3.4 (US) $1.8 (EU3) $2.7 (China)
8
Chronic HBV Currently Demands Complex,
Lifelong Therapy To Sustain Viral Suppression
HBV complexity will almost
certainly require combination
therapy to effect a true cure
SOC chain-terminating nucleoside
analogues (tenofovir and entecavir)
control replication—but >90% of
patients relapse quickly on treatment
discontinuation
HBV:DNA virus with cccDNA that
stays inside the nucleus and
acts as a reservoir to
sustain the infection
CURE COMPLEXITYLESS MORE
HIV:Retrovirus that
integrates into the host
genome resulting in
lifelong infection
HCV: An RNA virus with
no reservoir
9
Poised to Repeat Transformational HCV Treatment Success in HBV
10
Prior to 2014:
• Very low HCV cure rates (10-50%); commensurately low product sales
• Injectable interferon was the backbone of treatment
Sofosbuvir-based regimens were the inflection point that changed HCV
treatment forever
• 1st approved oral nucleotide achieved cure rates >85%
• Eliminated the need for interferon
• >400,000 patients treated in first 36 months post launch
• 8x increase in patient initiation from 2013 to 2015
• Peak sales in US: ~$12B
Previous Pharmasset, Idenix, and Abbvie leadership are now at
Antios to repeat history with ATI-2173 for HBV
HCV Milestones: Improved Safety and Efficacy
Mavyret
Telbivudine
Protease Inhibitor
(Boceprevir or
Telaprevir) with INF/RIVINF-alpha 2b
(IFN)
INF-alpha 2b and
ribavirin Combination
(IFN + RBV)
First commercially
available HBV vaccine
INF-alpha
Adefovir
Entecavir
Tenofovir Tenofovir
alafenamide
Harvoni
Viekira Pak
1990’s 2010’s 2020
HBV Milestones
Lamivudine
(Nuc)
2000’s
Sovaldi
Olysio
The HBV Market is Well Positioned to Parallel the
Innovation Seen in HCV
Sofosbuvir-based regimens were the inflection
point that changed HCV treatment forever
1st approved oral nucleotide achieved cure rates >85%
>400,000 patients treated in first 36 months post launch
8x increase in patient initiation from 2013 to 2015
Peak sales in US: ~$12B
HCV Classes: PI, Nuc, NS3/4A, NS5A, NS5B
New Classes: ASPIN, CAM, STOP, RNA destabilizer, siRNA/ASO
HCV
SVR
Rates
<10% <46% <56-60%
Addition of Interferon Free All-Oral regimens
85-98%
11
The Only ASPIN in Development Leverages a Unique
Mechanism To Empower Combination Therapy
Chain-terminating nucleoside analogues
like tenofovir and entecavir compete for
positions in the replicating viral DNA,
expending themselves through incorporation
to block some DNA synthesis through
chain termination
ATI-2173 actively binds to and distorts
the HBV polymerase enzyme’s active
site to catastrophically disrupt ALL
aspects of polymerase activity (protein
priming, chain elongation, and DNA
synthesis)
12
Combination
Therapy is
Within Reach
ATI-2173 combined with a complementary
mechanism, in a convenient, once-daily
regimen, could completely shut down HBV
replication—and potentially cure HBV
infected individuals
13
Arbutus Bio (AB-729)
Antios Partner
Arrowhead (JNJ-3989)
Vir Biotech (VIR-2218)
Assembly Bio (ABI-H0731)
Assembly Bio (ABI-H3733)
Arbutus Bio (AB-836)
Enanta (EDP-514)
Aligos Ther (ALG-00184)
ETV, entecavir; siRNA,
small/short interfering
ribonucleic acid; TDF,
tenofovir.
ATI-2173 Creates Wide Opportunity for Powerful
Combination Regimens
14
Building On Experience to Optimize
Treatment Potential
*Yoo, et al. Hepatol 2007; 45:1172-1178, Yoo, et al. Hepatol 2007; 46:1041-1048.†Clevudine was first approved in South Korea in 2006.
ATI-2173
• Clevudine demonstrated sustained off-treatment antiviral efficacy vs SOC in HBV-infected patients in
South Korean trials*,†
• However, Pharmasset voluntarily discontinued further development due to reversible proximal skeletal
muscle myopathy seen in some patients after long-term dosing
• ATI-2173 is a liver-targeted phosphoramidate prodrug of clevudine
• ATI-2173 is ion-trapped in the liver as clevudine monophosphate,
leading to:
▪ High liver clevudine triphosphate levels
▪ Low systemic clevudine exposure
• 1-year finite duration of therapy further reduces potential myopathy risk
ATI-2173 leverages that sustained potency, while enhancing safety
15
ATI-2173 Significantly Reduces Systemic
Clevudine Exposure
Squires et al. 2021 EASL; Abstract 1240, *Lim, S. G. et al. 2008 Aliment Pharmacol Ther
• In a phase 1B study, ATI-2173 was rapidly
cleared from the blood within 4 to 6 hours
• Clevudine exposure was dose proportional
and multiple-fold below 30 mg dose of
clevudine
• 56 ng/mL was the historical clevudine
Cmin during treatment*
0 8 16 24
0
20
40
60
80Clevudine
56 ng/mL
Pla
sm
a C
once
ntr
ation
(n
g/m
L)
Hours
50mg–Day 28
25mg–Day 28
16
ATI-2173 Phase 1b Safety Data Similar to Placebo
Mayers et al. 2021 EASL; Abstract 1251.
TEAE, treatment-emergent adverse event.
No serious adverse events or adverse events leading to study drug discontinuation
MedDRA System Organ Class
Preferred Term
All Cohorts
Placebo
(n=7)
n (%)
Cohort C
10 mg
(n=6)
n (%)
Cohort A
25 mg
(n=5)
n (%)
Cohort B
50 mg
(n=6)
n (%)
Subjects with any TEAE 5 (71.4) 1 (16.7) 3 (60.0) 4 (66.7)
Thrombocytosis 0 1 (16.7) 0 0
Secondary thrombocytopenia 0 0 0 1 (16.7)
External ear pain 0 0 0 1 (16.7)
Nausea 0 0 0 1 (16.7)
Fatigue 0 0 1 (20.0) 0
Inflammation 1 (14.3) 0 0 0
Flu 0 0 0 1 (16.7)
Common cold 1 (14.3) 0 0 0
Coronavirus infection 0 0 1 (20.0) 1 (16.7)
ALT/AST high 2 (28.6) 0 0 0
Blood creatine phosphokinase increased 1 (14.3) 0 0 0
Bone pain 0 0 1 (20.0) 0
Headache 1 (14.3) 0 2 (40.0) 1 (16.7)
17
All Doses of ATI-2173 Demonstrated Potent
Antiviral Activity
*Marcellin, P et. al. 2004. Hepatology
Mayers et al. 2021 EASL; Abstract 1251.
Viral reductions with ATI-2173
corresponded to those seen
previously with clevudine
treatment: 2.5 to 3 log10*
• 25 mg ATI-2173 (n=5): 2.7 log10
• 50 mg ATI-2173 (n=6): 2.7 log10
• Placebo (n=7): 0.2 log10 increase
Ch
an
ge
Fro
m B
aselin
e (
HB
V D
NA
lo
g1
0IU
/mL
)
0 7 14 21 28
-5
-4
-3
-2
-1
0
1
Day
25mg
Placebo
50mg
18
Prolonged HBV RNA suppression with ATI-2173
demonstrates potential cccDNA activity
• 28-day ATI-2173 (25 or 50mg) treatment
decreases HBV RNA in all subjects
• Two subjects were below level of quantification
(BLQ) at baseline and throughout most of
study, thus were excluded from analysis
• Missing data from one subject
• RNA decreased on treatment and continued to
decrease off treatment for one month, similar to
DNA
• Reduction in HBV RNA was sustained for ATI-
2173-dosed subjects
• All ATI-2173 (25 or 50mg) treated subjects are
BLQ by W4 off-treatment and slowly trend toward
baseline by W24 off-treatment
• Placebo treatment is associated with no pattern of
change in HBV RNA
• One subject was BLQ at baseline and
throughout study, thus is excluded from
analysis
Sustained BLQ D28 W4 (D55) W12 (D111) W24 (D195)
Placebo subjects, N 6 6 5 5
Active subjects, N 8 8 7 7
Placebo, n (% of N)1
(17%)0
(0%)1
(20%)0
(0%)
25/50mg with BLQ, n (% of N)
5(63%)
8(100%)
7(100%)
3(43%)
Off treatment
19
Change by subject to EOTHBV RNA suppression correlates to reduced
cccDNA activity and may predict off-
treatment SVRs
0 28 56 84 112 140 168 196
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
0.2
0.4
Day
HB
V R
NA
(lo
g10 c
op
ies/m
L)
Ch
an
ge f
rom
Baselin
e
Change from Baseline
Placebo
ATI-2173 25 or 50mg
0 28 56 84 112 140 168 196
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
0.2
0.4
Day
HB
V R
NA
(lo
g10 c
op
ies/m
L)
Ch
an
ge f
rom
Baselin
e
Change from Baseline
Placebo
ATI-2173 25 or 50mg
ALT Normalizes With ATI-2173 Therapy
As expected, antigen levels remained unchanged during short duration of treatment
100
80
60
40
20
0
AL
T, U
/L
Day
0 7 14 21 28 35 42 49 56
ULN
Range
Placebo (n=7) ATI-2173 25 mg (n=5) ATI-2173 50 mg (n=6)
White shading indicates the 28-day treatment period. ALT, alanine aminotransferase; ULN, upper limit of normal.
20
ATI-2173 Showed Extended Off-treatment Responses
Mayers et al. 2021 EASL; Abstract 1251.
• 25 mg and 50 mg show equivalent
HBV DNA suppression
• One patient achieved SVR24
in 25 mg arm and was followed
until relapse
21
n treatment ff treatment
B
Placebo
B B B B
B B B B B B B
B B B B B B B B
B B B b B B
A I mg
B B B B B B
B B B
B B B B B
B B B B B
B B B B
B I m ebound detectable NA after B A flare
AT
I-2
17
3 2
5 m
g
Study Design
• ATI-2173 + TDF will be administered orally, once daily for 90 days in treatment naïve patients then stopped
• Treatment will be restarted for HBV-infected subjects during follow-up if viral rebound or a hepatic flare
• SVR24 data for HBV DNA will be available in mid-2022
• Addition of 2 cohorts, 1 with an siRNA and 1 with a core inhibitor in late-2021 (SAVE-2)
End of
Study
Follow-Up
24 weeks
Treatment
12 weeksScreening ≤8 weeks
SAVE-1 and SAVE-2 (Sustained Antiviral Efficacy) Trial
Cohort A: 25 mg HBV
Fully enrolled
ATI-2173 25 mg + TDF (n=8)
Placebo 25 mg + TDF (n=2)
Cohort B: 50 mg HBV
Fully enrolled
ATI-2173 50 mg + TDF (n=8)
Placebo 50 mg + TDF (n=2)
Cohort C: 50 mg HBV/HDV
Enrolling
ATI-2173 50 mg + TDF (n=8)
Placebo 50 mg + TDF (n=2)
Cohort E (other partner ): 25 mg
HBV
Start up
ATI-2173 25 mg + CI + TDF (n=8)
Placebo + TDF (n=2)
Cohort D (Arbutus): 25 mg HBV
Start up
ATI-2173 25 mg + siRNA + TDF
(n=8)
Placebo + TDF (n=2)
SA
VE
-1
SA
VE
-2
Phase 2a Study Design
22
Future Phase 2 Studies to Commence in H2 2022
Study Design
• Phase 2 studies with HBV mono-infected patients dosing for 1 year with ATI-2173 + TDF
• Treatment naïve study to include patients who have had no HBV treatment or have been off HBV treatment for > 6 months
• Treatment experienced study to include patients who have been controlled on NRTIs for > 1 year
• Studies will include both HBeAg positive and negative patients
• Global reach with sites in US, EU, and Asia
• Flexible approach allows additional studies with novel HBV agents.
Treatment
Experienced
Approximately n=140
TDF + Placebo
ATI-2173 + TDF
Follow-Up 24 weeksTreatment Duration up to 1 yearScreening ≤ 8
weeks
Primary Endpoint:
HBV DNA SVR 24 weeks
post-treatment
Secondary Endpoint:
HBsAg Loss
Treatment Naïve
Approximately n=100
23
TDF + Placebo
ATI-2173 + TDF
ATI-2173 Proprietary Manufacturing
Process in Place
API manufacture:
• Developed and optimized an 8 linear step chiral
process from the GMP starting material
• Used to produce 3 separate 25+ kg batches of API
• API produced is >99.7% pure
• Low cost of goods
• Primary supplier of API engaged; several potential
backup suppliers have been identified
Drug product manufacture:
• DP formulation developed
• Currently used to manufacture 25 mg capsules
• 2+ year shelf life for capsules
24
24
ATI-2173—Extended, Multilayer IP Protection
• ATI-2173: 9 patents issued (US and
international) including composition of
matter, method of use, and synthesis;
IP protection expected to 2042;
17 applications pending
• ATI-2173 combination: 1 patent
issued with protection to 2042;
15 applications pending
Robust portfolio of patents granted worldwide
(August 2021)
US, Japan, S Africa, Israel, Singapore, Australia,
Eurasia (Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, and Turkmenistan).
25
Inflection-point Progress Continues to add Value
2021 2022
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
1Q21: Series
B/Crossover
Financing
1Q21:
Phase 2a First
Patient Dosed
2Q21:
EASL 2021
Phase 1b Data
Presentations
3Q21:
SAVE-2:
Clinical Trial
Collaborations
Announced
2Q22:
SVR24
Off-treatment
Combination
Data
2Q21:
Chronic Tox
Skeletal Muscle
Histopath
3Q21:
Phase 2a
On-treatment
Combination
Data
1Q22: Phase 2a End-of-
treatment
Virology
Endpoints
Q422:
Off Treatment
Triplet
Combination
Data
Q421:
New Product
Announcement
3/4Q22:
First Patient
Dosed In
Phase II
26
Antios Vision—A Cure for HBV
ATI-2173 has demonstrated potent HBV viral suppression with durable off-treatment suppression in early studies
Liver-targeting offers the potential for an enhanced safety profile for ATI-2173 by lowering systemic exposure to clevudine
The only active site polymerase inhibitor nucleotide (ASPIN) in development—a potential future cornerstone for curative HBV combination therapy
Cumulative sales potential exceeds $9B in US, China, and EU
Antios maintains a robust IP portfolio, wholly-owned proprietary manufacturing process, and strategic flexibility to pursue beneficial biopharmaceutical partnerships
ATI-2173 could be combined with a complementary drug class to create an oral regimen that sustainably shuts down all viral replication
27