1. health and fitness
2. disease
3. cancer

Corporate Presentation
October 2014
Forward-Looking Statements
This presentation contains forward-looking statements. These statements are not guarantees of future performance and involve a
number of unknown risks, assumptions, trends, uncertainties and factors that are beyond our control. Given these risks, assumptions
and uncertainties, you should not place undue reliance on these forward-looking statements. Forward-looking statements in this
presentation include statements regarding development plans, potential therapeutic indications and the potential of any of our product
candidates to address unmet medical needs. The clinical data included in this presentation is preliminary and the studies and trials are
ongoing. There can be no assurance that the data generated at the end of the studies and trials will be consistent with the preliminary
results described in this presentation. In addition, future data generated in the studies and trials may demonstrate trends not apparent
at this time. There can be no assurance that future studies and trials will generate positive results or that any of our product candidates
will receive regulatory approvals. All statements contained in this presentation are made only as of the date of this presentation and
are subject to uncertainty and changes. Except as required by law, we expressly disclaim any responsibility to update our forwardlooking statements, whether as a result of new information, future events or otherwise.
Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include,
among others, those that are set forth under the heading “Risk Factors” in TetraLogic Pharmaceuticals Corporation’s (the “Company”)
Form 10-K filed with the Securities and Exchange Commission (the “SEC”) on March 19, 2014 and its Form 10-Q filed with the SEC on
August 5, 2014. You can review the Company’s filings and other documents for free by visiting EDGAR on the SEC’s website:
www.sec.gov.
“TetraLogic Pharmaceuticals” is a registered trademark and “TetraLogic” and the “TetraLogic Pharmaceuticals” logo are unregistered
trademarks of the Company. Other trade names, trademarks and service marks appearing in this presentation are the property of their
respective owners. Solely for convenience, the trademarks, service marks and trade names in this presentation are referred to without
the ® and TM symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the
fullest extent under applicable law, their rights thereto.
This presentation is not an offer to sell or a solicitation of an offer to buy securities of the company. Any offering of the company’s
securities will be made by means of a prospectus or other appropriate offering document that will contain or incorporate by reference
detailed information about the company and the proposed offering.
2
TetraLogic Overview
Initial Focus on Apoptosis
ONCOLOGY

Clinical trials in MDS, Ovarian Cancer and CRC
INFECTIOUS DISEASE

Phase 1 clinical trial with birinapant in HBV in 4Q14
Expansion into Dermatology

Phase 2 clinical trial with SHAPE (suberohydroxamic
acid phenyl ester) in early-stage CTCL in 4Q14
Future Pipeline Expansion into Related
Therapeutic Areas
3
Birinapant – Focused on Apoptosis
Programmed cell death (“apoptosis”)

Fundamental mechanism to maintaining human health

Enables abnormal cells to naturally undergo self-destruction

Tightly regulated process

Dysfunctional in cancer and infectious disease
Birinapant – SMAC Mimetic which “unblocks”
apoptosis

Selected from a library of over 3,000 internally discovered compounds

Studied in ~ 300 cancer subjects

Clinical activity in multiple indications
Strong IP position: composition of matter patent on
birinapant through 2030
4
Birinapant’s Novel Mechanism of Action
Mimics the Endogenous Protein SMAC

SMAC antagonizes IAPs and enables
TNF to drive damaged cells to selfdestruct


Cancerous and virally-infected cells
avoid apoptosis
IAPs block apoptosis and divert the TNF
signaling to pro-survival
TNF
TNF
cIAP-1
SMAC
SMAC
cIAP-1
caspases
caspases
NF-kB
XIAP
XIAP
APOPTOSIS
ABNORMAL CELL
SURVIVAL
5
Birinapant’s Novel Mechanism of Action
Potential to Re-establish the Body’s Ability to Eliminate Abnormal Cells


Birinapant blocks the amplified IAPs and thus re-establishes the TNF apoptotic signal
Birinapant also re-establishes the TRAIL apoptotic signal
TNF
Birinapant
(SMAC mimetic)
TRAIL
cIAP-1
NF-kB
Birinapant
(SMAC mimetic)
caspases
XIAP
APOPTOSIS
ABNORMAL CELL
SURVIVAL
6
Birinapant in Infectious Disease
Birinapant in Hepatitis B
~ 2 Billion people in the world have been infected with
hepatitis B (1 in 3 people), including 12 million in US
~ 400 Million people worldwide are chronically
infected, including > 1 million in US
There is no cure for chronic hepatitis B infection

Leads to increased risk of cirrhosis and liver cancer

~ 1 million deaths annually worldwide, including 5,000 in US, from
hepatitis B and its complications

Loss of surface antigen (HBsAg) or seroconversion ≈ functional cure
8
Existing HBV Drugs are Unsatisfactory
PEG-interferon (PEGASYS)

48 week course can result in HBsAg seroconversion, but
only 3-5% per year (natural conversion rate is ~ 0.5%)

Significant side effects such as flu-like symptoms,
depression
Reverse Transcriptase inhibitors: tenofovir,
entecavir, lamivudine

Can improve patient outcomes, but do not significantly
decrease HBsAg levels nor result in HBsAg seroconversion

Life-long treatment required
9
A New Mouse Model for Human Hepatitis B
Method: Hydrodynamic injection of human hepatitis B plasmid (pAAV-HBV1.2)
Advantages include:
a.
b.
c.
d.
e.
f.
Chronicity
Some animals undergo spontaneous 'cure’ (C57Bl/6) but others do not (C3H)
Immuno-competent animals
Response is associated with loss of HBsAg
Response is associated with development of anti-HBsAg antibodies
Genetic model allows independent confirmation of birinapant’s effect
As such it is an excellent model of human disease
10
Birinapant Accelerates Clearance of HBV in Mice…
There is loss of HBsAg with loss of HBV-DNA
BIRINAPANT
BIRINAPANT
108
Vehicle (n=6)
Vehicle (n=6)
Enteacovir (n=6)
104
Entecovir (n=6)
Birinapant (n=6)
103
101
IU/ml
102
HBsAg
copies/ml
105 106
104
103
Entecovir
Entecovir
102
HBV-DNA
107
Birinapant (n=6)
0
14
28
42
0
14
28
42
Time post first dose (days)
11
Birinapant Clears Hepatitis B Virus (HBV) In Vivo
Decrease in Circulating HBV-DNA with Birinapant

TNF is required for birinapant's
effect; consistent with the anticancer mechanism of action

Birinapant is additive with
polymerase inhibitors such as
entecavir
Note: Studies conducted in lab of Dr. Marc Pellegrini, Walter and Eliza Hall Institute of Medical Research, Australia
12
Birinapant Clears Hepatitis B Virus In Vivo
Decrease in HBV-DNA in the Liver with Birinapant

> 100-Fold Reduction in HBV
DNA in the Liver at 35 days
Note: Studies conducted in lab of Dr. Marc Pellegrini, Walter and Eliza Hall Institute of Medical Research, Australia
13
Birinapant Kills HBV Infected Hepatocytes
Birinapant (H&E 24hr after 1 dose)
Apoptosis Identified by TUNEL Staining
of Fragmented DNA
HBV-core
TUNEL
DAPI = DNA
14
2000
ALT
AST
500
500
750
1000
1000
1500
Untreated
Vehicle
Birinapant
250
IU/ml
1250
1500
Death of Infected Hepatocytes Causes Transient Elevation of Liver Enzymes
12
24
48
12
Time post birinapant treatment (hours)
24
48
15
Knock Out Animals Independently Confirm Birinapant’s Mechanism of Action
cIAP1 & cIAP2 liver knock-outs accelerate HBV clearance, loss of HBsAg and appearance of antiHBsAg antibodies
104
P<0.001
30
Anti-HBsAg
antibody
10
20
20
IU/ml
40
40
60
101
IU/ml
80
cIAP1 liver-null &
cIAP2 null
0
Proportion of mice with detectable
serum HBV-DNA (%)
XIAP null
***
103
Wildtype
102
100
HBsAg
2
4
6
8
Time post infection (weeks)
10
12
nd
Taken at 2 weeks
16
Phase 1b/2a in Subjects with Chronic Hepatitis B
Study Objectives
PRIMARY
 Safety and tolerability of birinapant in subjects with chronic hepatitis
B being treated with tenofavir or entecavir
SECONDARY
 Pharmacokinetics of birinapant, tenofavir and entecavir
 Efficacy of birinapant in reducing HBsAg out to day 85
Study Population
 Subjects with chronic hepatitis B currently taking either tenofavir or
entecavir for a period of ≥ 3 months with a measurable HBsAg titer
Dose and Schedule
 Birinapant will be administered once weekly for 4 doses
 Dosing cohorts: up to 6 cohorts with 8 subjects per cohort treated
with drug or placebo in a 3:1 ratio
17
Potential Broad Applicability in Other Viral and Mycobacterial Infections
HIV Assays: Normal PBMC samples infected in-vitro
Induced apoptosis in HIV-infected CD4+ cells
TB Assays: in-vivo mouse model
Reduction in lung burden after 3 doses
120
80
60
CFU/lung
% Alive
100
40
20
0
NT
0.1
1
10
Birinapant (µM)
Decreased Reverse Transcriptase Activity (24h)
1000
Donor 1
Birinapant
(n=17)
Donor 2
800
Donor 3
cpm
Control
(n=15)
600
(0.33 Log10 CFU/lung; p = 0.012)
400
200
0
NT 0.1 1 10
NT 0.1 1 10
NT 0.1 1 10
Birinapant
18
Birinapant in Oncology
Birinapant Safety and Pharmacodynamics
Well-tolerated at pharmacologically active doses

Tested in ~ 300 subjects with solid and hematological cancers

Several subjects have continued >12 months

Dose-limiting toxicities:


Elevated serum amylase & lipase, Bell’s Palsy

Occurred above Recommended Phase 2 Dose
Safely combined with multiple chemotherapeutic regimens
Target suppression (cIAP1) and favorable PK in tumors

Greater than 50 hour half-life in tumors

Selective and prolonged target suppression in tumors

NF-ҡB suppression in AML blasts
Signals of activity in patients

Colorectal cancer

Myelodysplastic syndrome
20
Birinapant in Oncology
Myelodysplastic Syndromes (MDS)

~ 13,000 new diagnoses of MDS every year in US

~ 40% are higher-risk (RAEB1 and RAEB2)

Current therapies include Celgene’s azacitidine (Vidaza™) and Eisai's
decitabine (Dacogen™)

Only ~ 30% of higher-risk patients respond to azacitidine

~ 33% of patients diagnosed with MDS progress to secondary AML

RAEB1 median survival is 18 months with 25% progressing to AML

RAEB2 median survival is 10 months with 33% progressing to AML
Potential utility in other solid and liquid tumors

AML, CRC, Ovarian Cancer
21
Birinapant in Combination with Azacitidine in Higher-Risk MDS
Rationale

IAPs overexpressed in MDS

Disease evolution associated with enhanced IAP activity and up regulation of NF-ҡB
Birinapant single agent activity

Hematological activity in relapsed/refractory secondary AML (sAML)
–
In one subject decrease in bone marrow blasts from 60% to 10%
Birinapant synergistic with azacitidine

Azacitidine is an inducer of TNF

Synergy with combination both in vitro and in vivo

In Phase 1 clinical trial, exacerbation of skin reactions at sites of subcutaneous azacitidine injections

Significant reductions in bone marrow blast count in 3/9 treated patients:
1.
One prior cycle of azacitidine, blast count reduction from 25% to 2% at the end of cycle 1
2.
Naïve to azacitidine, blast count reduction from 17% to 2% at the end of cycle 3
3.
Refractory to single agent azacitidine, blast count reduction from 21% to 7% at the end of
cycle 2
22
Randomized Phase 2 Trial Design: 1st Line Higher Risk MDS
Birinapant + azacitidine vs. azacitidine
birinapant +
azacitidine
RR
azacitidine
RR
1:1 randomization
(n = 148)
Commenced trial
1H 2014
Interim Review
Mid-2015
Data Expected
End-2015
ASSUMPTIONS

Primary Endpoint: Response Rate (RR)

Overall Alpha = 5.0%, 1-Sided (Show an absolute 20% improvement in RR with 80% power)

Interim analysis will be conducted after 74 subjects complete 4 cycles of therapy
23
Birinapant in Oncology – Additional Programs
Ovarian Cancer

Open-label Phase 1/2 clinical trial of birinapant and Amgen’s conatumumab is ongoing
Colorectal Cancer

Proof of Concept established for birinapant plus irinotecan in advanced CRC


Irinotecan-refractory subjects: 4mo PFS = 32%; 6mo PFS = 18%
Intend to start a randomized Phase 2 clinical trial of birinapant in combination with
FOLFIRI/Avastin in 2nd-line KRAS-mutant CRC in 3Q2015
24
SHAPE
A Novel, Tissue-Targeted Therapy
SHAPE is Differentiated from Currently-Marketed HDAC Inhibitors
Novel topical HDAC Inhibitor with issued US
composition of matter patent through 2028 (plus
PTA)
Intentionally designed to maximize HDAC-inhibition
in the skin but limit systemic exposure
Fraction Remaining (%)
Human Blood vs. Human Skin Homogenate
26
SHAPE: Active in the Skin
Ethanol-based Vehicle
0.5% SHAPE (3.5 mg/mL)

Activity in the skin demonstrated by acetylation in keratinocytes

Stable in a gel formulation, allowing for convenient topical application
27
First Indication: CTCL
Cutaneous T-Cell Lymphoma
 CTCL affects > 30,000 patients in North America
 Early-stage disease (Stages IA-IIA) represents ~75% of all CTCL cases
 Chronic disease with 5 year survival rate ~ 88%
 Current therapies for early-stage disease include: Topical Corticosteroids, Topical
Retinoids (Targretin®), Topical Nitrogen Mustard (Valchlor®), Phototherapy
 Poorly tolerated
 Highly irritating to skin
 Slow onset of response (median ~ 6 months)
Potential broader utility in autoimmune skin disorders
 Atopic dermatitis, Alopecia areata, Psoriasis
28
One Month Treatment with SHAPE Led to Cutaneous Responses in Early-Stage CTCL
Phase 1 Clinical Trial of SHAPE in Stage IA-IIA CTCL: Design
5:1 randomization
(n = 18)
0.1% SHAPE or
Placebo
RR
0.5% SHAPE or
Placebo
RR
1% SHAPE or
Placebo
RR
Treatment duration: Maximum 28 days, 2 week follow up
Dosing frequency: BID (twice daily)
RESULTS

Four subjects (~27%) demonstrated PRs by 50% reduction in CAILS score from baseline at Days
28 or 42

Subjects on placebo demonstrated no significant improvements

No significant safety events observed: no SAEs, no discontinuations, no DLTS, no systemic
sequelae (AEs: mild skin burning, erythema)
29
Proposed Phase 2 Trial Design: 1st Line CTCL (Stage IA-IIA)
SHAPE (0.5%) BID vs SHAPE (1.0%) QD and BID
1:1:1 randomization
(n = 60)
0.5% SHAPE BID
RR
1% SHAPE QD
RR
1% SHAPE BID
RR
Commence trial
4Q 2014
Data Expected
End-2015
ASSUMPTIONS

Evaluate dose, efficacy at 6 months (vs 1 month), time to response and tolerability of
treatment of >2% body surface area

Determine treatment effect to design registration study (comparison to Valchlor)
30
Clinical Milestones
ONCOLOGY
PRE-CLINICAL
Myelodysplastic Syndromes (MDS)
Birinapant
PHASE 1
PHASE 2
Randomized Phase 2 clinical trial initiated 2Q14;
interim analysis expected 2Q15
Cutaneous T-Cell Lymphoma (CTCL)
SHAPE
Randomized Phase 2 trial expected to commence
4Q14; data expected year-end 2015
Colorectal Cancer (CRC)
Randomized Phase 2 clinical trial expected to
commence in 3Q15
Ovarian Cancer
Phase 1/2 clinical trial initiated 4Q13;
data expected year-end 2014
Birinapant
Birinapant
INFECTIOUS DISEASE
Hepatitis B
Birinapant
Phase 1b/2a clinical trial expected to commence 4Q14;
data expected mid-2015
31
Investment Highlights
Novel therapeutic approaches in
oncology and infectious disease
Strong clinical data
Multiple value-creating milestones
Proven management team
32
Thank you