Corporate Presentation. August 2014

Transcription

1 Corporate Presentation August 2014

2 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 forward-looking 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-KfiledwiththeSecuritiesandExchangeCommission (the SEC ) on March 19, 2014 and its Form 10-Q filed with the SEC on May 8, You can review the Company s filings and other documents for free by visiting EDGAR on the SEC s website: 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

3 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

4 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

5 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 SMAC ciap-1 ciap-1 SMAC XIAP caspases NF- B caspases XIAP APOPTOSIS ABNORMAL CELL SURVIVAL 5

6 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 TRAIL Birinapant (SMAC mimetic) ciap-1 Birinapant (SMAC mimetic) XIAP caspases NF- B APOPTOSIS ABNORMAL CELL SURVIVAL 6

7 Birinapant in Infectious Disease

8 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 5000 in US, from hepatitis B and its complications Loss of surface antigen (HBsAg) or seroconversion functional cure 8

9 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

10 Birinapant Clears Hepatitis B Virus In Vivo Decrease in Circulating HBV-DNA with Birinapant 10 8 day antibody 200 g i.p. Birinapant 30mg/kg i.p HBV DNA (copies/ml) IgG1 ctrl + vehicle (n=16) * 10 3 IgG1 ctrl + Birinapant (n=16) anti-tnfα Ab + vehicle (n=16) anti-tnfα Ab + Birinapant (n=16) * p 0.05 unpaired t-test * Time after 1st 1 dose (days) (wks) TNF is required for birinapant's effect; consistent with the anti-cancer 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 10

11 Birinapant Clears Hepatitis B Virus In Vivo Decrease in HBV DNA in the Liver with Birinapant + vehicle + Birinapant 1.4 * 1.2 HBV-DNA / GAPDH >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 11

12 Birinapant Causes a Decline in Hepatitis B Surface Antigen Day 0-8 Entecavir daily (oral) Day 0 7 Birinapant (i.p.) 10 4 Entecavir (n=6) Birinapant (n=6) * 10 3 DMSO (n=6) Entecavir Birinapant (n=6)]* p value 0.05 HBsAg [IU/ml] * Time 14 after first dose 28 (wks) 42 Time after 1 st dose (days) Entecavir does not cause this decline, implying a fundamental difference in mechanism Intend to start a Phase 1 clinical trial in Hepatitis B late 2014 Note: Studies conducted in lab of Dr. Marc Pellegrini, Walter and Eliza Hall Institute of Medical Research, Australia 12

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 13

14 Phase 1 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 14

15 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 Decreased Reverse Transcriptase Activity (24h) Donor 1 Donor 2 Donor 3 Control (n=15) Birinapant (n=17) (0.33 Log 10 CFU/lung; p = 0.012) 15

16 Birinapant in Oncology

17 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 17

18 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 18

19 Birinapant in Combination with Azacitidine in Higher-Risk MDS Rationale IAPs overexpressed in MDS Disease evolution associated with enhanced IAP activity and upregulation 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 19

20 Randomized Phase 2 Trial Design: 1 st Line Higher Risk MDS Birinapant + azacitidine vs. azacitidine birinapant + azacitidine RR 1:1 randomization (n = 148) azacitidine RR 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 20

21 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 3Q

22 SHAPE A Novel, Tissue-Targeted Therapy

23 SHAPE is Differentiated from Currently-Marketed HDAC Inhibitors Inhibits HDAC1, 2, 3, & 6 isoforms Contains ester bond to promote pre-systemic metabolism by serum esterases Intentionally designed to maximize HDAC-inhibition in the skin but limit systemic exposure Negligible levels of systemic exposure translates to reduced risk of HDACi class-associated toxicities Discovered at Harvard, the Dana-Farber Cancer Institute, the Broad Institute and MIT Issued US composition of matter patent through 2028 (plus PTA) 23

24 SHAPE: Novel Tissue-Targeted Design 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 Human Blood vs. Human Skin Homogenate Fraction Remaining (%) 24

25 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 25

26 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 26

27 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 0.1% SHAPE or Placebo RR 5:1 randomization (n = 18) 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) 27

28 Proposed Phase 2 Trial Design: 1st Line CTCL (Stage IA-IIA) SHAPE (0.5%) BID vs SHAPE (1.0%) QD and BID 0.5% SHAPE BID RR 1:1:1 randomization (n = 60) 1% SHAPE QD RR 1% SHAPE BID RR Commence trial 4Q 2014 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) Data Expected End

29 Clinical Milestones Hepatitis B Phase 1 clinical trial expected to commence 4Q14; data expected mid-2015 Myelodysplastic Syndromes Randomized Phase 2 clinical trial initiated 2Q14; interim analysis expected 2Q15 Ovarian Cancer Phase 1/2 clinical trial initiated 4Q13; data expected year-end 2014 Early-Stage Cutaneous T-Cell Lymphoma Randomized Phase 2 trial expected to commence 4Q14; data expected year-end 2015 Colorectal Cancer Randomized Phase 2 clinical trial expected to commence in 3Q15 29

30 Investment Highlights Novel therapeutic approaches in oncology and infectious disease Strong clinical data Multiple value-creating milestones Proven management team 30

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