Robert Hindes MD - Trek comprehensive confidential investor ak4 deck 2016

Making infectious disease drugs for allTREKtx-Confidential 1

TREK Therapeutics, PBC (TREKtx)

Confidential Comprehensive Slide Deck


Experienced LeadershipManagement Team

Ann Kwong, PhDCEO

• Founder of the infectious disease program at Vertex, played leading and innovative role in the discovery, development and commercialization of telaprevir and VX-787 (Flu inhibitor)

• Founder of HCV DRAG: consortium that produces consensus guidelines for HCV drug development

Founder

Robert Hindes, MDCMO

• Major roles in the clinical development for entecavir and daclatasvir (BMS) and sofosbuvir at Pharmasset/Gilead

• Deep experience with the DAVP, CROs and CTIs around the world

Jerry Zeldis, MDChairman of the Board and Founder

• Launched 8 drugs as CMO of Celgene• Highly successful startup track record

Xiao Tong, PhDVP Research

• Lead Virologist on HCV project teams (Schering/Merck)

• Helped to develop and launch boceprevir (Schering/Merck)

• Responsible for virology support for multiple HCV and influenza programs (Roche)

Kevin Bittorf, PhD, MBAVP CMC and Business Development

• Led the formulation and manufacturing of telaprevir (Vertex)

• Managed CMC partnerships in N. America, Europe, and Asia

Michael Bator, MBACFO

• Experienced equity research analyst, healthcare investor, and senior management advisor in Pharmaceuticals and Biotechnology

Camilla Graham, PhD, MPHVP Medical and Government Affairs

• Led medical affairs at Vertex through the launches of telaprevir and ivacaftor (for cystic fibrosis).

• At Harvard Medical School/Beth Israel Deaconess, she worked with government agencies and payers on access to HCV treatments


Distinguished Clinical Advisory Board

Clinical Advisory Board• Ira Jacobson, Board chairman at Icahn

School of Medicine at Mount Sinai, USA• Marc Bourliere, Hôpital Saint Joseph,

France• Hugo Cheinquer, Universidade Federal do

Rio Grande do Sul, Brazil• Doug Dieterich, Icahn School of Medicine at

Mount Sinai, USA• Geoffrey Dusheiko, University College

London Medical School, UK• Jordan Feld, University of Toronto, Canada• Adrian Gadano, Hospital Italiano de Buenos

Aires, Argentina• Tarek Hassanein, Southern California GI &

Liver Centers, USA• Adeeba Kamarulzaman, Univ of Malaya,

Malaysia

• George Lau, Humanity and Health Liver Clinic, China

• Eric Lawitz, Texas Liver Institute, University of Texas, USA

• Mark Sulkowski, Johns Hopkins University School of Medicine. USA

• Tracy Swan, Treatment Action Group, USA

• Gyongyi Szabo, UMASS Medical School, USA

• Heiner Wedemeyer, Hannover Med School, Germany

• Lai Wei, Peking University, China• Stefan Zeuzem, JW Goethe University

Hospital, Germany


• Mission: To create safe new affordable and accessible drugs to treat infectious diseases and commercialize them for global populations

• TREKtx current focus is HCV» License and develop assets to

create world-class regimens

TREKtx’s Vision and Current Focus


HCV Treatments are “Breaking the Bank”

“What they have done with this particular drug will break the country, it will make pharmacy benefits no longer sustainable.”

- Steven Miller, CMO of Express Scripts

» Harvoni is currently being sold for $45-95,000 per regimen

» There is not enough money in the healthcare system to support treating all 3 million HCV patients in the US at that price

» Insurers and PBMs see the pricing model as unsustainable, and many are unwilling to pay for patients

~120 million patients ex-US who currently

cannot afford treatment

The Sovaldi Tax: Gilead Can't Justify The Price It's

Asking For Hepatitis C Therapy

The Apothecary: Insights into health care and entitlement reform

GUEST POST WRITTEN BY

Steve Miller

Dr. Miller, M.D., is senior vice president and chief medical officer of Express Scripts.

A cure for hepatitis C is within reach for 170 million people around the world — thanks to

the charitable efforts of poor and sick Americans who are picking up the tab by paying

outrageous prices for their own treatment. It’s like Robin Hood in reverse.

This is what happens when a pill is priced at $1,000 a day in the U.S., and an entire treatment

regimen of 84 of those pills costs just $900 in Egypt. Exact same medicine, completely

different pricing.

While it is a nice gesture by hepatitis C patients in the U.S. to help people they’ll never meet,

it’s truly unfortunate. Gilead Sciences, the manufacturer of the drug Sovaldi, is generating

enormous profits on the backs of patients here and ensuring significant profits in other…

http://www.forbes.com/sites/theapothecary/2014/06/17/the-sovaldi-tax-gilead-cant-justify-the-price-its-asking-americans-to-pay/print/

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TREKtx’s Solution

Top Management Team

Available High Potency, Well-

Characterized Assets

WW Demand for Affordable Therapy

Making infectious disease drugs for all 7

ASSET OVERVIEW

Making infectious disease drugs for all 8

TD-6450 (NS5A)


• TD-6450 is a highly potent third generation NS5A inhibitor that was initially developed by Theravance Biopharma

• TD-6450 has excellent bioavailability as a powder in a capsule» Formulation optimization is ongoing» We will examine co-formulating TD-6450 and FDV

TD-6450: A Brief Clinical Overview • Designed to have improved activity against DCV GT1 RAVs of 1st generation NS5A Inhibitors

• Potent VL drop observed in GT1a/1b, but not in GT2 or 3 patients

• PK: QD dosing supported by 60-66 hour T1/2 (half-life)

• Metabolized by liver with very little renal excretion

• No clinically significant food effect

• Investigating potential of creating a long acting injectible formulation

TD-6450 Revised slide


TD-6450: Compared to Benchmark 5A InhibitorsMax ↓VL log10 with monotherapy

Inhibitors Company GT1a GT1bTD-6450, 120 mg 240 mg TBPH/TREKtx -4.63

-4.98Not Done

-4.65

Elbasvir, 50 mg Merck -4.2 -5.1

GS-5816, 150 mg Gilead -4.2 -4.3

ACH-3102, 25 mg Achillion -4.04 -4.04

Daclatasvir, 60 mg (1a) 10 mg (1b) BMS -3.75 -4.3

PPI-668, 240 mg Presidio -3.71 -3.8

Ledipasvir, 90 mg (1a) 10 mg (1b) Gilead -3.1 -3.3

TD-6450 monotherapy is best-in-class in GT1a


NS5A Inhibitors Replicon IC50s (nM) by GT Inhibitors Company GT1a GT1b GT2 GT3 GT4 TD-6450 TBPH/TREKtx 0.006 0.006 0.2-0.6 0.4 0.004

ACH-3102 Achillion 0.014 0.012 <0.14 <0.14 <0.14

Elbasvir Merck 0.004 0.003 0.003-0.3 0.02 0.003

Ledipasvir Gilead 0.034 0.004 21-210 35 0.11

GS-5816 Gilead 0.012 0.015 0.008-0.014 0.012 0.009

Daclatasvir BMS 0.05 0.009 0.1 0.15 0.012

PPI-668 Presidio ~0.102 ~0.011 ~0.105 ~1.02 ~0.05

• GT1b: all show similar replicon potency, achieve similar max VL↓ in monotherapy

• GT1a: TD-6450 comparable to elbasvir and GS-5816 in replicon potency but with better VL↓

• GT4: all have good replicon potency; some have demonstrated clinical efficacy» GS-5816 achieved 3.5 log VL↓ in GT4 monotherapy» Elbasvir plus grazoprevir achieved 100% SVR in naïve patients (C-EDGE)

TD-6450 plus FDV is expected to confer high SVRs in GT1 and GT4


TD-6450 Displays a High Barrier to Resistance

GT1a mutants (fold change EC50) GT1b mutants (fold change EC50)

RAV M28T Q30E Q30R L31V L31M Y93H Y93N L31V Y93H L31V+Y93H A92E

DCV 100x 1300x 160x 400x 80x 500x 2,500x 5x 50x 10,000x 0.7x

Elbasvir 15x NA 16x 61x 10x 220x 929x 4x 17x NA NA

TD-6450 5x 0.8x 1x 10x 1x 42x 133x 1.7x 167x 417x 83xClinical VL ↓ √ NA NA NA √ # # NA # # #

• Higher barrier to resistance confers higher antiviral potency in the clinic• TD-6450 was designed to inhibit DCV resistance-associated variants (RAVs)

» Smaller decrease in sensitivity (fold change EC50) than DCV and elbasvir for all major RAVs except for Y93H and A92E in GT1b

» TD-6450 reduced VL in patients with pre-existing low-level resistance NS5A mutations

√: > 3 log10 VL reduction in 3-day TD-6450 monotherapy in patients with the pre-existing 5A mutations#: major resistance mutations during VL rebound post-dosing


TD-6450 Demonstrated Dose-Dependent Antiviral Activity 100% of GT1a patients had at least 3 log10 reduction in HCV RNA

Reduction in HCV RNA (log10 IU/mL reported as n(%)TD-6450

60 mg (N=7)TD-6450

120 mg (N=7)TD-6450

240 mg (N=7)

≥ 3.0 7 (100) 7 (100) 7 (100)

≥ 3.5 7 (100) 6 (86) 6 (86)

≥ 4.0 3 (29) 5 (71) 6 (86)

≥ 4.5 0 4 (57) 6 (86)

≥ 5.0 0 2 (29) 3 (43)

≥ 5.5 0 1 (14) 2 (29)

Subjects < LOD 0 3 (43) 4 (57)

Subjects < LOD at Day 14 0 1 (14) 2 (29)


7 patients achieved HCV RNA <LOD, which was maintained for 28 days in 2 patients


TD-6450 Demonstrated Dose-Dependent Antiviral Activity 100% of GT1a patients had at least 3 log10 reduction in HCV RNA

Reduction in HCV RNA (log10 IU/mL reported as n(%)TD-6450

60 mg (N=7)TD-6450

120 mg (N=7)TD-6450

240 mg (N=7)

≥ 3.0 7 (100) 7 (100) 7 (100)

≥ 3.5 7 (100) 6 (86) 6 (86)

≥ 4.0 3 (29) 5 (71) 6 (86)

≥ 4.5 0 4 (57) 6 (86)

≥ 5.0 0 2 (29) 3 (43)

≥ 5.5 0 1 (14) 2 (29)

Subjects < LOD 0 3 (43) 4 (57)



7 patients achieved HCV RNA <LOD, which was maintained for 28 days in 2 patients


FALDAPREVIR (PI)


• 2nd generation HCV protease inhibitor (PI)» Similar to simeprevir (Olyssio)

Faldaprevir (FDV)

Faldaprevir: A Brief Clinical Overview• FDV has strong activity against GT 1 • PK: QD dosing (t1/2 ~ 20 hrs), liver metabolized• Side effects include increased indirect bilirubin, GI upset

(diarrhea), sun sensitivity (but not rash)• Reformulation may reduce GI side effects


• TREKtx clinical strategy is dynamic given the potential for further acquisitions, but the initial trial designs remain unchanged• TREKtx has several factors working in our favor from a

regulatory perspective:1. Well characterized assets 2. Deeply experienced management team

TREKtx’s Clinical Strategy: Speed and Efficiency

TREKtx received favorable feedback on its first protocol from the FDA in 7 days


Clinical Paths

• The decision to pursue a next gen low cost provider approach vs. developing a best in class product will be based on the outcome of ongoing BD discussions

• Focused on finding partners to license TREKtx assets, run clinical trials and commercialize

• High interest from KOLs for FDV +TD-6450 to be used in combination with sofosbuvir to treat naïve and treatment-experienced GT4 patients in Egypt

• Not emphasizing internal clinical development for these markets

• Targeting GT1b patient population with FDV + TD-6450 +/- RBV, but plan to add VX-222 to treat GT1a

• Initiating Phase 2a GT1a and 1b studies in New Zealand

• Enroll Phase 2b and 3 GT1b study in several countries

• Focused on finding partners to license TREKtx assets, run clinical trials and commercialize in China, Russia, Ukraine, etc

US & Western Europe Developing Countries(e.g., Egypt)

The Middle Market(e.g., Romania, Turkey)

Revised slide


• The purpose of the study was TD-6450 dose selection and support for future Geno 4 Phase 2b/3 studies in Egypt

• FDA approved the IND within 7 days of submission; separate DDI study, placebo arm, sequential dosing were not required• 120 mg FDV QD was selected based on FDV’s extensive clinical

data; TD-6450 is dosed at 60 mg and 120 mg QD (N=12)• There is no control arm, the site and patients are blinded• Ribavirin was added to maximize efficacy, ± RBV will be

studied in Ph2b

TREKtx’s First Ph2a Study

TREKtx GT4 Ph2a study started in the US in October 2015

Revised slide


Positioning

• TREKtx is uniquely positioned with two potent, well characterized assets

» FDV & TD-6450» These assets position TREKtx to move rapidly towards commercialization» Capitalize on the GT1b and GT4 regimen in the “Middle Market”

• In developed markets, the superiority of TD-6450 in GT1 to all other NS5A inhibitors strengthens TREKtx’s optionality

» Multiple opportunities to create a potential “best in class” regimen by acquiring a nuc or novel MOA asset

• TREKtx has begun to connect with and seek partnering opportunities in major markets such as Egypt, Russia, and China

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Health & Medicine

Robert Hindes MD - Trek comprehensive confidential investor ak4 deck 2016