Publicidad
Publicidad

Más contenido relacionado

Presentaciones para ti(20)

Publicidad

Similar a Robert Hindes MD - Trek comprehensive confidential investor ak4 deck 2016(20)

Publicidad

Robert Hindes MD - Trek comprehensive confidential investor ak4 deck 2016

  1. Making infectious disease drugs for allTREKtx-Confidential TREK Therapeutics, PBC (TREKtx) Confidential Comprehensive Slide Deck 1
  2. Making infectious disease drugs for allTREKtx-Confidential Management Team Ann Kwong, PhD CEO • 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, MD CMO • 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, MD Chairman of the Board and Founder • Launched 8 drugs as CMO of Celgene • Highly successful startup track record Xiao Tong, PhD VP 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, MBA VP CMC and Business Development • Led the formulation and manufacturing of telaprevir (Vertex) • Managed CMC partnerships in N. America, Europe, and Asia Michael Bator, MBA CFO • Experienced equity research analyst, healthcare investor, and senior management advisor in Pharmaceuticals and Biotechnology Camilla Graham, PhD, MPH VP 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 2
  3. Making infectious disease drugs for allTREKtx-Confidential 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 3
  4. Making infectious disease drugs for allTREKtx-Confidential • 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 4
  5. Making infectious disease drugs for allTREKtx-Confidential “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/ 5 Revised slide
  6. Making infectious disease drugs for allTREKtx-Confidential Top Management Team Available High Potency, Well- Characterized Assets WW Demand for Affordable Therapy 6
  7. Making infectious disease drugs for all ASSET OVERVIEW 7
  8. Making infectious disease drugs for all TD-6450 (NS5A) 8
  9. Making infectious disease drugs for allTREKtx-Confidential • 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 9 Revised slide
  10. Making infectious disease drugs for allTREKtx-Confidential Max ↓VL log10 with monotherapy Inhibitors Company GT1a GT1b TD-6450, 120 mg 240 mg TBPH/TREKtx -4.63 -4.98 Not 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 10
  11. Making infectious disease drugs for allTREKtx-Confidential 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 11
  12. Making infectious disease drugs for allTREKtx-Confidential 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 83x Clinical 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 12
  13. Making infectious disease drugs for allTREKtx-Confidential 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) Subjects < LOD at Day 28 0 1 (14) 1 (14) 7 patients achieved HCV RNA <LOD, which was maintained for 28 days in 2 patients 13
  14. Making infectious disease drugs for allTREKtx-Confidential 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) Subjects < LOD at Day 28 0 1 (14) 1 (14) 7 patients achieved HCV RNA <LOD, which was maintained for 28 days in 2 patients 14
  15. Making infectious disease drugs for allTREKtx-Confidential FALDAPREVIR (PI) 15
  16. Making infectious disease drugs for allTREKtx-Confidential • 2nd generation HCV protease inhibitor (PI) » Similar to simeprevir (Olyssio) 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 16
  17. Making infectious disease drugs for allTREKtx-Confidential • 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 received favorable feedback on its first protocol from the FDA in 7 days 17
  18. Making infectious disease drugs for allTREKtx-Confidential • 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) 18 The Middle Market (e.g., Romania, Turkey) Revised slide
  19. Making infectious disease drugs for allTREKtx-Confidential • 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 GT4 Ph2a study started in the US in October 2015 19 Revised slide
  20. Making infectious disease drugs for allTREKtx-Confidential 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 20 Revised slide
Publicidad