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Business Overview BUSINESS OVERVIEW January 2012 1 About Trevi Founded in 2011 by members of the executive management team of Penwest Pharmaceuticals, which was acquired by Endo Pharmaceuticals in Q4 2010 Angel investors include Trevi management and board members Trevi’s strategy is to develop compounds, primarily for orphan diseases, with the goal of completing key development work and securing a marketing partner at an optimal valuation point for the Company and its investors In-licensed worldwide rights to a Phase 2 asset, N albuphine HCL ER, in May 2011. Currently seeking orphan drug designation in the US and EU. Also prosecuting patent applications Preparing to commence clinical studies in early 2012 2 2 Management and Board of Directors Key Management and Founders: Jennifer Good President and CEO Formerly President and CEO of Penwest Thomas Sciascia, M.D. Chief Medical Officer Formerly SVP of Clinical and Regulatory and CMO at Penwest Board of Directors: Peter Drake Co-Founder of Vector Securities, Vector Fund Management and Deerfield Management Robert Hennessey Former President and CEO of Genome Therapeutics David Meeker, M.D. Chief Executive Officer, Genzyme Corporation William O’Shea Former President and COO of Sepracor Anne Van Lent President AMV Advisors. Former EVP and CFO of Barrier Therapeutics 3 3 Nalbuphine ER Opportunity Target Indication: Treatment of chronic uremic pruritus in dialysis patients Definition of Uremic Pruritus (itching) caused by uremia. Uremia is a Pruritis: metabolic condition in patients with chronic renal failure that leads to renal replacement therapy (Hemodialysis, Peritoneal Dialysis or Renal Transplant) Estimated # of patients: U.S. 170,000 patients Europe 135,000 patients Market is increasing due to steady growth of end stage renal disease and patients on dialysis No approved therapies in the US or Europe Estimated Peak Market $400-$600 million Potential (US and EU) Protection: Seeking orphan drug protection in both the U.S (7 years) and Europe (10 years) and prosecuting patent applications 4 4 Chronic Uremic Pruritus and Market Opportunity 5 Uremic Pruritus Disease Definitions Uremic Pruritus in ESRD Patients on Dialysis • Uremic pruritus is itching experienced by patients with chronic kidney failure undergoing dialysis1 • It is most common on the back, but also on arms, head, abdomen • It can be worse during rest, with dry skin, heat, sweat & stress • Initially patients do not show any changes in skin appearance2 • In moderate to severe cases, excoriations by scratching with or without impetigo can occur (see photo) 2 Source: 1Patel et. al., 2007, An Update on Pruritus Associated with CKD. Am J of Kidney Dis (2007) 50: 11-20. 2Mettang et. al., 2002, Uraemic pruritus – new perspectives and insights from recent trials. Nephro. Dial. Transplant. (2002) 17:1558-1563. 6 6 Causes-Uremic Pruritus Causes of Uremic Pruritus (UP) • The pathophysiological mechanism(s) of UP in these patients remains largely unknown • Several hypotheses for the cause have been proposed, including: • Metabolic disturbances such as hypercalcemia , hyperphosphatemia, secondary hyperparathyroidism • Iron deficiency anemia • Changes in the opioidergic system 7 7 Standard of Care – Uremic Pruritus No consensus treatment guidelines exist, but most physician’s interviewed and some facilities report the following step-wise treatment algorithm for UP: 1. Ensure dialysis is achieving serum phosphate and calcium levels in target range and hemoglobin is in adequate range; also encourage patient compliance with dietary restrictions and phosphate binding therapy 2. Ensure normal parathyroid hormone levels 3. Begin treatment with OTC emollients (Aveeno , Eucerin , Lac -Hydrin, Lubriderm, Moisturel or anti-itch versions) and Capsaicin cream 4. Initiate oral antihistamine therapy (Benadryl, Atarax , Periactin , Vistaril, Tavist , Hismanal) 5. Refer to Dermatologist − Initiate a trial of phototherapy with UVB light three times weekly (dermatology consult) Source: Primary market research conducted with 10 US nephrologists, February 2011. Bay State Medical Center treatment algorithm ( at www.promotingexcellence.org/tools/pe5714.html) 8 8 Treatment Outcomes with Uremic Pruritis Nephrologists Report Failure in ~ Half of Moderate and Severe Cases • The treatment options available to 100% Failure nephrologists work well for mild 90% patients; less so for moderate and severe patients 80% • Nephrologists are unsuccessful with 70% nearly 40% of moderately affected patients and nearly 50% of severely 60% affected patients 50% Success • Nephrologists reported a 3.9 out of 7 as their level of satisfaction to 40% current therapies 30% • Treatment failures are referred to a dermatologist for UVB therapy, 20% which helps approx 50% of patients 10% 0% Mild Moderate Severe Source: Primary market research conducted with 10 US nephrologists, February 2011. 9 9 Uremic Pruritus: Morbidity and Mortality Issues • Pisoni (2006) et al concluded that moderate to extreme pruritus leads to a sleep disturbance which explains in large part the increased mortality risk. The persistence of pruritus in the moderate to extreme group correlates with morbidity issues centering around life quality declines and ineffective pruritic treatment related poly-pharmacy. • Narita (2006) et al reported only 3% of mild patients (N=826) were on an oral medication (anti-histamine or sedative). Severe uremic pruritic patients had statistically higher medication use relative to other patients of less pruritic intensity. Below is the relative difference in the Kaplan-Meier Survival curve distributed by itch intensity 10 10 End Stage Renal Disease and Dialysis Market US Dialysis Population is Growing Steadily • In 2009, over 575,000 patients U.S. ESRD & Dialysis Patient Trends had ESRD1 700,000 • Approximately 400,000 ESRD 650,000 patients were receiving dialysis 2 600,000 in 2009 • Patients receiving dialysis has 550,000 grown 3-4%/yr for the past 500,000 decade, despite a slight 450,000 downward trend the in percent of ESRD patients receiving 400,000 dialysis3 350,000 • By 2020 there are projected to 300,000 ESRD Patients be 785,000 ESRD patients due to aging “baby boomers” and 250,000 Dialysis Patients rising diabetes rates4 200,000 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Source: 1US Renal Data System – Incident and Prevalent counts by quarter (see Q4 2009 at www.usrds.org) 2US Renal Data System 2010 Annual report V.2, Atlas of ESRD in the US (at www.usrds.org); NOTE: report includes data thru 2008, 2009 % ESRD on dialysis is extrapolated and the 2009 dialysis patient number is calculated from the actual ESRD number of patients 3US Renal Data System 2010 Annual report V.2, Atlas of ESRD in the US (at www.usrds.org); NOTE: 2009 percent is extrapolated 4ASN press release Nov 2007, Gilbertson. 11 11 Uremic Pruritus Market Size - US Over 60% of Dialysis Patients Reported Chronic Pruritus Dialysis Patient Pruritus • A patient-based survey of pruritus in Assessment dialysis patients was conducted in 1 n = 12,839 patients 2002-03 in 12 countries 35% • 61% Of patients reported chronic 30% 29% 29% pruritus1 • 24% Of patients reported severe 25% Severe = 24% pruritus1 20% 18% • These rates are similar to those found in a 1996 -2001 survey1 15% 14% • Translates into US UP market of 10% 10% (patients): • Mild = 116,000 5% • Moderate = 72,000 0% • Severe = 96,000 Not Somewhat Moderately Very Much Extremely Source: 1Pisoni et. al., 2006, Pruritus in haemodialysis patients: international results from the Dialysis Outcomes and Practice Patterns Outcomes Study (DOPPS), Nephro Dial Transplant (2006) 21: 3495-3505. Countries included: US (1,444 pnts), UK, France, Spain, Italy, Germany, Belgium, Sweden, Canada, Australia, New Zealand, Japan 12 12 Uremic Pruritus Market Size - EU EU Market Size is Similar to the US Market Size • The EU ERA-EDTA registry recently reported the number of dialysis patients at December 31, 2009 as 309,407 • Prevalence of moderate to severe Uremic Pruritus in the European Community is 42-45%, resulting in a prevalence of 130,000-139,000 patients at December 31, 2009 • A European Medicines Agency orphan designation document stated the number of UP patients as 131,000 in the EU in 2002 • Based on these two sources, we estimate EU moderate to severe UP patient population is to be 135,000 13 13 Competitive Landscape Nalfurafine (Remitch) – Toray Industries/Torii Pharma • Approved in 2009 in Japan for uremic pruritus resistant to conventional therapies1 − Selective kappa-opioid receptor agonist − Oral, once-daily capsule in 2.5mcg and 5.0mcg doses − Cost = $21/day; $7,665/year − First full year sales in Japan (March 2010) = $42.8 million2 − 2011 full year sales (March 2011) in Japan = $94.4 million • Efficacy in a placebo controlled Phase 3 study • Licensed to Acologix for US development—company ran out of money and rights reverted back to Toray • October 2011—Toray announced that North American rights licensed to Mitsubishi Source: 1 Toray Industries, March 23, 2009 Press Release. Launch of REMITCH® Capsules 2.5 µg , new oral antipruritus drug. 2 Torii Pharmaceuticals 2010 Annual Report (year ending March 31, 2010) 14 14 Competitive Landscape Other Potential Competitors • Cara Therapeutics (private; pain focus, CT) − Studying 2 selective kappa agonists for pain (CR845 & CR665) − CR845 has completed a Phase 2 study in post-op pain (I.V.) − Company stated it has preclinical anti-itch activity1 and they are pursuing the development for UP (but no clinical studies identified) and
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