For Partnering Interest

PLEASE CONTACT

Stuart Sedlack

SVP, Business Development

T: 650.273.5748 x112

E:stuart@vpd.net

For Patients

CLICK ON THE LINK TO VIEW CLINICAL TRIALS FOR VPD-737

clinicaltrials.gov/tigercat/CP

Overview

VPD-737 (serlopitant) is a potent oral NK1 receptor antagonist that Tigercat Pharma, Inc., licensed from Merck in 2012. It is highly selective for the human NK1 receptor and in both animal and human testing it has been well tolerated. The pharmacokinetics have been studied in animals and humans as well as the receptor binding allowing for rational dose selection for further trials.

Beginning in 2005, Merck evaluated serlopitant in 13 Phase 1 studies and two Phase 2b studies, comprising over 900 subjects and patients. In the Phase 1 studies, single doses of 400 mg and multiple doses of 50 mg per day up to 28 days were generally well tolerated in healthy young males and in healthy elderly males and females (age ≤80 years). Merck also assessed serlopitant for safety and efficacy in a Phase 2 study in overactive bladder and in a Phase 2 study for alcohol dependence.

ROLE OF SUBSTANCE P AND NK1 RECEPTORS IN PRURITUS

Although pruritus is a frequent symptom of many dermatological and systemic conditions its pathophysiology is poorly understood. Pruritus is a cutaneous sensory perception transmitted via neuropeptide-containing unmyelinated nerve fibers in the papillary dermis and epidermis. Substance P and its receptor, neurokinin receptor 1 (NK1), have been implicated by a number of preclinical and clinical studies to be important in the pathogenesis of pruritus.

Tigercat Pharma, Inc., is currently assessing VPD-737 in two Phase 2b studies. The first study, a randomized, double blind, placebo controlled study over six weeks is studying the safety and efficacy of VPD-737 in 240 patients with chronic pruritus. The study is being conducted in 24 sites within the United States and the primary endpoint is change in pruritus severity as measured by the Visual Analog Scale. Tigercat is also studying VPD-737 in a randomized, double blind, placebo controlled study over eight weeks to assess the safety and efficacy of VPD-737 in 60 patients with prurigo nodularis, a severe form of pruritus characterized by pruritic nodules and lesions. This study is being conducted in 4 sites within Germany and the primary endpoint is change in pruritus severity as measured by the Visual Analog Scale.

CHRONIC PRURITUS

Pruritus (itch) is a sensation that provokes a desire to scratch and can have many causes related either to the skin or to systemic illness. Itch related to an underlying condition such as renal or liver failure may respond to treatment of the underlying disease. In other cases nonspecific treatment with mediators of inflammation such as antihistamines or corticosteroids can offer some relief. However, in many cases of chronic itch (defined as lasting 6 weeks or more) these treatments are ineffective. Chronic itch is associated with significant morbidity and decrease in quality of life including difficulty sleeping. In some patients chronic rubbing or scratching of the skin as a result of itch leads to secondary skin changes such as in prurigo nodularis or lichen simplex chronica further increasing morbidity.

The precise prevalence of this condition is unknown but represents a significant number of patient visits to dermatologists. A population based cross-sectional study of 19,000 adults revealed that about 8-9% of the general population experienced acute pruritus, which was a dominant symptom across all age groups. Moreover, pruritus was strongly associated with chronic pain and it is well known that the incidence of chronic itch increases with age. Recent surveys indicate a point-prevalence of chronic pruritus to be around 13.5% in the general adult population. Prurigo-NOS (Not Otherwise Specified) is as common as psoriasis or rosacea and approximately 1.2 million US visits are made annually of which 50% are to dermatologists.

REFERENCES

1. Toyoda M, Nakamura M, Makino T, Hino T, Kagoura M, Morohashi M. Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis. The British journal of dermatology. Jul 2002;147(1):71-79.

2. El-Nour H, Lundeberg L, Al-Tawil R, Granlund A, Lonne-Rahm SB, Nordlind K. Upregulation of the axonal growth and the expression of substance P and its NK1 receptor in human allergic contact dermatitis. Immunopharmacology and immunotoxicology. 2006;28(4):621-631.

3. Jarvikallio A, Harvima IT, Naukkarinen A. Mast cells, nerves and neuropeptides in atopic dermatitis and nummular eczema. Archives of dermatological research. Apr 2003;295(1):2-7.

4. Carstens EE, Carstens MI, Simons CT, Jinks SL. Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. Neuroreport. Mar 10 2010;21(4):303-308.

5. Andoh T, Nagasawa T, Satoh M, Kuraishi Y. Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice. The Journal of pharmacology and experimental therapeutics. Sep 1998;286(3):1140-1145.

6. Ohmura T, Hayashi T, Satoh Y, Konomi A, Jung B, Satoh H. Involvement of substance P in scratching behaviour in an atopic dermatitis model. European journal of pharmacology. May 3 2004;491(2-3):191-194.

7. Stander S, Siepmann D, Herrgott I, Sunderkotter C, Luger TA. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PloS one. 2010;5(6):e10968.

8. Duval A, Dubertret L. Aprepitant as an antipruritic agent? The New England journal of medicine. Oct 1 2009;361(14):1415-1416.

9. Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J. Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. The British journal of dermatology. Mar 2011;164(3):665-667.

10. Santini D, Vincenzi B, Guida FM, et al. Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. The lancet oncology. Oct 2012;13(10):1020-1024.

11. Vincenzi B, Tonini G, Santini D. Aprepitant for erlotinib-induced pruritus. The New England journal of medicine. Jul 22 2010;363(4):397-398.

12.Mir O, Blanchet B, Goldwasser F. More on aprepitant for erlotinib-induced pruritus. The New England journal of medicine. Feb 3 2011;364(5):487.

13.Torres T, Fernandes I, Selores M, Alves R, Lima M. Aprepitant: Evidence of its effectiveness in patients with refractory pruritus continues. Journal of the American Academy of Dermatology. Jan 2012;66(1):e14-15.