Developing the next generation of dermatology products to treat serious skin diseases

Transcription

1 Developing the next generation of dermatology products to treat serious skin diseases Tom Wiggans Chairman and Chief Executive Officer

2 Forward Looking Statements This presentation contains "forward-looking statements" as defined under the U.S. federal securities laws including, but not limited to, statements regarding Peplin s future clinical development program, the timing of FDA filings and its target market. Actual events could differ materially from those anticipated in the forward-looking statements as a result of certain factors, including but not limited to: the results and duration of clinical trials, the ability to retain and attract key employees, and other events and important factors disclosed in Peplin s filings with the U.S. Securities and Exchange Commission and its disclosures to the ASX. Peplin disclaims any obligation to update any such forward-looking statements after the date of this presentation. 2

3 Peplin Highlights Breakthrough treatment for actinic keratosis and skin cancers Novel mechanisms of action Short duration of therapy Enhanced cosmetic outcome Compelling and consistent clinical data First Phase 3 study completed. Two additional Phase 3 studies enrolling. March 31, 2008: $26.1m in cash Sufficient to complete Phase 3 trials Global product rights 3

4 Investment Thesis Large market for actinic keratosis and other skin diseases High level of patient dissatisfaction with current therapies Long treatment durations Poor patient compliance Local side effects during extended treatment Novel, Phase 3 product with compelling, consistent clinical trial results Strong intellectual property Strong financial position Significant value building milestones over next 2 quarters 4

5 Euphorbia Peplus Common plant European origin Early 1800 s sap used topically to treat dermatological conditions warts, corns, waxy growths, skin cancers Effective home remedy to treat skin cancers (1) 1) Australasian Journal of Dermatology,

6 Peplin History Peplin founded to explore the folklore observation of anticancer activity of the sap of Euphorbia peplus Documented the sap s anti-cancer activity in human skin cancers Selected PEP005 as lead candidate for its Pre-clinical pharmacology Toxicology Purification and formulation technology INDs filed for AK and BCC Completed Phase 3 trial Company headquarters moved from Australia to US Pursued activityguided fractionation to identify key active ingredient 6

7 PEP005 (ingenol mebutate) MOA Dual mode of action Rapid removal of tumor (necrosis) and prevention of the tumor relapse (immune response) 1. Local necrosis (1) Disruption of mitochondrial membrane Mitochondrial breakdown Cellular cytotoxicity (necrosis) 2. Activation of immune system (2) Activation of adhesion molecules (e.g. E-selectin) (3) Recruitment of neutrophils (e.g. IL-8) Production of tumor-specific antibodies 1) Cancer Research 64: , ) J Immunol. 177: , ) Cancer Immunol. Immunother. 57: ,

8 PEP005 (ingenol mebutate) Gel Pipeline Indication Pre-clinical Phase 1 Phase 2 Phase 3 Actinic Keratosis Non-head treatment sites Head treatment sites Basal Cell Carcinoma Squamous cell carcinoma Cutaneous warts Other cancers 8

9 Actinic Keratosis (AK) 1) Dermatol Surg 2007;33: ) Lewin Group, The Burden of Skin Diseases ) US office visits for AK, NAMCS database (Avg. for ) 4) Journal of Dermatological Treatment,2006; 17: Caused by accumulated sun damage Can unpredictably transition to Squamous Cell Carcinoma (SCC) 67% of cases had prior AK diagnosis (4) 1,300 to 2,300 US deaths per year (1) Expensive and difficult treatment Affects more than 58 million Americans (2), increasing with age 5.6 million office visits annually (3) 8.2 million office visit estimates have been published (2) $1.2 billion annual direct cost in US (2) 25% of all treatments involve topical therapies (4) 9

10 Market Opportunity Actinic keratosis is one of the most frequently diagnosed skin disease by US dermatologists Topical treatment in the US Cryotherapy 75% Topical 16% Cryo plus topical 9% Topical treatments during office visits Total office visits (1) Proportion treated Treatment visits Topical treatments (2) Annual topical treatments 5.6 M 90% 5.0 M 25% 1.26 M 1) US office visits for AK, NAMCS database (Aug. for ) 2) Journal of Dermatological Treatment, 2006; 17:

11 In-office Procedures Approach Cryotherapy (liquid nitrogen) Levulan Kerastick (2) (aminolevulinic acid HCl) Major benefits Quick and inexpensive Historically attractive reimbursement Well established modality Single topical application Major short-comings Only discrete lesions Short term localized pain and irritation Potential long term scarring 1 year recurrence rate of 72% (1) Declining reimbursement (3) Irradiation 14 to 18 hours later Burning and stinging Requirement for dedicated equipment Low reimbursement 1) British Journal of Dermatology 2007; 157 (Suppl. 2): ) Product Full Prescribing Information 3) 2008 CMS Medicare Fee Schedule 11

12 Topical Treatments (1) Long durations of treatment Product Course Efficacy: Complete clearance AWP Cost /Tx (3) Side effects Aldara (imiquimod 5%) 2x/wk for 16 wks 45% $793 Erythema, flaking/ scaling/dryness, scabbing/crusting Carac (fluorouracil cream 0.5%) 1x/d for 4 wks 48% $150 Erythema, dryness, burning, erosion, pain Efudex (Fluorouracil cream 5%) Generic 5% 5-FU 2x/day for 4 wks ~50% (2) $745 $494 Burning, crusting, contact dermatitis, erosion, erythema Solaraze (diclofenac sodium 3%) 2x/day for days 14-47% $421 Contact dermatitis, rash, dry skin/ scaling 1) Product Full Prescribing Information 2) Supplement to The Journal of Family Practice, May ) Redbook, March

13 The Peplin Solution PEP005 (ingenol mebutate) Gel for AK: Product Profile Description Patient applied topical gel Course of therapy Once-a-day for two or three consecutive days Packaging Two or three single use mini-tubes Side effect profile Localized erythema, flaking or scaling, crusting, vesicles and swelling. Peaks in 3-8 days, resolves in 2-4 weeks Treatment area Concentration Non-head (2 day) 0.05% (PEP005 Gel) Head (3 day) 0.015% (PEP005 Gel) 13

14 PEP005 (ingenol mebutate) Gel for AK Strong Clinical Data IND filed June 2004 Advancement in AK trials ( ) Single dose Phase 1 (lesion-directed) Two dose Phase 2a (lesion-directed) Two dose Phase 2b (field-directed therapy-body) 2 and 3 day Phase 2a/b (field-directed-body) 2 and 3 day Phase 2a/b (field-directed-face) 2 day Phase 3 (field-directed body) Exposure to PEP005: >950 subjects Four key clinical trials PEP , REGION-Ia: treatment sites on body and scalp PEP & -015: treatment sites on face and face/scalp 14

15 AK Phase 2 (PEP ): Study Design Treatment location Status Number of patients Design Endpoints Body and scalp Patients with 4-8 AK lesions in a 25 cm 2 treatment area on the arm, shoulder, chest, back or scalp Complete 222 Multi-center, double blind, double dummy, randomized, vehicle-controlled Four arms: 3 active + 1 vehicle Concentration Vehicle 0.025% 0.05% 0.05% Group N/A D1,2,3 (Low) DV,2,3 (Medium vehicle D1) D1,2,3 (High) Evaluating safety and efficacy Pt Number

16 AK Phase 2 (PEP ): Efficacy Results AK clearance rates - Intent to Treat 80% 60% 40% 20% 0% Vehicle Low Medium High Complete clearance 75% clearance Medium strength data 0.05% (Two days) Vehicle P-value N=55 N=60 Complete clearance rate 44% 12% Partial clearance rate 62% 22% <

17 AK Phase 2 (PEP ): Safety Time course of local skin response 17

18 AK Phase 3: Study Design Treatment location Status Number of patients Design Endpoints Non-Head (trunk and extremities) Patients with 4-8 AK lesions in a 25 cm 2 treatment area Complete (May 2009) 250 total patients Randomized, double-blind, vehicle-controlled conducted at multiple sites Special Protocol Assessment (SPA) 2 days of treatment Concentration = 0.05% Primary: Complete clearance rate Secondary: Partial clearance rate (clearance of majority of AK lesions within the area) 18

19 REGION-I Efficacy Results REGION-I Clearance Results 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Vehicle PEP005 Overall Arm Back Back of Hand Chest Complete Clearance Partial Clearance Median % Reduction 19

20 REGION-I Safety Results 6 5 REGION-I: Local Skin Responses PEP005 Gel Vehicle 4 LSRs Days 20

21 REGION-I vs. PEP Complete clearance rate (arms/shoulders/chest/back) 014 Active 31% (27/86) vs Vehicle 6% (5/85) 006 Active 45% (19/42) vs Vehicle 14% (6/43) Partial clearance rate (arms/shoulders/chest/back) 014 Active 52% (27/86) vs Vehicle 9% (5/85) 006 Active 67% (28/42) vs Vehicle 21% (9/43) Of interest is the much higher vehicle responses seen in the 006 study vs the 014 study 21

22 AK Phase 2b (PEP ): Study Design Treatment location Status No. of patients Design Head (face and scalp) Field-treatment Complete, January Randomized, double-blind, vehicle-controlled, multiple sites 6 active arms: 0.005%, 0.010% or 0.015% at 2 or 3 days of treatment vs. vehicle at 2 or 3 days Enpoints Concentration Group ITT (1) Pt No. Group Vehicle 2 day Rx 33 3 day Rx 0.005% 2 day Rx 33 3 day Rx 0.01% 2 day Rx 34 3 day Rx 0.015% 2 day Rx 33 3 day Rx Primary: Complete clearance rate ITT (1) Pt No Secondary: Partial clearance rate (clearance of majority of AK lesions within the area) 1) ITT = Intent to Treat 22

23 PEP Efficacy Results (2-Day) Day Clearance Rates - Intent to Treat 0.0 Vehicle Low Medium High Complete clearance 75% clearance High strength data (0.015% x 2 days) Active N=33 Vehicle N=33 P-value Complete clearance rate 36.4% 0.0% <0.001 Partial clearance rate 51.5% 3.0% <0.001 Median % reduction* 75% 0.0% n/a *Calculated within per protocol population, not ITT 23

24 PEP Efficacy Results (3-Day) Day Clearance Rates - Intent to Treat 0.0 Vehicle Low Medium High Complete clearance 75% clearance High strength data (0.015% x 3 days) Active N=32 Vehicle N=33 P-value Complete clearance rate 50.0% 9.0% <0.001 Partial clearance rate 71.9% 12.1% <0.001 Median % reduction* 84.5% 0.0% n/a *Calculated within per protocol population, not ITT 24

25 AK Phase 2b Study (PEP ): Safety Composite Local Skin Response Mean Composite LSR D Vehicle 2D 0.005% 2D 0.010% 2D 0.015% 3D Vehicle 3D 0.005% 3D 0.010% 3D 0.015% Day 25

26 Non-Melanoma Skin Cancer Most prevalent cancer worldwide Basal cell carcinoma (BCC): 80% Squamous cell carcinoma (SCC): 16% 1.2 million cases in US in 2004 (1) US$1.4 billion in 2004 (1) Incidence: 3-8% worldwide increase annually since 1964 (2) Gold standard is surgical excision 1) Lewin Group The Burden of Skin Diseases ) J Am Acad Dermatol 2007; 56:

27 PEP005 (ingenol mebutate) Gel for sbcc Tumor directed application 1 or 2 treatments Higher concentration than AK treatment Benefits over surgery Reduced pain, scarring Improved cosmesis No sutures, infections Proof of concept in PEP study 70% histology confirmed lesion clearance at 12 weeks (p=0.02) with 2 day treatment of 0.05% PEP005 27

28 sbcc Phase 2 (PEP ): Study Design Up to 110 patients in the US Open label, maximally tolerated dose study 2 dosing regimens: q.d. for one day or q.d. for two days, a week apart Ten concentrations from 0.025% to 0.25% PEP005 (ingenol mebutate) Gel Physician applied spot-therapy to 4 to 15 mm sbcc lesion on trunk Punch biopsy at screening for histologic diagnosis Full excision of lesion at 3 months post-treatment Study is ongoing 28

29 Milestones Initiate Non-head AK Phase 3 (REGION-Ia) Results Head AK Phase 2b End of Phase 2 meeting with the FDA Results Non-head AK Phase 3 (REGION-Ia) Initiation of Head AK Phase 3 program Initiation of Non-head AK Phase 3 (REGION-Ib) Completion of AK development program File New Drug Application Sept 2008 Jan Q Q Q Q 2009 YE 2009 Mid

30 Clear Route to Market Highly targeted sales approach Small specialty sales force can cover key customers 10,500 practicing dermatologists in the US 6,000 treat 90% of all the AK cases Effectively covered with sales force of reps Reimbursement is established Existing reimbursement scheme for AK treatments Payers receptive, anxious to get their money s worth Operating PEP005 manufacturing plant GMP manufacturing plant established in Queensland 30

31 Investment Thesis Large market for actinic keratosis and other skin diseases High level of patient dissatisfaction with current therapies Long treatment durations Poor patient compliance Local side effects during extended treatment Novel, Phase 3 product with compelling, consistent clinical trial results Strong intellectual property Strong financial position Significant value-building milestones over next 2 quarters 31

32 Developing the next generation of dermatology products to treat serious skin diseases Tom Wiggans Chairman and Chief Executive Officer