The commercialisation of SCENESSE is a long awaited dream of many scientists and patients around the world. For Clinuvel it marks the start of a new

Transcription

1 The commercialisation of SCENESSE is a long awaited dream of many scientists and patients around the world. For Clinuvel it marks the start of a new phase. 1

2 Australia is the birthplace of a great number of inventions and innovations. As of 24 October SCENESSE afamelanotide 16mg, developed from bench to bed by the Australian based company Clinuvel Pharmaceuticals, can be added to the list. In the process the Company optimised the chemistry, developed the formulation, identified the indications, and introduced the product to the wider medical community. SCENESSE is the first commercially available systemic photoprotectant for the treatment of the most extreme form of light and UV intolerance: erythropoietic protoporphyria, EPP. It is very rare to develop a novel molecule, formulation and indication; in this case it has been achieved with a relatively small team from inception to commercial stage. 2

3 Warning against speculative statements that may be made at today s AGM, the public is requested to read the Forward Looking or Safe Harbour Statement. 3

4 There are four sections being discussed today. 4

5 Clinuvel s business plan was presented in 2005, consisting of involvement and engagement with the top academics worldwide. Nearly 10 years later the leading academic centers in the fields of interest have been involved in the development of SCENESSE. Their feedback is incorporated in Clinuvel s clinical programs. 5

6 In some disorders, patient organisations are fundamental to the success of a clinical program, since they represent the patients voices. Patient organisations will often communicate the patients feedback after a trial completion, the drawbacks of study designs and be the representative body to elucidate the need to treat the disease. 6

7 Clinuvel has built up considerable regulatory knowhow over the years, spanning several continents and many countries. 7

8 Overall Clinuvel s value lies in the aggregate elements, IP, specific knowhow, its registration dossier and manufacturing processes for its final product. 8

9 It took nearly 10 years under Clinuvel s management to develop SCENESSE to a commercial product. This is the first time a systemic photoprotectant of the melanocortin family has obtained regulatory approval. The planning to further develop and commercialise new markets, indications and follow on products is being discussed. A clear sequence needed to be followed within the unique limitations of Clinuvel to be able to execute on our commercial plans, as will be outlined over the coming slides. The table indicates the probability of a new drug reaching marketing authorisation as it enters each step of the development process. 9

10 The integral value of Clinuvel starts with SCENESSE, the first drug used in an extreme disorder caused by daylight, UV. The initial risks in this business were high. Additionally there were unique risks associated with Clinuvel, some unduly assigned, some due to illegitimate markets, others due to the lack of understanding during the development of a novel technology with a new mode of action. 10

11 Erythropoietic protoporphyria was targeted it was understood that SCENESSE could be of therapeutic benefit. Additional criteria, such as high unmet medical need, no alternative treatment and market exclusivity, were essential for the choice of EPP as Clinuvel s lead indication. Patients need and demand were the prominent reason to progress SCENESSE in the clinic. Clearly there was no competition. EPP is predominantly seen in Caucasian populations Fitzpatrick skin types I III. EPP is the most extreme form of light deprivation and patients suffer acute pain when skin is exposed to certain wavelengths of light and UV. It is also a rare disease, with a recognised need to treat from regulatory authorities in the form of orphan drug designations. With a positive vote from the European Medicines Agency on Marketing Authorisation, Clinuvel now has a proof of concept for medicinal photoprotection with SCENESSE, allowing the Company to progress to a commercial phase and pursue expanded programs with its technology. Progress would only occur when reimbursement was secured. In 2010 the Company received the first proof of support from payors, with the Italian government agreeing to reimburse supply for adult EPP patients. This program has continued for nearly five years. Further proof arrived in 2012 with insurers in Switzerland agreeing to reimburse the drug. 11

12 Our European Marketing Authorisation provides confidence to expand the program into broader markets, with vitiligo the first target. Despite its high prevalence and significant impact on patients, there are no fully effective therapies for vitiligo. To date the mainstay of treatment has been narrowband UVB light, an expensive therapy requiring intensive commitment from patients. Topical and systemic steroids are prescribed off label in vitiligo, but their effectiveness varies. Vitiligo is seen as having the greatest impact on patients with darker skin Fitzpatrick skin types IV VI for whom the disease is often described as causing an identity crisis. Early clinical results with SCENESSE as an adjunct to narrowband UVB have indicated that the clinical benefit is larger and faster in these patients. The Company sees it as ethically necessary to pursue treatment for these patient groups. As a result, the Company has different target markets for its two lead indications, treating EPP in Caucasian populations in the Northern Hemisphere, as well as a limited population in Japan, and treating vitiligo in darker skin types in North American, Asia and Africa. 12

13 In parallel to the vitiligo program, the Company will seek broader application of SCENESSE, with a commitment to focusing on paediatric EPP patients. Recent advances in our understanding and IP will allow us to expand our offering to complementary therapies. It must be noted, however, that this was only possible having proven the concept of medicinal photoprotection and the safety and efficacy of SCENESSE. 14

14 Clinuvel will now be able to capitalise on its in house expertise and lead the field of melanocortins, with topical formulations of alpha MSH analogues the next step in our development. 15

15 16

16 The financials of Clinuvel reflect the quarterly statements and annual filings. The Company has been debt free and maintained a consistent burn over the past years. Purposefully, CUV required raised capital in nine rounds, whereby it is stressed that in the last three issuances capital was raised at premium. 17

17 The Company has sought to maintain a balanced register. 18

18 The Company has invested the majority of its clinical expenditures to date in the lead program, EPP. Expenses include non cash adjustments. 19

19 The Company is rapidly transforming from a pure R&D focused to a commercially driven entity. Relevant staff are being hired to succeed in the European distribution. 20

20 21

21 The progress of European regulatory review from beginning to approval was gradual. As more information about mode of action, disease, physicians experiences and patients benefit became known, the EMA arrived at a full understanding of the clinical use and benefit of SCENESSE. Drug substance: Amino acids and impurities Drug product: dosage form, release inconsistently, manufacturing method Pharmacology: pharmacokinetic and pharmacodynamic relationship, mode of action Toxicology: melanoma, CNS effects, irreversible naevi Pharmacology: mode of action, dosing rationale Clinical safety: pigmentation, accumulation, prolonged drug in blood, CNS, eyes Clinical efficacy: rationale of drug, evaluation of efficacy 22

22 The end points from both studies show how SCENESSE was clinically evaluated over five studies involving around 350 patients. Decisions to continue the EPP program were based on both trial results safety and efficacy as well as ongoing regulatory, physician and patient feedback. Over the course of the program we saw increasing support from these communities. Programs in Italy 2010 and Switzerland 2012 have given an indication of the drug under conditions of use, and five years of special access scheme SAS data, with 115 patients receiving treatment under these programs over the past 12 months. 23

23 24

24 EPP is a poorly understood disorder. Due to the fear of debilitating skin reactions to UV/light, patients become deprived of light exposure and the ability to lead a normal life. For most EPP patients the disease dictates many life decisions and can lead to anxiety and depression. The lack of treatment or viable prevention for EPP reactions to date means many patients are forced to lead indoor and withdrawn lives or risk severe burns starting a phototoxic reaction that may last weeks depending on the individual. In some cases it leads to hospitalisation and distress. 25

25 Independently evaluated against other disorders, EPP is considered to be a severe, chronic disorder in need of annual treatment. 26

26 Reviewing the pharmaceutical landscape, recent trends reflect a premium for orphan drugs. 27

27 In benchmarking SCENESSE against other orphan drugs developed, and viewing returns on investment, a number of observations are being made. The most recent numbers on drug development are US$1b for the entire program, Clinuvel s A$120M holds up well as one of the most economical programs in the orphan drug field. 28

28 In the clinical phase and commercial phase both on overseas markets and Nasdaq there are few orphan drug pharmaceuticals at US$200M. Benchmarking CUV against peers provides some insight in market valuations. 29

29 Italy and Switzerland have given more than two years of conditions of use and five years of special access scheme SAS data in EPP patients. The table shows reimbursement for SCENESSE by insurers and regional authorities in these two countries, and in recent times, also from other European nations. The drug has been well tolerated. Of those patients who have discontinued treatment, the majority have done so for reasons unrelated to treatment. 30

30 EU distribution is in preparation following the EMA approval on 23 October 2014 morning 24 Oct Melbourne. 31

31 The first key strategic markets for EPP had been identified by Clinuvel. The markets in blue are under consideration. 32

32 Modelling EPP by analysts and peers presumes a number of variables. Once pricing is established in EU, an adequate market size can be estimated. In Clinuvel s case the 5 years of experience during the Special Access Schemes provides data for modelling. 33

33 Vitiligo attracts much attention in North America given the magnitude of the clinical problem most apparent in patients of colour due to the contrast between vitiligo and non vitiliginous lesions. 34

34 Penetration rates in a low case scenario is being discussed, given the demographics and patient population known. 35

35 Patients of skin colour who lose their pigmentation often see a gradual progression of disease. It causes much distress and sense of helplessness. Patients who lose a large surface area of pigmentation present such as the patient in Day 0 left hand side. This patient s de pigmentation is generalised over the entire body surface. Typical is loss of total pigmentation of hand and feet. Repigmentation of these areas is a particular clinical dilemma. In this patient total repigmentation was achieved, whereby the feet are still de pigmented, but some proximal to distal repigmentation is started. 36

36 Close up reveals the follicular pattern repigmentation islands throughout the epidermis. The Day 176 images are particularly important as rate and depth of repigmentation is assessed. 37

37 A further close up shows individual islands of pigment developing. 38

38 These islands represent the melanocyte stem cells near a hair follicle. The maturation of melanocytes enables the first pigmentation to become visible. 39

39 Clinuvel is known as the company which treats vitiligo in darker skin populations, whereby VIP catch the eye of the imagination. Many of the industry publications focus on the positive results from CUV

40 41

41 Support from Clinuvel Board, investors and staff have been fundamental to Clinuvel s success. The greatest assets of the Company are its people. 42

42 43