Introduction to Nitec Pharma AG
Anders Härfstrand, CEO Nitec Pharma AG Kägenstrasse 17 CH-4153 Reinach Swiss Equity biotech day, 31 March 2009
Disclaimer
Confidential: for information purposes only and not for disclosure or distribution to third parties in whole or in part. This document has been prepared by Nitec Pharma AG ("Nitec" or the "Company") with the sole objective to introduce the Company and its operations in the context of general communication activities. Some of the information in these materials is still in draft form. The information in this documents is subject to discussion, verification, completion and change. This document does not constitute or form part of, and should not be construed as, an offer, solicitation or invitation to purchase or subscribe for any securities, and neither this document nor anything contained herein shall form the basis of or be relied on in connection with or act as any inducement to enter into any contract or commitment whatsoever. Any purchase of the securities should be made solely on the basis of information contained in a final offer document to be published in connection with any such sale of securities. Such final document will include a description or risk factors relevant to any such investment in the securities. This document does not constitute a recommendation regarding securities. This document and the information contained herein is for discussion purposes only and does not purport to contain all information that may be required to evaluate any of the entities discussed herein, their financial position or their securities. This document contains forward-looking statements which have been prepared on the basis of a number of assumptions which may prove to be incorrect. Readers are cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and that actual results may differ materially from those expressed or implied by these forward-looking statements as a result of various factors. In particular, the diagrams included herein aim to illustrate a general proposition, rather than to represent that the specific outcome discussed will be achieved. Nitec undertakes no obligation to update or revise any of the information contained in this document. The information and opinions contained in this document are provided as at the date of this document or as of the date specified and are subject to change without notice. The information contained in this document has not been independently verified. Accordingly, no representation or warranty express or implied is made as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctness of the information or opinions contained herein. None of the Company, shareholders or any of their respective affiliates or representatives shall have any liability whatsoever for any loss howsoever arising from any use of this document or its contents or otherwise arising in connection with the document. This document does not constitute a prospectus according to Articles 652a or 1156 of the Swiss Federal Code of Obligations. THIS DOCUMENT IS NOT FOR RELEASE, PUBLICATION OR DISTRIBUTION IN THE U.S.A., Canada, Australia or Japan. This document is directed only at persons within the United Kingdom who have professional experience in matters relating to investments falling within article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 (as amended) (the "Order") or (iii) who fall within article 49(2)(a) to (d) ("high net worth companies, unincorporated associations etc.") of the Order. By attending this presentation, you agree to be bound by the foregoing limitation, and to keep this document and information confidential. . Swiss Law applies to this presentation.
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Key highlights
LODOTRA, the lead product, approved and partnered in the EU for rheumatoid arthritis and in a second Phase 3 trial for US filing with multiple opportunities to expand label into other indications
TRUNOC, second product candidate, with multiple commercial opportunities and blockbuster sales potential in clinical stage
Experienced, commercially - focused management team and organization
”Our vision is to become a leading specialty pharmaceutical company for the treatment of chronic inflammation and pain-related diseases by delivering innovative and effective treatment solutions”
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Company history
1998-2003
● Merck KGaA initiates development of Lodotra for the treatment of Rheumatoid Arthritis idea to match therapeutic delivery with circadian rhythm engagement of SkyePharma plc ● Jul 04 - Spin-out from Merck KGaA ● Sep 04 - US$10m Series A financing round (Atlas 69%, GLSV 31%) ● Start of Phase 3 trial for European approval of Lodotra ● Lodotra European Phase 3 trial successful ● Filed for marketing approval in 15 European countries under the so-called De-Centralised Procedure (“DCP”) ● ● ● ● Feb - Lodotra marketing partnership with Merck KGaA in Germany Mar - CHF32m Series B financing round (NGN Capital 50%, Atlas 35%, GLSV 15%) July - TruNoc in-licensed from PAZ GmbH Sep - Two Agreements signed with SkyePharma
2004-2005
2006
2007
● Dec – 505(b)(2) agreement with the FDA ● Jan - Lodotra European Phase 3 trial results published in “The Lancet” ● Mar - Lodotra US Phase 3 trial starts
2008
● Sep – Further financing secured: Euro 7.5m venture loan (Kreos Capital) and CHF 24m new round of equity financing (TVM Capital and Deutsche Bank) ● Dec - Lodotra recommended for approval in the EU in the RA indication ● April - Lodotra launch in Germany by Merck Serono and partnered for the rest of Europe by Mundipharma
2009
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Focused product candidate pipeline, multiple commercial opportunities
Pre-clinical Phase 1 Phase 2 Phase 3 Marketing authorisation Launch
Lodotra
Rheumatoid Arthritis (morning stiffness) Rheumatoid Arthritis (signs & symptoms)(a) Severe Asthma (label expansion) Polymyalgia Rheumatica(b) (label exp.)
(Q1 2009) United States European Union (Q1 2010)
TruNoc (tarenflurbil)(c)
Neuropathic Pain (c) Osteoarthritis
( 2009)
(a) (b) (c)
FDA filing expected in Q1 2010 Phase 2 to commence in Q1 2009 Phase 2 study has demonstrated proof-of-concept in acute pain as an analgesic in hospitalised patients with post-surgery pain and in an acute pain model. Nitec is focusing on chronic indications
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Rheumatoid arthritis (‘RA’)
• • • • •
Chronic, progressive, painful, disabling autoimmune disease Affects ~1% of world population Affects people of all ages Pathologically elevated pro-inflammatory cytokine rhythm leads to morning stiffness Body’s immune system attacks own joint tissues
– affects multiple joints including hands
and feet
• • •
Morning stiffness one of the most disabling symptoms of the disease Significant burden on family carers and social services Sufferers often unable to work
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Benefits of night time glucocorticoids
Proof of Concept study utilising prednisone administered at 2:00 am has demonstrated a significant reduction in RA clinical symptoms in 26 corticoid naïve patients
Nocturnal versus morning prednisone efficacy
1440 Morning Stiffness (min) Pain Rest (VAS) 2:00 am
Day 1 vs. Day 5 Average reduction (Day 1 vs Day 5) 189 min -78%
420 300 180 60
8 6 4 2
5 mg 7.5mg
7:30 am
Day 1 vs. Day 5 47 min -15%
2:00 am
Day 1 vs. Day 5 -2.5 VAS -63%
7:30 am
Day 1 vs. Day 5 0.1 VAS +3%
“Administration of low doses of prednisolone at 2 a.m. had favourable effects on the duration of morning stiffness, joint pain, Lansbury index, Ritchie index, and morning serum concentration of IL-6.” – Arvidson et al. 1997
Sources: Arvidson et al., Annals of Rheumatic Diseases, 1997.
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Morning stiffness, the most prevalent symptoms in RA
Morning stiffness Joint or muscle pain Joint pain especially in the morning Joint swelling Fatigue Pain associated with prolonged sitting Joints that are tender to touch Feeling down/Malaise Red and puffy hands Firm bumps of tissue under the skin on your arms Flu-like symptoms/Fever Loss of appetite/Weight loss 0% 2% 9% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 16% 27% 14% 20% 28% 43% 48% 67% 44% 47% 58% 68% 68% 84% 64% 80% 92% 93% 90% 93% 86% 92%
Corticosteroid users (n=100)
Source: Medical Marketing Economics, LLC, “Lodotra Patient Study.” May 2008
Non-corticoidsteroid users (n=50)
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Single pulse delayed release
Standard prednisone vs Lodotra
25 Single-pulse delayed release
Prednisone mean plasma concentrations (ng/ml)
Standard prednisone (5mg) Lodotra (5mg)
100%
20
80% Dissolution rate
15
4 hrs. 2 hours 5 hour 3 1 >5
50%
10
5
10% Lag phase 0 2 4 6
Lag time point
8 10
0
0
5 10 15 20 Post-dose time (hours)
25
Time (hours)
Start
Note:
Single dose of standard prednisone (immediate release) versus Lodotra (n=26)
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Lodotra significantly reduces morning stiffness
(phase 3 results*) Study design (n=288)
•
• • •
Superiority to standard treatment – reduction of morning stiffness (~33% reduction after 3 months; baseline 3 hours) – sustained reduction of morning stiffness (~50% reduction after open-label phase) – reduction in IL-6 levels (~30% reduction after 3 months, ~40% after open-label phase)
Multi-centre, randomised, double blind, 3 month treatment, 2 arms – Lodotra in evening, placebo in morning – Placebo in evening, standard prednisone in morning 9 month open-label follow-up Primary endpoint: reduction of morning stiffness
*Three months results published in The Lancet, 2008 (371:205-14)
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Lodotra shows a statistically significant reduction in IL-6
● Statistically significant median reduction in IL-6 levels of approximately 30% after 3 months and approximately 40% after 12 months
Interleukin-6 [units/1] 10,000
Relative change from baseline in IL-6
8,000
6,000
● Of the 50% of the Lodotra-treated patients who showed a reduction in the duration of morning stiffness of more than 34% they also showed a 55% reduction in IL-6 levels
4,000
2,000
0
● Of the 16% of the Lodotra-treated patients who showed a 100% reduction of morning stiffness they also showed a 64% reduction in IL-6 levels (a)
Note: Source:
Prednisone Lodotra IR Baseline
Prednisone Lodotra IR 3 months Median Mean
Prednisone Lodotra IR 12 months
Patients on immediate-release prednisone in CAPRA-1A trial were switched to Lodotra after three months and treated for a further nine months in the CAPRA-1B open-label phase Boxes represent first and third quartile (25% and 75%), whiskers represent 10% and 90% quartile; IR, immediate release CAPRA-1A and CAPRA-1B clinical data
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Lodotra: regulatory status in the US
● 13 December 2007: “End of Phase 2” meeting with FDA ● 2nd pivotal phase 3 trial for FDA registration (“CAPRA-2”) - 3-months vs placebo, 300 pts, US and EU sites - results in Q4 2009 ● Results from the EU trial (“CAPRA-1”) relevant for the US application ● Primary endpoint: ACR 20 ● Key secondary endpoint: morning stiffness ● Label: indicated to treat signs and symptoms of RA including morning stiffness. ● Packaging insert includes IL-6 ● All patients recruited and randomized as of February 2009 ● 505(b)(2) filing anticipated H1 2010
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Multi pharma treatment is standard of practice
Treated RA Patients > 4.5 million (US/EU)
> 80%* 10-30%* 70-100%* 20-30%* 20-30%*
DMARDs - Methotrexate - others
● Limitations: - Non-responders - Toxicity - Slow onset of action
Biologics
NSAIDs (Analgesics, COX2)
Oral glucocorticoidsmainly Predniso(lo)ne
● Limitations: - Side effects at higher doses >10mg/day - Current formulations suboptimal
Circadian Cytokine Modulator (CCM)
● Limitations: - Non-responders - Serious side effects - Inconvenient (IV) - Expensive
● Limitations: - Stomach ulcers - Cardiovascular risk
● Limitations: - Not for substitution
Lodotra
● 1st line therapy ● Combination therapy
* Management estimates
Despite several innovative developments and use of combination therapies, RA patients still experience considerable morning stiffness, pain and immobility
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Lodotra for severe asthma
•
Severe Asthma
• •
Chronic inflammatory disease of the airways − nocturnal attacks, life threatening, frequent visits to ER Increase in night-time pro-inflammatory cytokines − nocturnal symptoms, reduction in lung function Adverse side effects with current standard of care (e.g. osteoporosis, diabetes, weight gain) Follows a clear circadian pattern Delivers prednisone at time of need to reduce nocturnal and associated day time symptoms 53 million asthmatics in 7 largest pharmaceutical markets (US, Japan, UK, Germany, France, Spain and Italy) Approximately 5% of all asthma sufferers have severe asthma and take oral glucocorticoids on regular basis Rising disease prevalence due to environmental and lifestyle factors Sufferers seen by pulmonologists – can be targeted by specialist sales force Phase 2 Proof of Concept trial ongoing Demonstrate superiority to standard treatment regarding respiratory function
• CCM rationale • •
Market dynamics
• • • • •
Current status and next steps
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Nocturnal asthma: circadian variation of symptoms
Timing of dyspnoeic episodes in asthma
Skloot, Mt Sinai J Med (2002) 69;140
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Lodotra life cycle management: phase 2a study – severe asthma
n = 12 Diagnosed severe asthma patients Standard prednisone morning administration
n = 12 Lodotra evening administration Evaluation of safety and efficacy
• • • • • • •
Open label, single treatment arm explorative study, 12-patient clinical trial 4 week base line period – 4 week treatment period Dose of glucocorticoid identical for both treatment periods: individual doses of prednisone/Lodotra Primary endpoints investigated: superiority to standard regimen in improving pulmonary function and asthma symptoms Reduction in number of night-time awakenings Increase in morning peak flow Top line results favourable. To be presented Q3 09
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TruNoc – overview
Strong second product candidate Defined and differentiated MOA Multiple commercial opportunities, blockbuster potential
• • • • • • • • • • •
In-licensed from PAZ GmbH in 2007 (exclusive WW rights in chronic inflammation and pain) Inhibits NF-κB & AP-1 but not COX I/II Inhibition of IL-6 Potential to be first disease modifying osteoarthritis drug (DMOAD) Neuropathic pain, such as diabetic neuropathy, post herpetic neuralgia, phantom/post-amputation pain, spinal cord injury Osteoarthritis, rheumatoid arthritis and RA-related diseases, such as ankylosing spondylitis Parent compound (flurbiprofen) marketed in EU and US since 1977 TruNoc well tolerated in clinical studies involving approximately 270 persons Third party ran a phase 3 trials in 2,400 Alzheimer’s Disease patients at doses significantly higher than those envisaged by Nitec (endpoints not met program, discontinued) Proof of concept demonstrated in man in acute pain model in phase 2 trial Phase 2 trials in osteoarthritis and neuropathic pain planned in 2009 (IB in progress)
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Large safety data set
Current status and next steps
Expected target milestones
H1 2009 H2 2009 2010 2011
European launch in RA indication Lodotra in RA Partnering (Europe/RoW) Partnering US CAPRA-2 results for FDA filing FDA filing US launch Lodotra in Severe Asthma and PMR TruNoc
Results of phase 2 PoC in Severe Asthma Start label expansion trial in Asthma Clinical Trial Application Start phase 2 trial in Neuropathic Pain Start phase 2 trial in Osteoarthritis
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Key highlights
LODOTRA, the lead product, approved and partnered in the EU for rheumatoid arthritis and in a second Phase 3 trial for US filing with multiple opportunities to expand label into other indications
TRUNOC, second product candidate, with multiple commercial opportunities and blockbuster sales potential in clinical stage
Experienced, commercially - focused management team and organization
“Our vision is to become a leading specialty pharmaceutical company for the treatment of chronic inflammation and pain-related diseases by delivering innovative and effective treatment solutions”
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Thank you for your attention!
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www.nitecpharma.com