Biotie Therapies Oyj Biotie Therapies Corp. Varsinainen yhtiökokous Annual General Meeting 26 May 2015

Transcription

1 Biotie Therapies Oyj Biotie Therapies Corp. Varsinainen yhtiökokous Annual General Meeting 26 May

2 Timo Veromaa President & CEO 2

3 Company Highlights 2014 through Q Continued advances in Phase 3 program for lead asset tozadenant Further information provided on design of Phase 3 program (April 2015) Patient recruitment expected to commence in the middle of SYN120 Phase 2a study recruiting patients in Parkinson s Dementia BTT1023 Phase 2a study open for recruitment; Orphan Drug designation granted in the EU for primary sclerosing cholangitis Selincro now available in 29 European countries by partner Lundbeck, with increasing royalties in Q1 Plans to strengthen capital structure by up to approximately 95 million through a directed issue of convertible notes and warrants and a US IPO to finance the tozadenant Phase 3 trial announced in April The plans are subject to shareholder approval in today s Annual General Meeting and to US regulatory review 3 1. Pending the successful outcome of ongoing financing plans

4 Portfolio of Innovative CNS Medicines Portfolio Indication Phase 1 Phase 2 Phase 3 Marketed Status Development Product Candidates tozadenant Parkinson s Disease Recruitment for pivotal Phase 3 trial expected to begin mid-2015 SYN120 Parkinson s Disease Dementia Alzheimer s Disease Currently enrolling Phase 2a trial with top-line data expected by YE Phase 2 trial ready (funding dependent) BTT1023 Primary Sclerosing Cholangitis Currently enrolling Phase 2 proofof-concept trial with interim data expected by YE-2016 Commercial Product Selincro Alcohol Dependence Launched across Europe in partnership with Lundbeck 4

5 Key Portfolio Developments: Tozadenant New Mechanism Selective A 2a adenosine receptor antagonist Potential to be the first new MoA in the US and Europe for the treatment of Parkinson s in 20 years Demonstrated improvements in symptoms of patients treated with standard of care Significant Need Parkinson s affects 1 in 100 people over the age of million patients worldwide, including at least 1 million in the U.S. Prevalence will increase as the global population ages Robust Compelling Data Phase 2b trial demonstrated a statistically significant and clinically meaningful improvement in primary endpoint Met multiple clinically important secondary endpoints Well tolerated in more than 500 unique exposures Clear Path to Approval Completed Phase 2b trial that could qualify as first of two pivotal trials Confirmatory pivotal study that is anticipated to form the basis for approval expected to start in mid

6 Tozadenant Phase 2b Efficacy Results Change in OFF State Time Change in ON State Time Change in LS Mean (hours per day) 2,5 2,0 1,5 1,0 0,5 0,0-0,5-1,0-1,5-2,0-2,5-0,76 0,83 * Adjusted p-value vs placebo < 0.01 * 2,01 1,54 1,17-1,39-1,86-1,92 * * -1,63 1,64 Placebo Tozadenant 60 mg BID Tozadenant 120 mg BID Tozadenant 180 mg BID Tozadenant 240 mg BID 6 Source:. Hauser et al. (2014), Lancet Neurology

7 Tozadenant Phase 2b Efficacy Results (Continued) Change in UPDRS Parts I III and Part III Baseline to End of Treatment (Week 12) 0 UPDRS Parts I III Combined Score UPDRS Parts III Score (ON) * Adjusted p-value vs placebo <0.05 Change in LS Mean (UPDRS score) ,9-1,0 Placebo -2,8-5,0-5,1 * * Tozadenant 60mg BID -3,2 * Tozadenant 120mg BID -5,5 * -3,5 * Tozadenant 180mg BID -3,8 * -5,8 Tozadenant 240mg BID 7 Source:. Hauser et al. (2014), Lancet Neurology

8 Tozadenant Positive Phase 2b results highlight potential as a new therapy for Parkinson s disease Efficacy Conclusions At doses of 120 and 180 mg twice daily, tozadenant meaningfully reduced mean daily OFF time as compared with placebo even in patients taking multiple other Parkinson s medications Statistically significant efficacy also demonstrated on multiple secondary endpoints: Change in total daily ON time at the 120 mg BID tozadenant dose UPDRS scores for Parts I III combined at all tozadenant doses and Part III at all tozadenant doses except 60 mg BID CGI-S and CGI-I at all tozadenant doses PGI-I at the 120 mg BID tozadenant dose Efficacy robustly confirmed in multiple sensitivity analyses and ON time increased with no concomitant increase in dyskinesia Minimum effective (60 mg BID) and maximum feasible (180 mg BID) tozadenant dose established 8 Source:. Hauser et al. (2014), Lancet Neurology

9 Tozadenant Generally Safe and Well-Tolerated Tozadenant has been found to be generally safe and well tolerated in 60 mg and 120 mg Increased incidence and rate of discontinuation due to adverse events in 240 mg BID tozadenant dose group Common CNS treatment emergent adverse events were observed (1) and were mild to moderate in nature Phase 2b study results published in Lancet Neurology did not report any clinically significant drug effect on laboratory test results, ECG measurements or physical examinations in patients treated with tozadenant 9 Source:. Hauser et al. (2014), Lancet Neurology (1) Dyskinesia, nausea, dizziness, constipation, Parkinson s disease worsening, and insomnia

10 Tozadenant Planned Pivotal Phase 3 Study Design DOUBLE-BLIND TREATMENT PERIOD (PART A) OPEN-LABEL TREATMENT PERIOD (PART B) PD patients with motor fluctuations (levodopa related end of dose wearing-off ) Tozadenant or placebo in addition to levodopa and any standard PD medicines Primary endpoint: Time spent in off state at 24 weeks vs. baseline S c r e e n R a n d o m i z e Weeks Weeks Weeks ---- Tozadenant 120 mg twice daily (n=150) Tozadenant 60 mg twice daily (n=150) Placebo twice daily (n=150) Tozadenant 120 mg * open-label twice daily Follow-up N= Weeks Weeks ---- Tozadenant 120 mg * open-label twice daily Follow-up N= 450 Patient Second Open-Label Study If the double-blind portion of the first trial meets its primary efficacy endpoint, Biotie will initiate another open-label trial in 450 Parkinson s patients in parallel to the ongoing open-label trial to establish the requisite number of unique patient exposures required for approval 10

11 Tozadenant De-risked Clinical Program Design similar to already successful Phase 2b study 150 patients per arm, almost double the number from Phase 2b study Focused on doses demonstrated to have been optimal in Phase 2b Highly selective identification of key centers and geographies Key success factors learned from own Phase 2b and preladenant Phase 3 11

12 Key Portfolio Developments: other pipeline products SYN120 Phase 2a study in Parkinson s disease dementia (PDD) largely funded by USD 2 million grant from Michael J. Fox Foundation 80 patient randomised, double-blinded placebo control study Top-line results of the study are expected in the second half of 2016 As a result of focus on tozadenant, development in Alzheimer s disease (AD) remains on hold Revised strategy has resulted in 16.5 million non-cash impairment on asset, as PDD market is smaller than AD; could reverse if AD study started BTT-1023 (VAP-1 antibody) Phase 2a study in primary sclerosing cholangitis (PSC) started recruitment in Q Co-funding decision for approximately 1 million from NIHR 1 in the UK The Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMA) issued a positive opinion recommending orphan drug designation in February NIHR Efficacy and Mechanism Evaluation (EME) Programme

13 Key Portfolio Developments: other pipeline products Nepicastat Phase 2 study in treatment-seeking cocaine addicts fully funded by NIDA completed recruitment in August 2014 Top-line data from the study became available in January 2015 Primary end-point of study was not successfully met Biotie will not continue with the development and this has resulted in 11.1 million non-cash impairment being recognized NIHR Efficacy and Mechanism Evaluation (EME) Programme

14 Key Portfolio Developments: marketed product Selincro (with Lundbeck) Now on the market in more than 29 countries Favorable reimbursement decisions have been issued in a number of European markets, including France, Spain and the United Kingdom, where NICE issued its final positive guidance in November 2014 Sales (and royalties) significantly increased in Q1 Lundbeck s sales and marketing activities have now been stepped up 14

15 Selincro First approved drug treatment for the reduction of alcohol consumption Selincro received EU marketing authorization in February 2013 Global rights licensed to Lundbeck Currently on the market across Europe Positive reimbursement decisions received, including UK, France and Spain Selincro is part of a new kind of patient-centered healthcare solution for reducing harmful alcohol consumption The medicine is taken, if necessary, before drinking 15

16 Selincro Lundbeck Deal Biotie is entitled to milestone payments of up to 94m Lundbeck has made payments of 22m to date Selincro is currently available across Europe Approximately 47 million people in the EU5, 42 million people in the US and 19 million people in Japan have engaged in heavy episodic drinking in the last 30 days, according to a 2014 study Lundbeck s partner for the development and commercialization of Selincro in Japan is Otsuka, with Phase III clinical development ongoing Biotie is eligible for royalties on Lundbeck s sales of Selincro 16

17 Expected Newsflow and Clinical Development Timeline BTT 1023 Phase 2 started BTT 1023 Phase 2 interim analysis Tozadenant Phase 3 double blind top-line data Tozadenant Phase 3 Double-blind study begins SYN120 Phase 2a (PDD) top-line data Selincro royalties continue 17

18 Proposed Financing The company plans to strengthen its capital structure to finance a Phase 3 double-blinded clinical trial, including the open label extension, of its lead product candidate tozadenant by in aggregate approximately EUR 95 million. Two tranches: 1. Directed issue in the form of Convertible Notes and Warrants 2. US Offering The Company intends to use the proceeds of the convertible notes and the US Offering and potential other offerings in connection with the US Offering, together with its current liquid assets and future revenue from Lundbeck in respect of Selincro to finance the tozadenant Phase 3 Trial at least through to the next major milestone, namely top-line data on the primary endpoint of the double-blinded portion of the trial at 24 weeks, which is currently expected by the end of

19 Main terms and conditions of the convertible notes The aggregate principal amount of the convertible notes will be EUR 33.1 million and each convertible note will entitle the holder to convert such note into one (1) new share in the company. The convertible loan, represented by the convertible notes, will be subscribed for and the proceeds thereof will be paid to the company shortly after the AGM. Each convertible note will have a conversion price of EUR 0.15 per share. The convertible notes automatically convert into new shares in the company upon completion of the US Offering. Based on the proposed authorisation a maximum of 221,000,000 new shares may be issued under the convertible notes. The convertible notes can be repaid by the Company after 1 May 2035 if, and to the extent, they have not been converted. The holders may also declare the convertible notes to be repaid in the event of certain defaults by the Company, including but not limited to the event that the aggregate gross proceeds of the convertible notes, the US Offering and potential other offerings prior to the completion of the US Offering would exceed USD 95 million. 19

20 Main terms and conditions of the warrants The subscribers of the convertible notes will for each convertible note also receive one (1) warrant entitling the holder to subscribe for one (1) new or treasury share in the company. Each warrant entitles the holder to subscribe for one (1) new or treasury share in the company at a subscription price of EUR The warrants, irrespective of the contemplated US Offering, may be exercised for a period of five (5) years from a date falling approximately five (5) months after issuance of the warrants. Based on the proposed authorisation a maximum of 221,000,000 shares (new or treasury) may be issued under the warrants. 20

21 Subscription price determination The conversion price of the convertible notes and exercise price of the warrants have been determined by: 1. Considering the share price of the company s shares in public trading on NASDAQ OMX Helsinki Ltd 2. The non-secured and interest free nature of the convertible notes 3. Availability and terms of possible other financing alternatives. 21

22 Deviation from the shareholder s pre-emption right The company considered various strategies for financing the tozadenant Phase 3 trial. The Company concluded that sufficient financing was not available from existing shareholders or from non-us sources on satisfactory terms. The issuance of the convertible notes and warrants, and the carrying out of the US Offering and potential other offerings in connection with the US Offering, is the most favourable option for the company to raise the large amount of capital required to conduct such a study. This strategy will enable the product to move quickly into clinical trials for the benefit of patients, and consequently, to maximize the value of tozadenant to the company and its shareholders. There are, therefore, weighty financial reasons from the company s perspective for deviating from shareholders pre-emptive subscription rights in the issuance of convertible notes and warrants, and shares in the US Offering. 22

23 Convertible Notes Offering April 23, 2015 / May 7, 2015 At AGM Post-AGM At U.S. Offering Investors commit to purchase 33.1m of notes convertible into Biotie Finnish shares at 0.15 per share and warrants convertible at 0.17 per share Biotie shareholders vote whether to authorize the issuance of new shares underlying the convertible notes and warrants as well as for the U.S. offering Board of Directors resolves to issue notes to the investor syndicate Notes are automatically converted into Biotie shares at a conversion price of 0.15 per share US Based Investors Certain Existing Shareholders Investor Syndicate 33.06m Investor Syndicate Investor Syndicate 27.50m 5.56m 33.06m cash Convertible notes Convertible notes 220.4m Shares The aggregate issue of convertible notes include 220.4m warrants convertible into Biotie shares at 0.17 per share, paid in cash upon exercise, to be exercised for a period of 5 years from 5 months after issuance 23

24 U.S. ADS Offering Offer Size Up to $62 million Units Offered: ADSs (1) Price Per ADS: Number of ADSs: Exchange: Use of Proceeds: Targeted Timing of Offering: TBD TBD NASDAQ Global Market (US) To finance the Tozadenant Phase 3 Trial at least through to the next major milestone, namely top-line data on the primary endpoint at 24 weeks, which is currently expected by the end of 2017 Q2'15 or Q3' ) The American Depository Shares (ADSs) will be securities listed on the NASDAQ Global Market (US) and traded in US$, each representing a fixed number of issued Biotie shares.

25 After the US Offering Biotie will still be a listed Finnish company, headquartered in Turku Biotie will have listed equity in both Finland and the United States, which in total will make the company s share capital Shares listed on NASDAQ-OMX in Helsinki ADS (representing a number of shares) listed on NASDAQ in New York There can be movement between the amount of share capital listed in Helsinki and New York, but the total remains the same Biotie will need to operate under the securities laws in Finland and the United States Financial results will still be reported quarterly There are some additional corporate governance requirements for the United States All stock exchange releases will be made in Finland and the United States 25

26 26