Alcobra Ltd. (NASDAQ:ADHD) June 2016

Transcription

1 Alcobra Ltd. (NASDAQ:ADHD) June

2 Forward-Looking Statements This presentation includes statements that are, or may be deemed, forward-looking statements. In some cases, these forward-looking statements can be identified by the use of forward-looking terminology, including the terms believes, estimates, anticipates, expects, plans, intends, may, could, might, will, should, approximately, potential or, in each case, their negative or other variations thereon or comparable terminology, although not all forward-looking statements contain these words. They appear in a number of places throughout this presentation and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, the expected milestones, and the development, of our lead product candidate and its various indications, including the timing of our clinical trials, the potential of MDX to address the market opportunity in ADHD, the potential to use MDX to treat Fragile X Syndrome and our ability to protect our proprietary technology and enforce our intellectual property rights. In addition, historic results of scientific research and clinical and preclinical trials do not guarantee that the conclusions of future research or trials would not suggest different conclusions or that historic results referred to in this press release would not be interpreted differently in light of additional research and clinical and preclinical trials results. By their nature, forward-looking statements involve risks and uncertainties because they relate to events, competitive dynamics, and healthcare, regulatory and scientific developments and depend on the economic circumstances that may or may not occur in the future or may occur on longer or shorter timelines than anticipated. Although we believe that we have a reasonable basis for each forward-looking statement contained in this presentation, we caution you that forward-looking statements are not guarantees of future performance and that our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate may differ materially from the forward-looking statements contained in this presentation as a result of, among other factors, the factors referenced in the Risk Factors section of our annual report on Form 20-F for the year ended December 31, 2015 filed with the Securities and Exchange Commission. In addition, even if our results of operations, financial condition and liquidity, and the development of the industry in which we operate are consistent with the forward-looking statements contained in this presentation, they may not be predictive of results or developments in future periods. Any forward-looking statement that we make in this presentation speaks only as of the date of such statement, and we undertake no obligation to update such statements to reflect events or circumstances after the date of this presentation. 2

3 Financial highlights Financial metric Reported financials (Q1 2016) Cash, marketable securities & deposits Fully diluted shares (adj.) $65.2 million 29.4 million Top institutional shareholders on file Franklin Deerfield RA Alyeska Baker Brothers Perceptive Great Point Ghost Tree Venrock Balyasny Broadfin Palo Alto Regals Sabby Knoll 3

4 Alcobra Ltd. MDX is a novel drug candidate for Cognitive Disorders Consistent pro-cognitive effect and favorable tolerability demonstrated in multiple controlled clinical studies MDX in late-stage development for ADHD Pivotal, Phase III study in Adults with ADHD ongoing; data by YE 2016 Phase II/III pediatric ADHD study to start 2016 MDX designated Orphan Drug and awarded Fast Track for Fragile X Syndrome Phase II findings on Daily Living Skills improvement Cash position supports development activities through the end of

5 About Metadoxine Extended Release (MDX) MDX MDX is a once-daily, proprietary dual-release formulation of Metadoxine (pyridoxol L-2- pyrrolidone-5-carboxylate) Metadoxine Since the 1980s, Metadoxine has been available in immediate release forms (<1hr t ½ ) for acute treatment of Alcohol Intoxication and chronic treatment of Alcoholic Liver Disease in Italy, Portugal, Hungary, Russia, India, China, Mexico and Thailand An estimate of 13+ million patient days of therapy on Metadoxine (acute/chronic) since its introduction In 30+ years of product availability no major safety/tolerability issues have been published Multiple peer reviewed publications on the chronic use of Metadoxine at mg levels (1) 1. Caballeria et al (J Hep, 1998) n=69, 3 months, 1500mg Cacciatore et al (Clin Trial J, 1988) n=30, 300mg IM twice daily for 30 days, then 500mg tablet 3 times a day for 5 months (6 months 1500mg) Bono et al (Int J Clin Pharm Res, 1991) n=20, 900mg IV twice daily (10 days mg) 6

6 Intellectual Property Over 30 submitted patents globally may provide multiple layers of protection to 2028 and beyond: Dual-release composition US PATENT #8,476,304 ISSUED JULY 2013 INTERNATIONAL PATENTS ISSUED/ALLOWED (EU, JP, AU, MX, RU, HK, IN) Use of Metadoxine for cognitive disorders and impairments US PATENT #8,710,067 FOR ADHD TREATMENT ISSUED APRIL 2014 US PENDING APPLICATION FOR COGNTIVE DISORDERS INTERNATIONAL PATENTS ISSUED (NZ, MX, AU, CN) IP term is before any regulatory exclusivities (NCE and/or pediatric use) and any patent term extensions 7

7 ADHD Attention deficit-hyperactivity disorder (ADHD) is a neurobehavioral disorder characterized by difficulty in maintaining attention, hyperactivity and impulsive behavior; affects 8-10% of children & 4-5% of the adults worldwide; Marketed ADHD treatments: Ritalin, Concerta, Adderall, Vyvanse Psychostimulants Strattera, Intuniv, Kapvay Non-stimulants Strong Effect Rapid Onset Non-Scheduled Non-Addictive Scheduled Substance Significant Side Effects Titration required Moderate Effect Delayed onset Significant Side Effects Titration required 8

8 Total ADHD Market TRxs (US): 67M TRxs in 2015 with a 5-year CAGR of 6.3% TRxs (Millions) Strattera Launch Vyvanse Launch Intuniv Launch % Annual Growth versus Previous Yr. 14.8% 16.1% 6.5% 0.2% 7.2% 11.8% 9.3% 12.4% 10.4% 4.5% 6.2% 4.9% 5.8% 2015 Total ADHD Sales in US = $9.6 billion Data Source: IMS, NPA, TRxs 9

9 ADHD Medications have shown Rapid Market Uptake and Revenue Growth - minimal impact of generics introductions Product (launch) Class Owner Years to Peak Share 1 Peak Share 1 Peak Sales 2 Concerta (2000) Stimulant J&J 2 26% $1.3 BB Adderall XR (2001) Strattera (2002) Stimulant Shire 5 26% $1.1 BB Non-Stimulant Eli Lilly 2 18% $784 MM Vyvanse (2007) Stimulant Shire ($2.6bn acquisition) 6 17% $1.7 BB Intuniv (2009) Non-Stimulant Shire 4 4% $335 MM 1 US Market; Company analysis based on IMS data 2 Source: Company annual reports; Strattera and Vyvanse sales still growing 10

10 MDX Clinical Studies in ADHD Comprehensive development history shows consistent pro-cognitive benefits and tolerability Study Phase Number of Subjects & Sites Study Design Phase I (PK) Phase IIa Phase IIb Phase IIb Phase III Phase II (PK) 16 healthy adult subjects 1 site 40 adult ADHD subjects 1 site 120 adult ADHD subjects 2 sites 36 adult ADHD subjects 1 site 300 adult ADHD subjects 20 sites 82 adolescent ADHD subjects 6 sites PK, repeated-dose Open-label, single-dose Randomized, double-blind, placebocontrolled, parallel-group Randomized, double-blind, placebocontrolled, crossover-comparison Randomized, double-blind, parallel, fixeddose Randomized, double-blind, fixed dose Duration of Treatment 5 days 1 day 6 weeks Single dose 6 weeks Single dose 1. Manor I, et al. J Clin Psychiatry. 2012;73: Manor I, et al. Postgrad Med. 2013;125: Manor I et al. Postgrad Med 2013; 125(4): Adler L. Symposium presentation at the 60th Annual Meeting of the American Academy of Child & Adolescent Psychiatry; October 19 27, 2013; Orlando, FL. 5. Adler L. Symposium presentation at the 61st Annual Meeting of the American Academy of Child & Adolescent Psychiatry; October 20 25, 2014; San Diego, Ca 6. Manor I et al. Postgrad Med 2014; 126(5): Posters presented at AACAP s 61st Annual Meeting, San Diego, CA, October 23, Data on file 11

11 MDX 1 st P3 adult ADHD study (AL012) Safety & Tolerability No statistically or clinically significant differences in adverse events seen between MDX and Placebo Adverse Events in 5% of Patients in Any Group AE MDX 1400 mg/d (n = 152) No. (%) of Patients Placebo (n = 146) No. (%) of Patients Headache 23 (15.1) 18 (12.3) Nausea 13 (8.6) 9 (6.2) Fatigue 11 (7.2) 12 (8.2) Decreased appetite 8 (5.3) 0 No drug-related serious AEs were reported. No statistically or clinically significant differences seen between MDX and Placebo on cardiac functions, lab tests, physical exams, etc. 12

12 MDX 1 st P3 adult ADHD study (AL012) key observations Study failed to meet primary endpoint Week On multiple endpoints, MDX consistently favorable over placebo Improvement from baseline of drug treated group consistent with previous MDX studies Response variability of entire sample unusually large; Placebo group shows significant response CAARS CHANGE FROM BASELINE Placebo MDX p= MDX Studies LS Mean ± SD Phase III MDX Study; n=300 MDX 12.0 ± 12.6 Placebo 9.9 ± 11.4 Phase IIb MDX Study 1 ; n=120 MDX 12.5 ± 8.8 Placebo 8.9 ± 9.2 Atomoxetine (Strattera) Studies Michelson D et al, Study 1 n = 267 Study 2 n = 248 Mean ± SD Atomoxetine 9.5 ± 10.1 Placebo 6.0 ± 9.3 Atomoxetine 10.5 ± 10.9 Placebo 6.7 ±

13 Pivotal adult Phase III study (MEASURE) Lessons from AL012 implemented in design of the pivotal study for MDX in adults (the MEASURE study) Larger study (conservatively powered based on AL012 effect size) Up to 750 patients enrolled Selectivity in site participation Introduce double-blinded variable placebo period to exclude extreme placebo responders. Reduce visit frequency (to bi-weekly) and duration (3 core assessments); minimize burden to subject & rater and promote quality Extend trial duration (10 weeks) to target reduction of placebo response esource platform for real-time, central expert review of clinical assessments 14

14 MDX for ADHD next steps Adult Pediatric FDA confirmation that positive efficacy results from a single Phase III study will be sufficient to demonstrate efficacy for approval of MDX in the adult subpopulation. Data from MEASURE, the pivotal adult ADHD study, is expected by YE FDA further confirmed that two positive pediatric studies (one Phase II + one Phase III) will be sufficient to demonstrate efficacy in this sub-population. First pediatric ADHD registration study expected to launch in

15 MDX for treatment of Fragile X Syndrome Fragile X Syndrome is a rare neuro-genetic disorder Most common known genetic cause of autism Most common inherited form of intellectual disability Approximately 50,000 Americans affected (1:4000 males) Unmet need: No FDA approved therapies Lack of significant benefits on primary or secondary outcomes in multiple advanced clinical trials in past 2-3 years 16

16 MDX Phase II Trial in Fragile X (AL014) 6-week, randomized, multicenter, placebo-controlled, double-blind, parallel group, study of MDX once daily in FXS patients (NCT ) 62 adolescents and adults (Age 14-55), 12 study sites (11 in US) Efficacy assessments: Behavioral Cognitive ADHD-RS Vineland-II ABC KiTAP RBANS-LL 17

17 AL014: ITT analyses Vineland-II: Daily Living Skills Personal: Eating/Drinking, Dressing/Undressing, Personal Hygiene. Domestic: Household Tasks/Chores Cooking, Cleaning, Organizing, Household Safety. Community: Time/Date Understanding and Management, Earning/Managing Money, Phone Use, TV/Radio/Computer Use, Outdoor Activities, Work Skills, Travelling. LS Mean Change from Baseline in Vineland-II DLS 3 2 p = Effect Size: 0.56 Improvement Placebo MDX No statistically significant findings on the primary endpoint No statistically significant findings on Vineland-II-Socialization, ABC Statistically significant/directional findings on KiTAP, RBANS 18

18 MDX for Fragile X Syndrome next steps MDX demonstrated a statistically significant benefit on a clinically meaningful, functional secondary endpoint: Vineland-II Daily Living Skills (p= 0.044, effect size 0.56) MDX was generally well tolerated and no safety concerns were identified FDA agreement to a single, pivotal study in adolescents and adults with FXS, using Vineland-II DLS as primary endpoint Study to initiate after pivotal adult ADHD study results are available MDX awarded Orphan Designation and Fast Track by FDA 19

19 Summary: Alcobra Ltd. Consistent pro-cognitive effect and favorable tolerability demonstrated in multiple controlled clinical studies with MDX Several 2016 milestones: Pivotal, Phase III study in Adults with ADHD data Launch of first registration study in children with ADHD Pivotal program for Fragile X Syndrome IP portfolio extends to 2028 before regulatory/ip extensions Cash position supports development activities through the end of

20 Alcobra Ltd. NASDAQ:ADHD