Corporate Update. July, 2018 NASDAQ: GNMX. 2018, Aevi Genomic Medicine

Transcription

1 Corporate Update July, 2018 NASDAQ: GNMX

2 Forward-Looking Statement This presentation includes certain estimates and other forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, including statements with respect to anticipated operating and financial performance, clinical results, potential partnerships, licensing opportunities and other statements of expectation. Words such as expects, anticipates, intends, plans, believes, assumes, seeks, estimates, should and variations of these words and similar expressions, are intended to identify these forward-looking statements. While we believe these statements are accurate, forward-looking statements are inherently uncertain and we cannot assure you that these expectations will occur and our actual results may be significantly different. These statements by the Company and its management are based on estimates, projections, beliefs and assumptions of management and are not guarantees of future performance. Important factors that could cause actual results to differ from those in the forward-looking statements include the factors described in the Company s filings with the U.S. Securities and Exchange Commission. The Company disclaims any obligation to update or revise any forward-looking statement based on the occurrence of future events, the receipt of new information, or otherwise. 2

3 Management Team Michael F. Cola Chief Executive Officer Garry A. Neil, MD Chief Scientific Officer Brian D. Piper Chief Financial Officer Sol J. Barer, PhD Chairman 3

4 Investment Highlights Aevi is focused on unlocking the potential of genomic medicine Exclusive option to the genomic discoveries from The Center for Applied Genomics (CAG) at Children s Hospital of Philadelphia (CHOP) in the area of R/O diseases (<300k US patients) Lead asset (AEVI-001) is a first-in-class mglur neuromodulator in Phase 2b clinical trials in a genetic subset of patients with ADHD Second asset (AEVI-002) is a first-in-class monoclonal antibody in a Phase Ib trial for severe pediatric-onset Crohn s Disease 4

5 Current Situation FDA Feedback on AEVI-004 June 22 nd Aevi announced that it had received positive feedback from the FDA on an improved version of AEVI-001 (AEVI-004). AEVI-004 is a co-crystal of fasoracetam with a higher melting point and better flow and stability characteristics which has been engineered to have the same solubility, permeability, and bioavailability as fasoracetam. FDA provisionally deemed it NCE eligible with minimal requirements to go directly to Phase III AEVI-004 should have composition of matter (COM) patents through 2039 This molecule should have a long patent life and enhance the ability to study additional indications. 5

6 Current Situation June 12 th Aevi announced the results of an interim analysis of the placebo arm of Part A (mglur+) of the ASCEND trial which requires an increase in the sample size from 42 patients to 64 We currently anticipate data for Part A in Q AEVI-004 increases the importance of Part B (mglur-) of the ASCEND Trial Part B of ASCEND trial will study 82 patients without mglur mutations Part B should move very rapidly as we have over 1500 mglur- patients in the ASCEND database. Combined analysis of Part A and Part B would provide greater power and enhance our ability to detect a smaller treatment effect and increase the probability of positive top-line data. Current cash runway is through early Q1 2019, ASCEND topline data, and initial anti-light data. 6

7 Aevi Genomic Medicine Pipeline Compound Indication Preclinical Phase 1 Phase 2 Status AEVI-001/ AEVI-004 AEVI-002* (anti-light mab) AEVI-005* mglur+ Genetic Subset in ADHD (pediatric, age 6-17) mglur+ Genetic Subset in ASD Severe Pediatric Onset Crohn s Disease Undisclosed pediatric rare disease Top-Line Data Q Plan to Initiate Q Initial Data Year-end 2018 Initiating in vitro POC work * Partnered with Kyowa Hakko Kirin (KHK) 7

8 AEVI-001 in ADHD Overview

9 CAG Breakthrough Discovery Research led by Dr. Hakon Hakonarson indicated ~20% of ADHD patients have underlying mglur network mutations 10 fold increased frequency of copy number variations (CNV s) in the mglur gene network detected in ADHD population vs. normal controls These mutations were found in several related neuropsychiatric diseases Elia, Glessner et al. Nature Genetics,

10 AEVI-001: Potential for Superior Product Profile Small molecule glutamate modulator: Originator: Nippon Shinyaku Oral non-stimulant Excellent PK/metabolic profile Crosses blood-brain barrier: Shown to ameliorate cognitive impairment in animal behavioral models, 1,2,3 at concentrations achievable in humans Pan-selective activator/modulator of mglurs 4,5 Prior human exposure in vascular dementia: ~1000 elderly patients, up to 12 months Excellent safety profile Not effective for the study indication 1. Ogasawara et al. (1999) Pharmacol Biochem Behav, 64(1): Nakagawa et al. (1988) Jpn J Pharmacol, 46(Suppl.): Abst O Nakagawa et al. (1990) Jpn J Pharmacol, 52(Suppl. I): Abst P Oka et al. (1997) Naunyn Schmiedebergs Arch. Pharmacol, 356(2): Hirouchi et al. (2000) Eur J Pharmacol, 387(1):

11 AEVI-001: ADHD Development Program SAGA Phase 2 (Completed) mglur+ ADHD, Adolescents N=96, Ages Missed primary endpoint ASCEND Part A: Phase 2 (Recruiting) mglur+ Genetic Subset ADHD N=42-64, Ages 6-17 ASCEND Part B: Phase 2 No mglur mutation ADHD N=82, Ages 6-17 Phase 3: using AEVI-004 mglur+ or possibly all ADHD N=TBD, Ages 6-12 Phase 3: using AEVI-004 mglur+ or possibly all ADHD N=TBD, Ages

12 AEVI-001 (ASCEND) 2 Part (A,B) Sequential Adaptive Confirmatory Efficacy Trial in mglur+ ADHD Multi-center (20-25 US sites) Inclusion criteria: 6-17 years of age ADHD-RS-5 28 Positive for 8 gene subset, including CNTN4 (Part A) - or - non-mutated (Part B) Primary endpoint: ADHD-RS-5 Key secondary endpoint: CGI-I 1:1 randomization Placebo-controlled Dose optimization: mg BID Screening Period (up to 4 weeks inclusive of washout, if applicable) Dose-optimization Period (4 weeks) Dose Maintenance Period (2 weeks) Visit #: /ET Dose: 100 mg BID, 200 mg BID, or 400 mg BID, Dose optimization based on response assessment Maintenance on optimal dose End of treatment: Day 42 Follow-up Call (1 week) Week:

13 SAGA Responder Analysis Summary Post-hoc analysis of patients responding to AEVI-001 revealed a 8-gene subset predictive of response to AEVI-001 accounts for approximately 8-10% of pediatric ADHD patients. 1 Novel discovery: prevalence of CNTN4 mutations in ADHD Represents approximately 5% of pediatric ADHD All CNTN4 mutation+ patients (n=6) on AEVI-001 achieved clinical response More severe ADHD phenotype with emotional dysregulation features CNTN4 mutation association with neurodevelopmental diseases supports study in ASD 1 Data on file and Elia, J. et al, Glutamatergic network gene mutations in children and adolescents with ADHD. Poster presented at: 6th World Congress on ADHD; April 21, 2017; Vancouver, Canada 13

14 Change in ADHD-RS Score from Baseline Change in ADHD-RS Score from Baseline Comparative Analysis of 8 Gene Subset from the SAGA Trial 0 SAGA Change in ADHD-RS (N=96) Placebo AEVI SAGA 8-Gene Subset Change in ADHD-RS (n=39) Placebo AEVI n=22-10 n=50 p=ns Δ = 12 p < 0.001* -15 n=46 n= Baseline Week 1 (100 mg BID) Week 2 (200 mg BID) Week 3 (400 mg BID) Week 4 (Optimized Dose) Week 5 (Maintenance Dose) Week 6 (Maintenance Dose) Baseline Week 1 (100 mg BID) Week 2 (200 mg BID) Week 3 (400 mg BID) Week 4 (Optimized Dose) Week 5 (Maintenance Dose) Week 6 (Maintenance Dose) ADHD-RS: parent reported scale on hyperactivity and inattention, 18 questions; scored

15 9-Gene Subset Responders: ADHD Total Addressable Market Overall US ADHD Market US market sales: ~$11.1B 1 and growing at ~2 % CAGR 1 Stimulants dominate market: ~90 % of sales 1 ~6M pediatric (ages 6-17) patients and ~10M adult patients in US 2,3 8-Gene Subset ADHD Market (~8-10% of ADHD patients) 4 ~600K pediatric patients and ~1M adult patients $2B - $3B market size based upon current premium pricing and compliance / adherence Additional lifecycle opportunities where mglur mutation are found: ASD, Tourettes, Bipolar, etc 1.IMS NSP, (Visser S et al Journal of American Academy of Child and Adolescent Psychiatry 2014, 53(1):34-46) 3. (Kessler R et al American Journal of Psychiatry 2006, 163(4):716-23) 4.Data on file and Elia, J. et al, Glutamatergic network gene mutations in children and adolescents with ADHD. Poster presented at: 6 th World Congress on ADHD; April 21,

16 AEVI-004: Fasoracetam Co-crystal

17 Pharmaceutical Co-Crystals pharmaceutical Co-crystals offer the possibility of exploring different pharmaceutical properties and enhancing the final drug product 2,3 Schultheiss N., Newman A. Crystal Growth & Design 2009, 9:

18 Co-crystal Pharmaceuticals: Recent FDA Guidance Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry 1 Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry was issued February Farxiga (dapagliflozin propanediol) Entresto (sacubitril/valsartan) 18

19 Aevi-004 Co-crystal: Advantages AEVI-004, a co-crystal of fasoracetam, has enhanced physical properties: Stability Higher Melting point AEVI-004 was engineered to maintain: Solubility Permeability Bioavailability Maintained Bolla & Nangia, Chem. Comm. 54: ,

20 FDA feedback on AEVI-004 FDA provisionally agreed that AEVI-004 is a co-crystal and therefore NCE eligible. FDA provisionally agreed existing tox path studies are acceptable to support AEVI-004 with minimal preclinical bridging studies Switching to AEVI-004 for Phase 3 should have minimal impact on program cost and timing 20

21 ADHD AEVI-001 Regulatory Exclusivity Hatch-Waxman Data Exclusivity 5 years for NCE EMA Exclusivity (NCE) 10 years Aevi-001 Additional Test and Treat Patent Term Exclusivity = 20 years Aevi-004 Co-crystal Composition of Matter Patent Term Exclusivity = 20 years Provisional Patents Filed 2019 Note: Hatch-Waxman exclusivity starts upon approval of NDA by FDA 21

22 AEVI-002 Program in Severe Pediatric Onset Crohn s Disease

23 AEVI-002: Anti-LIGHT mab Program First-in-Class Biologic from Kyowa Hakko Kirin Initial development in Severe Pediatric Onset IBD Phase 2 human monoclonal antibody Program Update Decoy Receptor 3 DcR3 Immune Cell LIGHT Study design: 8 12 patient study in refractory Crohn s Disease patients >18 years CHOP IBD center: no patients enrolled to date HVEM LTbR 3 additional sites activated: Salt Lake City, Vanderbilt and Emory External recruiting support initiated Initial data expected year-end 2018 Our Approach: Therapeutic antibody which mimics DcR3 regulation by binding LIGHT 23

24 AEVI-002 Site Expansion Anti-LIGHT mab Phase 1b program in severe pediatric onset IBD Three additional US sites were added this spring (Emory, Vanderbilt, Salt Lake City) with Vanderbilt and SLC recruiting for the last quarter. No patients enrolled yet but prescreening of patients is proceeding. Feasibility currently ongoing for ex-us sites. (Israel and Columbia most likely) 24

25 AEVI-005 Novel Orphan Disease Program

26 AEVI-005: Novel Orphan Program Collaboration with Kyowa Hakko Kirin First-in-class monoclonal antibody targeting a specific cell surface marker implicated in an ultra-orphan auto-immune pediatric disease Preclinical stage Aevi-led translational work will commence leveraging CHOP Biobank samples and genomics data. In-vitro proof of concept in 9-12 months Program expected to be ready for clinic in months Financial and other terms of the deal not disclosed 26

27 Thank You!