SMTC1100: Progressing to Patient Clinical Trials

Transcription

1 SMTC1100: Progressing to Patient Clinical Trials Action Duchenne Conference 9 th November 2013

2 Legal Disclaimer FORWARD LOOKING STATEMENTS This Document contains forward-looking statements. These statements relate to, among other things, analysis and other information that are based on forecasts of future results and estimates of amounts not yet determinable. These statements also relate to the Company s future prospects, developments and business strategies. Forward-looking statements are identified by their use of terms and phrases such as believe, could, envisage, estimate, expect, intend, may, plan, will or the negative of those, variations or comparable expressions, including references to assumptions. The forward-looking statements in this Document are based on current expectations and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by those statements. Given the risks and uncertainties associated with a company of this nature, potential investors should not place reliance on forward-looking statements. These forward-looking statements speak only as at the date of this Document. The Company does not undertake any obligation to update forward-looking statements or risk factors other than as required by any relevant regulations, whether as a result of new information, future events or otherwise. 2 Utrophin Modulation Programme Action Duchenne 2013

3 Muscle Integrity Repeated anchor points Finite number of springs Section through a muscle fibre Finite number of binding sites Less springs Still functional but lower weight capacity Costamere Contractile apparatus Contraction and relaxation stress transmitted through costamere anchor sites Less dystrophin (Becker) Still functional but lower stress tolerance No springs Structural failure Dystrophin or Utrophin No dystrophin (Duchenne) Structural failure 3 Utrophin Modulation Programme Action Duchenne 2013

4 Utrophin: A Replacement for Dystrophin Normal muscle fibre MATURING MUSCLE FIBRE Foetal Foetal/Immature Mature DMD muscle fibre DMD + utrophin drug muscle fibre Utrophin: Dystrophin: DEGENERATION 4 Utrophin Modulation Programme Action Duchenne 2013

5 Continual Expression of Utrophin Prevents Muscular Dystrophy in mdx Mouse Nature Medicine, 4, (1998) 5 Utrophin Modulation Programme Action Duchenne 2013

6 Summit s Utrophin Modulation Programme Developing first and best in class medicines for utrophin modulation Includes lead candidate SMT C1100 and next generation molecules: DISCOVERY (1-4 Years) OPTIMISATION (1-2 Years) PRECLINICAL (1-2 Years) PHASE 1 (1 Year) PHASE 2 (1-2 Years) Lead: SMT C1100 Next Generation Utrophin programme builds on the research from Oxford University: Utrophin biology: Prof Kay Davies group (MRC Functional Genomics Unit) Medicinal chemistry: Prof Steve Davies group (Dept of Chemistry) Co-founders of Summit 6 Utrophin Modulation Programme Action Duchenne 2013

7 Development of SMT C Utrophin Modulation Programme Action Duchenne 2013

8 SMT C1100 Nonclinical Summary Only disease modifying treatment for DMD regardless of the dystrophin mutation Designed to modulate utrophin transcription Activity demonstrated in target the cells: DMD myoblasts / developing myotubes Established proof-of-concept in dystrophin deficient animal model Effective in worsened disease caused by forced exercise Orally taken drug appropriate for the pediatric population No problems in regulatory preclinical safety and toxicology studies to date 8 Utrophin Modulation Programme Action Duchenne 2013

9 Overview of Key Efficacy Data 1. More Utrophin Fibres 2. Reduced Muscle Damage 3. Improves Muscle Function Mdx Mdx + SMT C % 80% 60% 40% 20% 0% Regeneration Necrosis Non muscle area mdx mdx+c1100 Normalised Force Increment Vehicle mdx Exer mdx Exer mdx+ SMTC1100 Daily dosing with SMT C1100 Fall in biomarkers of muscle damage; regeneration, fibrosis, fibre death Protection against loss of forelimb grip strength Source: PLoS ONE, Volume 6, Issue 4, May Utrophin Modulation Programme Action Duchenne 2013

10 Successful Phase 1 Trial Completed in 2012 Repeat dose Phase 1 healthy volunteer trial showed a paediatric formulation of SMT C1100 (100mg/kg, taken twice a day for 10 days): Safe and well tolerated Achieved stable plasma concentrations after 4 days Individuals with the lowest plasma levels still expected to modulate utrophin expression for at least 14 hours a day Blood level required for utrophin modulation activity in mdx and cell models Based on these data, SMT C1100 is progressing into patient clinical trials 10 Utrophin Modulation Programme Action Duchenne 2013

11 Current and Future Activities Phase 1b Biomarker Programme Long-term Toxicology Drug Product Manufacture Phase 2 11 Utrophin Modulation Programme Action Duchenne 2013

12 Biomarker Programme Utrophin / Mechanism Related: 1. UTRN localisation by quantitative IF 2. Total utrophin protein 3. Total utrophin mrna Muscle Health: Regeneration & Inflammation From Muscle: 1. Muscle regeneration markers 2. Inflammatory markers From Plasma: 3. mirnas 4. Active Fibrosis Supported by 12 Utrophin Modulation Programme Action Duchenne 2013

13 Phase 1b DMD Patient Trial 12 ambulatory DMD patients aged 5 to 11 years old Three escalating dose groups 10 days of oral dosing Tolerability & Safety PK levels SMT C1100 and metabolites Identify doses for Phase 2 Proof of Concept (PoC) trial UK-based study (4 sites) Ethics and regulatory approval granted 13 Utrophin Modulation Programme Action Duchenne 2013

14 On-Going Activities Phase 1b Clinical Trial Opening of trial sites and the start of patient recruitment Preparation for Phase 2 DMD proof of concept trial Double blind PoC trial ~40-50 ambulatory DMD patients At least 24 weeks dosing International study Development of next generation utrophin modulators Identify candidates with enhanced pharmacokinetic properties and complimentary mechanisms Collaboration with Oxford University Subject to review by advisers and regulators 14 Utrophin Modulation Programme Action Duchenne 2013

15 Thank you to the Community 15 Utrophin Modulation Programme Action Duchenne 2013