OPMD WEBINAR 15 May 2018 NASDAQ: BNTC | ASX: BLT
MEETING AGENDA • Welcome and opening remarks (Greg West) • Corporate overview (Greg West) • OPMD overview (Bernard Brais) • OPMD unmet medical need (Georgina Kilfoil) • BB‐301 – Benitec’s OPMD therapeutic (David Suhy and Georgina Kilfoil) • Mechanism of action • Nonclinical silence and replace • Pathway to the clinic • Planned clinical program • Market potential • Wrap‐up (Greg West) 2
SAFE HARBOR STATEMENT If we make any forward-looking statements, we note that such statements involve risks and uncertainties relating to the difficulties in our plans to develop and commercialize our product candidates, the timing of the initiation and completion of preclinical and clinical trials, the timing of patient enrolment and dosing in clinical trials, the timing of expected regulatory filings, the clinical utility and potential attributes and benefits of ddRNAi and our product candidates, potential future out-licenses and collaborations, our intellectual property position and the ability to procure additional sources of financing. 3
CORPORATE OVERVIEW NASDAQ: BNTC | ASX: BLT Greg West, Chief Executive Officer
BUSINESS OVERVIEW Proven Technology First company into human clinical studies under a US IND with systemically delivered non- Benitec has created a novel withdrawable RNAi (TT-034) combination of gene therapy and gene silencing Robust Pipeline to change treatment Assets in oncology (Phase 2 entry, 1Q18), orphan genetic disorders (Phase 1/2a entry, paradigms of human 1Q19), retinal disease, and infectious disease. disease Valuable Products Human therapeutic products for commercialization, partnering, and collaborations 5
HIGHLIGHTS EGFR-targeted gene Unique ‘silence and replace’ Other programs could be Programs silencing therapy therapeutic designed to treat clinic-ready in late 2019 confirmatory Phase 2 trial OPMD with IND filing in Q1 advancing to clinic initiated in Q1 2018 2019 Listed on ASX (2002, BLT) US$50M capital raised US shelf registration Capital and NASDAQ (2015, BNTC) since 2014 statement filed June 2017 markets access 19 staff with scientific In-house manufacturing Extensive commercial Strong in-house operations in Hayward CA, expertise for process and drug development including 9 PhDs with deep optimization and scalability expertise capabilities gene therapy expertise 6
DIVERSE PROGRAM PIPELINE Early stage clinical Late stage clinical Program Delivery Discovery Preclinical IND-Enabling Commercial rights (IND – Ph 2) (Ph 2 – Ph 3) Oncology – head and neck squamous cell carcinoma (HNSCC) HNSCC Plasmid Global BB-401 Intratumoral HNSCC ddRNAi Global BB-501 Intratumoral Orphan disease - oculopharyngeal muscular dystrophy (OPMD) OPMD AAV Global BB-301 Intramuscular Infectious disease – hepatitis B (HBV)* HBV AAV Global BB-103 Intravenous Retinal disease - wet age-related macular degeneration (AMD) AMD Novel AAV Global BB-201 Intravitreal *Continued development dependent on partnership or funding 7
Bernard Brais M.D.C.M., M.Phil., Ph.D., FRCP(C) Professor of Neurology and Genetics Co‐Director, Rare Neurological Diseases Group Montreal Neurological Institute McGill University Bernard.Brais@Mcgill.ca 8
Outline of presentation OPMD prevalence OPMD diagnosis Progression and treatments of OPMD End of life in OPMD 9
OPMD is a world wide late‐onset muscular dystrophy with variable prevalences Quebec South ‐ West Bukhara Jews 1:1000 Northern UK France in Israel USA (>1500 >1:100000 1:100000 1:600 1: 15000 (GCN)n + cases) 10
(Taylor, 1915) (Tomé & Fardeau, 1980) 1915: First French Canadian families (Taylor) 1962: Victor and Adams name OPMD the disease affecting a Ashkenazi Jewish family, New England Journal of Medicine. OPMD is a dominant dystrophy that presents with eyelid drooping and dysphagia that starts in the late forties‐early fifties 1980: Description of a diagnostic pathological marker: Intranuclear inclusions (INI) by Tomé and Fardeau 1995: objective dysphagia in OPMD: Bouchard’s Cold Water test defined as swallowing 80ml of cold water >7 seconds as supporting the diagnosis of OPMD 1998: Brais et al. in Nature Genetics describe the cryptique (GCN)n/Alanine repeat mutations in PABPN1 as the cause OPMD worldwide 11
Progression of OPMD Dysphagia 100% Average age of onset of 90% (GCN)13 cases: 47 years old 80% 70% (GCN)13 (9): Quebec (n:178) 60% (GCN)15 (11): Uruguay (n: 49) 50% 40% 30% 20% 10% 0% 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 Aspiration pneumonias 55 12
Treatments for dysphagia Indications: moderate to severe dysphagia Cricopharyngeal dilatation (needs to be repeated) Cricopharyngeal myotomy (morbidity and mortality) Cricopharyngeal paralysis with Botox (unproven) Cricopharyngeal myotomy 13
Progression of OPMD Eyelid Ptosis 1 (GCN)13 (9): Quebec (n:178) 0,9 (GCN)15 (11): Uruguay (n: 49) 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 55 14
Treatment of the eyelid ptosis Indications: More than 50% coverage of pupil, night driving more difficult and cervical pain Frontal suspension is the permanent solution Kalin‐Hajdu, E., et al., Codere, F. Ophthalmic Plastic & Reconstructive Surgery . 2017. 15
Progression of OPMD Lower limb weakness 1 (GCN)13 (9): Quebec (n:178) (GCN)15 (11): Uruguay (n: 49) 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 No treatment for the progressive Loss of walking limb girdle weakness 65 is rare 16
Progression of OPMD End of life in OPMD 9 30 11 (GCN)13 (9): Quebec (n:178) (GCN)15 (11): Uruguay (n: 49) 25 20 15 10 5 0 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 Increasingly poor quality of life past 65 with a reasonably normal life expectancy. 17
OPMD UNMET MEDICAL NEED NASDAQ: BNTC | ASX: BLT Georgina Kilfoil, Chief Development Officer
LIVING WITH OPMD • Slow progressing muscle wasting disease Eyelid drooping (ptosis) • Rare autosomal inheritance • Caused by a defect in the PABPN1 gene • Typical age of onset is 40s or 50s Swallowing difficulty (dysphagia) • Available therapies limited to palliative care Proximal limb weakness 19
OPMD PATIENT PRESENTATION & DIAGNOSIS Referral Diagnosis Presenting factors pathway outcomes Initial Presentation Disability Family history • Specialty depends on triggering Neurologist Ageing Functional symptom Impairment PRIMARY CARE PHYSICIAN Dysphagia Diagnosis Malnutrition & weight loss DYSPHAGIA in OPMD Otorhinolaryngologist • Performed by neurologist or geneticist Functional Impairment Readmissions Leg weakness Hospitalization Malnutrition/ dehydration Social Morbidity concerns Gastro Ophthal mology Ptosis Mortality 20 Source: GlobalData Report Oct 2017
DYSPHAGIA - MOST SERIOUS FEATURE OF OPMD Dysphagia • Can be life‐threatening • KOLs recognize this as the Dysphagia most serious feature of OPMD • Treatment is driven by patient preference and severity Not life threatening More of an inconvenience to patients than Ptosis OPMD Ptosis Proximal Limb Weakness • Often the symptom that • Not life threatening motivates patient to seek care • Impacts patient’s QOL • Satisfactorily fixed with • Limb More of an inconvenience corrective surgery (frontal Ptosis to patients sling highly preferred vs Weakness blepharoplasty) 21 Source: GlobalData Report Oct 2017
MUCH ROOM FOR IMPROVEMENT WITH CURRENT INTERVENTIONS FOR DYSPHAGIA Highest Satisfaction Advantages Disdvantages Cricopharyngeal myotomy Often effective Expensive, may need repeat, irreversible Counselling and advance directives Inexpensive Not a solution Not permanent, may need frequent repeat, not Endoscopic dilation Often effective, not as invasive as surgery effective in everyone Inexpensive and extremely important, and Dietary Modification Hard to stay compliant, not always effective sometimes effective Not invasive, and relatively inexpensive Time consuming, need for frequent visits Swallow therapy Effective for some Expensive, temporary, need for frequent visits Botulinum toxin injections Potential in the future None available Pharmacological therapy Neuromuscular electrical stimulation Non‐invasive Uncomfortable, temporary, need for frequent visits Lowest Satisfaction While CP myotomy and counselling are the most satisfactory treatments, there is much room for improvement 22 Source: GlobalData Report Oct 2017
BB-301 OPMD THERAPEUTIC NASDAQ: BNTC | ASX: BLT David Suhy, Chief Scientific Officer Georgina Kilfoil, Chief Development Officer
ASPIRATION FROM DYSPHAGIA Pharyngeal Muscles Cricopharyngeus Muscle Trachea: Esophagus: To Lungs To Stomach 24
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