Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (September 2021)
47 slides from Neuren Pharmaceuticals's investor presentation, Sep 13, 2021
Slide 1: Improving the Lives of People with Neurodevelopmental Disabilities
IMPROVING THE LIVES OF PEOPLE WITH NEURODEVELOPMENTAL DISABILITIES 13 September 2021 1
Slide 2: Disclaimer
DISCLAIMER 1. This presentation has been prepared by Neuren Pharmaceuticals Limited ARBN 111 496 130 (the Company or Neuren) in relation to the Company conducting: • a placement of fully paid ordinary shares (New Shares) to institutional and sophisticated investors under section 708A of the Corporat
Slide 3: Disclaimer (cont'd)
DISCLAIMER (CONT’D) Forward looking statements 12. This presentation contains forward looking statements about future events which reflect the Company’s intent, belief and expectation as at the date of this presentation. As a result, forward looking statements involve risks and uncertainties. Althou
Slide 4: Investment Highlights
INVESTMENT HIGHLIGHTS Neuren (ASX: NEU) is a biotechnology company developing new therapies in global markets for multiple serious neurological disorders that emerge in early childhood 1 2 3 Two patented drugs In Phase 3 and Phase 2 clinical Near term inflection point (trofinetide and NNZ-2591) deve
Slide 5: Capital Raise for Near Term Crystallisation of Value
CAPITAL RAISE FOR NEAR TERM CRYSTALLISATION OF VALUE Raising ~A$22m (via a A$20m Placement and A$2m Share Purchase Plan) Neuren Today Post-raising In 2023 ~A$250m market cap ▪ Trofinetide Rett ▪ Well capitalised to ▪ NNZ-2591 Phase 3 syndrome Phase 3 bring NNZ-2591 to ready for 4 results Q4 2021 Pha
Slide 6: Leading Pipeline in Neurodevelopmental Disorders
LEADING PIPELINE IN NEURODEVELOPMENTAL DISORDERS Commercial Compound Indication Preclinical Phase 1 Phase 2 Phase 3 Partner Results Rett expected syndrome1 Q4 2021 (North America) Trofinetide Fragile X syndrome1 (North America) Phelan- Commence McDermid expected syndrome2 H2 2021 Commence Angelman e
Slide 7: Treating Neurodevelopmental Disorders
TREATING NEURODEVELOPMENTAL DISORDERS Rett Fragile X Phelan- Angelman Pitt Hopkins Prader-Willi McDermid MECP2 FMR1 SHANK3 UBE3A TCF4 15q11-q13 Neuren’s drugs target the critical Impaired communication between role of IGF-1 in this neurons, abnormal formation/pruning upstream process, using analogs
Slide 8: Commercial Advantages of Orphan Drugs
COMMERCIAL ADVANTAGES OF ORPHAN DRUGS Compared with existing markets that have apparently attractive large $ sales revenue in which established products have to be displaced, Orphan Drugs have many advantages Serious and urgent unmet need results in strong support from patient community and leading
Slide 9: Transforming Milestones Approaching
TRANSFORMING MILESTONES APPROACHING Results in Q4 2021 for trofinetide Phase 3 trial in Rett syndrome Partnered with Acadia (NASDAQ:ACAD) for North America, Neuren has access to US data for ex-North America registration Up to US$455m milestone payments, plus double digit % royalties, plus one
Slide 10: The Three Key Drivers of Near Term Value
THE THREE KEY DRIVERS OF NEAR TERM VALUE Realise Neuren’s share Implement commercial Confirm efficacy of of trofinetide value in strategy for trofinetide NNZ-2591 in Phase 2 the US through ACADIA’s ex-North America, trials for 4 valuable Phase 3 results and New using US data for indications Drug App
Slide 11: Strong Momentum from Near-Term Catalysts
STRONG MOMENTUM FROM NEAR-TERM CATALYSTS 2021 2022 Achieved Imminent Expected EU Orphan designations for Phelan- Submit NNZ-2591 Submit NNZ-2591 IND McDermid, Angelman, and Pitt Hopkins IND applications application for Prader-Willi Successful Phase 1 trial results for NNZ-2591 for Pitt Hopki
Slide 12: Prader-Willi Syndrome Overview
PRADER-WILLI SYNDROME OVERVIEW Prader-Willi syndrome (PWS) is a debilitating neurodevelopmental disorder, caused by defects in the 15q11-q13 region of chromosome 15 The estimated incidence is 1 in 10,000 – 30,000 males and females across all races and ethnicities (potentially 76k patients in US,
Slide 13: Funding Prader-Willi and Phase 3 Readiness
FUNDING PRADER-WILLI AND PHASE 3 READINESS Capital raise enables Neuren to accelerate NNZ-2591 to Phase 3 in 4 indications Pursue opportunity in Prader-Willi syndrome FDA granted Orphan Drug designation on 2 September 2021 Compelling efficacy in Magel2-null mouse model - NNZ-2591 normalized fa
Slide 14: Offer Details
OFFER DETAILS 14
Slide 15: Offer Details
OFFER DETAILS Neuren is conducting a capital raising of A$22 million via an institutional placement and share purchase plan • The Offer comprises: • a placement of fully paid ordinary shares in the Company (“New Shares”) to institutional investors to raise approximately A$20 million; and Offer Struc
Slide 16: Use of Funds
USE OF FUNDS Uses A$m IND application and Phase 2 clinical trial for NNZ-2591 in Prader-Willi syndrome 7.0 Foundational work for Phase 3 trials across all 4 indications for NNZ-2591 11.8 Working capital & Offer costs 3.21 Total 22.0 1 Assuming full subscription of the Offer 16
Slide 17: Offer Timetable
OFFER TIMETABLE Event Date, AEST Trading halt Thursday, 9 September 2021 Record Date for SPP Friday, 10 September 2021 Placement announced & Shares resume trading on ASX Monday, 13 September 2021 Placement settlement of new Shares Thursday, 16 September 2021 Placement issue of new Shares Friday, 17
Slide 18: Trofinetide for Rett Syndrome
TROFINETIDE FOR RETT SYNDROME 18
Slide 19: Trofinetide Licence Agreement with Acadia
TROFINETIDE LICENCE AGREEMENT WITH ACADIA Partnership commenced in August 2018, providing the necessary funding and capabilities to execute Phase 3 and commercialise trofinetide in the US Redacted agreement is available in ACADIA’s 2018 10K filing Territory North America (Neuren retains all righ
Slide 20: Rett Syndrome Opportunity
RETT SYNDROME OPPORTUNITY Estimates US Europe Japan China urban Other Asia Potential patients1 10,000 13,000 3,000 28,000 6,000 Patients currently identified 5,000 4,000 1,000 2,000 ‘00s 1 Potential patient estimates derived by applying the mid-point of the published prevalence estimate range to the
Slide 21: Rett Syndrome Phase 3 Program
RETT SYNDROME PHASE 3 PROGRAM Double-blind Open-label Continued Access LAVENDER LILAC LILAC-2 TROFINETIDE TROFINETIDE TROFINETIDE PLACEBO Baseline Week 12 Week 52 LAVENDER™ enrolment completed – top-line results expected in Q4 2021 180 females aged 5 to 20 years RSBQ (caregiver) and CGI-I (phy
Slide 22: Rett Syndrome Phase 2 - RSBQ and CGI-I
RETT SYNDROME PHASE 2 - RSBQ AND CGI-I Clinical improvement measured by RSBQ Clinical improvement measured by CGI-I p=0.042 p=0.029 RSBQ is a caregiver rating, reflecting the CGI-I is a clinician rating of how much the severity of the syndrome. Mean subject’s overall illness has improved or improvem
Slide 23: Maximising Probability of Success
MAXIMISING PROBABILITY OF SUCCESS The Phase 3 co-primary endpoints were both positive in the Phase 2 trial In the Phase 2 trial clinical improvement continued increasing through to end of treatment - the Phase 3 trial at 12 weeks is twice the duration of the Phase 2 trial The Phase 3 sample si
Slide 24: NNZ-2591 for Multiple Neurodevelopmental Disorders
NNZ-2591 FOR MULTIPLE NEURODEVELOPMENTAL DISORDERS 24
Slide 25: Estimates of Target Patient Populations
ESTIMATES OF TARGET PATIENT POPULATIONS Disorder Gene Published prevalence Potential patients mutation estimates US1 Europe1 Asia1, 2 Phelan- SHANK3 1/8,000 to 1/15,000 males and 22,000 28,000 81,000 McDermid females Angelman UBE3A 1/12,000 to 1/24,000 males 14,000 18,000 52,000 and females Pitt Hop
Slide 26: NNZ-2591 Mechanism of Action
NNZ-2591 MECHANISM OF ACTION NNZ‐2591 is a synthetic analog of cyclic glycine proline, a peptide that occurs naturally in the brain, designed to be more stable, orally bioavailable and readily cross the blood‐brain barrier NNZ-2591 can regulate the amount of IGF-1 that is available to activate IGF-1
Slide 27: Foundations in Place for Multiple Indications
FOUNDATIONS IN PLACE FOR MULTIPLE INDICATIONS Neuren is leveraging experience from Rett syndrome program across all areas to execute much faster development for NNZ-2591 2022 Phase 2 data in multiple indications Commence Phase 2 trials 2021 INDs approval by FDA in multiple indications Identify Devel
Slide 28: Ideal Attributes Leading into Phase 2
IDEAL ATTRIBUTES LEADING INTO PHASE 2 Novel mechanism of action Clear and consistent efficacy in mouse models of each syndrome Biochemical effects in the brain and optimum dose confirmed Demonstrated high oral bioavailability and blood-brain barrier penetration IND-enabling program of non-
Slide 29: Three Phase 2 Trials Commencing H2 2021
THREE PHASE 2 TRIALS COMMENCING H2 2021 Prioritising speed to data – results in H2 2022: Angelman syndrome trial in Australia Phelan-McDermid and Pitt Hopkins trials in US Up to 20 patients in each trial First trials maximise opportunity to demonstrate effects: Pediatric patients 13 we
Slide 30: Phase 1 Clinical Trial Highlights
PHASE 1 CLINICAL TRIAL HIGHLIGHTS Twice daily dosing for 7 days was safe and well tolerated at all dose levels tested in healthy volunteers No SAEs, no clinically significant findings in lab or cardiac tests All AEs mild or moderate and resolved during the trial At highest dose all AEs were
Slide 31: Appendix
APPENDIX 31
Slide 32: Stock Information (ASX: NEU)
STOCK INFORMATION (ASX: NEU) Current risk-adjusted valuation per Current share register share (MST Access) - A$3.93 composition before Offer (114 million quoted shares – 52 week price range: A$1.00 - A$2.53 top 20 hold 50%) Institutions, 30% NEU share price (A$) 1 year 2.60 2.40 Management, 2.20 7%
Slide 33: Management and Board
MANAGEMENT AND BOARD Management team has devised and executed Neuren’s Orphan Drug programs since 2013 Extensive international pharmaceutical business experience Successfully developed drugs from pre-clinical through to FDA approval Executed multiple partnering transactions Jon Pilcher Larry
Slide 34: Correcting Impaired Signaling in Neurons
CORRECTING IMPAIRED SIGNALING IN NEURONS Neurodevelopmental disorders result from different gene mutations, but all feature impaired signaling between neurons, with abnormal length and density of the dendritic spines that connect the neurons via synapses This impaired signaling causes behavioral
Slide 35: Consistent Efficacy and Dose Response in Phelan-McDermid Model
CONSISTENT EFFICACY AND DOSE RESPONSE IN PHELAN- MCDERMID MODEL PMS is caused by a deletion or other change in the 22q13 region of chromosome 22, which includes the SHANK3 gene, or a mutation of the gene. In the shank3 knockout mouse model, wild type mice and knockout mice were treated with placebo
Slide 36: Consistent Efficacy and Dose Response in Phelan-McDermid Model
CONSISTENT EFFICACY AND DOSE RESPONSE IN PHELAN- MCDERMID MODEL Motor function Anxiety Repetitive behavior Daily living Daily living 36
Slide 37: Biochemical Effects Confirmed in Shank3 Model
BIOCHEMICAL EFFECTS CONFIRMED IN SHANK3 MODEL In biochemical testing, NNZ-2591 was shown to normalise the abnormal length of dendrite spines between brain cells, the excess activated ERK protein (pERK) and the depressed level of IGF-1 in shank3 knockout mice. 2000 4 16000 Dendritic length (m) 1500
Slide 38: Consistent Efficacy in Angelman Model
CONSISTENT EFFICACY IN ANGELMAN MODEL AS is caused by a deletion or mutation in the ubiquitin protein ligase E3A (UBE3A) gene on chromosome 15. In the ube3a knockout mouse model, which resembles features of AS in humans, wild type and knockout mice were each treated with placebo or NNZ- 2591 for 6 w
Slide 39: Consistent Efficacy in Pitt Hopkins Model
CONSISTENT EFFICACY IN PITT HOPKINS MODEL PTHS is caused by the loss of one copy or a mutation of the TCF4 gene on chromosome 18. In the tcf4 mutation mouse model, which exhibits features of PTHS in humans, wild type mice and knockout mice were treated with placebo or NNZ-2591 for 6 weeks. Treatment
Slide 40: Consistent Efficacy in Prader-Willi Model
CONSISTENT EFFICACY IN PRADER-WILLI MODEL PWS is caused by mutations in the 15q11-q13 region of chromosome 15. In the Magel2-null mouse model, which exhibits features of PWS in humans, wild type mice and knockout mice were treated with placebo or NNZ-2591 for 6 weeks. Treatment with NNZ-2591 normali
Slide 41: Consistent Efficacy in Prader-Willi Model
CONSISTENT EFFICACY IN PRADER-WILLI MODEL 41
Slide 42: Risk Factors
RISK FACTORS 42
Slide 43: Risk Factors
RISK FACTORS This section sets out some of the key risks associated with any investment in the Company, together with risks relating to participating in the Placement and SPP which may affect the value of the Company’s securities. The risks are not set out in order of importance and do not constitut
Slide 44: Risk Factors (cont'd)
RISK FACTORS (CONT’D) Competition The Company’s current and potential future competitors might include companies with significantly greater resources than Neuren. These competitors may develop products or services that are more effective and/or cheaper than those being developed by the Company, and
Slide 45: Risk Factors (cont'd)
RISK FACTORS (CONT’D) Change in the Australian tax system Any future changes in Australian tax law, including changes in interpretation or application of the law by the courts or taxation authorities in Australia, may affect the taxation treatment of the acquisition, holding and disposal of the New
Slide 46: Foreign Selling Restrictions
FOREIGN SELLING RESTRICTIONS 46
Slide 47: Foreign Selling Restrictions
FOREIGN SELLING RESTRICTIONS This presentation does not constitute an offer of new ordinary shares (“New Shares”) of the Company in any jurisdiction in which it would be unlawful. In particular, this presentation may not be distributed to any person, and the New Shares may not be offered or sold in
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