Neuren Pharmaceuticals Limited · ASX:NEU
Neuren Pharmaceuticals — Investor Presentation (May 2024)
56 slides from Neuren Pharmaceuticals's investor presentation, May 29, 2024
Slide 1: Corporate Presentation 29 May 2024
For personal use only Corporate Presentation 29 May 2024 IMPROVING THE LIVES OF PEOPLE WITH NEURODEVELOPMENTAL DISABILITIES Pa g e□ 1
Slide 2: Forward looking statements
Forward looking statements This presentation contains forward looking statements that involve For personal use only risks and uncertainties. Although we believe that the expectations reflected in the forward looking statements are reasonable at this time, Neuren can give no assurance that these expe
Slide 3: Leadership in neurodevelopmental disorder therapy development
Leadership in neurodevelopmental disorder therapy development Developing new therapies for debilitating neurodevelopmental disorders that emerge in early childhood and are characterised by impaired connections and signalling between brain cells For personal use only World’s 1st and only approved the
Slide 4: Seeking a ground-breaking impact on neurodevelopmental disorders
Seeking a ground-breaking impact on neurodevelopmental disorders Rett Fragile X Phelan-McDermid Angelman Pitt Hopkins Prader-Willi For personal use only MECP2 FMR1 SHANK3 UBE3A TCF4 15q11-q13 Neuren’s drugs Impaired communication between neurons, abnormal target the critical role of IGF-1 formation/
Slide 5: Commercial and late-stage pipeline
Commercial and late-stage pipeline Commercial Indication Compound Geography Preclinical Phase 2 Phase 3 Registration rights For personal use only US Trofinetide Rett RoW NNZ-2591 World Trofinetide World Fragile X NNZ-2591 World Positive Phase 2 Phelan-McDermid NNZ-2591 World results Positive Phase 2
Slide 6: Financial strength to maximise growth opportunities
Financial strength to maximise growth opportunities A$m 2023 Profit After Tax For personal use only A$157.1m 6
Slide 7: Growing sustainable income from commercialised product
Growing sustainable income from commercialised product DAYBUE Net Sales (US$m) Royalty and Sales Milestone Payments to Neuren (A$m) For personal use only 420 147 370 138 70 87 177 80-87.5 61 67 76 13 27 45-55 76-82 10 12 23 4 21-23 Q2 2023 Q3 2023 Q4 2023 CY2023 Q1 2024 CY2024 Acadia Q2 2023 Q3 2023
Slide 8: Three key drivers transforming near term value
Three key drivers transforming near term value For personal use only 1 trofinetide Realise Neuren’s share of value in the US through 3 Acadia’s successful Confirm efficacy of NNZ-2591 in Phase 2 trials for multiple commercialization of indications, with global rights retained by Neuren Positive to
Slide 9: DAYBUE / Trofinetide
For personal use only DAYBUE / Trofinetide 9
Slide 10: North America – DAYBUE US launch in April 2023
North America – DAYBUE US launch in April 2023 US Canada Economics to Neuren: US$10m upfront in 2018 For personal use only Potential Rett patients 6,000 - 600 - 9001 9,0001 NDS accepted for priority review, US$10m in 2022 following acceptance of NDA for review Currently identified Rett 5,0001 po
Slide 11: Meaningful real world benefits reported
Meaningful real world benefits reported LILAC-2 Caregiver Exit Interviews1 Real World Experience1 Area/type of improvement with trofinetide For personal use only “It was her engagement level with the world reported by ≥15% of caregivers, n (%) Caregivers N=25 (%) outside of her – to me and to friend
Slide 12: Persistency rates improving in new patient cohorts
Persistency rates improving in new patient cohorts Persistency Rates (Based on confirmed discontinuations and patients who were 60 days past their scheduled refill) For personal use only 80% 75% 76% 66% 68%70% 64% 63% Acadia estimates 58% 58% 51% 50% 50% 47% 40% n.a. n.a. n.a. n.a. n.a. Month 4 Mont
Slide 13: Outside North America
Outside North America Economics to Neuren: Europe Japan Other US$100m upfront For personal use only Potential Rett 9,000 - 1,000 - ~30,0002 US$35m following 1st commercial sale in Europe patients 14,0001 2,0001 US$15m following 1st commercial sale in Japan Currently ~4,0002 ~800 - ~2,0002 US$10m f
Slide 14: NNZ-2591
For personal use only NNZ-2591 14
Slide 15: Regulating IGF-1 in the brain
Regulating IGF-1 in the brain Reversible binding • NNZ-2591 is a synthetic analog For personal use only regulates of cyclic glycine proline, a bioavailability IGF peptide that occurs naturally in IGF-1 Binding Produce Protein‐3 the brain, designed to be more essential stable, orally bioavailable and
Slide 16: Multiple indications opportunity for NNZ-2591
Multiple indications opportunity for NNZ-2591 For personal use only • Positive results from Phelan McDermid syndrome and Pitt Prader-Willi Hopkins syndrome Phase 2 trials syndrome • Top-line results from Angelman syndrome Phase 2 trial expected in Other Pitt Hopkins Q3 2024 undisclosed syndrome indi
Slide 17: NNZ-2591 has ideal attributes leading into Phase 2
NNZ-2591 has ideal attributes leading into Phase 2 ✓ Novel mechanism of action For personal use only ✓ Clear and consistent efficacy in mouse models of each syndrome ✓ Biochemical effects in the brain confirmed ✓ Optimum dose identified ✓ Demonstrated high oral bioavailability and blood-brain barrie
Slide 18: Clear efficacy and dose response in Phelan-McDermid syndrome model
Clear efficacy and dose response in Phelan-McDermid syndrome model Memory Learning Sociability In biochemical testing, NNZ-2591 was shown to For personal use only normalize the abnormal length of dendritic spines that form the synapse, the excess activated ERK protein (pERK) and the depressed level
Slide 19: Consistent efficacy in Pitt Hopkins, Angelman and Prader-Willi models
Consistent efficacy in Pitt Hopkins, Angelman and Prader-Willi models Hypoactivity Daily living Learning & Memory Sociability Repetitive behavior Motor performance For personal use only Pitt Hopkins Hypoactivity & anxiety Daily living Daily living Sociability Motor Cognition Angelman Obesity Circula
Slide 20: Key features of first Phase 2 trials
Key features of first Phase 2 trials Overall aim – expedite data that informs the design of subsequent registration trials and prepare for Phase 3 in parallel For personal use only Screening NNZ-2591 treatment Follow-up /Baseline Up-titration to 12 mg/kg BID Week 0 Week 4 Week 10 Week 17 Week 19 Pha
Slide 21: Phase 2 trial results validating multi-indication platform
Phase 2 trial results validating multi-indication platform Phelan-McDermid syndrome Pitt Hopkins syndrome N=18, 13 weeks N=11, 13 weeks For personal use only General safety & Safe and well tolerated, with no meaningful Safe and well tolerated, with no meaningful tolerability trends in laboratory val
Slide 22: Phelan-McDermid syndrome (PMS)
For personal use only Phelan- McDermid syndrome (PMS) 22
Slide 23: PMS has overwhelming unmet medical need
PMS has overwhelming unmet medical need Cause of the syndrome Broad and severe impact on life From Voice of the Patient Report For personal use only Intellectual impairment Externally-Led Patient-Focused Drug Deletion or variation in the Behavioural issues Development Meeting 8 Nov 2022 SHANK3 gene
Slide 24: PMS is historically under-diagnosed, but this is changing
PMS is historically under-diagnosed, but this is changing Estimated prevalence is 1% of people with autism - 1/8,000 to 1/15,000 males and females1 For personal use only US Europe Japan China Other2 Potential PMS patients 17,000 – 32,0003 21,000 – 41,0003 5,000 - 9,0003 51,000 – 95,0003 16,000 - 31,
Slide 25: PMS affects all genders and ages
PMS affects all genders and ages % currently diagnosed patients by % currently diagnosed patients by age group1 For personal use only gender1 36% 34% 29% 48% 17% 52% 15% 16% 13% 12% 9% 5% 5% 5% 4% 1% Male Female < 12 m 1-2 yrs 3-4 yrs 5-10 yrs 11-20 yrs21-30 yrs31-40 yrs41-60 yrs 60+ Patients curren
Slide 26: Neuren is leading development of a first approved treatment for PMS
Neuren is leading development of a first approved treatment for PMS Phase 2 Program Status Limited products in development Neuren engaging with all For personal use only stakeholders • Phase 2 clinical development in the US under an IND Company Product Development Stage • End of Phase 2 Meeting with
Slide 27: Neuren's Phase 2 trial in children with PMS
Neuren’s Phase 2 trial in children with PMS First study in pediatric patients, collecting the data needed to design a registration study 4 US sites: Rush University, Massachusetts General Hospital, Boston Children’s Hospital and Texas Children’s Hospital For personal use only n subjects: 18 Screenin
Slide 28: Phase 2 clinical trial results highlights
Phase 2 clinical trial results highlights • NNZ-2591 was safe and well tolerated, with no clinically significant changes in laboratory For personal use only values or other safety parameters during treatment • Significant improvement was assessed by both clinicians and caregivers across multiple eff
Slide 29: Safety and tolerability summary
Safety and tolerability summary NNZ-2591 was safe and well tolerated For personal use only TEAEs in 2 or more subjects ✓ Well tolerated Event N=18 Event N=18 ✓ Most Treatment Emergent Adverse n (%) n (%) Events (TEAE) were mild to moderate • 1 Serious TEAE (gastroenteritis) Constipation 2 (11.1) Som
Slide 30: Efficacy endpoints summary
Efficacy endpoints summary Efficacy measures and p-values1 (Total/Overall scores) Global Behaviour For personal use only • Statistically significant CGI-I <0.0001 Aberrant Behavior 0.0013 improvement vs baseline in CIC 0.0003 Checklist-2 total 10/14 efficacy CGI-S 0.0156 Behavior Problems Inventory
Slide 31: Best practice implemented for PMS-specific CGI-I and CIC measures
Best practice implemented for PMS-specific CGI-I and CIC measures • Both CGI-I and CIC scores Clinical Global Impression of Caregiver Impression of reflect overall improvement Improvement (CGI-I) Change (CIC) For personal use only from baseline Scoring Clinician gives an overall score Caregiver give
Slide 32: PMS CGI-I (clinician) results by subject and by domain
PMS CGI-I (clinician) results by subject and by domain Mean CGI-I score of 2.4 with 16 out of 18 children showing improvement For personal use only Improvement 32
Slide 33: PMS CIC (caregiver) results by subject and by domain
PMS CIC (caregiver) results by subject and by domain Mean CIC score of 2.7 with 15 out of 18 children showing improvement For personal use only Improvement 33
Slide 34: PMS CGI-S and Caregiver Top 3 Concerns results by domain
PMS Clinical Global Impression of Severity (CGI-S) and Caregiver Top 3 Concerns results by domain 7 subjects improved by one point on the overall CGI-S score after 13 weeks of treatment and For personal use only improvement was observed in the most common concerns of caregivers (communication, behav
Slide 35: Quality of Life Inventory-Disability results by subject and by subscale
Quality of Life Inventory-Disability results by subject and by subscale For personal use only Improvement Improvement 35
Slide 36: Aberrant Behavior Checklist-2 results by subject and by subscale
Aberrant Behavior Checklist-2 results by subject and by subscale For personal use only Improvement Improvement Subjects with a score of zero not shown 36
Slide 37: Child Sleep Habits Questionnaire results by subject and by subscale
Child Sleep Habits Questionnaire results by subject and by subscale For personal use only Improvement Improvement Subjects with a score of zero not shown 37
Slide 38: Gastrointestinal Health Questionnaire results by subject and by subscale
Gastrointestinal Health Questionnaire results by subject and by subscale For personal use only Improvement Improvement Acknowledgment: GIHQ developed by Kathleen J. Motil, MD, PhD, Baylor College of Medicine 38
Slide 39: ORCA T-Score and MB-CDI Total Vocabulary results by subject
ORCA T-Score and MB-CDI Total Vocabulary results by subject Improvements in communication observed in ORCA T-Score and MB-CDI Total Vocabulary, as well as domains/subscales in CGI-I, CGI-S, CIC and Caregiver Top 3 Concerns For personal use only ORCA T-Score MB-CDI Total Vocabulary Improvement Improv
Slide 40: Clinician and caregiver testimonials
Clinician and caregiver testimonials Clinicians Caregivers “Marked improvement in expressive language and “Using more words while retaining eye contact… Improved For personal use only moderate improvement in socialization.” pretend play… Initiating eye contact” “Teachers noted improvement in learnin
Slide 41: Pitt Hopkins syndrome (PTHS)
For personal use only Pitt Hopkins syndrome (PTHS) 41
Slide 42: PTHS overview
PTHS overview Cause of the syndrome Broad and severe impact on life Patients stories For personal use only Intellectual impairment Pitt Hopkins Research Foundation Deletion or variation in the Behavioural issues TCF4 gene on chromosome Sensory processing disorder “She was tested earlier for Angelman
Slide 43: PTHS is historically under-diagnosed, but this is changing
PTHS is historically under-diagnosed, but this is changing Estimated prevalence is 1/34,000 to 1/41,000 males and females1 For personal use only US Europe Japan China Other2 Potential PTHS patients 6,000 – 7,0003 8,000 – 9,0003 1,000 - 2,0003 18,000 – 22,0003 6,000 - 7,0003 Pitt Hopkins Syndrome Cen
Slide 44: Neuren is leading development of a first approved treatment for PTHS
Neuren is leading development of a first approved treatment for PTHS Neuren Program Status Limited products in development Neuren engaging with all For personal use only stakeholders • Positive Phase 2 trial • Clinical development in the US under an IND Company Product Development Stage • Orphan Dru
Slide 45: Neuren's Phase 2 trial in children with PTHS
Neuren’s Phase 2 trial in children with PTHS First study in pediatric patients, collecting the data needed to design a registration study For personal use only 5 US sites: Rush University, Screening NNZ-2591 treatment Follow-up UTSW, UCSF, UAB, Colorado Children’s Hospital /Baseline Up-titration to
Slide 46: Phase 2 clinical trial results highlights
Phase 2 clinical trial results highlights • NNZ-2591 was safe and well tolerated, with no meaningful trends in laboratory values or other For personal use only safety parameters during treatment • Statistically significant improvement from baseline assessed by both clinicians and caregivers in all 4
Slide 47: Safety and tolerability summary
Safety and tolerability summary NNZ-2591 was safe and well tolerated ✓ Well tolerated TEAEs in 2 or more subjects For personal use only ✓ All Treatment Emergent Event N=16 Event N=16 Adverse Events (TEAE) n (%) n (%) were mild to moderate, mostly not drug related • 0 Serious TEAE Constipation 3 (19)
Slide 48: Efficacy endpoints summary
Efficacy endpoints summary Efficacy measures and p-values1 (Total/Overall scores) Mean CGI-I 2.6 of For personal use only • PTHS Specific Endpoints and Median of 3.0 with p-value = 0.0039 Completers (MITT) Including N=11 discontinued • Mean CIC 3.0 of N=15 and Median of 3.0 with CGI-I 0.0039 0.0205
Slide 49: Best practice implemented for PTHS-specific CGI-I and CIC measures
Best practice implemented for PTHS-specific CGI-I and CIC measures • Both CGI-I and CIC scores Clinical Global Impression of Caregiver Impression of reflect overall improvement Improvement (CGI-I) Change (CIC) For personal use only from baseline Scoring Clinician gives an overall score Caregiver giv
Slide 50: PTHS CGI-I (clinician) results by subject and by domain
PTHS CGI-I (clinician) results by subject and by domain Mean CGI-I score of 2.6 with 9 out of 11 children showing improvement For personal use only CGI-I Overall Score by subject Forest Plot of mean CGI-I Domain Scores MITT Population MITT Population Subject Improvement 50
Slide 51: PTHS CIC (caregiver) results by subject and by domain
PTHS CIC (caregiver) results by subject and by domain Mean CIC score of 3.0 with 8 out of 11 children showing improvement For personal use only CIC Overall Score by subject Forest Plot of mean CIC Domain Scores MITT Population MITT Population Subject Improvement 51
Slide 52: PTHS CGI-S and Caregiver Top 3 Concerns results by domain
PTHS Clinical Global Impression of Severity (CGI-S) and Caregiver Top 3 Concerns results by domain 6 subjects improved by one point on the overall CGI-S score after 13 weeks of treatment and For personal use only improvement was observed in the most common concerns of caregivers (communication, self
Slide 53: Clinician and caregiver testimonials
Clinician and caregiver testimonials Clinicians Caregivers “Is now able to explore environment… can move towards “Increased babbling and jargoning….More inflections with people to initiate contact and… can seek out whatever … eye contact and consonant sounds rather than just noises.” wants to play w
Slide 54: Highlights
For personal use only Highlights 54
Slide 55: Highlights
Highlights 1 2 3 For personal use only DAYBUETM (trofinetide) Total economics to Neuren Successful DAYBUE US approved by US FDA as the from global trofinetide launch, with 2023 net sales of first and only treatment for partnership with Acadia up to US$177m and 2024E net Rett syndrome, launched by US
Slide 56: Contact
For personal use only CONTACT Jon Pilcher, CEO [email protected] +61 438 422 271 56
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