1. NeuroVia, NV1205 Clinical Trials
Developing a safe and effective treatment for children with Childhood Cerebral Adrenoleukodystrophy
Masoud Mokhtarani MD
Chief Medical Officer
ALD Life Family Weekend Meeting, London, 6 May 2018

2. NeuroVia Founded in 2013; a venture-backed company in San Francisco
Based on work from Oregon Health Science University with sobetirome in X-ALD animal model
Two ongoing studies:
PEDALS an interventional study with NV1205 in CCALD
SADDLE an observational study in X-ALD children

3. Upregulation of ABCD2 By NV1205 Restores Peroxisome’s Ability to Degrade VLCFA
ABCD2 gene promoter has a thyroid hormone response element and is regulated by thyroid hormone
NV1205 is thyroid hormone receptor modulator capable of upregulating the ABCD2 gene

4. NV1205 Upregulates ABCD2 gene in Patients’ Fibroblasts
Thyroid hormone and NV1205 upregulate ABCD2 gene in all phenotypes
Maximum effect seen in CCALD
Sob: Sobetirom NV1205; *p<0.05
Hartley, Kirkemo, et al. Endocrinology (2017)

5. NV1205 Upregulates ABCD2 Gene and Lowers VLCFA in Brains
VLCFA Reduction after 12 weeks of oral administration in ABCD1 KO mice
ABCD2 Expression in Brain after 2 Weeks Systemic Tx *
NV1205 enters into CNS and upregulates ABCD2 gene within 2 weeks
VLCFA is reduced significantly in brain after 12 weeks of oral treatment with NV1205
Sob 0.4: NV ug/kg; Sob 2.0: NV ug/kg; Hypo: Hypothyroid mice; WT: wild type mice; *p,0.05
Hartley, Kirkemo, et al. Endocrinology (2017)

6. NV1205 Lowers VLCFA in Serum, Adrenal Glands, and Testes of ABCD1 KO Mice
Oral treatment of ABCD1 Knock out mice with vehicle, T3/T4 , or NV1205 (Sob 0.4: NV ug/kg; Sob 2.0: NV ug/kg) and wild type mice (WT) for up to 12 weeks ; * p<0.05
Hartley, Kirkemo, et al. Endocrinology (2017)

7. PEDiatric AdrenoLeukodystrophy Study
PEDiatric AdrenoLeukodystrophy Study
NV : Phase I/II, Open-Label, Dose Escalation Study of the Safety, Pharmacokinetics and Pharmacodynamics of NV1205 in Pediatric Male Subjects with Childhood Cerebral Adrenoleukodystrophy (CCALD)

8. NV1205-009 Study Objectives PRIMARY OBJECTIVE
To evaluate the safety and pharmacokinetics of NV1205 in pediatric subjects diagnosed with CCALD
EXPLORATORY OBJECTIVE
To assess the effect of NV1205 on expression of the ABCD2 gene, levels of VLCFA, brain lesions, and neurological function score

9. NV Study Design
Cohorts of 3 subjects receive 4 weeks of treatment with multiple safety checks
Subsequent cohorts to receive higher doses after safety check by the data safety monitoring board (DSMB)
Subjects will roll into long term treatment for up to 2 years
An expanded access study will be offered after the 2-yr is complete
Up to 25 patients may be enrolled

10. Major Inclusion Criteria and Procedures
Eligible Patients
Pediatric patients with MRI evidence
Loes score of <15
No access/ineligible for transplant
No prior transplant
No Lorenzo’s oil or other VLCFA lowering agents
Procedures
7 visits during the first 3 months; q3 months thereafter
Long term treatment under DSMB supervision
Brain MRI
Neurological assessment
VLCFA
Travel assistance (transport, lodging, expenses) available for out of area families

11. PEDALS is a Global Study
Colombia
Australia
Russia
Ukraine
Chile
Argentina
United Kingdom
France

12.
NV : A Non-Interventional Study to Prospectively Assess Baseline Status and Disease Progression in Male Children with X-Linked AdrenoLEukodystrophy
Identify markers of disease status and disease progression
Asymptomatic, symptomatic and transplanted patients up to 13y
VLCFA, NFS, MRI every 6 months
Current US sites: Stanford, UPMC, MGH, U of Florida, Seattle
Expanding globally