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

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

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

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)

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: NV1205 80ug/kg; Sob 2.0: NV1205 400 ug/kg; Hypo: Hypothyroid mice; WT: wild type mice; *p,0.05 Hartley, Kirkemo, et al. Endocrinology (2017)

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: NV1205 80ug/kg; Sob 2.0: NV1205 400 ug/kg) and wild type mice (WT) for up to 12 weeks ; * p<0.05 Hartley, Kirkemo, et al. Endocrinology (2017)

PEDiatric AdrenoLeukodystrophy Study www.ccald.com PEDiatric AdrenoLeukodystrophy Study NV1205-009: 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)

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

NV1205-009 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

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

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

www.ccald.com NV1205-008: 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