The first-in-human Phase 1 study described herein will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SPG302 in healthy volunteers and ALS participants

This study is a Phase 1 randomized, double-blind, placebo-controlled, single, and multiple ascending dose study in HV with food effect cohort, and a repeat dose expansion cohort(s) in participants with ALS.

The study consists of 3 parts, as follows:

• Part 1: SAD in HV with up to 6 cohorts including a food effect cohort.
• Part 2: MAD over 5 days in HV with up to 5 cohorts
• Part 3: ALS cohorts with once daily (QD) dosing over 28 day cycles

Inclusion Criteria:

• Age 18-55
• Must be in good health with no significant medical history
• Clinical laboratory values within normal range or < 1.2 times ULN
• BMI 18-32 (inclusive)
• Contraceptive use by men or women consistent with local regulations
• Able and willing to provide written informed consent

Exclusion Criteria:

• Any physical or psychological condition that prohibits study completion
• Known cardiac disease
• Active or history of malignancy in the past 5 years
• Serious infection within 1 month of screening
• Acute illness within 30 days of Day 1
• Surgery, bone fracture, or major musculoskeletal injury in the past 3 months
• History of suicidal behavior or suicidal ideation
• Active cigarette smokers and users of nicotine-containing products
• HIV, hepatitis B and hepatitis C positive
• SBP >140 or <90
• DBP >90 or <40
• HR <40 or >100
• QTcF >450ms, cardiac arrhythmia, or clinically significant abnormal ECG
• Prescriptions, over-the-counter, or herbal medication within 7 days
• Vaccines within 14 days
• Other investigational products within 30 days
• Blood donation within 30 days
• Plasma donation within 7 days
• Pregnant or breastfeeding
• Otherwise unfit, on metabolic-altering lifestyle/diet, positive urine drug screen or intake of alcohol or caffeine-containing products

ALS Cohort Inclusion Criteria:

• Age 18-80
• ALS TRICALS risk score
• Stable dose of standard of care treatment
• Contraception use by men or women consistent with local regulations
• Able and willing to provide written informed consent

ALS Cohort Exclusion Criteria:

• Underlying physical or psychological condition prohibiting study completion
• Known cardiac disease
• Active or history of malignancy in the past 5 years
• Serious infection within 1 month of screening
• Acute illness within 30 days of Day 1
• History of suicidal behavior or suicidal ideation
• Active cigarette smokers and users of nicotine-containing products
• Neurodegenerative disease
• External respiratory support or supplemental oxygen requirement
• HIV, hepatitis B and hepatitis C positive
• SBP >140 or <90
• DBP >90 or <40
• HR <40 or >100
• QTcF >450ms, cardiac arrhythmia, or clinically significant abnormal ECG
• Vaccines within 14 days
• Other investigational products within 30 days
• Blood donation within 30 days
• Plasma donation within 7 days
• Pregnant or breastfeeding
• Otherwise unfit

Double blinded