Table 1.

Revusiran-Related Microscopic Findings Across Toxicology Species

Tissues/microscopic findings	Species
	Rat				Monkey			Mouse
	Duration
	Acute	6-Week	26-Week	2-Year rat carcinogenicity	Acutea	6-Week	39-Week	8-Week
	Doses (mg/kg)
	30, 100, 300	30, 100, 300	15, 30, 100	10, 30, 100 or AD-59206b	300	30, 100, 300	15, 75, 200	30, 100, 300
	NOAEL (mg/kg)
	300 mg/kg	30 mg/kg	30 mg/kg	N/A	300 mg/kg	300 mg/kg	200 mg/kg	300 mg/kg
Adrenal gland	No findings	No findings	Increased vacuolation, cortex ≥30 mg/kg w/full recovery	No findings	No findings	No findings	Decreased vacuolation, cortex ≥15 mg/kg w/full recovery	No findings
Injection sites	Hemorrhage, mixed cell and/or mononuclear cell infiltrates ≥30 mg/kg	Inflammatory infiltrates and vacuolation, macrophages ≥30 mg/kg w/full recovery	Vacuolation, macrophages ≥15 mg/kg w/full recovery	No findings	No findings	Vacuolation, macrophages 300 mg/kg w/full recovery	No findings	Vacuolation, macrophages ≥30 mg/kg
Kidney	No findings	Basophilic granules, tubules ≥30 mg/kg w/partial recovery	Basophilic granules, tubules ≥30 mg/kg w/partial recovery	Basophilic granules ≥10 mg/kg and tubule cell hypertrophy ≥10 mg/kg and AD-59206	No findings	No findings	No findings	No findings
Liver	No findings	Hepatocellular vacuolation ≥30 mg/kg w/partial recovery	Hepatocellular vacuolation ≥15 mg/kg and pigmented, KC at ≥30 mg/kg w/partial recovery	Hepatocellular vacuolation ≥10 mg/kg	No findings	Vacuolation, KC at ≥100 mg/kg w/partial recovery	Vacuolation, KC at ≥75 mg/kg w/full recovery	Hepatocellular vacuolation and mixed cell infiltrates ≥30 mg/kg
Lymph nodesc	No findings	Vacuolation, macrophages ≥30 mg/kg w/full recovery	Vacuolation, macrophages ≥15 mg/kg w/full recovery	No findings	No findings	Vacuolation, macrophages ≥30 mg/kg w/partial recovery	Vacuolation, macrophages ≥15 mg/kg w/partial recovery	No findings
Pancreas	No findings	No findings	No findings	No findings	No findings	No findings	Depletion, zymogen in males 200 mg/kg w/partial recovery	No findings
Spleen	Necrosis; follicles ≥100 mg/kg and vacuolation ≥30 mg/kg	No findings	No findings	No findings	No findings	No findings	No findings	No findings

^aNo microscopic examination performed.

^bRat-active surrogate at 30 mg/kg.

^cIncludes axillary, mandibular, mesenteric, and/or inguinal lymph nodes.

KC, Kupffer cell(s); N/A, not applicable; NOAEL, no observed adverse effect level.