Table 1 Summary of toxicology studies of BMTP-78 in nonhuman primates

1

Multiple dose range study s.c injections of BMTP-78

Macaca fascicularis

M

1 dose every 3 days for 2 weeks s.c

0.3, 3, 30, 100 and 200 mg kg⁻¹ (3)

Kidney toxicity (after 100 mg kg⁻¹ dose)

Lesions at s.c. injection site

2

Multiple dose i.v. infusion

Macaca fascicularis

M

4 weekly i.v.

3 mg kg⁻¹ (3)

Necrotizing and inflammatory lesions at i.v. injection site (3)

Kidney lesions (1)

3

Single dose i.v. infusion

Macaca fascicularis

M

Single infusion

0.75 mg kg⁻¹ (2)

None

4

Dose range study of weekly infusions of BMTP-78

Macaca mulatta

M

4 weekly i.v.

Low: 1 mg kg⁻¹ (1)

Mid-low: 3 mg kg⁻¹ (1)

Mid-high: 6 mg kg⁻¹ (1)

High: 9 mg kg⁻¹ (1)

Dose-dependent kidney toxicity (3 at ⩾3 mg kg⁻¹ doses)

Lesions at i.v. injection site (3 at ⩾3 mg kg⁻¹ doses)

Heart toxicity (1 at 9 mg kg⁻¹ doses)

5

22-day repeat infusion of BMTP-78

Macaca mulatta

F

4 infusions every 5 days i.v. Followed by 29-day recovery period

Control: vehicle (4)

Low: 3 mg kg⁻¹ (5)

Mid-low: 9 mg kg⁻¹ (8) Mid-high: 15 mg kg⁻¹ (1) High: 30 mg kg⁻¹ (2)

Heart toxicity (15 at ⩾3 mg kg⁻¹ doses), lethal at mid-high doses (5 at ⩾9 mg kg⁻¹ doses)