Fig. 5: Evaluation of the toxicological, PK and PD characteristics of HER2-XPAT protein and unmasked HER2-uTCE in NHPs.

HER2-XPAT protein was administered via short i.v. infusions (∼1–3 h), whereas the unmasked counterpart, due to its short half-life, was administered via 48-h continuous i.v. infusion to provide prolonged systemic exposure. a, A dose-escalation study with a single dose of HER2-XPAT protein administered to each cynomolgus monkey. *At doses below 21 mg kg⁻¹, a HER2-XPAT prototype was used. b, Dose de-escalation study of uTCE in NHPs administered as a 48-h continuous infusion due to its short half-life. c, Plasma concentrations in NHPs following administration of a single i.v. dose of HER2-XPAT protein (42 mg kg⁻¹, n = 2 NHPs; 25 mg kg⁻¹, n = 4 NHPs; 6 mg kg⁻¹, n = 12 NHPs; 2 mg kg⁻¹, n = 12 NHPs) or a 48-h continuous infusion of uTCE (0.2 mg kg⁻¹ d⁻¹, n = 1 NHP; 0.1 mg kg⁻¹ d⁻¹, n = 1 NHP; 0.06 mg kg⁻¹ d⁻¹, n = 1 NHP). Data represent mean plasma concentration (±s.d. when n > 3 NHP treated) for the NHPs treated at each dose within one single experiment. d,e, Activation of circulating CD4⁺ T cells (d) and CD8⁺ T cells (e) 24 h after drug administration (HER2-XPAT protein, n = 16 NHPs; HER2-uTCE, n = 5 NHPs). f–h, Highest plasma levels of TNF-α (f), IL-6 (g) and IFN-γ (h) measured 0–24 h following drug administration (HER2-XPAT protein, n = 23 NHPs; HER2-uTCE, n = 8 NHPs). Note that the normal ranges for cytokine levels in NHP are as follows: IL-6 0.3–1.2 pg ml⁻¹, TNF-α 1–10 pg ml⁻¹, IFN-γ 1.1–8.0 pg ml⁻¹ (ref. ⁴⁴). Data in d–f represent a single sample from each NHP receiving the test material within each single experiment. TNF, tumor necrosis factor; IFN, interferon.

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