Conclusions Cumulative PD readouts to date are consistent with the anticipated pharmacological effect of MDNA11 demonstrating dose dependent activation of various biomarkers on effector cells without concomitant stimulation of immune suppression. Updated PK, PD and ADA data will be presented as dose escalation continues.
2 years ago
P1 data • PK/PD data • IO biomarker
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CD8 (cluster of differentiation 8) • IL2RA (Interleukin 2 receptor, alpha) • IL2 (Interleukin 2) • FCGR2A (Fc fragment of IgG receptor IIa) • FCGR2B (Fc Fragment Of IgG Receptor IIb)
Conclusions MDNA11 is well tolerated with no DLTs up to target dose of 60 mg/kg (DL4) and enrolment for 90 mg/kg (DL5) has initiated. There is dose-dependent increase in plasma exposure and evidence of single-agent anti-tumor activity in 4 of 10 (SD) patients.
Recombinant human interleukin-2 (rhIL-2, aldesleukin) is Food and Drug Administration approved for the treatment of metastatic melanoma and renal cell carcinoma and has achieved durable response in a subset of patients. In a NHP model, MDNA11 was well tolerated while triggering durable and potent immune responses including expansion of lymphocytes without significant effect on Tregs and eosinophils, the latter been linked to an increased risk of vascular leak syndrome. MDNA11 is a next generation long-acting IL-2 immunotherapeutic with a highly favorable pharmacodynamic profile that translates to a strong therapeutic efficacy in preclinical tumor models and a strong and durable immune response in NHP.
over 2 years ago
Preclinical • Journal
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CD8 (cluster of differentiation 8) • IL2 (Interleukin 2)
Background: Use of IL-2 (Proleukin) remains limited due to its short half-life, toxicity, and its ability to preferentially activate Tregs resulting in unwanted immune suppression. The long-acting MDNA11 Superkine has superior potency over IL-2 at activating naïve CD8 T-cells and NK cells, while exhibiting diminished Treg activation. This molecule potently inhibited tumor growth and induced durable regression and long-term memory response. Studies in NHP showed prolonged proliferation of immune effector cells lasting almost two weeks post-MDNA11 administration.