MEDI-547 / AstraZeneca - LARVOL DELTA

BT5528, a Bicycle Toxin Conjugate targeting EphA2 has potent anti-tumor activity without bleeding or coagulation abnormalities in preclinical models (AACR 2018) - "...EphA2 is considered a high-value target for cancer therapeutics, but development of an antibody drug conjugate targeting EphA2 (MEDI-547) was stopped in early clinical development after severe adverse events, including bleeding toxicity were seen (Annunziata et al, 2013)...The BTCs show profound efficacy, without the limiting toxicity observed with previous Antibody Drug Conjugate approaches. IND-enabling studies for BT5528 are currently underway."

Preclinical • Non Small Cell Lung Cancer • Sarcoma • Triple Negative Breast Cancer

MMAE delivery using the Bicycle toxin conjugate BT5528. (PubMed, Mol Cancer Ther) - "We show that BT5528 gives rise to rapid update into tumours and fast renal elimination followed by persistent toxin levels in tumours without prolonged exposure of parent drug in the vasculature. This fast in, fast out kinetics gave rise to more favourable toxicology findings in rats and monkeys than were observed with MEDI-547 in preclinical and clinical studies."

Journal • Oncology • EPHA2

Immunotherapy targeting HPV 16/18 generates potent immune responses in HPV-Associated Head and Neck Cancer. (PubMed, Clin Cancer Res) - "These data demonstrate that MEDI0457 can generate durable HPV16/18 antigen-specific peripheral and tumor immune responses. This approach may be used as a complementary strategy to PD-1/PD-L1 inhibition in HPV-associated HNSCCa to improve therapeutic outcomes."

Journal

BT5528, an EphA2-targeting Bicycle Toxin Conjugate (BTC): Profound efficacy without bleeding and coagulation abnormalities in animal models (AACR 2019) - "EphA2 has long been a high-value target for cancer therapeutics, but development of an Antibody Drug Conjugate targeting EphA2 (MEDI-547) was stopped in early clinical development after severe adverse events were seen (Annunziata et al, 2013). The EphA2 targeting BTC BT5528 shows potent anti-tumour activity in a range of solid tumour xenograft models without the limiting toxicity observed with previous Antibody Drug Conjugate approaches. IND-enabling studies for BT5528 are currently underway."

Preclinical