PhaseBio Pharmaceuticals said today it has signed an exclusive global license to develop MedImmune’s Phase I–ready reversal agent for parent company AstraZeneca’s marketed blood thinner Brilinta® (ticagrelor).
The exclusive worldwide licensing agreement, whose value was not disclosed, covers PB2452, an intravenous neutralizing Fab antibody fragment intended to reverse the antiplatelet effects of Brilinta (marketed in Europe as Brilique®) by binding to it and its active metabolite AR-C124910XX.
PhaseBio reasons that the addition of a reversal agent to Brilinta would differentiate the therapy in the blockbuster blood thinner market and could encourage the expansion of its patient population. Brilinta finished 2016 close to the billion-dollar sales “blockbuster” threshold with $839 million, up 39% from a year earlier.
Over the first nine months of 2017, Brilinta has generated $780 million, up 31% from January–September 2016.
Unlike other P2Y12 antagonist antiplatelet agents, which bind to their targets permanently, Brilinta can reversibly bind to its receptor, making the blood thinner the only oral antiplatelet with the potential to be reversed, according to PhaseBio and MedImmune.
PB2452 is designed to enable reversal of the antiplatelet effects of ticagrelor in rare emergency situations, and reduce the period patients must wait before surgery. At present, there are no FDA-approved treatments capable of reversing the effects of antiplatelet agents when patients experience severe bleeding or require urgent surgery.
Promising Preclinical Results
Through its global biologics R&D arm MedImmune, AstraZeneca began preclinical development of PB2452 (udner the name MEDI2452) in 2014. In preclinical studies, PhaseBio said, PB2452 showed high affinity and specific binding to ticagrelor, and was shown to reverse ticagrelor-mediated inhibition of platelet aggregation and normalize bleeding.
“PB2452’s compelling preclinical data support its potential to be a first-in-class reversal agent for ticagrelor. The profile of PB2452 and the planned development pathway fits nicely with PhaseBio’s niche focus on orphan cardiovascular disorders,” PhaseBio CEO Jonathan P. Mow said in a statement.
Mow said PhaseBio plans to begin a Phase I study of PB2452 in the first half of 2018.
PhaseBio’s pipeline is led by PB1046, a long-acting vasoactive intestinal peptide (VIP) selective agonist of VIP receptor 2 (VPAC2) in Phase II development for pulmonary arterial hypertension, Phase I development for Duchenne muscular dystrophy (DMD)-related cardiomyopathy, and in combination with pipeline candidate PB1120 in preclinical development for cystic fibrosis.
The company’s treatments have been developed using its proprietary elastin-like polypeptide (ELP) biopolymer technology, which uses recombinant ELP biopolymers to which peptides and proteins can be genetically fused and small-molecule drugs can be chemically conjugated. The ELP platform is intended to create treatments that require less-frequent dosing, and thus better patient compliance.
“We are excited that MedImmune has chosen to partner with PhaseBio for this medically important asset, which also allows us to diversify our pipeline beyond our ELP technology platform,” Mow added.