Basking Biosciences has announced the publication of preclinical research in Communications Biology—a Nature Portfolio journal—showing that its lead candidate, BB-031, restored blood flow in a microfluidic model of arterial occlusion using blood samples from acute ischaemic stroke patients by selectively inhibiting Von Willebrand factor (vWF), which is described by the company as a key mediator of clot initiation, growth and stabilisation. This research was led by scientists at the University of Pittsburgh (Pittsburgh, USA) and The Ohio State University (Columbus, USA).
The study evaluated how BB-031 reopens vessels and compared its performance with the two approved fibrinolytics: alteplase (tPA) and tenecteplase (TNK). In the model, fully occlusive, platelet-rich clots were formed under arterial flow conditions, allowed to mature for up to six hours, and then treated. Results showed that BB-031 restored blood flow through occluded channels more effectively than both tPA and TNK, including clots that had matured for three-to-six hours. BB-031 also worked by preventing vWF from recruiting new platelets to the clot surface—a process that continually reinforces platelet-rich arterial clots and makes them resistant to current fibrinolytics.
“The model allowed us to see what may be happening to arterial clots in prolonged settings, providing a closer analogue to clinical reality,” said Susan Shea (University of Pittsburgh, Pittsburgh, USA), senior author on the study. “This advance allowed us to better interrogate the potential advantages of a vWF-targeting strategy, complementing our earlier studies.”
Blood samples from acute ischaemic stroke patients showed restored blood flow with BB-031 compared with the vehicle. Importantly—according to Basking—clots formed in the model reproduced the clot composition reported in human samples from patients who have undergone endovascular thrombectomy. These include fibrin, platelets, and vWF, supporting the model as a relevant system for studying arterial thrombosis and treatment, the company further claims.
“These findings show that BB-031 restores blood flow in an occlusive thrombus after a clot has already formed and matured,” commented Shahid Nimjee, co-founder, chief scientific officer and stroke clinical lead of Basking. “VWF continually recruits platelets that reinforce arterial clots, thereby engendering resistance to current therapies. By selectively inhibiting vWF, BB-031 stops that reinforcement and allows blood flow to return, even when treatment is administered hours after the occlusion forms. This gives us clear insight into how BB-031 works in human clot formation and strengthens the rationale for our clinical programme in acute ischaemic stroke.”
In a recent press release, Basking highlights the fact that fibrinolytics—the pharmacological standard of care for stroke since 1996—are limited by a narrow treatment window of three-to-4.5 hours as well as serious bleeding risks. Mechanical thrombectomy, adopted globally in 2015, can extend treatment up to 24 hours, but is available only in specialised centres, and the current literature supports limiting it to patients who present with large vessel occlusion (LVO) strokes.
According to Basking, BB-031—a first-in-class, targeted, reversible thrombolytic therapy—offers a different approach. It selectively and reversibly inhibits vWF, and can be paired with BB-025, which is Basking’s direct-acting reversal agent designed to rapidly restore normal haemostasis within minutes, enabling potential urgent surgical intervention in the event of bleeding, if needed.
“This publication adds important mechanistic evidence to our programme, and it is encouraging to see our approach validated in blood samples from stroke patients,” said Julia Owens, chief executive officer (CEO) of Basking. “Findings like these strengthen our conviction as we advance BB-031 through our phase-two RAISE trial and work toward a treatment that could reach many stroke patients who do not currently receive acute treatment.”
