Basking Biosciences has announced positive topline data from its phase-one study of BB-025, an investigational, rapid-acting reversal agent designed to specifically bind to and neutralise BB-031—the company’s lead candidate—within minutes. BB-031 is an investigational ribonucleic acid (RNA) aptamer designed to selectively inhibit von Willebrand factor (vWF) and restore blood flow in patients with acute ischaemic stroke, and BB-025 is being developed to give clinicians a way to rapidly reverse BB-031 activity if clinically required.
“These results confirm what we designed BB-025 to do: neutralise BB-031 quickly, with a safety profile that supports its use alongside BB-031 in acute care settings,” said Shahid Nimjee, chief scientific officer and stroke clinical lead of Basking. “Clinicians need a reversal agent that works quickly and is durable, and these data demonstrate both.”
The primary objective of this first-in-human study was to assess the safety and tolerability of single escalating doses of BB-025 administered as intravenous bolus injections in healthy volunteers. To demonstrate BB-025’s ability to rapidly reverse the activity of BB-031, the study also evaluated BB-025 administered following a single dose of BB-031.
All 60 healthy adult subjects enrolled in the study received a single administration of BB-025 at doses up to 12mg/kg, either alone or following a single dose of BB-031, at doses up to 6mg/kg. When administered following a single dose of BB-031, BB-025 produced a complete, rapid and stable reversal of BB-031 activity, restoring vWF activity and platelet function within five minutes of administration. This reversal was demonstrated both 30 minutes and five hours after BB-031 administration, supporting a clinically meaningful window for reversal, as claimed by Basking in a recent press release.
BB-025 was generally safe and well-tolerated across all tested doses, with no evidence of a dose-response relationship in the incidence of treatment-emergent adverse events (TEAEs). There were no deaths, life-threatening TEAEs or serious adverse events during the study, and no TEAEs led to treatment discontinuation. BB-031 was also generally safe and well tolerated at doses up to 6mg/kg. Adverse events of special interest, including bleeding events and infusion-related reactions, were non-severe and transient.
“Having a reversal agent like BB-025 is a key aspect of BB-031’s differentiation from other thrombolytics in development for acute ischaemic stroke. BB-031 is the only investigational acute intervention with a clinically validated reversal agent,” said Julia Owens, chief executive officer (CEO) of Basking. “These data show that the effects of BB-031 can be reversed, and that this can be done quickly. If approved, this could give clinicians a level of flexibility that does not exist with current therapies. It brings us closer to a paired, reversible approach to treating acute ischaemic stroke.”
Detailed results from the study will be presented at a future medical meeting, according to Basking. Following this phase-one study—and pending discussions with the US Food and Drug Administration (FDA)—the company intends to incorporate BB-025 into the BB-031 acute ischaemic stroke clinical development programme.
