'Reversible' blood thinner may cut bleeding

risk
AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE

In an academic-industrial collaboration, researchers have developed an antibody that blocks the

formation of blood clots without triggering bleeding, a serious risk associated with current blood
thinners. The study was conducted in multiple animal models. Paving the way for safe use in
humans one day, the authors also developed a second antibody that can rapidly reverse the drug's
effects, offering an additional safety check. Blood clots can cause heart attack, stroke, and other
heart and vascular diseases. Patients with these conditions are commonly treated with drugs that
prevent blood from clotting, but carry a high risk for causing uncontrolled bleeding. Coagulation
factor XIa (FXIa), a protein that plays a key role in blood clot formation, has emerged as a major
drug target, but achieving FXIa-specific inhibition remains challenging. Here, Tovo David and
colleagues designed an antibody that specifically binds FXIa and blocks its enzymatic activity. The
antibody staved off clotting in human blood as well as in mice and rabbits. The drug appeared safe
in monkeys, which showed no signs of spontaneous bleeding even when given doses far higher than
those required to prevent clotting. Even though increased bleeding was not detected in these animal
studies, because deficiency of FXI in humans can be associated with bleeding, the researchers also
developed a second antibody as an antidote to rapidly reverse the anti-FXIa antibody's activity. With
further development, the reversible FXIa-specific antibody may offer a new and potentially safer
class of anticoagulant drug.

###

For news media only:

Article #1: "Factor XIa-specific IgG and a reversal agent to probe factor XI function in thrombosis and
hemostasis," by T. David; S.R. Coughlin at University of California, San Francisco in San Francisco,
CA, Y.C. Kim; L.K. Ely; I. Rondon; T. Mikita at Pfizer Inc. in San Francisco, CA; H. Gao; A.J. Coyle
at Pfizer Inc. in Boston, MA; P. O'Brien at Pfizer Inc. in San Diego, CA; M.W. Bolt at Pfizer Inc. in
Andover, MA; J.L. Garcia; E.A. Flounders at PMI Preclinical in San Carlos, CA.

Contact: Shaun R. Coughlin at Shaun.Coughlin@ucsf.edu (email). Thomas Mikita at +1-415-748-

9194 (phone), or Thomas.Mikita@Pfizer.com (email).

For more information, please visit the MedPak

here: http://www.eurekalert.org/jrnls/scitransmed/summaries-08-24-16.php#A