change was that in the purification, here they simply added a purification simplification step as is commonly used in monoclonal antibodies to purify the first step. This increased the downstream yield. This does not have an effect on the general properties of the molecule. The whole document is based on bioanalytics. What is the comparability between GEN 1 and GEN 2? They are quite comparable despite the difference in how they fed the cells. The rest of the data package is how GEN 2 behaves in healthy c volunteers and patients. This is the rest of the data package. The PAS will be comprised of crunching of the numbers and writing the report. Management says that results are encouraging that the molecules are comparable in efficacy and safety. It has been tested in 120 healthy volunteers and 100 patients. Very encouraged by the data but regulators often have their own set of questions. Hopefully approval early next year. In Europe are looking for a final decision later this year. What was the EMA looking for? What the EMA is looking for is not that dissimilar from what the FDA. The EMA has shifted their focus from GEN1 to GEN2 after the oral explanation meeting in February and March. They are focused on the GEN 2 and have asked for a package of data on the GEN2 manufacturing and analytics. It is essentially the same package they are giving the FDA. In addition, they would like to see the updated clinical data comparing GEN1 to GEN2. They also want to look at the healthy volunteers pharmacokinetics and pharmacodynamics. The only different thing they are requesting is an updated PK/PD. Parts of this data will be submitted this simmer and parts in the fall. They will review it all in October and render an opinion in November. This is a special one off timeline reflecting the interest in AndexXa. They are doing a lot of work in Europe trying to figure out what their strategy should be. Haven’t made a decision on whether to go it alone or with collaborators in targeted countries. Need to put infrastructure in place a year or so before launch. Europe has been at the forefront of treating thrombosis and there are probably twice as many patients on Xa inhibitors as in the US. Pricing is about one-third of what it is in the US. Xarelto and Eliquis have about the same revenues. There is much greater Xa use in the UK, Germany and France and less in Spain and Italy. There is also opportunity in Austria, Switzerland and the Scandinavian countries. Will be dependent on price and factor Xa usage.

Betrixaban estimates have been coming down. Will it really ramp in 2019.Are learning a lot about how hospital view a prophylactic drug. Requires a lot of education. They are encouraged because they know that the patients are there and that the data package is good. In this population, 50% of clots that do occur happen outside of the hospital. Know the patients are there and that the data is good. There are 5 million patients in the US at high risk and patients are at high risk for clots when they leave the hospital. There are 15 different publications that support the data that shows that it reduces the risk of clots without increasing the risk of major bleeds. Also data on rehospitilization, stroke etc. Finally are seeing