BAYER & HEMOPHILIA

Hemophilia Products and Pipeline

For more than 25 years, has been committed to delivering science for a better life by advancing a portfolio of innovative treatments. Hematology at Bayer includes marketed products as well as a number of compounds in various stages of development for hemophilia, sickle cell anemia, and other blood disorders. Bayer has a long history of research and development in the area of hemophilia A, exemplified best by the company’s development of Kogenate ® and Kovaltry ® and continuing with the development of a longer-acting recombinant factor VIII (rFVIII) product. Besides improving FVIII replacement therapy, Bayer is also pursuing alternative treatment approaches in hemophilia, including gene therapy and inhibition of tissue factor pathway inhibitor (TFPI) in early stage development.

Hemophilia Facts1

Hemophilia A, also known as factor VIII deficiency or classic hemophilia, is a largely inherited disorder in which one of the proteins needed to form blood clots - factor VIII - is missing or reduced. Hemophilia A is the most common type of hemophilia and over time can cause prolonged or spontaneous , Berkeley, Whippany, Wuppertal and Leverkusen, especially into the muscles, joints or internal organs causing California New Jersey Germany significant damage.1 Serves as a global As Bayer's North Bayer made one of the largest manufacturing biotech drug American headquarters, investments in its history: over €500 million to There are an estimated development center, Whippany houses the expand production capacities to produce and is the global consumer, medical care the company’s new rFVIII and long-acting manufacturing center and pharmaceutical rFVIII therapies. for a recombinant businesses, including factor VIII treatment for their hemophilia hemophilia A. franchise. 4 0 0 0 0 0 people globally living with hemophilia.

Therapies Bayer continues to develop innovative therapies that reduce the burden of regular infusions and advance care for people living with hemophilia A around the world. Currently, Bayer has two hemophilia therapies:

Kogenate ® is Bayer’s first recombinant product, which Kovaltry ® is an unmodified full-length recombinant received U.S. FDA and European approvals more than factor VIII product that in clinical trials has demonstrated 20 years ago. control of bleeds and protection from bleeds in hemophilia A patients when used prophylactically two Clinical data show the product provides or three times per week. efficient hemostatic control, is well-tolerated, and has a proven safety profile in people Kovaltry ® provides with hemophilia A.2,3 appropriate patients with the benefits of potentially The Joint Outcome Study (JOS), the first and reduced dosing and may only randomized clinical trial to evaluate joint decrease the significant outcome after routine prophylaxis use of burden associated with recombinant factor VIII, showed an 84 percent frequent infusions, reduction in the risk of joint damage with improving adherence to Kogenate ® compared with on-demand therapy prophylaxis. in boys. And, at the age of six years, 93 percent of those who received routine prophylactic The approval was based on the LEOPOLD (Long-Term treatment had normal joints as compared to Efficacy Open-Label Program in Severe Hemophilia A only 55 percent in the on-demand group.4 Disease) Clinical Development Program, which consisted of three multinational clinical trials designed to evaluate the pharmacokinetics, efficacy and safety of Kovaltry ®. The combined trials found Kovaltry ® to be well tolerated and effective for treatment and prophylaxis of bleeding episodes in hemophilia A patients of all age groups.

Kovaltry ® is developed through advanced manufacturing. Pipeline In addition, Bayer remains committed to the hemophilia community through development of innovative therapies:

BAY 94-9027 Beyond Factor VIII Replacement BAY 94-9027 is a longer-acting rFVIII therapy.5 Bayer is also committed to research and develop innovative therapies that bypass rFVIII replacement:

Overall results showed efficacy of different regimens of Inhibition of TFPI may offer an alternative twice per week, every five days, and every seven days prophylactic therapy option for hemophilia when treatment was tailored to patient’s observed patients with or without inhibitors. bleeding tendency.

Dimension Therapeutics, a gene therapy company. Efforts will be focused on developing and making available a hemophilia A treatment based on the advanced adeno-associated virus (AAV) delivery technology.

Bayer entered into a joint venture with gene-editing startup CRISPR Therapeutics, investing over $300 million to develop new medicines for different indications using emerging gene therapy technology.

HEMOPHILIA SOLUTIONS

Hemophilia Solutions is the comprehensive platform that KidK Self-Infusion Program delivers an array of tools, services, disease education, and partnerships designed to strengthen the patient’s management of their disease, as well as highlights Bayer’s support for the entire hemophilia community. Bayer continues to maintain a steadfast commitment to Offers the KidK Self-Infusion Program, a the hemophilia community and patients worldwide that global educational initiative aimed at teaching has spanned more than three decades. children with hemophilia how to self-infuse. Through Hemophilia Solutions, Bayer: Since the program’s launch in 2008, more than 50,000 kits have been distributed in Hemophilia Joint Visualizer nearly 50 countries and over 26 languages.

FactorTrack

Delivers the Hemophilia Joint Visualizer (HJV) tool, an interactive web-based system developed to facilitate an educational dialogue on joint health between doctors Provides access to FactorTrack, an and their patients. This tool illustrates the award-winning, customizable mobile impact of good treatment decisions and application for people with hemophilia A, adherence to prophylaxis on joints. making it easier to track and record infusions to help with adherence to prophylaxis regimen. HemophiliaLEAD

Hemophilia Advocacy Advisors Board (HAAB)

Offers HemophiliaLEAD, a leadership development platform offering information and materials for Bayer’s patient advocate Convenes the Hemophilia Advocacy Advisors development programs Step Up Reach Out Board (HAAB), a group of patient advocates (SURO) and AFFIRM. Both programs are from across the globe dedicated to identifying designed to help identify and train the next unmet advocacy needs in the bleeding generation of advocates within the bleeding disorders community, empowering advocates disorders community. and national organizations.

Bayer Hemophilia Awards Program (BHAP) International Hemophilia Training Centre (IHTC) Provides sole sponsorship of the World Federation of Hemophilia’s (WFH’s) International Hemophilia Training Centre (IHTC) program. The program gives healthcare professionals Founded the Bayer Hemophilia Awards Program from developing countries training in the (BHAP) in 2002, the largest of its kind in the diagnosis and management of hemophilia industry, to fund hemophilia research and and related bleeding disorders. education around the world. CONTRIBUTED 230 AWARDS 575 FROM 85 $28M FELLOWS TRAINED COUNTRIES

PURSUING CAREERS 400+ IN HEMOPHILIA CARE PUBLICATIONS, POSTER PRESENTATIONS 93% & OTHER SCIENTIFIC COMMUNICATIONS

1 Srivastava, Dr. Alok, et al. Guidelines for the Management of Hemophilia. 2nd ed. Montreal: Blackwell, 2012. 2 Abshire, T.C., Brackmann, H.H., et al. Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy. Thromb Haemost. 2000. 83(6):811-816. 3 Kreuz, W., Gill, J.C., et al., Full-length sucrose-formulated recombinant Factor VIII for treatment of previously untreated or minimally treated young children with severe A. Thromb Haemost. 2005.93(3):457–67. 4 Manco-Johnson, M., Abshire, T.C., et al. Prophylaxis versus Episodic Treatment to Prevent Joint Disease in Boys with Severe Hemophilia. N Engl J Med. 2007. 357(6):535-544. 5 PROTECT Clinical Trials. Available at: https://clinicaltrials.gov. Accessed September 2015.