Pexelizumab

Updated data from the phase III POLARIX study continue to demonstrate a statistically significant reduction in the risk of disease worsening or death for people with previously untreated diffuse large B-cell lymphoma (DLBCL)1Patients receiving Polivy plus R-CHP for DLBCL reported similar health-related quality of life outcomes, during and after fixed-duration treatment, to those receiving the current standard-of-care, with superior progression-free survival2 Basel, 12 December 2022 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that new and updated data for its first-in-class anti-CD79b antibody-drug conjugate Polivy® (polatuzumab vedotin) were presented at the 64th American Society of Hematology (ASH) Annual Meeting & Exposition, 10-13 December. Data from the POLARIX study support the potential benefit of Polivy in combination with MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) to improve outcomes for people with previously untreated diffuse large B-cell lymphoma (DLBCL).1 “Too many patients with diffuse large B-cell lymphoma see their cancer relapse or progress after initial treatment. This highlights the need to improve on a standard-of-care that has remained unchanged for the last two decades,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “These updated POLARIX data indicate the potential benefits that this Polivy based-regimen could bring to people living with this aggressive type of lymphoma, and demonstrate our commitment to developing new treatment options.” After a median follow up of three years, progression-free survival (PFS) data continued to show a statistically significant reduction in the risk of disease worsening or death with Polivy plus R-CHP compared with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP; [hazard ratio (HR) 0.76; 95% confidence interval (CI): 0.60-0.97]). After a median follow-up of 39.7 months, overall survival (OS) data was immature with few events in each arm and remained similar between Polivy plus R-CHP and R-CHOP (HR 0.94; 95% CI: 0.67-1.33; p=0.73). In the longer follow-up analysis, no new safety signals were identified.1 Health-related quality of life (HRQoL) data from the POLARIX study were also presented, showing that most patients with previously untreated DLBCL receiving Polivy plus R-CHP or R-CHOP reported clinically meaningful improvements in lymphoma symptoms after the first cycle of treatment across both arms (82.3% and 81.3% of patients, respectively). Improvements in fatigue and physical functioning were similar with Polivy plus R-CHP versus R-CHOP, with 74.8% versus 68.2% of patients reporting improvements in fatigue and 42.4% versus 39.6% of patients reporting clinically meaningful improvements in physical functioning at any time point. Reported improvements were sustained during and after first-line therapy, up to the 24-month follow-up. This HRQoL analysis of the POLARIX study demonstrates that these patient-reported outcomes are not compromised with improved PFS, highlighting the potential of Polivy to help manage the burden of DLBCL.2 The need for more effective treatments for patients with previously untreated DLBCL was underscored in an economic analysis of the total cost of care in relapsed or refractory (R/R) DLBCL. The study evaluated healthcare costs and resources in the second-line setting and beyond, and found that total healthcare costs increased with each additional line of treatment.3 Separately, an analysis of the POLARIX study also presented at ASH showed that over the next ten years, Polivy plus R-CHP has the potential to reduce the number of patients receiving second-line treatment by 27% compared to R-CHOP, potentially improving the chance of a positive outcome for more patients and significantly reducing the overall treatment burden of DLBCL.4 Based on the pivotal data from the POLARIX study, more than 50 countries have approved Polivy in combination with R-CHP for the treatment of adult patients with previously untreated DLBCL, including the EU, Japan and, most recently, Canada. The company's supplemental Biologics License Application was accepted by the U.S. Food and Drug Administration, and a decision is expected by 2 April, 2023. Polivy is currently approved in more than 80 countries and regions worldwide, including in the U.S. and Europe, as a readily available, fixed-duration treatment option for R/R DLBCL in combination with bendamustine and MabThera/Rituxan, after at least two prior therapies. Roche continues to explore areas of unmet need where Polivy has the potential to deliver additional benefit, including in ongoing studies investigating combinations of Polivy with CD20xCD3 T-cell engaging bispecific antibodies, Lunsumio® (mosunetuzumab) and glofitamab, including the phase III SUNMO study in combination with Lunsumio, and with MabThera/Rituxan in combination with gemcitabine and oxaliplatin in the phase III POLARGO study. About the POLARIX studyPOLARIX [NCT03274492] is an international phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy® (polatuzumab vedotin) plus MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomised 1:1 to receive either Polivy plus R- CHP plus a vincristine placebo for six cycles, followed by rituximab for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of rituximab. The primary outcome measure is progression-free survival (PFS) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goal of first-line therapy: decreasing the risk of disease worsening. About diffuse large B-cell lymphoma (DLBCL)DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL. DLBCL is an aggressive (fast-growing) type of NHL.5 While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.6,7 Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.8 About Polivy® (polatuzumab vedotin)Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells. Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL. Polivy is currently marketed in the EU for the treatment of relapsed or refractory diffuse large B-cell lymphoma. About Roche in haematologyRoche has been developing medicines for people with malignant and non-malignant blood diseases for more than 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab) and Lunsumio® (mosunetuzumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies glofitamab, targeting both CD20 and CD3 and cevostamab, targeting both FcRH5 and CD3, Tecentriq® (atezolizumab), a monoclonal antibody designed to bind with PD-L1, and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavor to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law.References[1] Herrera A, et al. Risk Profiling of Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) by Measuring Circulating Tumor DNA (ctDNA): Results from the POLARIX Study. Presented at: ASH Annual Meeting and Exposition; 2022 Dec 10-13. Abstract #542.[2] Friedberg J, et al. Health-Related Quality of Life (HRQoL) in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin and Prednisone (Pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) in the Phase III POLARIX Study. Presented at: ASH Annual Meeting and Exposition; 2022 Dec 10-13. Abstract #2949.[3] Gatwood J, et al. Total cost of care in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). Presented at: ASH Annual Meeting and Exposition; 2022, Dec 10-13. Abstract #3527.[4] Boissard F, et al. Epidemiological Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone (Pola-R-CHP) Use in Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) in Terms of Second Line (2L) Treatment: An Ad Hoc Analysis from the POLARIX Study. Presented at: ASH Annual Meeting and Exposition; 2022 Dec 10-13. Abstract #2958.[5] Cancer.Net. Leukemia – Lymphoma –Non-Hodgkin: Subtype. [Internet; cited 2022 December]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes. [6] Maurer M, Ghesquières H, Jais J, et al. Event-free survival at 24 months is a robust end point for disease- related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol. 2014;32(10):1066-1073.[7] Sehn L, Gascoyne R. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood. 2015;125(1):22-32.[8] Globocan 2020. World Fact Sheet. [Internet; cited 2022 December]. Available from: http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58Nathalie AltermattPhone: +41 79 771 05 25Karsten KleinePhone: +41 79 461 86 83Nina MählitzPhone: +41 79 327 54 74 Dr. Barbara von SchnurbeinPhone: +41 79 699 97 44Sileia Urech Phone: +41 79 935 81 48 Roche Investor Relations Dr. Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.comDr. Sabine BorngräberPhone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.comDr. Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.comDr. Gerard Tobin Phone: +41 61 68-72942 e-mail: gerard.tobin@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 12122022_MR_ASH_POLARIX_en

The HAVEN 7 study was designed to further confirm the benefit of preventative treatment (prophylaxis) with Hemlibra from birth in previously untreated or minimally treated infants with severe haemophilia A without inhibitorsIn the study, 77.8% of participants had no bleeding episodes that required treatment1In addition, real-world efficacy and safety data from the EUHASS database and ATHN 7 study were also presented 2,3 Basel, 11 December 2022 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced interim results from the phase III HAVEN 7 study. The study shows Hemlibra® (emicizumab) achieved meaningful bleed control with a favourable safety profile in infants (up to 12 months) with severe haemophilia A, without factor VIII inhibitors: 77.8% of participants did not have any bleeds that required treatment and 42.6% did not have any treated or untreated bleeds at all.1 These results help support the use of Hemlibra in this population, in which it is already approved in many countries around the world. The new data were presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in New Orleans from 10-13 December 2022. The burden of severe haemophilia A in infants and on their parents and caregivers is significant. The World Federation of Haemophilia treatment guidelines consider the standard of care in haemophilia to be regular prophylaxis initiated at a young age, as studies have shown that early prophylaxis improves long-term outcomes, while reducing the risk of intracranial haemorrhage. 4-6 However, for many infants with haemophilia A, prophylaxis is not started until after the first year of life because of the high treatment burden.7-11 Hemlibra provides a flexible treatment option that can be administered subcutaneously from birth at different dosing frequencies. “These initial results support the benefit of starting Hemlibra from birth given that early preventative treatment is essential in infants,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Haemophilia can substantially reduce quality of life for those affected, starting at infancy, which is especially distressing for parents and caregivers. We continue to explore Hemlibra's potential benefits to a broad range of people with haemophilia A.” HAVEN 7 is a phase III, multi-centre, open-label study evaluating the efficacy, safety, pharmacokinetics and pharmacodynamics of Hemlibra in infants with severe haemophilia A without factor VIII inhibitors. The results of this interim analysis, which included data from 54 participants, showed that 77.8% of participants (n=42) did not have any bleeds which required treatment, while 42.6% (n=23) did not have any treated or untreated bleeds at all. There were no treated spontaneous bleeds in any participants, and all treated bleeds were traumatic. A total of 77 bleeds occurred in 31 participants (57.4%); 88.3% were traumatic. Mean model-based annualised bleeding rate (ABR) (95% CI) at the time of interim analysis was 0.4 (0.23–0.65) for treated bleeds. 1 Hemlibra’s safety profile was consistent with previous studies, with no new safety signals observed. Nine people (16.7%) reported a Hemlibra-related adverse event (AE), all of which were local injection site reactions. Eight participants (14.8%) reported 12 serious AEs, unrelated to Hemlibra. There were no deaths, thromboembolic events or cases of thrombotic microangiopathy, reinforcing Hemlibra’s favourable safety profile. No intracranial haemorrhages occurred.1 Primary analysis will be conducted at 52 weeks. The study also has an additional seven-year follow-up period to collect long-term data such as safety and joint health outcomes, further building upon our understanding of the benefit of Hemlibra in this population.EUHASS database and ATHN 7 study Roche also presented data from the European Haemophilia Safety Surveillance (EUHASS) database and the prospective observational ATHN 7 study at ASH 2022. Data from EUHASS, which collects real-world safety data on treatments for inherited disorders, showed the safety profile of Hemlibra in people with haemophilia A was favourable and consistent with clinical trial data. 2 Data from ATHN 7, exploring the efficacy of Hemlibra in women with haemophilia A, showed two of the three female participants had no bleeds; the third had one treated bleed associated with a dental procedure and one untreated bleed associated with menses. Ongoing evaluation is vital to further understand the safety and efficacy profile of Hemlibra in this rare and under-represented population.3 Hemlibra is approved as a treatment for people with haemophilia A with factor VIII inhibitors in more than 110 countries worldwide, and for people without factor VIII inhibitors in more than 100 countries worldwide. It has been studied in one of the largest clinical trial programmes in people with haemophilia A with and without factor VIII inhibitors, including eight phase III studies.About Hemlibra® (emicizumab) Hemlibra is a bispecific factor IXa- and factor X-directed antibody. It is designed to bring together factor IXa- and factor X, proteins involved in the natural coagulation cascade, and restore the blood clotting process for people with haemophilia A. Hemlibra is a prophylactic (preventative) treatment that can be administered by an injection of a ready-to-use solution under the skin (subcutaneously) once-weekly, every two weeks, or every four weeks (after an initial once-weekly dose for the first four weeks). Hemlibra was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed globally by Chugai, Roche and Genentech. It is marketed in the United States by Genentech as Hemlibra (emicizumab-kxwh), with kxwh as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.About haemophilia A Haemophilia A is an inherited, serious disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Haemophilia A affects around 900,000 people worldwide, 4,12 approximately 14% and 48% of whom have a moderate or mild form of the disorder,13 respectively. However, the severity of haemophilia A is not always reflective of bleeding behaviour, as some people with non-severe haemophilia may experience symptoms similar to those with severe haemophilia and warrant prophylaxis.14 All severities of haemophilia A can significantly reduce the quality of life for people affected, as well as their family and caregivers. People with haemophilia A either lack or do not have enough of a clotting protein called factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa- and X, which is a critical step in the formation of a blood clot to help stop bleeding. Depending on the severity of their symptoms, people with haemophilia A can bleed frequently, especially into their joints or muscles. 13 These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility and long-term joint damage.15 A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies. Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII, making it difficult, if not impossible, to obtain a level of factor VIII sufficient to control bleeding.4About Roche in haematologyRoche has been developing medicines for people with malignant and non-malignant blood diseases for more than 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab) and Lunsumio® (mosunetuzumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies glofitamab, targeting both CD20 and CD3 and cevostamab, targeting both FcRH5 and CD3, Tecentriq® (atezolizumab), a monoclonal antibody designed to bind with PD-L1, and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavor to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law.References[1] Pipe S, et al. Emicizumab Prophylaxis for the Treatment of Infants with Severe Hemophilia A without Factor VIII Inhibitors: Results from the Interim Analysis of the HAVEN 7 Study. Presented at American Society of Hematology (ASH) virtual congress; 2022 December 10. Abstract 187. [2] Nissen F, et al. Real-World Safety of Emicizumab: Interim Analysis of the European Haemophilia Safety Surveillance (EUHASS) Database. Presented at American Society of Hematology (ASH) virtual congress; 2022 December 10. Abstract 192.[3] Recht M, Emicizumab and Females with Hemophilia A: Case Series from ATHN 7. Presented at American Society of Hematology (ASH) virtual congress; 2022 December 10. Abstract 1162. [4] Srivastava A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020; 26 (Suppl 6): 1-158.[5] Manco-Johnson MJ, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. New England Journal of Medicine. 2007;357(6):535–544.[6] Andersson NG, et al. Intracranial haemorrhage in children and adolescents with severe haemophilia A or B - the impact of prophylactic treatment. British Journal of Haematology. 2017;179(2):298–307; 4.[7] Spagrud LJ, et al. Pain, distress, and adult-child interaction during venipuncture in pediatric oncology: an examination of three types of venous access. Journal of Pain and Symptom Management. 2008;36: 173–84. [8] Van den Berg HM, et al. Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood 2019;134:317–320.[9] Valentino LA, et al. Central venous access devices in haemophilia. Haemophilia. 2004;10: 134–146. [10] Valentino LA & Kapoor M. Central venous access devices in patients with hemophilia. Expert Rev Med Devices 2005;2: 699–711. [11] Mancuso M, et al. Prophylaxis in children with haemophilia in an evolving treatment landscape. Haemophilia. 2021;27: 889–896.[12] Iorio A et al. Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males. Ann Intern Med 2019 Oct 15;171(8):540-546.[13] World Federation of Hemophilia. Report on the annual global survey 2020. [Internet; cited 2022 November] Available from: http://www1.wfh.org/publications/files/pdf-2045.pdf.[14] Collins PW, et al. Clinical phenotype of severe and moderate haemophilia: Who should receive prophylaxis and what is the target trough level? Haemophilia, 2021;27: 192-198.[15] Franchini M, et al. Haemophilia A in the third millennium. Blood Rev. 2013; 179-84. Roche Group Media Relations Phone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Nathalie AltermattPhone: +41 79 771 05 25 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Dr. Barbara von SchnurbeinPhone: +41 79 699 97 44 Sileia Urech Phone: +41 79 935 81 48 Roche Investor Relations Dr. Bruno EschliPhone: +41 61 68-75284 e-mail: bruno.eschli@roche.com Dr. Sabine BorngräberPhone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.com Dr. Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Dr. Gerard Tobin Phone: +41 61 68-72942 e-mail: gerard.tobin@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 11122022_MR_ASH Hemlibra_ STAGE 3_V1.0_en