Eculizumab

If approved, PiaSky will be the first monthly subcutaneous (SC) treatment for paroxysmal nocturnal haemoglobinuria (PNH) in the EU Additionally, with the option to self-administer, PiaSky may provide an alternative to existing intravenous (IV) C5 inhibitors, potentially helping to reduce treatment burden1The recommendation is based on the COMMODORE 2 study results, where SC PiaSky given every month demonstrated equivalent disease control and comparable safety to IV eculizumab given every two weeks2,3 Basel, 28 June 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for PiaSky® (crovalimab) for the treatment of paroxysmal nocturnal haemoglobinuria (PNH). The CHMP has recommended PiaSky, a novel recycling monoclonal antibody that inhibits the complement protein C5, for use in adults and adolescents (12 years of age or older with a weight of 40 kg) who are either new to, or have been previously treated with C5 inhibitors. If approved, PiaSky will be the first monthly subcutaneous (SC) treatment for PNH in the European Union, with the option to self-administer following adequate training. This may provide an alternative option to current C5 inhibitors that require regular intravenous (IV) infusions, potentially helping to reduce treatment burden and disruption to the lives of people with PNH and their caregivers.1 A final decision regarding the approval of PiaSky is expected from the European Commission in the near future. “People living with PNH face lifelong treatment, often requiring frequent intravenous infusions and time-consuming clinic visits,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “With the option to self-administer once a month, today’s recommendation may therefore offer patients and caregivers in Europe more freedom in their day-to-day lives.” PNH is a rare and life-threatening blood condition, which affects approximately 20,000 people worldwide. In PNH, red blood cells are destroyed by the complement system – part of the innate immune system. This causes symptoms such as anaemia, fatigue and blood clots, and can lead to kidney disease. C5 inhibitors – treatments that block part of the complement system cascade – have been shown to be effective in treating PNH. PiaSky is a novel C5 inhibitor that is recycled within the bloodstream, allowing the medicine to bind and inhibit the C5 protein multiple times and to act longer in the body with a small volume of medicine. This enables SC administration every four weeks, following an initial IV infusion and weekly SC loading doses in the first month of treatment.1,2,4-6 The CHMP recommendation is based on the results from the Phase III COMMODORE 2 study in people with PNH who have not been previously treated with C5 inhibitors. Results from the study demonstrated that PiaSky, administered as SC injections every four weeks, achieved disease control and was well-tolerated. PiaSky was non-inferior with comparable safety to eculizumab, an existing standard of care C5 inhibitor, given intravenously every two weeks. The rate of adverse events in people treated with PiaSky was similar to treatment with eculizumab (78% versus 80%, respectively). The application included supportive data from two additional Phase III studies, the COMMODORE 1 study, in people with PNH switching from currently approved C5 inhibitors, and the COMMODORE 3 study in people new to C5 inhibitor treatment in China.2,7,8,9 PiaSky is the first monthly SC treatment approved in the US, Japan and China for people with PNH based on results of the COMMODORE studies.2,7,9 PiaSky is being investigated in a broad clinical development programme, including five ongoing Phase III studies and three earlier phase studies in complement-mediated diseases, including PNH, atypical haemolytic uremic syndrome and sickle cell disease.2,7,9-14About PiaSky® (crovalimab) PiaSky® (crovalimab) is a novel recycling monoclonal antibody that inhibits the complement protein C5 and is designed to block the complement system – a vital part of the innate immune system that acts as the body’s first line of defence against infection. PiaSky has been engineered by Chugai Pharmaceutical Co. Ltd to address certain needs of people living with complement-mediated diseases, including providing patients with a potential for self-administration following adequate training. PiaSky works by binding to C5, blocking the last step of the complement cascade and delivering rapid and sustained complement inhibition. It is also recycled within the bloodstream, enabling small volume subcutaneous administration every four weeks. In addition, PiaSky binds to a different C5 binding site from current treatments, which has the potential to provide a treatment option for people with specific C5 gene mutations who do not respond to current therapies. PiaSky is a monthly subcutaneous treatment approved in the US, Japan and China for people with paroxysmal nocturnal haemoglobinuria, based on the Phase III COMMODORE studies. It is also being evaluated in atypical haemolytic uremic syndrome and sickle cell disease.1,2,7,9-14 About the COMMODORE 2 study The COMMODORE 2 study is a Phase III, randomised, open-label study evaluating the efficacy and safety of PiaSky® (crovalimab) versus eculizumab in people with paroxysmal nocturnal haemoglobinuria (PNH) who have not been treated previously with C5 inhibitors. The study’s co-primary efficacy endpoints measure transfusion avoidance and control of haemolysis (the ongoing destruction of red blood cells measured by lactate dehydrogenase levels). The adults enrolled in the study were randomised in a 2:1 ratio to be treated with either subcutaneous (SC) PiaSky every four weeks or intravenous eculizumab every two weeks. The participants who were less than 18 years old were included in a non-randomised treatment arm and were treated with SC PiaSky every four weeks.3 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 endeavour 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 fifteenth 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.References1Fukuzawa T, et al. Long lasting neutralisation of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases. 2017; Sci Rep 7, 1080.2Roth A, et al. The Phase III, Randomised COMMODORE 2 Trial: Results from a Multicentre Study of Crovalimab vs Eculizumab in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients Naïve to Complement Inhibitors. Presentation at European Hematology Association (EHA) Annual Congress; 2023 June 08-13. Abstract #S181.3 COMMODORE 2 (NCT04434092). [Internet; cited June 2024] Available at: https://www.clinicaltrials.gov/ct2/show/NCT04434092. 4Grand View Research. Paroxysmal nocturnal hemoglobinuria (PNH) treatment market size, share and trends analysis report by treatment and segment forecasts, 2018 – 2025. [Internet; cited June 2024]. Available at: https://www.grandviewresearch.com/industry-analysis/paroxysmal-nocturnal-hemoglobinuria-pnh-market. 5 National Organization for Rare Diseases. Paroxysmal nocturnal hemoglobinuria. [Internet; cited June 2024]. Available at: https://rarediseases.org/rare-diseases/paroxysmal-nocturnal-hemoglobinuria/.6Harder M, et al. Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation. Blood. 2017;129:970-980.7Scheinberg P, et al. Phase III Randomised, Multicentre, Open-Label COMMODORE 1 Trial: Comparison of Crovalimab Vs Eculizumab in Complement Inhibitor-Experienced Patients with Paroxysmal Nocturnal Hemogobinuria (PNH). Presentation at European Hepatology Association (EHA) Annual Congress; 2023 June 08-13. Abstract #S183.8COMMODORE 1 (NCT04432584). [Internet; cited June 2024] Available at: https://www.clinicaltrials.gov/ct2/show/NCT04432584.9Liu H, et al. Six-month Crovalimab Extension in the Phase III COMMODORE 3 Study: Updated Efficacy and Safety Results in Complement Inhibitor-Naive Patients with Paroxysmal Nocturnal Hemoglobinuria. Poster presentation at European Hematology Association (EHA) Annual Congress; 2023 June 08-13. Abstract #P785.10COMMUTE-p (NCT04958265). [Internet; cited June 2024] Available at: https://www.clinicaltrials.gov/ct2/show/NCT04958265.11COMMUTE-a (NCT04861259). [Internet; cited June 2024] Available at: https://www.clinicaltrials.gov/ct2/show/NCT04861259.12Nishimura J, et al. Crovalimab for Treatment of Patients With Paroxysmal NocturnalHemoglobinuria And Complement C5 Polymorphism – Experience From The Composer Phase I/II Study. EHA Library. 2020; Abstract PB1992.13CROSSWALK-a (NCT04912869) ClinicalTrials.gov. [Internet; cited June 2024]. Available at: https://clinicaltrials.gov/ct2/show/NCT04912869.14CROSSWALK-c (NCT05075824) ClinicalTrials.gov. [Internet; cited June 2024]. Available at: https://clinicaltrials.gov/ct2/show/NCT05075824. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Sileia UrechPhone: +41 79 935 81 48 Nathalie AltermattPhone: +41 79 771 05 25 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262 Yvette PetillonPhone: +41 79 961 92 50 Dr. Rebekka SchnellPhone: +41 79 205 27 03 Roche Investor Relations Dr. Bruno Eschli Phone: +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 Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 28062024_MR_PiaSky_CHMP_opinion_en

Transfusion avoidance results were comparable between SB12 and reference eculizumab-treated groups, supporting clinical efficacy between SB12 and reference eculizumab INCHEON, Korea, June 14, 2024 (GLOBE NEWSWIRE) -- Samsung Bioepis Co., Ltd. today presented the post-hoc analysis of the Phase 3 clinical study results for EPYSQLI™ (SB12), a biosimilar to Soliris1 (eculizumab), at the 29th European Hematology Association 2024 (EHA2024) Hybrid Congress held in Madrid, Spain and virtually, from June 13 to 16, 2024. The post-hoc analysis of SB12 pivotal Phase 3 study compared the proportion of patients remaining transfusion-free (“transfusion avoidance”) among those treated with SB12 or reference eculizumab (ECU), respectively. Eculizumab is known to significantly reduce hemolysis resulting in improvements in anemia as indicated by increased hemoglobin stabilization and reduced need for red blood cell (RBC) transfusions.2 For this study, 50 adults with PNH who were complement-inhibitor naïve were randomized (1:1) to treatment sequence I (TS1: SB12 to ECU, n=25) or II (TS2: ECU to SB12, n=25), to receive 600 mg of SB12 or ECU intravenously every week for first 4 weeks and 900 mg for the fifth week, followed by 900 mg every 2 weeks thereafter. At Week 26, patients were switched to ECU or SB12, respectively, and received infusion until Week 50 (i.e., Period 1 followed by Period 2 from Week 26). This efficacy analysis was conducted in pooled patients treated with SB12 or ECU in either Periods 1 or 2. Transfusion avoidance was 68.1% for patients who received SB12 versus 72.9% for patients who received reference eculizumab, with a difference of -5.3% [95% confidence interval (CI), (-18.9%, 8.4%), p-value 0.4492], resulting in non-significant difference between the two treatment groups. “This post-hoc analysis supports the previously demonstrated comparable clinical efficacy of SB12 with reference eculizumab in treating PNH patients, with no significant difference in reducing transfusion burden compared to reference eculizumab,” said Hyejin Kim, Vice President and Medical & Lifecycle Safety Team Leader at Samsung Bioepis. “Our dedication to make a meaningful difference to our patients remain steadfast. We will continue to work collaboratively with clinicians and physicians to further expand the treatment options for patients with orphan diseases.” Details of the SB12 abstract are as follows: Abstract title: Transfusion Avoidance with EPYSQLI™(SB12), A Biosimilar to Reference Eculizumab: A Post-hoc Analysis from the Pivotal Phase 3 StudyAbstract number: P1916Program type: e-Poster PresentationAuthors: Jun Ho Jang, Jihye Park, Younsoo Kim, Jihyun Han and Paola Russo In May 2023, the European Commission (EC) approved SB12 as a biosimilar to Soliris (eculizumab) under the brand name EPYSQLI for the treatment of adults and children with PNH. In March 2024, EPYSQLI was granted an indication expansion for the treatment of adults and children with atypical haemolytic uremic syndrome (aHUS).3 About EPYSQLI (Eculizumab Biosimilar) in the European Union (EU) EPYSQLI is indicated in adults and children for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). EPYSQLI is not approved for and should not be used for the treatment of generalised myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). EPYSQLI must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with hematological disorders or renal disorders. EPYSQLI EU Important Safety Information The EU Summary of Product Characteristics for EPYSQLI includes the following Special warning and Precautions: Meningococcal Infection EPYSQLI increases patient's susceptibility to Meningococcal infection (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving eculizumab unless the risk of delaying eculizumab therapy outweighs the risks of developing a meningococcal infection. Patients who initiate eculizumab treatment less than 2 weeks after receiving a tetravalent meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines against serogroups A, C, Y and W 135 are recommended in preventing the commonly pathogenic meningococcal serogroups. Vaccines against serogroup B where available are also recommended. Patients must receive vaccination according to current national vaccination guidelines for vaccination use. Vaccination may further activate complement. As a result, patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease, such as haemolysis (PNH) or TMA (aHUS). Therefore, patients should be closely monitored for disease symptoms after recommended vaccination. Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to official local guidance on the appropriate use of antibacterial agents. Cases of serious or fatal meningococcal infections have been reported in eculizumab-treated patients. All patients should be monitored for early signs of meningococcal infection, evaluated immediately if infection is suspected, and treated with appropriate antibiotics if necessary. Patients should be informed of warning signs and symptoms and steps taken to seek medical care immediately. Other Systemic Infections Patients may have increased susceptibility to other type of serious infections, especially with Neisseria and encapsulated bacteria. Infusion Reactions Administration of eculizumab may result in infusion reactions or immunogenicity that could cause allergic or hypersensitivity reactions (including anaphylaxis). Eculizumab administration should be interrupted in all patients experiencing severe infusion reactions and appropriate medical therapy administered. Anticoagulant therapy Treatment with EPYSQLI should not alter anticoagulant management. PNH Laboratory Monitoring PNH patients should be monitored for signs and symptoms of intravascular haemolysis, including serum lactate dehydrogenase (LDH) levels, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days). aHUS Laboratory Monitoring aHUS patients receiving eculizumab therapy should be monitored for thrombotic microangiopathy by measuring platelet counts, serum LDH and serum creatinine, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days). Treatment Discontinuation for PNH If patients discontinue treatment with eculizumab they should be closely monitored for signs and symptoms of serious intravascular haemolysis. Treatment Discontinuation for aHUS If aHUS patients discontinue treatment with eculizumab, they should be monitored closely for signs and symptoms of severe thrombotic microangiopathy complications. The most common adverse reaction observed with eculizumab treatment in clinical trials was found to be headache, whereas the most serious adverse reaction was found to be meningococcal infection. Refer to the Summary of Product Characteristics for EPYSQLI’s full safety information. About Samsung Bioepis Co., Ltd. Established in 2012, Samsung Bioepis is a biopharmaceutical company committed to realizing healthcare that is accessible to everyone. Through innovations in product development and a firm commitment to quality, Samsung Bioepis aims to become the world's leading biopharmaceutical company. Samsung Bioepis continues to advance a broad pipeline of biosimilar candidates that cover a spectrum of therapeutic areas, including immunology, oncology, ophthalmology, endocrinology, hematology and nephrology. For more information, please visit: www.samsungbioepis.com and follow us on social media – follow us on social media – X, LinkedIn. MEDIA CONTACT Yoon Kim, yoon1.kim@samsung.com References: 1 Soliris is a trademark of Alexion Pharmaceuticals 2 European Medicines Agency. Soliris Product Information. https://www.ema.europa.eu/en/documents/product-information/soliris-epar-product-information_en.pdf. Accessed May 2024 3 European Medicines Agency. Epysqli Product Information. https://www.ema.europa.eu/en/documents/product-information/epysqli-epar-product-information_en.pdf. Accessed May 2024