CD79B

AbbVie has announced that its IgG1-bispecific antibody Tepkinly (epcoritamab) has been recommended by the European Medicines Agency’s human medicines committee to treat specific cases of follicular lymphoma (FL). The Committee for Medicinal Products for Human Use (CHMP) has recommended that the drug, which is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration, be granted conditional marketing authorisation as a monotherapy for adults with relapsed or refractory (R/R) FL who have received at least two prior therapies. The CHMP’s recommendation of the therapy was supported by positive results from the phase 1/2 EPCORE NHL-1 clinical trial, which evaluated the safety and efficacy of Tepkinly in more than 120 adults with R/R FL. FL is the second-most common form of non-Hodgkin lymphoma, accounting for up to 30% of all cases. The disease is considered incurable, with patients frequently relapsing and the prognosis worsening after each subsequent relapse. Administered subcutaneously, Tepkinly is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induce T-cell-mediated killing of CD20-positive cells. Mariana Cota Stirner, vice president, therapeutic area head for haematology at AbbVie, said: “Patients with FL are likely to face disease recurrence and shorter durability of response with each subsequent line of treatment. “This positive opinion recognises the unmet need in the EU for individuals with R/R FL, following failure of other therapies.” AbbVie announced earlier this year that Tepkinly had been recommended by the National Institute for Health and Care Excellence to treat certain adults with diffuse large B-cell lymphoma (DLBCL). The agency’s decision specifically applies to patients who have DLBCL that has returned or not responded to at least two previous treatments, including Roche’s CD79b-directed antibody-drug conjugate Polivy (polatuzumab vedotin), unless this is contraindicated or not tolerated. AbbVie and Genmab also received accelerated approval by the US Food and Drug Administration (FDA) last month for epcoritamab, under the brand name Epkinly, to treat adults with R/R FL. Both companies share commercial responsibilities for epcoritamab in the US and Japan, while AbbVie is responsible for further global commercialisation.

Sobi has announced that Zynlonta (loncastuximab tesirine) has been recommended by the National Institute for Health and Care Excellence (NICE) as a treatment option for two aggressive types of non-Hodgkin lymphoma. The CD19-directed antibody-drug conjugate (ADC) has specifically been recommended for use in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL). Those eligible will have received at least two systemic treatments, including Roche's CD79b-directed antibody-drug conjugate Polivy (polatuzumab vedotin), unless this is contraindicated or not tolerated. Over 10,000 people are diagnosed with a type of non-Hodgkin lymphoma every year in the UK. In its final draft guidance, NICE noted the evolving treatment pathway and the need for new treatment options for people with DLBCL and HGBCL. Sharon Hall, general manager at Sobi UK, said: “We are delighted with the news that NICE has positively recommended this important novel treatment for patients in England and Wales. “As a chemotherapy-free treatment option with a manageable safety and tolerability profile, Zynlonta has the potential to fulfil an unmet need.” The regulator’s decision was supported by results from the mid-stage LOTIS-2, which collected data on 145 people with relapsed or refractory DLBCL, including HGBL, that had not responded to two or more previous systemic treatments. The primary outcome of overall response rate was 48.3%, and 24.8% of patients reached complete remission. Median overall survival was 9.53 months and median progression-free survival was 4.93 months. “The addition of [Zynlonta] to the NICE-recommended options available for DLBCL and HGBCL is important news for patients with these aggressive forms of non-Hodgkin lymphoma,” said Andrew Davies, professor of haematological oncology at the University of Southampton. “With its off-the-shelf availability, it provides additional options for patients experiencing rapid progression of disease and requiring urgent care,” he added. In July 2022, ADC Therapeutics granted Sobi rights to develop and commercialise Zynlonta for all haematologic and solid tumour indications outside of the US, greater China, Singapore and Japan. Under the terms of the agreement outlined at the time, ADC Therapeutics is eligible to receive up to $435m.

Longer-term data from pivotal studies of fixed-duration Columvi and Lunsumio continue to show durable responses in people with heavily pre-treated lymphomas1,2New data reinforce the potential of combination regimens in earlier treatment settings and add to the robust body of evidence supporting ongoing Phase III studies3,4,5,6 Basel, 11 December 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that new data from its CD20xCD3 T-cell engaging bispecific antibody programme, including eight oral presentations, were presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, 9-12 December 2023. Based on 32-month and 3-year follow-ups of two pivotal studies for fixed-duration treatments of Columvi® (glofitamab) and Lunsumio® (mosunetuzumab), respectively, data show that remissions were maintained in the majority of patients with heavily pre-treated lymphomas.1,2 Additionally, new early-phase data of novel Columvi or Lunsumio combination regimens support ongoing investigation in Phase III studies in earlier lines of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).3,4,5,6“Updated data from pivotal studies of Columvi and Lunsumio continue to provide compelling evidence for how fixed-duration therapies can deliver sustained, long-term benefit for people with difficult-to-treat lymphomas,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Our data at ASH also demonstrate progress in evaluating our bispecific antibodies in earlier stages of disease and additional types of lymphoma so more people can benefit from our therapies.”Longer follow-up data from pivotal studies of fixed-duration Columvi and Lunsumio show benefit is maintained beyond the end of treatmentExtended follow-up data from the pivotal Phase II NP30179 study of Columvi administered for up to 12 cycles (approximately eight months) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy showed favourable long-term outcomes. After a median follow-up of 32 months, 55% of patients with a complete response (CR) were in remission at 24 months. Most of these patients remained progression-free and alive 18 months after completing the fixed-duration treatment. In patients who had received prior chimeric antigen receptor (CAR) T-cell therapy, the median duration of CR was 22.0 months (95% confidence interval [CI]: 6.7–not reached). No new safety signals were observed since the previous analysis.1Data from a three-year follow-up analysis of the pivotal Phase II GO29781 study of Lunsumio in patients with R/R FL who have received at least two prior lines of therapy were presented. Results showed continued durable responses and a manageable safety profile after treatment (up to approximately 12 months), with 59% of patients completing treatment after eight cycles (approximately five months). 72.7% of the patients with a CR were alive and without disease progression, 30 months after their first response. In the overall population, median progression-free survival (PFS) was 24 months (95% CI: 12.0–not evaluable [NE]) and overall survival (OS) was not yet reached. No new safety signals were observed since the previous analysis.2Additional data presented reinforce the potential of novel combination regimens in earlier treatment settingsDiffuse large B-cell lymphomaData from the Phase Ib/II GO40516 study of Lunsumio plus Polivy® (polatuzumab vedotin) in patients with R/R LBCL were presented and simultaneously published in Nature Medicine.3,7 Results showed that at 24 months median follow-up, the median PFS was 11.4 months (95% CI: 6.2–18.7), and median OS was 23.3 months (95% CI: 14.8–NE), highlighting the combination’s potential in R/R LBCL. The overall safety profile of patients with R/R LBCL treated with Lunsumio plus Polivy was manageable. Cytokine release syndrome (CRS) events were generally low grade (Grade 1: 10.2%; Grade 2: 5.1%; Grade 3: 3.1%).3 Lunsumio in combination with Polivy is being evaluated as an outpatient therapy for patients with R/R DLBCL in the ongoing Phase III SUNMO study.Results from both arms of the Phase Ib NP40126 study evaluating Columvi in combination with MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), and Columvi in combination with Polivy plus MabThera/Rituxan, cyclophosphamide, doxorubicin and prednisone (Pola+R-CHP) in previously untreated DLBCL were presented. After a median of 12 months follow-up, data from the Columvi plus Pola+R-CHP arm showed that 91.7% of patients had a CR with no progression observed. Of the patients with a CR, 95.5% were still in remission, with a 12-month PFS rate of 91.5%. Safety profiles were highly consistent with earlier analyses from this study.4 These data support the ongoing Phase III SKYGLO study in previously untreated DLBCL.Follicular lymphomaThe Phase II MorningSun study, evaluating a subcutaneous (SC) formulation of Lunsumio in patients with selected B-cell non-Hodgkin lymphomas, showed that SC Lunsumio is active and has a manageable safety profile in patients with first-line (1L) low-tumour burden FL. Data showed that 83.3% of patients achieved a complete metabolic response (95% CI: 62.6-95.3) and responses were ongoing at data cut-off. CRS was generally low grade (Grade 1: 36.7%; Grade 2: 6.7%) and occurred in cycle one only.5 Subcutaneous Lunsumio is also being investigated in combination with oral lenalidomide in 1L FL in the Phase Ib/II CO41942 study. New data demonstrated promising efficacy and manageable safety; data showed that 89.2% of patients achieved a CR and CRS events were either Grade 1 (47.5%) or 2 (2.5%), all of which were confined to cycles one to two.6 The data support further investigation of this SC formulation of Lunsumio and highlight its potential as a tailored monotherapy or combination outpatient therapy for FL, including in community practices.5,6Totality of data presented underscores the strength of Roche's broad, industry-leading development programme, which aims to address the diverse needs, preferences and experiences of people with blood cancersBoth Columvi and Lunsumio are being investigated in Phase III studies that will expand the understanding of their impact in earlier lines of treatment. This includes the Phase III STARGLO study evaluating Columvi in combination with GemOx in patients with R/R DLBCL who are ineligible for autologous stem cell transplant; the Phase III SKYGLO study evaluating the efficacy and safety of Columvi plus Pola+R-CHP in previously untreated DLBCL; the Phase III GLOBRYTE study evaluating Columvi monotherapy in R/R mantle cell lymphoma; the Phase III SUNMO study investigating Lunsumio plus Polivy in R/R DLBCL; and the Phase III CELESTIMO study investigating Lunsumio plus lenalidomide in patients with R/R FL.About Columvi® (glofitamab)Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T-cells and CD20 on the surface of B-cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T-cells, a type of immune cell, and two regions that bind to CD20, a protein on B-cells, which can be healthy or malignant. This dual-targeting brings the T-cell in close proximity to the B-cell, activating the release of cancer cell-killing proteins from the T-cell. A clinical development programme for Columvi is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma and other blood cancers.About Lunsumio® (mosunetuzumab)Lunsumio is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T-cells and CD20 on the surface of B-cells. This dual-targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. A robust clinical development programme for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.About Polivy® (polatuzumab vedotin)Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed 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 those expressing 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.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), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3, Tecentriq® (atezolizumab), 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 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 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] Hutchings M, et al. Glofitamab Monotherapy in Relapsed or Refractory Large B-Cell Lymphoma: Extended Follow-Up from a Pivotal Phase II Study and Subgroup Analyses in Patients with Prior Chimeric Antigen Receptor T-Cell Therapy and by Baseline Total Metabolic Tumor Volume. Presented at: ASH Annual Meeting and Exposition; 2023 Dec 9-12. Abstract #433.[2] Schuster S, et al. Mosunetuzumab Monotherapy Continues to Demonstrate Durable Responses in Patients with Relapsed and/or Refractory Follicular Lymphoma after ≥2 Prior Therapies: 3-Year Follow-up from a Pivotal Phase II Study. Presented at: ASH Annual Meeting and Exposition; 2023 Dec 9-12. Abstract #603.[3] Budde E, et al. Mosunetuzumab Plus Polatuzumab Vedotin Demonstrates a Favorable Safety Profile and Efficacy in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Primary Analysis of a Phase Ib/II Study. Presented at: ASH Annual Meeting and Exposition; 2023 Dec 9-12. Abstract #613.[4] Topp M, et al. Glofitamab Plus R-CHOP Induces High Response Rates with a Manageable Safety Profile in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): A 12-Month Analysis from a Phase Ib Study. Presented at: ASH Annual Meeting and Exposition; 2023 Dec 9-12. Abstract #3085.[5] Flinn I, et al. Subcutaneous Mosunetuzumab Is Active and Has a Manageable Safety Profile in Patients with Previously Untreated, Low-Tumor Burden Follicular Lymphoma: Initial Results from the Phase II Morningsun Study. Presented at: ASH Annual Meeting and Exposition; 2023 Dec 9-12. Abstract #3029.[6] Morschhauser F, et al. Preliminary Findings of a Phase Ib/II Trial Indicate Manageable Safety and Promising Efficacy for Mosunetuzumab in Combination with Lenalidomide (M+Len) in Previously Untreated (1L) Follicular Lymphoma (FL). Presented at: ASH Annual Meeting and Exposition; 2023 Dec 9-12. Abstract #605.[7] Budde LE et al. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Nature Medicine. 2023. https://doi.org/10.1038/s41591-023-02726-5 Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 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 Dr. Rebekka SchnellPhone: +41 79 205 27 03 Sileia UrechPhone: +41 79 935 81 48 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 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 11122023_MR ASH 2023_Bispecifics_en