Roche presents pivotal data at ASH 2021 for novel cancer immunotherapy mosunetuzumab

• Results to be presented for the first time show mosunetuzumab induces high and durable complete response rates in people with follicular lymphoma who have received two or more prior therapies¹
• New efficacy data from Roche’s portfolio of cancer immunotherapies demonstrate potential of bispecific antibodies to expand upon current treatment options across several blood cancers

Basel, 11 December 2021 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that new pivotal data on its CD20xCD3 T-cell engaging bispecific antibody, mosunetuzumab, will be presented for the first time at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition from 11-14 December 2021.

Emerging data continue to show the promising benefit-risk profile of mosunetuzumab in relapsed or refractory (R/R) follicular lymphoma (FL), a slow-growing, or indolent, form of non-Hodgkin lymphoma (NHL). Pivotal results from the phase I/II GO29781 study demonstrated that mosunetuzumab induces durable complete responses lasting at least 18 months in heavily pretreated patients with R/R FL who have received two or more prior therapies, with a 60.0% complete response (CR) rate and a median progression-free survival of 17.9 months (95% CI: 10.1-not evaluable). Median duration of response was 22.8 months among responders (95% CI: 9.7-not evaluable). The most common adverse event (AE) was cytokine release syndrome (CRS), which was generally low grade (mainly Grade 1-2).¹

“Despite initial successful treatment, many people with follicular lymphoma often experience relapse. Mosunetuzumab could potentially become a highly efficacious treatment option that can be administered without the need for cell collection or genetic engineering,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “With mosunetuzumab, we also aim to offer a therapy that can be administered in the outpatient setting to people with this devastating blood cancer.”

Roche recently submitted the initial marketing authorisation application for mosunetuzumab to the European Medicines Agency, with the hope to bring this drug as soon as possible to people with NHL. Genentech plans to submit the new data to the U.S. Food and Drug Administration in the near future for approval consideration. If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in NHL.

Additionally, as part of Roche’s broad pipeline of haematology immunotherapies and application of novel combinations, key data for the bispecific antibodies mosunetuzumab, glofitamab and cevostamab are being presented, including:

• Initial results from the phase Ib CO41942 study of mosunetuzumab in combination with lenalidomide in people with R/R FL who have received at least one prior line of therapy demonstrated encouraging preliminary efficacy and a tolerable safety profile.²
• Data from the phase Ib/II GO40516 study evaluating mosunetuzumab in combination with Polivy® (polatuzumab vedotin) showed promising efficacy and favourable safety in heavily pretreated patients with aggressive R/R NHL with an objective response rate (ORR) of 65.0% and a CR rate of 48.3%. CRS occurred in 18% of patients, and all events occurred in Cycle 1 and were Grade 1-2.³
• A phase I/Ib NP30179 dose-escalation study evaluating glofitamab as a monotherapy and in combination with Gazyva®/Gazyvaro® (obinutuzumab) following pretreatment with Gazyva/Gazyvaro in patients with R/R B-cell NHL showed promising activity in both R/R FL and R/R mantle cell lymphoma (MCL), an uncommon but aggressive form of lymphoma with poor prognosis for those who progress.⁴
  • Preliminary results in heavily pretreated patients with R/R FL showed high response rates across all treatment groups, including high-risk subgroups, with an ORR of 81.0% for the glofitamab monotherapy group and an ORR of 100% for the glofitamab plus Gazyva/Gazyvaro combination therapy group.⁵ For patients with R/R MCL, treated with glofitamab monotherapy following Gazyva/Gazyvaro pretreatment, the ORR was 81.0%.⁶ Across both studies, the most common AE was CRS, with the majority of events being low grade (Grade 1-2).^5,6
• Results of the phase Ib/II NP39488 study of glofitamab in combination with Polivy demonstrated encouraging preliminary efficacy and a tolerable safety profile in people with difficult-to-treat R/R diffuse large B-cell lymphoma. With a median follow up of 3.2 months (95% CI: 1.4-3.5), an ORR of 73.0% was observed with a 51.5% CR rate, with patients showing durable responses at ≥6 months. No Grade 3 or higher CRS events were observed, and the safety profile of the combination was consistent with that of the individual medicines.⁷
• Data from the phase I GO39775 dose-escalation and expansion study investigating cevostamab in heavily pretreated patients with R/R multiple myeloma (MM) showed the first-of-its kind FcRH5xCD3 bispecific antibody induced clinically meaningful, target dose-dependent increases in ORR without an increase in the rate of CRS, with an ORR of 54.5% in the 160 mg dose group. Results from double step-up dosing suggest this approach could help mitigate CRS and potentially improve the safety profile compared to single step-up dosing.⁸

Our investigational cancer immunotherapies, mosunetuzumab and glofitamab, are T-cell engaging bispecific antibodies designed to engage with CD3 on the T cell and CD20 on the tumour cell, bringing them close in proximity and enabling the T cell to eliminate the tumour cell. Although these bispecific antibodies have similar modes of action, they differ in their structure and clinical profiles. Cevostamab, another investigational T-cell engaging bispecific antibody, is designed to target FcRH5 on myeloma cells and CD3 on T cells and is currently being evaluated in people living with R/R MM.

Roche’s broad and comprehensive clinical development programme will continue to evaluate mosunetuzumab, glofitamab and cevostamab as monotherapies and in combination with other established and/or novel therapies for malignant haematological conditions with the goal of providing treatment solutions tailored to the patient journey for each disease.

Keep up to date with ASH 2021 news and updates by using the hashtag #ASH21 and follow Roche on Twitter via @Roche and on LinkedIn.

About Roche’s investigational CD20xCD3 bispecifics in haematology
Roche is currently developing two T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, designed to target CD20 on the surface of B cells and CD3 on the surface of T 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. Mosunetuzumab and glofitamab differ in their structures, and both are being developed by Roche as part of our ongoing strategy to explore multiple bispecific formats in order to identify those that maximise potential clinical benefits for patients. Mosunetuzumab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. Glofitamab is based on a novel structural format that we call ‘2:1,’ which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions that bind to CD20 and one ‘Fab’ region that binds to CD3. The clinical development programmes for mosunetuzumab and glofitamab include ongoing investigations of these molecules as monotherapies and in combination with other medicines for the treatment of people with CD20-positive B cell (non-Hodgkin lymphomas), including diffuse large B-cell lymphoma and follicular lymphoma .

About cevostamab (FcRH5xCD3 bispecific antibody)
Cevostamab (BFCR4350A) is an FcRH5xCD3 T-cell engaging bispecific antibody designed to target FcRH5 on myeloma cells and CD3 on T cells. FcRH5 is a unique and differentiated target, expressed on nearly all myeloma cells. Cevostamab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets FcRH5 and the other ‘Fab’ region targets CD3. This dual targeting activates and re-directs a patient’s existing T cells to engage and eliminate target FcRH5-expressing myeloma cells by releasing cytotoxic proteins into the myeloma cells.

About the GO29781 study
The GO29781 study [NCT02500407] is a phase I/II, multicentre, open-label, dose-escalation study evaluating the safety and pharmacokinetics of mosunetuzumab in people with relapsed or refractory B-cell non-Hodgkin lymphoma. Outcome measures include complete response rate (best response) by independent review facility (primary endpoint), objective response rate, duration of response, progression-free survival, safety and tolerability (secondary endpoints).

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 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, and Hemlibra® (emicizumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, 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
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics, as well as growing capabilities in the area of data-driven medical insights help Roche deliver truly personalised healthcare. Roche is working with partners across the healthcare sector to provide the best care for each person.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. In recent years, the company has invested in genomic profiling and real-world data partnerships and has become an industry-leading partner for medical insights.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than
thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the thirteenth consecutive year, Roche has been recognised as one of the most sustainable companies in the pharmaceutical industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. 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.

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References
[1] Budde LE, et al. Mosunetuzumab Monotherapy is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/ Refractory (R/R) Follicular Lymphoma (FL) who have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study. Presented at: ASH Annual Meeting and Exposition; 2021 Dec 11-14. Abstract #127.
[2] Morschhauser F, et al. Mosunetuzumab in Combination With Lenalidomide has a Manageable Safety Profile and Encouraging Activity in Patients With Relapsed/Refractory Follicular Lymphoma: Initial Results From a Phase Ib Study. Presented at: ASH Annual Meeting and Exposition; 2021 Dec 11-14. Abstract #129.
[3] Budde LE, et al. Mosunetuzumab Plus Polatuzumab Vedotin has Promising Efficacy and a Favorable Safety Profile in Patients with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma: Updated Results from a Phase Ib/II Study. Presented at: ASH Annual Meeting and Exposition; 2021 Dec 11-14. Abstract #533.
[4] Medscape. Mantle Cell Lymphoma. [Internet; cited 2021 December]. Available from: https://emedicine.medscape.com/article/203085-overview
[5] Morschhauser F, et al. Glofitamab as Monotherapy and in Combination with Obinutuzumab Induces High Complete Response Rates in Patients (pts) with Multiple Relapsed or Refractory (R/R) Follicular Lymphoma (FL). Presented at: ASH Annual Meeting and Exposition; 2021 Dec 11-14. Abstract #128.
[6] Phillips T, et al. Glofitamab Step-Up Dosing Induces High Response Rates in Patients (pts) With Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL), most of whom had failed prior Bruton’s tyrosine kinase inhibitor (BTKi) therapy. Presented at: ASH Annual Meeting and Exposition; 2021 Dec 11-14. Abstract #130.
[7] Hutchings M, at al. Glofitamab (Glofit) in Combination with Polatuzumab Vedotin (Pola): Phase Ib/II Preliminary Data Support Manageable Safety and Encouraging Efficacy in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). Presented at: ASH Annual Meeting and Exposition; 2021 Dec 11-14. Abstract #525.
[8] Trudel S, et al. Cevostamab monotherapy continues to show clinically meaningful activity and manageable safety in patients with heavily pre-treated relapsed/refractory multiple myeloma (RRMM): updated results from an ongoing Phase I study. Presented at: ASH Annual Meeting and Exposition; 2021 Dec 11-14. Abstract #157.

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