Saturday, Dec 7, 2019

Genentech Announces New Data on Novel CD20-CD3 Bispecific Cancer Immunotherapies in People With Difficult-to-Treat Lymphomas

Mosunetuzumab data to be presented at the American Society of Hematology 2019 Annual Meeting Plenary Scientific Session demonstrate durable complete responses in people with relapsed or refractory non-Hodgkin’s lymphoma

Preliminary safety and efficacy data for CD20-TCB support potential of combination approaches with anti-CD20 therapies

South San Francisco, CA -- December 7, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new data on two investigational CD20-CD3 T-cell engaging bispecific antibodies, mosunetuzumab and CD20-TCB, in people with relapsed or refractory (R/R) B-cell non-Hodgkin’s lymphoma (NHL). Results from the Phase I/Ib GO29781 study of mosunetuzumab, including data from people previously treated with chimeric antigen receptor (CAR) T-cell therapy, will be presented at the 61^st American Society of Hematology (ASH) 2019 Annual Meeting during the Plenary Scientific Session. The Plenary Scientific Session highlights the top six abstracts submitted to the meeting, as determined by the ASH Program Committee. Additionally, results from the Phase I/Ib NP30179 study evaluating CD20-TCB as a combination therapy with Gazyva^® (obinutuzumab) for people with R/R NHL, will be presented.

“Despite recent treatment advancements, slow-growing and aggressive non-Hodgkin’s lymphomas present increasingly difficult management challenges with each subsequent relapse,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We’re encouraged by these early results, which suggest that our novel bispecific cancer immunotherapies may help people with relapsed or treatment-refractory disease who need more options.”

The GO29781 study evaluated mosunetuzumab in patients with R/R NHL, including patients who have relapsed following, or are resistant to, CAR T-cell therapy – a patient population with limited treatment options. Results from this dose-escalation study showed encouraging efficacy with an objective response rate (ORR) of 62.7 percent (n=42/67) in slow-growing NHL and 37.1 percent (n=46/124) in aggressive NHL. Additionally, data demonstrated a complete response (CR) rate of 43.3 percent (n=29/67) in slow-growing NHL and 19.4 percent (n=24/124) in aggressive NHL. CRs showed durability, with 82.8 percent (n=24/29) of patients with slow-growing NHL remaining in remission up to 26 months off initial treatment and 70.8 percent (n=17/24) of patients with aggressive NHL, remaining in remission up to 16 months off initial treatment. Of the participants who received prior CAR T-cell therapy, the ORR was 38.9 percent (n=7/18), and 22.2 percent (n=4/18) achieved a CR. Adverse reactions included cytokine release syndrome (CRS) in 28.9 percent of patients with 20.0 percent at Grade 1 and 1.1 percent at Grade 3. Grade 3 neurological adverse events occurred in 3.7 percent of patients.

Results from the Phase I/Ib dose-escalation NP30179 study, evaluating CD20-TCB at doses ranging from 0.6 mg to 16 mg plus Gazyva in people with R/R B-cell NHL, showed an ORR of 54 percent (n=15/28) and a CR rate of 46 percent (n=13/28). This included an ORR and CR of 66.7 percent (n=4/6) in people with follicular lymphoma and an ORR of 50.0 percent (n=11/22) and a CR of 40.9 percent (n=9/22) in aggressive NHL. The most frequently observed adverse event across all treatment doses was CRS, occurring in 67.9 percent of patients (n=19/28), with the majority of events being low grade (Grade 1-2).

Both mosunetuzumab and CD20-TCB continue to be evaluated in a robust clinical development program, investigating the treatments as monotherapies and in combination with other therapies, in people with slow-growing and aggressive forms of NHL.

About Genentech’s Investigational Bispecifics
Genentech is currently developing two T-cell engaging bispecific antibodies, mosunetuzumab and CD20-TCB, 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 CD20-TCB differ in their structures, and both are being developed by Genentech as part of our ongoing strategy to explore multiple bispecific formats, to identify those that maximize potential clinical benefits for patients. The clinical development programs for mosunetuzumab and CD20-TCB 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’s lymphomas, including diffuse large B-cell lymphoma and follicular lymphoma.

About the GO29781 study
The GO29781 study [NCT02500407] is a Phase I/Ib, multicenter, open-label, dose-escalation study evaluating the safety and pharmacokinetics of mosunetuzumab in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Outcome measures include best objective response rate by revised International Working Group criteria, maximum tolerated dose, and tolerability.

About the NP30179 study
The NP30179 study [NCT03075696] is a Phase I/Ib, multicenter, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of CD20-TCB. In this study, CD20-TCB is assessed as a single agent and in combination with Gazyva, following pre-treatment with a one-time, fixed dose of Gazyva, in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose, and tolerability.

About Non-Hodgkin’s Lymphoma
There are two main types of lymphoma: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL). NHL has two subsets, aggressive and indolent (slow-growing).

NHL represents approximately 85 percent of all lymphomas diagnosed. According to the American Cancer Society, it is expected that nearly 74,000 people will be diagnosed with NHL in the United States in 2019, and nearly 20,000 will die from the disease.

Most cases of NHL start in B-lymphocytes, cells that are part of the body’s immune system and help to defend the body against infections. B-cell lymphoma develops when these cells become cancerous and begin to multiply and collect in the lymph nodes or lymphatic tissues such as the spleen.

Gazyva Indications

Gazyva^® (obinutuzumab) is a prescription medicine used:

• With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
• With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.
• With chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.

Important Safety Information
The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life threatening, including:

• Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.
• Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.

Who should not receive Gazyva:
Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past.

Additional possible serious side effects of Gazyva:
Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:

• Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort.
• Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva.
• Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.
• Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP.
• Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections.
• Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced.

The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81 percent), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within 6 months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness, and urinary tract infection.

A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86 percent) or marginal zone lymphoma (14 percent).The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

• Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.
• Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, plan to become pregnant, or are breastfeeding. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding.

Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please visit http://www.Gazyva.com for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Genentech in Hematology
For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology.

About Genentech
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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