MEI Pharma and Kyowa Kirin Report Clinical Data on Zandelisib at European Hematology Association 2022 Hybrid Congress

On June 10, 2022 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions utilizing the latest biotechnology, reported that data from the zandelisib clinical development program, including the Phase 2 TIDAL study evaluating the intermittent dosing of zandelisib, an orally administered investigational phosphatidylinositol 3-kinase delta ("PI3Kδ") inhibitor in clinical development for the treatment of B-cell malignancies, is highlighted in a poster and an oral discussion session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress (Press release, Kyowa Hakko Kirin, JUN 10, 2022, View Source [SID1234615870]).

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"While many patients with indolent non-Hodgkin’s lymphomas, such as follicular lymphoma, achieve durable responses with current standard of care therapies, patients generally continue to need multiple treatments throughout the course of their disease due to relapse, necessitating the development of novel treatment options," stated Professor Wojciech Jurczak, M.D., Ph.D. Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology in Kraków, Poland, presenter of the Phase 2 TIDAL study oral presentation and the Phase 3 COASTAL study principal investigator. "I believe the data presented at EHA (Free EHA Whitepaper) this year are very exciting and supportive of the zandelisib development program, particularly as we continue to enroll the Phase 3 COASTAL study evaluating zandelisib in combination with rituximab."

Clinical Data from the Phase 2 TIDAL Study Evaluating Zandelisib in Patients with Relapsed or Refractory Follicular Lymphoma

Study Details The ongoing TIDAL study (NCT03768505) is a global, open-label Phase 2 trial evaluating zandelisib as a single agent in two disease cohorts: one in relapsed or refractory (r/r) follicular lymphoma (FL) and one for r/r marginal zone lymphoma (MZL), in both cases after failure of at least two prior systemic therapies, including chemotherapy and an anti-CD20 antibody. Patients were administered zandelisib once daily for two 28-day cycles as response induction regimen, followed thereafter by once daily dosing for the first seven days of each subsequent 28-day cycle, an intermittent dosing (ID) regimen. The ID regimen was introduced to potentially allow Treg repopulation and to mitigate immune-mediated adverse events of special interest (AESI) without loss of disease control.

Enrollment in the FL cohort is complete; enrollment in the MZL cohort is ongoing. The FL cohort enrolled a total of 121 patients, with the first 91 consisting of the primary efficacy population (PEP) for the evaluation of overall response rate (ORR) and duration of response (DOR).

The median age of patients enrolled with FL was 64 years old. Enrolled patients were generally heavily pretreated; the median number of prior therapies was 3 (range 2-8) and 96% of patients had received prior chemoimmunotherapy. Further, 28 patients (23%) received prior stem cell transplant, 50 patients (41%) were refractory to last therapy, 41 patients (34%) had tumors ≥5 cm, and 68 patients (56%) were POD24 (progression of disease within 24 months of prior chemoimmunotherapy).

The primary efficacy endpoint is ORR as assessed by independent review committee (IRC) using a modified Lugano criteria. The data cutoff date is September 30, 2021, approximately 6 months after the last patient in the primary efficacy population (PEP) received their first dose of zandelisib. Data from the enrolling MZL cohort is not reported.

Efficacy The primary endpoint of ORR of zandelisib as a single agent in the PEP was 70.3% (N=64) as assessed by IRC; the complete response rate was 35.2% (N=32). Responses across sub-groups at high risk were all >63%:
• Refractory to last treatment: 64.3%
• >2 prior therapies: 63.3%
• POD24 (progression of disease within 24 months): 66.7% The ORR represents the primary endpoint of the TIDAL study. Responses were first observed in the first two cycles of therapy in 87.5% of all response (N=56), and 75% of all CRs (N=24) were observed in the first four cycles.

The disease control rate (CR+PR+SD) was 85%. As of the data cutoff date, the data are not sufficiently mature to accurately estimate the final DOR in the PEP. An additional data cut is planned for approximately 14 months after the last patient in the PEP is enrolled to evaluate DOR and provide more mature safety results. Best Change in SPD from Baseline* *7 patients not included because they did not have post-baseline imaging scans. (CR, complete response; MCR, metabolic complete response; SPD, sum of the product of the longest perpendicular diameters).

Safety and Tolerability With a median follow-up of 9.4 months (range 0.8-24) in the safety population of 121 pts, 9.9% (N=12) of patients had discontinued zandelisib due to any drug-related adverse event. Adverse events occurring in ≥ 10% of 121 patients regardless of relationship to zandelisib were: diarrhea, neutropenia, nausea, fatigue, abdominal pain, pyrexia, decreased appetite, constipation, rash and anemia.

Most Common Adverse Events Regardless of Relationship to Study Drug Grade 3 (AESI were diarrhea in 5% (N=6), colitis in 1.7% (N=2), cutaneous rash in 3.3% (N=4), stomatitis in 2.5% (N=3), and 0.8% (N=1) each for AST and ALT elevation, and non-infectious pneumonitis Primarily, Grade 3 AESIs to Date Occurred in Cycles 1-3. No Grade 4 or Grade 5 AESI were recorded. Cumulative Incidence of Time to First Occurrence of Grade 3 AESI Treatment-emergent COVID-19 infections (any grade) were reported in 8.3% (N=10) of patients, and 8.3% (N=10) of patients reported Grade 3 infections. Four COVID infections were fatal, as were 1 case each of pneumonia and tumor lysis syndrome.

Updated Clinical Data from the Phase 1B Study Evaluating Zandelisib in Patients with Relapsed or Refractory Follicular Lymphoma Poster Title: Zandelisib on Intermittent Dosing as a Single Agent or in Combination with Rituximab or Zanubrutinib in Relapsed or Refractory (r/r) Follicular Lymphoma (FL): Results from a Multi-Arm Phase 1b Study Session Title: Indolent & mantle cell non-Hodgkin lymphoma – Clinical Time: June 10, 2:30pm-3:45pm CEST Presenter: Jacob Drobnyk Soumerai, MD Abstract Code: P1114 Study Details The ongoing Phase 1B trial (NCT02914938) is an open-label, multi-arm, study evaluating zandelisib alone, in combination with rituximab or with zanubrutinib in about 160 patients with R/R chronic lymphocytic leukemia (CLL) or small Lymphocytic Lymphoma (SLL) or B-cell lymphoma. The presentation reports on the 69 patients enrolled with relapsed or refractory (r/r) follicular lymphoma (FL) across three groups: ‒ Group 1: Zandelisib single agent 60 mg once daily for two 28-day cycles then on the intermittent dosing (ID) schedule of 60 mg once daily on days 1-7 in cycles ≥3 ‒ Group 2: Zandelisib (same schedule as Group 1) in combination with rituximab 375 mg/m2 weekly x 4 in cycle 1 and on Day 1 of cycles 3-6 ‒ Group 3: Zandelisib 60 mg on ID from cycle 1 and zanubrutinib 80 mg twice daily Zandelisib administration was continued until disease progression or intolerance. Patients received a median of 2 prior therapies and 65% were POD24.

Safety and Tolerability With a median duration of drug exposure of 17.1 months in Group 1, 20.5 months in Group 2, and 7.1 months in Group 3, six patients (8.7%) discontinued therapy due to treatment related adverse events. Grade 3 AESI, ranging from 0% to 11% across all groups, were: diarrhea/colitis, AST/ALT increase, rash, infection and atrial fibrillation (with zanubrutinib only). No grade 4-5 adverse events of special interest were reported. One patient in Group 3 had reversible grade 4 drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Grade 3-4 neutropenia was observed in 11 pts (16%). Grade 3 AESIs by Treatment Group Excluding COVID-19, 7 patients (10.1%) had a grade 3 infection (2 had appendicitis, and 1 each had infectious diarrhea, CMV colitis, pneumonia, soft tissue infection, and tooth infection). COVID-19 was reported in 4 patients, fatal in 2: one with zandelisib alone and 1 with zandelisibrituximab. No other Grade 5 events were reported. Efficacy The overall response rate in the 65 evaluable patients was 84.6% (55/65) and the complete response rate was 24.6% (16/65). The overall response rate was 77.8% (14/18) in Group 1, 94.7% (18/19) in Group 2, and 82.1% (23/28) in Group 3. Response Rates The median duration of response in the heterogeneous patient groups with small patient populations was: 31.1 months in Group 1, 25.8 months in Group 2, and not yet mature in Group 3. The median drug exposure of 17.1, 20.5, and 7.1 months, respectively. Data cutoff: 10 Jan 2022.

Kaplan-Meier Estimate of Duration of Response "The data reported at the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) demonstrate the potential of zandelisib, an investigation clinical candidate employing a unique intermittent dosing schedule, to provide a high response rate in a well-tolerated manner either as a single-agent or in combination with other therapies," said Richard Ghalie, M.D., chief medical officer of MEI Pharma. "We remain encouraged by zandelisib’s potential as we continue its development using the intermittent schedule as an oral, chemotherapy-free, time-limited, therapeutic option to meet the needs of patients." "The data presented at the EHA (Free EHA Whitepaper) congress support zandelisib’s potential value as a single agent or combination therapy," said Yoshifumi Torii, Ph.D., Executive Officer, Vice President, Head of R&D Division of Kyowa Kirin. "We continue to work with MEI Pharma to conduct global clinical trials with the goal of providing innovative treatment options for patients with B-cell malignancies." About Zandelisib Zandelisib, a selective PI3Kδ inhibitor, is an investigational cancer treatment being developed as an oral, once-daily, potential therapeutic option for patients with B-cell malignancies. Clinical trials are investigating the efficacy and safety of zandelisib as a single agent and in combination with other modalities while administered on an Intermittent Dosing Regimen (ID) and in a timelimited manner when dosed in combination.

The ID leverages molecular and biologic properties specific to zandelisib. In November 2021, MEI Pharma and Kyowa Kirin announced data from ongoing Phase 2 TIDAL study (NCT03768505) evaluating zandelisib as a single agent for follicular lymphoma (FL) patients who received at least two prior systemic therapies. Zandelisib demonstrated a 70.3% objective response rate (ORR) as determined by an Independent Review Committee (IRC) assessment in the primary efficacy population (n=91). In addition, 35.2% of patients achieved a complete response. At the time of the data cutoff, the data were insufficiently mature to accurately estimate duration of response (DOR). In line with previously reported data from the Phase 1B study, zandelisib was generally well tolerated. With 9.4 months (range: 0.8-24) median duration of follow-up in the total study population (n=121), interim data demonstrated a discontinuation rate due to any drug related adverse event of 9.9%. Patients enrolled in the study will continue to be followed for safety and DOR. Ongoing zandelisib studies include the cohort in TIDAL evaluating patients with r/r marginal zone lymphoma (MZL) and continuing evaluation of the cohort of patients in the study with r/r FL.

Also ongoing is the Phase 3 COASTAL study (NCT04745832), comparing zandelisib plus rituximab to standard of care chemotherapy plus rituximab in patients with r/r FL or MZL who received more than one prior line of therapy, which must have included an anti-CD20 antibody in combination with chemotherapy or lenalidomide. COASTAL, which is also evaluating timelimited intermittent administration of zandelisib, is intended to support marketing applications in the U.S. and globally. Other ongoing studies include a Phase 2 pivotal study in Japan (NCT04533581) in patients with indolent B-cell non-Hodgkin’s lymphoma (iB-NHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) conducted by Kyowa Kirin. In March 2020, the FDA granted zandelisib Fast Track designation for the treatment of adult patients with r/r follicular lymphoma who have received at least two prior systemic therapies. In November 2021, the FDA granted zandelisib Orphan Drug designation for the treatment of patients with follicular lymphoma.

In April 2020, MEI and Kyowa Kirin entered a global license, development, and commercialization agreement to further develop and commercialize zandelisib. MEI and Kyowa Kirin will co-develop and co-promote zandelisib in the U.S., with MEI booking all revenue from the U.S. sales. Kyowa Kirin has exclusive commercialization rights outside of the U.S. About Follicular Lymphoma Follicular lymphoma (FL) is the most common indolent lymphoma, comprising about 20-30% of all non-Hodgkin lymphomas (NHL). The disease also forms on B cells, is chronic in most cases and tends to progress slowly. Most people diagnosed with FL are over 65 years of age. � Sometimes follicular lymphomas can transform into a more aggressive form of large B-cell lymphoma, a fast-growing (aggressive) type of NHL.

Genentech Announces Positive Data from Broad Blood Cancer Portfolio at European Hematology Association Annual Meeting

On June 10, 2022 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that it is presenting new long-term follow-up results and subanalyses from clinical trials of its approved therapies, as well as data on investigational medicines from its broad blood cancer portfolio, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Congress in Vienna (Press release, Genentech, JUN 10, 2022, View Source [SID1234615887]). Data include five-year results from the Phase III CLL14 study of fixed-duration Venclexta (venetoclax) plus Gazyva (obinutuzumab) in previously untreated chronic lymphocytic leukemia (CLL); the final analysis of the Phase III GALLIUM study of Gazyva plus chemotherapy in people with previously untreated advanced-stage follicular lymphoma (FL); and subanalyses from the Phase III POLARIX study of Polivy (polatuzumab vedotin) in combination with Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Genentech will also present data from its investigational T-cell engaging bispecific antibody development programs including mosunetuzumab and glofitamab in patients receiving later lines of therapy for non-Hodgkin’s lymphoma (NHL) and cevostamab and RG6234 in relapsed or refractory (R/R) multiple myeloma (MM).

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"With these new long-term data and other studies of fixed-duration therapies in our portfolio, we are working to lessen the treatment burdens associated with long-term cancer care."

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"Blood cancers remain challenging to treat at all stages, but by improving frontline treatment options we aim to increase the likelihood of meaningful clinical outcomes for these patients," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "With these new long-term data and other studies of fixed-duration therapies in our portfolio, we are working to lessen the treatment burdens associated with long-term cancer care."

Improving Clinical Outcomes with Effective Frontline Treatment Options

Five-Year Results of Phase III CLL14 Study of Venclexta Plus Gazyva

After a median of 65.4 months following treatment with Venclexta plus Gazyva, results confirm the combination continues to be an effective fixed-duration and chemotherapy-free option for patients with previously untreated CLL and coexisting conditions. The estimated investigator-assessed progression-free survival (PFS) rate at this follow-up was 62.6% with Venclexta plus Gazyva and 27.0% with Gazyva plus chlorambucil, and the estimated overall survival (OS) rate was 81.9% versus 77.0% (HR 0.72; 95% CI: 0.48-1.09; p=0.12). In addition, the analysis found that 72.1% of patients in the Venclexta plus Gazyva arm did not require another treatment for CLL in the five years following initial treatment (HR 0.42; 95% CI: 0.31-0.57; p<0.0001). No new safety signals were observed. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.

Final Analysis of Phase III GALLIUM Study of Gazyva

After eight years of follow-up in people with previously untreated FL, a meaningful improvement in PFS was maintained with Gazyva plus chemotherapy, confirming its role as a standard of care for first-line treatment. Seven-year investigator-assessed PFS was significantly improved with Gazyva plus chemotherapy (63.4%) compared with Rituxan plus chemotherapy (55.7%; HR 0.77; 95% CI: 0.64-0.93; p=0.006). This translated into a longer time to next anti-lymphoma treatment. At seven years, 74.1% of patients receiving Gazyva plus chemotherapy had not started new anti-lymphoma therapy compared to 65.4% receiving Rituxan plus chemotherapy (HR 0.71; 95% CI: 0.58-0.87; p=0.001). The incidence of serious adverse events was 48.9% with Gazyva plus chemotherapy and 43.4% with Rituxan plus chemotherapy.

Subgroup Analyses of Pivotal Phase III POLARIX Study

Exploratory subgroup analyses of the Phase III POLARIX study of Polivy with R-CHP compared to the current standard of care, Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated DLBCL further support the potential for Polivy to transform the standard of care for people with this aggressive type of lymphoma. One of the datasets being presented is an analysis of study participants from Asia (China, Hong Kong, Japan, South Korea and Taiwan). Among this subgroup, results showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP, reducing the risk of disease progression, relapse or death by 36% (HR 0.64; 95% CI: 0.40-1.03). The safety profile was generally comparable for both regimens.

Based on the positive POLARIX results from the overall study population, the European Commission (EC) approved Polivy plus R-CHP in May 2022 for the treatment of adult patients with previously untreated DLBCL.

Providing Novel Bispecific Antibodies for Patients Receiving Later Lines of Therapy in Lymphoma and Beyond

Pivotal Data from Phase II NP30179 Expansion Study of Glofitamab

The pivotal Phase II NP30179 expansion study included patients with heavily pre-treated and highly refractory DLBCL and showed fixed-duration glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, induced high and durable complete response (CR) rates. After a median follow-up of 12.6 months, 39.4% of patients (n=61/155) achieved a CR (primary efficacy endpoint) and half of them (51.6%; n=80/155) achieved an overall response (the percentage of patients with a partial or CR; secondary efficacy endpoint), as assessed by an independent review committee. Cytokine release syndrome (CRS) was the most common adverse event, occurring in 63.0% of patients. These data were recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting and have been submitted for approval to the European Medicines Agency (EMA). Submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration (FDA), are planned this year.

Subgroup Analysis and Mosunetuzumab Retreatment from Pivotal Phase II GO29781 study

An exploratory subgroup analysis showed mosunetuzumab could be an efficacious and tolerable option in patients aged <65 and ≥65 years who had R/R FL and had received two or more prior therapies. Patients ≥65 years old achieved a higher objective response rate (ORR) than those <65 years old (87.0% vs 77.0%, respectively). Lower rates of CRS and serious adverse events were observed in patients ≥65 years old (37%) compared to those <65 years old (52%). Additional data from the GO29781 study showed that retreatment with mosunetuzumab in patients who achieved a CR but whose disease subsequently progressed was effective and the safety of retreatment was consistent with initial treatment.

The EC recently approved mosunetuzumab for the treatment of people with R/R FL who have received at least two prior systemic therapies. The U.S. FDA granted mosunetuzumab Breakthrough Therapy Designation and Orphan Drug Designation for this same patient group.

The data being presented at EHA (Free EHA Whitepaper), as well as Phase III studies currently underway, will expand the understanding of glofitamab and mosunetuzmab and their impact in both later and earlier lines of treatment, with the aim of providing robust and durable treatment outcomes for people with different types of lymphomas.

Early Data from Novel Investigational Bispecific Antibodies in R/R MM

In line with Genentech’s commitment to improving outcomes and personalizing care for people with blood cancer, the company has expanded beyond lymphoma and leukemia, evaluating two investigational medicines in MM. This is the third most common type of blood cancer, diagnosed in more than 170,000 people around the world each year and involves plasma cells (antibody-producing cells in the bone marrow). Although advances in treatment have improved outcomes, MM remains an incurable disease characterized by multiple relapses, with an overall five-year survival rate of about 55%. Genentech is presenting data at EHA (Free EHA Whitepaper) on cevostamab, an investigational FcRH5xCD3 T-cell engaging bispecific antibody that is being evaluated as a monotherapy and in combination with other medicines to treat people with R/R MM, and on RG6234, a novel GPRC5DxCD3 T-cell engaging bispecific antibody that is being studied in a Phase I trial in people with R/R MM. While early, the clinical activity and safety profiles observed with these molecules look encouraging and support further exploration.

About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to help restore the process of apoptosis.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood cancers.

Venclexta Indications

Venclexta is a prescription medicine used:

to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
‒ are 75 years of age or older, or
‒ have other medical conditions that prevent the use of standard chemotherapy.
It is not known if Venclexta is safe and effective in children.

Important Safety Information

What is the most important information patients should know about Venclexta?

Venclexta can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids into their vein.

The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS.

Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose on the day of the first dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects. When restarting Venclexta after stopping for 1 week or longer, the patient’s doctor may again check for the risk of TLS and change the patient’s dose.

What patients should not take Venclexta?

Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased TLS.

Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other causing serious side effects.
Patients must not start new medicines during treatment with Venclexta without first talking with their doctor.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:

Have kidney or liver problems.
Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
Have a history of high uric acid levels in the blood or gout.
Are scheduled to receive a vaccine. Patients should not receive a "live vaccine" before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients are instructed to not breastfeed during treatment with Venclexta and for 1 week after the last dose.
What to avoid while taking Venclexta:

Patients should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood.

What are the possible side effects of Venclexta?

Venclexta can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta and may pause dosing.
Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection during treatment with Venclexta.
Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.

The most common side effects of Venclexta when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell count; low platelet count; low red blood cell count; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of arms, legs, hands, and feet.

The most common side effects of Venclexta in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.

Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.

These are not all the possible side effects of Venclexta. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

Please see the Venclexta full Prescribing Information, including the Medication Guide, for additional Important Safety Information.

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found only on certain types of B-cells. It is thought to work by attacking targeted cells both directly and together with the body’s immune system. Gazyva is part of a collaboration between Genentech and Biogen. Combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

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%), 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 six 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%) or marginal zone lymphoma (14%). 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 View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Polivy (polatuzumab vedotin-piiq)

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’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication

Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information

Possible serious side effects

Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often

The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the full Prescribing Information 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 View Source

Caribou Biosciences Reports Positive Additional Data from CB-010 Allogeneic CAR-T Cell Therapy Phase 1 ANTLER Trial at the European Hematology Association (EHA) 2022 Hybrid Congress

On June 10, 2022 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported the presentation of additional initial clinical data from its ANTLER Phase 1 trial for CB-010 in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) (Press release, Caribou Biosciences, JUN 10, 2022, View Source [SID1234615862]). Following a single dose at the initial dose level of CB-010, a 100% complete response (CR) rate (6 of 6 patients) was observed as best response. At 6 months following the single dose of CB-010, 40% of patients remained in CR (2 of 5 patients) as of the May 13, 2022 data cutoff date. The data are being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress, being held in Vienna, Austria, June 9-17, 2022.

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"The preliminary safety and efficacy results are promising. All six patients treated with CB-010 at the initial dose level of 40 million CAR-T cells achieved a complete response, and we are now enrolling dose level 2 and look forward to seeing this study mature," said Loretta J. Nastoupil, M.D., associate professor, Department of Lymphoma/Myeloma in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center and the presenting investigator on the ANTLER trial. "CB-010 was generally well-tolerated and the adverse events observed are consistent with autologous or allogeneic CAR-T cell therapies."

Additional data, which was received after the cutoff date of May 13, 2022 and was not included in the EHA (Free EHA Whitepaper) poster, showed the first patient treated in the ANTLER trial remained in CR at their 12-month evaluation.

"We believe the 100% complete response achieved in the ANTLER CB-010 trial is unparalleled for a single, starting dose of cell therapy and represents an important step toward showing the potential of our chRDNA genome-editing platform and pipeline of allogeneic cell therapies," said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. "As the first allogeneic anti-CD19 CAR-T cell therapy in the clinic with a PD-1 knockout, CB-010 is designed to have sustained antitumor activity by limiting premature CAR-T cell exhaustion in patients with r/r B-NHL. As we enroll patients in cohort 2 at dose level 2 of the ANTLER trial, we are grateful for the patients, caregivers, and investigators who have participated in this clinical trial. We continue to advance CB-010, as our goal is to develop an allogeneic cell therapy that may meaningfully rival autologous cell therapies and extend the potential reach of off-the-shelf treatments for patients."

This image is also available at: Patient response rates following treatment with CB-010, single dose at dose level 1, in the ANTLER Phase 1 trial

The EHA (Free EHA Whitepaper) poster presentation includes safety, tolerability, and initial antitumor activity data for CB-010 administered at dose level 1 (40×106 CAR-T cells) to 6 patients with r/r B-NHL who had relapsed after previous treatment with a median of 3 prior therapies (range 2-8).

Following treatment with CB-010, there were no cases of graft versus host disease in the six patients. Grade 3 or 4 treatment emergent adverse events (TEAEs) developed in 5 of 6 patients, see details in accompanying table. Two patients experienced Grade 1 CRS (33%) and one patient experienced Grade 3 ICANS (17%), which was characterized as a dose limiting toxicity (DLT), for which the patient received tocilizumab and steroids and recovered within 39 hours. This patient went on to achieve a CR.

Image of table available at: Treatment emergent adverse events in the ANTLER Phase 1 trial

Based on promising initial safety and efficacy data from cohort 1 at dose level 1 (40×106 CAR-T cells), the ANTLER trial is now enrolling patients in cohort 2 at dose level 2 (80×106 CAR-T cells). Additional data are expected by year end.

Details of the poster presentation at EHA (Free EHA Whitepaper) are as follows:

Title: First-in-human trial of CB-010, a CRISPR-edited allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knock out, in patients with relapsed or refractory B cell non-Hodgkin lymphoma (ANTLER study)

Abstract: 3103

Presenter: Loretta J. Nastoupil, M.D., section chief, new drug development; associate professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center

Date and Time: Friday, June 10, 2022, 16:30 – 17:45 CEST (10:30 – 11:45 am ET)

Session Title: Gene therapy, cellular immunotherapy and vaccination – Clinical

Location: Messe Wien Exhibition & Congress Center, Vienna, Austria

The poster is available on the Presentations page of the Investors section of Caribou’s website.

Caribou will host a webcast conference call today to discuss the data presented at EHA (Free EHA Whitepaper) on the initial ANTLER data for CB-010.

The live webcast and conference call at 8:00 am ET, with an accompanying presentation, will be accessible under Events in the Investors section of the company’s website. To participate in the conference call, dial 1-844-862-9351 (domestic) or 1-929-517-0932 (international) and reference conference ID #4657536. The archived audio webcast will be available on Caribou’s website following the call and will be available for 30 days.

About CB-010

CB-010 is the lead product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) in the ongoing ANTLER Phase 1 trial. CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology to insert a CD19-specific CAR into the TRAC gene and knock out PD-1 to boost the persistence of antitumor activity. CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knock out. Additional information on the ANTLER trial can be found at View Source using identifier NCT04637763.

About Caribou’s Novel Next-Generation CRISPR Platform

CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems are capable of editing unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced "chardonnays") that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

BIO International Convention Featuring Massive Bio Co-Founder

On June 10, 2022 Massive Bio Co-Founder and Chief Medical Officer Dr. Arturo Loaiza-Bonilla, MD, MSEd, reported that it will be featured in the BIO International Convention, presented by Biotechnology Innovation Organization (BIO) (Press release, Massive Bio, JUN 10, 2022, View Source [SID1234615871]). The BIO International Convention is the world’s largest gathering of leaders in the biotechnology and life sciences industries, bringing together thousands of biotechnology and pharmaceutical executives.

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This event takes place in-person at the San Diego Convention Center in San Diego, California from June 13th to June 16th. Keynote speakers of the convention include Venus Williams and Erin Andrews.

Dr. Bonilla is a speaker in the discussion titled "The Roles of AI and Big Data in Precision Healthcare: Perspectives from the Drug Development Pathway and the Patient Journey" and takes place on June 15th at 2:00 pm ET. During this conference, panelists will discuss the role of Big Data and AI at each stage of the drug development pathway as concurrently intertwined with the patient’s journey as part of the developing precision healthcare field.

BIO is committed to speaking up for the millions of families around the globe who depend upon our success. Their goal is to drive a revolution that aims to cure patients, protect our climate, and nourish humanity.

In addition to being a Co-Founder of Massive Bio, Dr. Bonilla is a renowned medical oncologist and has a distinguished clinical career in precision medicine oncology, immunotherapy, clinical trial design, digital health, and patient advocacy. Visit the event’s full agenda.

Register to attend the in-person event on BIO’s website. Tag @MassiveBio and use #BIO2022 to connect on Twitter and other social media websites during the BIO International Convention from June 13th to June 16th.

China NMPA Approves Tislelizumab for Recurrent or Metastatic Nasopharyngeal Cancer

On June 10, 2022 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported that the China National Medical Products Administration (NMPA) has approved BeiGene’s anti-PD-1 antibody, tislelizumab, in combination with chemotherapy as a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (NPC) (Press release, BeiGene, JUN 10, 2022, View Source [SID1234615888]).

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"The NMPA’s approval of tislelizumab in NPC is welcoming news to these many patients with the disease."

"NPC is one of the most common head and neck cancers in China and many parts of Asia. Treatment options have been limited, with chemotherapy primarily provided for front-line care. On behalf of these patients, today’s approval of tislelizumab, a potentially differentiated checkpoint inhibitor, for patients with recurrent or metastatic NPC could provide new hope," commented Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "We look forward to bringing this important immunotherapy to the underserved patient community in China."

"With nine approved indications in China, our 3,100+ science-based commercial team is working to make tislelizumab more broadly available to those who may benefit from this important immunotherapy," commented Xiaobin Wu, Ph.D., President, Chief Operating Officer, and General Manager of China, at BeiGene. "Today’s approval is a great step for patients in China with NPC."

"In the pivotal Phase 3 RATIONALE-309 trial, comparing two arms of patients receiving either tislelizumab in combination with standard chemotherapy, or a placebo with standard chemotherapy, we observed statistical and clinically meaningful improvement in progression-free survival in the tislelizumab arm as assessed by both independent review committee and clinical investigators, and a positive trend in overall survival. These results were consistent with the updated survival data with a follow up time of 15 months, and tislelizumab was generally well tolerated," said Li Zhang, M.D., professor at the Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China and Sun Yat-sen University Cancer, and the principal investigator of the trial. "The NMPA’s approval of tislelizumab in NPC is welcoming news to these many patients with the disease."

This approval was supported by clinical results from the randomized, double-blind, Phase 3 clinical trial RATIONALE 309 (NCT03924986) to evaluate the efficacy and safety of tislelizumab combined with gemcitabine and cisplatin versus placebo combined with gemcitabine and cisplatin as a first-line treatment for patients with recurrent or metastatic NPC.

As announced in May 2021, RATIONALE 309 met the primary endpoint of PFS at the planned interim analysis. Updated efficacy analyses at a median follow-up of 15.5 months, tislelizumab in combination with chemotherapy continued to demonstrate a clinically significant progression-free survival (PFS) benefit over chemotherapy and placebo for patients with RM-NPC. Meanwhile, the tislelizumab arm continued to demonstrate a positive trend in overall survival (OS) and improvement in time to disease progression or death after next-line therapy (PFS2). The safety profile of the tislelizumab and chemotherapy combination was generally manageable and consistent with safety profiles of each treatment agent. These data were presented at an ASCO (Free ASCO Whitepaper) Virtual Plenary session in April and at the ASCO (Free ASCO Whitepaper) Annual Meeting in June 2022.

About Nasopharyngeal Cancer (NPC)

Nasopharyngeal cancer (NPC) is a malignant, squamous cell carcinoma which arises from the epithelial cells of the nasopharynx, most commonly originating in the pharyngeal recess (the fossa of Rosenmüller).i There were an estimated 62,555 new cases of NPC in China in 2020, accounting for 46.8 percent of the worldwide incidence.ii Despite the heavy public health burden of NPC in southern China and other endemic areas, relatively little is known about the etiology and prevention of NPC.iii The major risk factors for NPC are genetic predisposition, Epstein-Barr virus (EBV) infection, and consumption of salt-preserved food.iv The median overall survival rate is about 20 months in advanced NPC;v with progressively worsening prognoses falling to a three-year survival of 7-40% reported in patients with recurrent or metastatic NPC, indicating a high medical unmet need with more effective treatment urgently needed.vi,vii,viii

About RATIONALE-309

RATIONALE-309 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial (NCT03924986) designed to evaluate the efficacy and safety of tislelizumab combined with gemcitabine and cisplatin (Arm A) versus placebo combined with gemcitabine and cisplatin (Arm B) as a first-line treatment for patients with RM-NPC.

The primary endpoint of the trial is progression-free survival (PFS) in the intent-to-treat (ITT) population as assessed by an independent review committee (IRC) per RECIST v1.1 criteria; secondary endpoints include IRC-assessed overall response rate (ORR), IRC-assessed duration of response (DoR), overall survival (OS), investigator-assessed PFS, time to second objective disease progression (PFS2), and safety.

A total of 263 patients were enrolled in the trial, with 131 and 132 randomized to Arm A and Arm B, respectively, with balanced baseline characteristics between both arms. Interim results from the trial were presented in December at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress. Those data showed that at a media follow-up time of 10 months, tislelizumab demonstrated a statistically significant improvement in terms of extending progression-free survival (PFS) as well as clinically meaningful benefit on other survival endpoints compared with chemotherapy and placebo and a generally manageable safety profile.

About Tislelizumab

Tislelizumab is an anti-programmed death receptor-1 (PD-1) inhibitor designed to help aid the body’s immune cells to detect and fight tumors. Tislelizumab, a humanized monoclonal antibody, is specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene has initiated or completed more than 20 potentially registration-enabling clinical trials in 35 countries and regions, including 17 Phase 3 trials and four pivotal Phase 2 trials.

Tislelizumab is approved by the China National Medical Products Administration (NMPA) as a treatment for nine indications, including multiple approvals in non-small cell lung cancer (NSCLC). Tislelizumab has been submitted for regulatory review as a potential treatment for unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic therapy in the U.S., and in NSCLC and second-line ESCC in Europe. In January 2021, BeiGene partnered with Novartis to accelerate the clinical development and marketing of tislelizumab in North America, Europe and Japan.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 16,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU and U.K., Canada, Australia and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, including a biologics license application (BLA) under FDA review, BeiGene and Novartis announced an option, collaboration and license agreement in December 2021 for BeiGene’s TIGIT inhibitor, ociperlimab, that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene is promoting five approved Novartis Oncology products across designated regions of China.