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Teva and Celltrion Announce Exclusive Biosimilar Commercial Partnership

On October 6, 2016 Teva Pharmaceutical Industries Ltd. (NYSE and TASE:TEVA), Celltrion, Inc. and Celltrion Healthcare reported that the companies have entered into an exclusive partnership to commercialize two of Celltrion’s mAb biosimilar candidates in the U.S. and Canada (Press release, Teva, OCT 6, 2016, View Source [SID:SID1234515633]). CT-P10 is a proposed mAb biosimilar to Rituxan (rituximab), which is used to treat patients with Non-Hodgkin’s Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Rheumatoid Arthritis (RA), Wegener’s Granulomatosis and Microscopic Polyangiitis (MPA). CT-P6 is a proposed mAb biosimilar to Herceptin (trastuzumab), which is used for the treatment of HER2-overexpressing breast cancer and for the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. Combined annual net sales for Rituxan and Herceptin are approximately $6.5 billion in the U.S. and Canada.

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"This commercial partnership with Celltrion enables Teva to expand into the upcoming wave of biosimilars and build on its strong position in the biosimilar space," said Siggi Olafsson, President & CEO of Global Generic Medicines, Teva Pharmaceuticals. "The introduction of two additional mAb biosimilar candidates into our near-term pipeline bolsters our biosimilar portfolio and continues to leverage Teva’s unique cross-functional capabilities across both specialty and generic medicines. We look forward to our partnership with Celltrion with its expertise in mAb biosimilar development and manufacturing."

Both CT-P10 and CT-P6 are currently in late-stage Phase III development and their primary endpoints have been successfully achieved. CT-P10 was submitted by Celltrion to the European Medicines Agency (EMA) for review in October 2015. In the meantime, Celltrion is preparing CT-P6 for submission in Europe seeking approval from the EMA this quarter. As part of the agreement, Teva will be responsible for all commercial activities in the U.S. and Canada, pending regulatory approvals for both products. Celltrion has responsibility for completing all clinical development and regulatory activities.

"With Teva’s strong legacy and U.S. commercial presence in Oncology, we are pleased to partner with Celltrion to bring additional biosimilar treatment options to patients," said Rob Koremans, M.D., President and Chief Executive Officer, Global Specialty Medicines, Teva Pharmaceuticals. "By bringing two near-term treatment options into our product offering, we will continue our commitment to serving those dealing with cancer and other serious diseases."

"As a global biopharmaceutical leader with established products as well as a robust biosimilar pipeline and novel drugs, we are very excited about our new partnership with Teva," said HyoungKi Kim, Chief Executive Officer, Celltrion, Inc. "Following on the heels of our global success with Remsima (Inflectra), our infliximab biosimilar, which has brought affordable and effective biologic treatment to many patients around the world with proven record of quality, efficacy and safety to the reference product, we are confident that we will be able to repeat the same success in the U.S and Canada with CT-P10 and CT-P6 through our partnership with Teva."

Under the terms of the agreement, Teva will pay Celltrion Healthcare $160 million upfront of which up to $60 million is refundable or creditable under certain circumstances. Teva and Celltrion Healthcare will share profit from the commercialization of the mAb biosimilars.

Data from Phase III POLLUX Study of Daratumumab Published in The New England Journal of Medicine

On October 6, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported The New England Journal of Medicine has published data from the Phase III POLLUX (MMY3003) study of daratumumab (Press release, Genmab, OCT 6, 2016, View Source [SID:SID1234515622]). The POLLUX data were presented at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June. Daratumumab was granted a Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) based on these data in July 2016.

The Phase III POLLUX study enrolled 569 patients who had relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid), or lenalidomide and dexamethasone alone. The study met the primary endpoint of improving progression-free survival (PFS) (Hazard Ratio (HR) = 0.37; 95% CI 0.27-0.52; p<0.001) for patients treated with daratumumab versus patients who did not receive daratumumab. Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone. The overall response rate was 93% in the group of patients treated with daratumumab versus 76% in the group that did not receive daratumumab. The rates of very good partial response or better (76% vs 44%) and complete response or better (43% vs 19%) were also higher for the group treated with daratumumab. Of patients treated with daratumumab, 22% were minimal residual disease negative, versus 5% in those who did not receive daratumumab; negative minimal residual disease translated into improved outcomes. The most common grade 3 or 4 adverse events in patients treated with daratumumab in combination with lenalidomide and dexamethasone versus those who received only lenalidomide and dexamethasone were neutropenia (51.9% vs 37.0%), thrombocytopenia (12.7% vs 13.5%), and anemia (12.4% vs 19.6%). Daratumumab-associated infusion-related reactions occurred in 48% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion. Overall, the safety profile was consistent with known toxicities of daratumumab monotherapy and combination therapy of lenalidomide and dexamethasone.

Data from another Phase III study (CASTOR) of daratumumab combined with subcutaneous bortezomib (a type of chemotherapy, called a proteasome inhibitor) and dexamethasone (a corticosteroid) compared with bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma was also recently published in the New England Journal of Medicine.1
"Following the publication of the Phase III CASTOR data, we are pleased that the positive data from the Phase III POLLUX study has now also been published in the New England Journal of Medicine," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "The data from this study formed the basis, along with data from the CASTOR study, of two regulatory submissions in August; the supplemental Biologics License Application submitted to the U.S. Food and Drug Administration and the submission of the variation to the Marketing Authorization to the European Medicines Agency."

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.2 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.3 Approximately 30,330 new patients are expected to be diagnosed with multiple myeloma and approximately 12,650 people are expected to die from the disease in the U.S. in 2016.4 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.5 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.6 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.7

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.8 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,8,9 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,8,9 antibody-dependent cellular phagocytosis10,11 and antibody-dependent cellular cytotoxicity.8,9 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.8,12

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma and a solid tumor.

Kite Pharma Initiates Phase 1b/2 Combination Study for KTE-C19 and Atezolizumab in Patients with Refractory Diffuse Large B-cell Lymphoma (DLBCL)

On October 6, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported the first patient was enrolled in ZUMA-6, a Phase 1b/2 clinical study of KTE-C19 in combination with atezolizumab, Genentech’s anti-PD-L1 cancer immunotherapy (Press release, Kite Pharma, OCT 6, 2016, View Source [SID:SID1234515618]). The trial is designed to evaluate the safety and efficacy of the combination in patients with refractory diffuse large B-cell lymphoma (DLBCL).

PD-L1 expression in DLBCL is associated with high-risk disease and poor outcomes. The interaction of PD-L1 and PD-1, which is expressed on KTE-C19, may dampen T-cell activity in some patients. As a result, use of the two compounds in combination could provide a synergistic effect since inhibiting PD-L1 with atezolizumab may enhance and prolong the activity and proliferation of KTE-C19.

"The ZUMA-6 combination study is a core element of our broad strategy to optimize KTE-C19 treatment outcomes and to significantly extend the important potential benefits of KTE-C19 monotherapy," said David Chang, M.D., Ph.D., Kite’s Executive Vice President, Research and Development, and Chief Medical Officer. "We view the scientific rationale for this combination study as compelling and look forward to advancing the study based on our extensive clinical experience."

Kite entered a clinical collaboration in March 2016 with Genentech, a member of the Roche Group, to evaluate the safety and efficacy of KTE-C19 in combination with atezolizumab. The first ZUMA-6 patient was enrolled at the end of September 2016.

About ZUMA-6

ZUMA-6 is the first industry-sponsored clinical trial to enroll patients to study the combination of an anti-CD19 engineered chimeric antigen receptor (CAR) T-cell and a checkpoint inhibitor. The study will proceed as a single-arm, open-label, multi-center study in patients with chemotherapy-refractory DLBCL. The Phase 1b portion of ZUMA-6 will assess the safety of KTE-C19 and atezolizumab given in sequence. The primary objective of the Phase 2 portion is to evaluate the combination’s safety and efficacy. The study also includes secondary analyses of key biomarkers of T-cell activity and other safety and efficacy endpoints. Kite will be the sponsor of the study, and the results will be used to evaluate options for further development of the combination. Additional information about the ZUMA-6 study will be available at www.clinicaltrials.gov by searching on NCT02926833.

About KTE-C19

Kite Pharma’s lead product candidate, KTE-C19, is an investigational therapy in which a patient’s T-cells are engineered to express a CAR to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T-cells to kill cancer cells. KTE-C19 has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.

Achilles Therapeutics launched with funds of £13.2 million to develop immunotherapies for cancer

On October 5, 2016 SYNCONA LLP and CANCER RESEARCH TECHNOLOGY (CRT) reported the formation of Achilles Therapeutics Ltd (Press release, Achilles Therapeutics, OCT 5, 2016, View Source [SID1234523124]).

The new private company will bring together world-class research from UCL (University College London) and the Francis Crick Institute, funded by Cancer Research UK and the National Institute for Health Research (NIHR).

Achilles Therapeutics will design therapies to target truncal tumour neo-antigens – unique flags to the immune system present on the surface of every cancer cell*, which were first discovered by Cancer Research UK and the NIHR University College London Hospitals (UCLH) Biomedical Research Centre (BRC) funded scientists at the Francis Crick Institute and UCL Cancer Institute.

Truncal tumour neo-antigens are present on all cancer cells in an individual patient’s tumour but not on healthy cells, so could allow scientists to target and destroy tumours without harming healthy tissues.

Syncona and CRT, with the support of UCL Business (UCLB) and the Crick, formed Achilles Therapeutics with a successful financing round of £13.2 million ($17.5 million) led by Syncona with the CRT Pioneer Fund and the UCL Technology Fund.

The company founders bring together world-class capability from three prestigious institutions. They are:

Professor Charles Swanton, Group Leader and Royal Society Napier Professor at the Francis Crick and UCL Cancer Institute working on cancer evolution and genome instability and a consultant at UCLH
Professor Karl Peggs, Group Leader of the Stem Cell Transplantation and Cellular Immunotherapy Group at UCL Cancer Institute and a consultant at UCLH
Dr Sergio Quezada, Group Leader of the Immune Regulation and Tumour Immunotherapy Group at UCL Cancer Institute
Professor Mark Lowdell, Director of the Centre for Cell, Gene & Tissue Therapeutics at the Royal Free Hospital.

CRT will receive equity milestones and royalties from products developed and commercialised by Achilles Therapeutics. Any such financial reward from the company will be shared with UCLB and the Crick.

The company has exclusive rights to develop and commercialise neo-antigen technologies arising from Cancer Research UK’s £14million TRACERx study**. This clinical study, involving 850 people with non-small cell lung cancer, tracks the evolution of patients’ cancers over time, in different parts of their tumours and in response to treatment. It receives infrastructure support from the NIHR University College London Hospitals BRC and is being carried out at the Clinical Research Facility at UCLH.

Professor Charles Swanton, scientific founder of Achilles Therapeutics and a Group Leader at the Francis Crick Institute, said: "Our research could provide a truly personalised approach to lung cancer therapy by targeting cell surface markers that are specific to each patient and present on all cancer cells rather than just a subset of cells. We’re delighted to be able to bring this exciting science closer to the clinic. We hope to create a new and kinder treatment for this hard-to-treat disease that results in around 36,000 patient deaths each year in the UK ***."

Iraj Ali, Partner with Syncona LLP and Director of Achilles Therapeutics, said: "In founding Achilles we believe we are working with the world leaders capable of exploiting the confluence of two of the most exciting and innovative fields in healthcare today: cancer bioinformatics and immuno-therapy. Our ambition is to build a company to deliver personalised therapies with transformative potential for cancer patients with the greatest need."

Chris Ashton, CEO of Achilles Therapeutics, said: "This company is underpinned by world-leading science, committed investors and leading health institutes. Bringing all of these major players together holds great promise for non-small cell lung cancer patients and I hope that working alongside one another we will see great successes in the future."

Lilly Highlights Advancements in its Oncology Portfolio with New Data at ESMO 2016

On October 5, 2016 Eli Lilly and Company (NYSE: LLY) reported that it will present data from several studies which further reinforce the advancement of its diverse clinical cancer portfolio during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper)’s (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, October 7-11 (Press release, Eli Lilly, OCT 5, 2016, View Source [SID:SID1234515631]). Presentations include new data on abemaciclib, a CDK 4 and CDK 6 inhibitor, and olaratumab, a PDGFRα blocking antibody that recently received a positive CHMP opinion, as well as data on: pemetrexed, a multi-targeted antifolate; ramucirumab, a VEGF Receptor 2 antagonist; necitumumab, an EGFR blocking antibody; and prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor. Of these presentations, four are featured in late-breaking abstracts (two on abemaciclib, and one each on pemetrexed and ramucirumab).

The presentations on pemetrexed, ramucirumab and necitumumab include data from a few of Lilly’s immuno-oncology clinical collaborations with Merck (known as MSD outside the U.S. and Canada) in trials that are evaluating these molecules in combination with Merck’s pembrolizumab. Notably, the first results from KEYNOTE-021G – which studied pembrolizumab in combination with pemetrexed-plus-carboplatin compared to pemetrexed-plus-carboplatin alone for the first-line treatment of patients with advanced nonsquamous non-small cell lung cancer regardless of PD-L1 expression – will be featured in the Presidential Symposium on October 9.

Lilly’s data at the ESMO (Free ESMO Whitepaper) 2016 Congress highlight the ongoing progress in expanding the potential of its portfolio molecules as well as the advancement of its clinical pipeline. These presentations underscore the company’s multi-faceted strategy in developing cancer treatments – to produce a diverse portfolio of novel agents that attack tumor cell growth and progression in multiple ways to improve patient outcomes. Specifically, this is a balanced approach based on three scientific pillars of tumor cell growth and progression:

Tumor cell signaling: Therapies that target cell signaling to interrupt the communication system that enables cancer cells to coordinate their basic activities;
Tumor microenvironment: Treatments attacking the tumor microenvironment which work by reducing the flow of nutrients and mitogens that support and feed tumor cells; and
Immuno-oncology: Therapies that use the patient’s own immune system to fight cancer.
"Lilly’s three-pillar oncology R&D strategy is unique," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "While there’s no single therapy or one way to attack tumor cell growth and progression that works for all patients, as an industry we are continually learning how some approaches work better than others in certain patient populations. Lilly is aggressively approaching cancer therapy development from many angles, including the study of combination therapies across the three pillars to address tumor heterogeneity and drug resistance, through our own efforts and research collaborations. Data to be presented at this year’s ESMO (Free ESMO Whitepaper) Congress demonstrate our intent to bring forth best-in-class treatment options to help patients around the world."

Select studies, along with the times and locations of their data sessions, are highlighted below.

Abemaciclib

Abstract Title: Interim results from neoMONARCH: a neoadjuvant phase II study of abemaciclib in postmenopausal women with HR+/HER2- breast cancer (BC)
Abstract #: LBA13; Proffered Paper session: Friday, October 7, 16:00 – 17:30 CEST
Author/Speaker: Sara Hurvitz, M.D., UCLA Jonsson Comprehensive Cancer Center
Location/Room: Stockholm
Abstract Title: Exploratory biomarkers in MONARCH 1, a phase II study of abemaciclib monotherapy in hormone-receptor positive (HR+) HER2- metastatic breast cancer (MBC)
Abstract #: LBA12; Poster Discussion session: Sunday, October 9, 16:30 – 17:30 CEST
Author/Speaker: Sara M. Tolaney, M.D., MPH, Dana-Farber Cancer Institute
Location/Room: Berlin
Immuno-Oncology Collaborations with Pemetrexed, Ramucirumab and Necitumumab

Abstract Title: Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-line therapy for advanced NSCLC: KEYNOTE-021 cohort G
Abstract #: LBA46_PR; Presidential Symposium session: Sunday, October 9, 16:25 – 18:20 CEST
Author/Speaker: Corey Langer, M.D., University of Pennsylvania
Location/Room: Copenhagen
Abstract Title: Interim safety and clinical activity in patients with advanced NSCLC from a multi-cohort phase 1 study of ramucirumab (R) plus pembrolizumab (P)
Abstract #: LBA38; Poster Discussion session: Monday, October 10, 09:30 – 10:30 CEST
Author/Speaker: Roy S. Herbst, M.D., Ph.D., Yale Cancer Center
Location/Room: Berlin
Abstract Title: Safety of necitumumab and pembrolizumab combination therapy in patients with stage IV non-small cell lung cancer (NSCLC): A phase 1b expansion cohort study
Abstract #: 1260P; Poster Display session: Saturday, October 8, 13:00 – 14:00 CEST
Author/Speaker: Benjamin Besse, M.D., Ph.D., Institut d’Oncologie Thoracique
Location/Room: Hall E
Olaratumab

Abstract Title: Exposure-response of olaratumab for survival outcomes and safety when combined with doxorubicin in soft tissue sarcoma (STS) patients
Abstract #: 1402PD; Poster Discussion session: Monday, October 10, 11:00 – 12:00 CEST
Author/Speaker: Robin L. Jones, BSc, MB, MRCP, M.D., Fred Hutchinson Cancer Research Center
Location/Room: Brussels
Abstract Title: ANNOUNCE 2: An open-label phase 1b, and a randomized, double-blind phase 2 study of olaratumab with gemcitabine plus docetaxel in the treatment of patients with advanced soft tissue sarcoma (STS)
Abstract #: 1420TiP; Poster Display session: Monday, October 10, 13:00 – 14:00 CEST
Author/Speaker: Andrés Redondo, M.D., Hospital Universitario La Paz
Location/Room: Hall E
Prexasertib

Abstract Title: A phase II study of the cell cycle checkpoint kinases 1 and 2 inhibitor (LY2606368; Prexasertib monomesylate monohydrate) in sporadic high-grade serous ovarian cancer (HGSOC) and germline BRCA mutation-associated ovarian cancer (gBRCAm+ OvCa)*
Abstract #: 855O; Proffered Paper session: Friday, October 7, 14:00 – 15:30 CEST
Author/Speaker: Jung-min Lee, M.D., Center for Cancer Research, National Cancer Institute, National Institutes of Health
Location/Room: Oslo
Ramucirumab

Abstract Title: Ramucirumab (RAM) as a second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Prognosis, efficacy, and safety by liver disease etiology
Abstract #: 617PD; Poster Discussion session: Saturday, October 8, 08:00 – 09:00 CEST
Author/Speaker: Takuji Okusaka, M.D., National Cancer Center Hospital
Location/Room: Copenhagen
Abstract Title: A randomized, double-blind, placebo-controlled phase III study of ramucirumab versus placebo as second-line treatment in patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein following first-line sorafenib (REACH-2)
Abstract #: 710TiP; Poster Display session: Saturday, October 8, 13:00 – 14:00 CEST
Author/Speaker: Andrew X. Zhu, M.D., Ph.D., Massachusetts General Hospital Cancer Center
Location/Room: Hall E

*This presentation on prexasertib includes data from an investigator-initiated trial sponsored by the Center for Cancer Research, National Cancer Institute (NCI), part of the National Institutes of Health.