On December 6, 2017 AstraZeneca, along with Acerta Pharma, its haematology research and development centre of excellence, and MedImmune, its global biologics research and development arm, will highlight significant progress in blood cancer research at the 59th 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exhibition in Atlanta, USA (Press release, AstraZeneca, DEC 6, 2017, View Source [SID1234522396]). Presentations will include new data from AstraZeneca’s emerging haematology portfolio in several cancer types including mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL), hairy cell leukaemia (HCL), acute myeloid leukaemia (AML), multiple myeloma and diffuse large B-cell lymphoma (DLBCL).

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "Following the recent accelerated approval of AstraZeneca’s first medicine for a blood cancer, Calquence, we will share a broad range of new data at ASH (Free ASH Whitepaper) highlighting our scientific progress in haematology as we seek to develop potential medicines that advance patient care."

Efficacy and safety of Calquence in the management of previously-treated MCL

Following the US Food and Drug Administration (FDA) accelerated approval of Calquence (acalabrutinib), a kinase inhibitor indicated for the treatment of adult patients with MCL who have received at least one prior therapy, data from the pivotal Phase II ACE-LY-004 clinical trial on which the accelerated approval was based, will be presented for the first time (Abstract #155). New details of the trial will be shared, including median time to response, pre-specified patient subgroup efficacy analyses, as well as safety analyses, further characterising the clinical profile of Calquence in this patient population.

Calquence as monotherapy and in combination in multiple CLL patient populations

Results will be presented from the Phase Ib/II ACE-CL-003 trial evaluating Calquence and obinutuzumab in treatment-naïve and previously-treated CLL patients (Abstract #432), which highlight the safety profile and activity of the combination. Long-term follow-up safety and efficacy data from the Phase I/II ACE-CL-001 clinical trial which tested Calquence as a monotherapy in a large cohort of patients with relapsed or refractory CLL (Abstract #498) will expand on findings previously reported; these data will highlight the favourable duration of response in this patient population.

Early-stage haematology portfolio

AstraZeneca will present additional data from its haematology portfolio, including findings from a Phase I trial of moxetumomab pasudotox, an anti-CD22 recombinant immunotoxin and potential new medicine in development for the treatment of people with previously-treated HCL (Abstract: #2765)
Early data on AZD2811, a novel nanoparticle inhibitor of aurora kinase B being tested in AML (Abstract #1368)
Preclinical data from trials on MEDI2228, a BCMA-targeting pyrrolobenzodiazepine-linked antibody drug conjugate being tested in multiple myeloma (Abstract #3153)
Data from a trial of vistusertib (AZD2014), a dual mTORC1/2 inhibitor being tested in DLBCL (Abstract #4113).
NOTES TO EDITORS

A full list of company-sponsored abstracts to be presented at ASH (Free ASH Whitepaper) are as follows:

Abstract Number
Title
Presentation Details
Abstract #155
Efficacy and safety of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma in the Phase II ACE-LY-004 study
Oral session, Saturday, December 9, 1 p.m. EST

Location: Georgia World Congress Center, Building A, Level 4, A411-A412
Abstract #1741
Pharmacodynamic evaluation of acalabrutinib in relapsed/refractory and treatment-naive patients with chronic lymphocytic leukemia in the Phase I/II ACE-CL-001 study
Poster sessions, Saturday, December 9, 5:30-7:30 p.m. EST

Location: Georgia World Congress Center, Building A, Level 1, Hall A2
Abstract #1268
Exposure-response of the Bruton tyrosine kinase inhibitor, acalabrutinib in the treatment of hematologic malignancies
Abstract: #1243
Concurrent treatment with Pim kinase inhibitor downregulates alternative non-homologous end-joining repair and decreases genomic instability in FLT3-ITD cells treated with topoisomerase 2 inhibitors
Abstract #1368
Preclinical and early Phase I clinical data of AZD2811 nanoparticle in AML, an aurora B kinase inhibitor
Abstract #432
Acalabrutinib with obinutuzumab in relapsed/refractory and treatment-naive patients with chronic lymphocytic leukemia: The Phase Ib/II ACE-CL-003 study
Oral session, Sunday, December 10, 1:15 p.m. EST

Location: Georgia World Congress Center, Building B, Level 5, Murphy BR 3-4
Abstract #498
Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: Updated results from the Phase I/II ACE-CL-001 study
Oral session, Sunday, December 10, 5:45 p.m. EST

Location: Georgia World Congress Center, Building B, Level 5, Murphy BR 3-4
Abstract: #2765
Negative minimal residual disease associated with extended response to moxetumomab pasudotox in patients with relapsed/refractory hairy cell leukemia: Long-term follow-up of bone marrow immunohistochemistry analyses from a Phase I study
Poster Session, Sunday, December 10, 6-8 p.m. EST

Location: Georgia World Congress Center, Building A, Level 1, Hall A2
Abstract: #3153
Preclinical evaluation of MEDI2228, a BCMA-targeting pyrrolobenzodiazepine-linked antibody drug conjugate for the treatment of multiple myeloma
Abstract #3442
Adverse events, resource use, and economic burden in patients with mantle cell lymphoma in the United States
Abstract #4326
Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in hematologic malignancies
Poster sessions, Monday, December 11, 6-8 p.m. EST

Location: Georgia World Congress Center, Building A, Level 1, Hall A2

Abstract #4060
Understanding ibrutinib treatment discontinuation patterns for chronic lymphocytic leukaemia
Abstract #4684
MCL treatment patterns and outcomes: A community oncology practice experience
Abstract #4113
Combined inhibition of mTOR and BTK signaling is required for optimal long-term growth inhibition in DLBCL models
About Calquence

Calquence (acalabrutinib; previously known as ACP-196) is a selective inhibitor of BTK. Calquence binds covalently to BTK, irreversibly inhibiting its activity, and has demonstrated this with minimal interactions with other immune cells in pre-clinical studies.5 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.1

The recommended dose of Calquence is one 100mg capsule taken orally approximately every twelve hours until disease progression or unacceptable toxicity.1 Calquence may be taken with or without food.1

Calquence is also in development for the treatment of multiple B-cell malignancies and other cancers including 1st-line MCL, chronic lymphocytic leukaemia (CLL), Waldenström macroglobulinemia (WM), follicular lymphoma, diffuse large B-cell lymphoma, and multiple myeloma. It is also being developed as a monotherapy and in combination trials for solid tumours. More than 35 clinical trials across 40 countries with more than 2,500 patients are underway or have been completed.

Calquence was granted Orphan Drug Designation by the US FDA for the treatment of adult patients with MCL in September 2015 and by the European Commission in March 2016 for the treatment of adult patients with CLL, MCL and WM.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that have the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On December 6, 2017 Foundation Medicine, Inc. (NASDAQ:FMI) reported that new data generated with FoundationOneHeme, its comprehensive genomic profiling (CGP) assay for hematologic malignancies and sarcomas, will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Foundation Medicine, DEC 6, 2017, View Source [SID1234522397]). Data from a broad range of blood cancers, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and non-Hodgkin lymphoma (NHL), including primary central nervous system lymphoma (PCL), demonstrate the value of integrating FoundationOneHeme into clinical care. The data presented is expected to demonstrate the potential for CGP to improve disease classification, to offer personalized prognostic information and to support therapeutic treatment decision making by informing treating physicians about the use of novel treatment options, including cancer immunotherapies.

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"Comprehensive genomic profiling (CGP) is proving to be an essential component for personalized cancer care, particularly as we learn more about the diverse genomic alterations in blood cancers," said Vincent Miller, M.D., chief medical officer at Foundation Medicine. "FoundationOneHeme is at the forefront of helping to identify new treatment approaches, including cancer immunotherapy, for individuals with blood cancers. Our new findings to be presented at ASH (Free ASH Whitepaper) support the ability of CGP to address high unmet medical needs across a wide range of hematologic malignancies, including rare conditions for which there are few treatment options."

Cancer immunotherapy is emerging as a therapeutic tool for patients with diverse hematologic malignancies. New results to be presented at ASH (Free ASH Whitepaper) using FoundationOneHeme show that more than one-quarter of patients with PCL had high tumor mutational burden (TMB), a genomic biomarker that has been shown across several cancer types to predict response to immuno-oncology treatment strategies, such as checkpoint inhibitors. Less than 50 percent of PCL patients achieve complete remission with current standard of care treatments, underscoring a need for new treatment options for these patients.

New results also support the role of FoundationOneHeme to guide therapy selection and predict response to treatment. In an oral study to be presented, FoundationOneHeme detected NTRK fusions in a wide variety of hematologic malignancies, and clinical response to a TRK inhibitor was subsequently observed in a patient with refractory AML and an ETV6-NTRK2 fusion. In another study to be presented, CGP offered insights that may facilitate risk-adapted clinical management decisions in patients with intermediate-and favorable-risk AML, potentially informing optimal use of autologous stem cell transplantation (auto-SCT) over conventional consolidation chemotherapy. For example, the study showed the presence of PTPN11 mutations to predict long term clinical outcomes following an auto-SCT.

Other results to be presented at ASH (Free ASH Whitepaper) demonstrate the ability of FoundationOneHeme to detect both known and novel BCL6 rearrangements in NHL, including cases that previously tested negative with standard-of-care single marker testing. BCL6 rearrangements have known diagnostic and prognostic utility in specific subtypes of NHL.

Foundation Medicine and collaborators will present a total of nine studies, including four oral presentations and five poster presentations, at the ASH (Free ASH Whitepaper) Annual Meeting from December 9-12, 2017 in Atlanta. The planned presentations are as follows:

Dec 9:

115 – Unrecognized clonal hematopoiesis of indeterminate potential in solid tumors: Implications for interpretation of molecular testing, Dec 9, 9:30am, C208-210 (Oral Presentation)
1423 – The role of comprehensive mutational profiling in predicting patients who may benefit from autologous hematopoietic cell transplant for acute myeloid leukemia, Dec 9, 5:30pm-7:30pm, Hall A2 (Poster Presentation)
1657 – A distinct mutation profile might contribute to the dismal outcome of triple negative patients with primary myelofibrosis, Dec 9, 5:30pm-7:30pm, Hall A2 (Poster Presentation)
Dec 10:

417 – Comprehensive genomic profiling identifies novel BCL6 rearrangements in diverse subtypes of Non-Hodgkin lymphoma as well as known rearrangements not detected using standard of care assays, Dec 10, 12:30pm, Marcus Auditorium (Oral Presentation)
476 – Comprehensive genomic profiling identifies genomic alterations that define Philadelphia-like B-acute lymphoblastic leukemia, Dec 10, 4:45pm, B213-B214 (Oral Presentation)
Dec 11:

794 – Characterization of NTRK fusions and therapeutic response to NTRK inhibition in hematologic malignancies, Dec 11, 4:45pm, B207-208 (Oral Presentation)
3800 – Recurrent copy number variants are highly prevalent in acute myeloid leukemia, Dec 11, 6:00pm-8:00pm, Hall A2 (Poster Presentation)
3996 – Comprehensive genomic profiling demonstrates differences in primary CNS lymphoma and systemic diffuse large B cell lymphoma and reveals biomarkers indicating potential benefit from immune checkpoint inhibitors, Dec 11, 6:00pm-8:00pm, Hall A2 (Poster Presentation)
4016 – Next generation sequencing of Castleman disease and follicular dendritic cell sarcomas associated with Castleman disease, Dec 11, 6:00pm-8:00pm, Hall A2 (Poster Presentation)

On December 6, 2017 Prometic Life Sciences Inc. (TSX: PLI) (OTCQX: PFSCF) (Prometic) reported that it will have two presentations at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held Dec. 9-12, 2017 in Atlanta (Press release, ProMetic Life Sciences, DEC 6, 2017, View Source [SID1234522398]).

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An oral presentation, entitled, "Pivotal Trial with Intravenous Plasminogen Replacement in Patients with Plasminogen Deficiency Demonstrates Long-Term Efficacy for Treatment and Prevention of Ligneous Lesions" will be presented by Dr. Charles T. Nakar, Indiana Hemophilia and Thrombosis Center. During the oral session, Dr. Nakar will present 48-week data demonstrating the long-term safety and efficacy of intravenous plasminogen replacement (RyplazimTM) in patients with plasminogen deficiency.

A poster presentation, entitled, "Computer Modeling Using Historical Data Demonstrates a Significant Reduction in Expected Extravascular Fibrinous Lesions Due to Congenital Plasminogen Deficiency While Receiving Intravenous Plasminogen Replacement" will be presented by Dr. Joseph M. Parker, Senior Director of clinical development of Prometic. Dr. Parker will present a poster of historical data computer modeling highlighting the significant treatment effect of RyplazimTM in reducing the extravascular ligneous lesions in pediatric and adult subjects with plasminogen deficiency.

"Data from these presentations demonstrates the remarkable safety and efficacy profile of plasminogen treatment we have observed to date," said Pierre Laurin, Chief Executive Officer at Prometic. "No currently-available treatment options have demonstrated a complete resolution of lesions in patients with plasminogen deficiency. We are continuing to work closely with the FDA with the goal of making our plasminogen replacement therapy available to patients as soon as possible."

Details of the oral presentation are as follows:

Presentation Title: Pivotal Trial with Intravenous Plasminogen Replacement in Patients with Plasminogen Deficiency Demonstrates Long-Term Efficacy for Treatment and Prevention of Ligneous Lesions

Presenter: Charles T. Nakar, M.D.

Session Title: Disorders of Coagulation or Fibrinolysis: Novel Therapies and Clinical Trials in Bleeding Disorders
Date/Time: Saturday, December 9, 2017 at 9:30 a.m. EST
Room: Georgia World Congress Center, Bldg B, Lvl 2, B207-B208

Details of the poster presentation are as follows:

Presentation Title: Computer Modeling Using Historical Data Demonstrates a Significant Reduction in Expected Extravascular Fibrinous Lesions Due to Congenital Plasminogen Deficiency While Receiving Intravenous Plasminogen (PLG) Replacement

Presenter: Joseph M. Parker, M.D.
Session Title: Disorders of Coagulation or Fibrinolysis: Poster II
Date/Time: Sunday, December 10, 2017 from 6:00 p.m. to 8:00 p.m. EST
Room: Georgia World Congress Center, Bldg A, Lvl 1, Hall A2

On December 5, 2017 At the American Society of Hematology (ASH) (Free ASH Whitepaper)’s 59th Annual Meeting and Exposition in Atlanta, Georgia, researcher Gustavo Milone, MD, and his team reported that will present a study that investigates the post-marketing trends of Novex, a biosimilar rituximab that has been approved in Argentina for the same indications as the reference product (MabThera, Rituxan) (Press release, mAbxience, DEC 5, 2017, View Source [SID1234594760]).1 Since Novex’s commercial launch, the first national pharmacovigilance plan for a biosimilar monoclonal antibody has been implemented, and data from this post-marketing surveillance show that, in terms of tolerability, this biosimilar has a similar safety profile to that of the reference product.

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In order to determine deviations from expected frequencies of adverse events (AEs), a prospective treatment registry for the biosimilar was implemented from the start of its commercialization on November 26, 2014. Data in the study are reported until June 30, 2017. Physicians, 180 in total, tracked age, gender, indication, dose, dose frequency, and date of treatment initiation and finalization for each patient receiving the biosimilar.

The study comprised the records of 525 patients who had at least 1 follow-up. The majority of patients were female (52%), the mean age was 63.3 years (range, 10-90), and most patients received the biosimilar rituximab for hematological disease (91.2% of cases). The treatment duration ranged from 154 to 309 days, with the number of treatment cycles varying from 1 to 12. Individual Case Safety Reports (ICSRs) were collected from 24 patients with 29 AEs.

The most frequently reported AEs were:

Acute infusion-related reaction (14)
Arrhythmia (3)
Pneumonia (2)
Stroke (2)
The researchers noted that 41 treatments with rituximab were initiated before the launch of the product; assuming treatment began with MabThera, these 41 treatments imply switching to the biosimilar from the reference.

Researchers investigating data from the post-marketing surveillance found a similar incidence of AEs after the use of rituximab biosimilar when compared to the published data of the reference product. Thus, in terms of tolerability, the biosimilar has a similar safety profile compared with its reference.

On December 5, 2017 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that updated clinical data from its lead product candidate CB-839, a first-in-class glutaminase inhibitor, will be presented at the 2017 San Antonio Breast Cancer Symposium, December 5-9, 2017 in San Antonio, Texas (Press release, Calithera Biosciences, DEC 5, 2017, View Source [SID1234535249]). The data demonstrate the clinical activity and tolerability of CB-839 in combination with paclitaxel, and highlight the unique mechanism of action of CB-839 in patients with advanced/metastatic triple negative breast cancer (TNBC). Based on these data, Calithera has opened a Phase 2 trial exploring the treatment combination in both first line and late line metastatic TNBC patients.

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"Effective treatment for triple negative breast cancer in the advanced and metastatic population remains a significant unmet need. In our Phase 1 study, we were pleased to have observed responses in patients who were heavily pretreated and the Phase 2 study will help us further understand the role of CB-839 in inhibiting glutaminase to help control the progression of cancer in advanced metastatic TNBC patients," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

In a poster presentation representing an update from data presented at SABCS 2016, Dr. Kevin Kalinsky from Columbia University Medical Center will present, "Phase I study of CB-839, a first-in-class inhibitor of glutaminase, in combination with paclitaxel in patients with advanced triple negative breast cancer," (Abstract PD3-13). Eligible patients must have locally advanced/metastatic TNBC, with no restrictions on prior exposure to taxanes, or the number of prior therapies. As of October 23, 2017, 49 triple negative breast cancer patients had been treated with doses of CB-839 of 400, 600 or 800 mg bid in combination with 80 mg/m2 IV paclitaxel, weekly, three weeks out of four; 44 were evaluable for response. Patients were heavily pretreated, having received a median of 3 prior therapies for advanced metastatic disease. A majority of patients had received prior taxane therapy in either the neo-adjuvant (37%) or metastatic setting (51%). Among all evaluable patients treated with CB-839 doses of at least 600 mg bid (n=37), there were 8 partial responses (22%) and disease control (response or stable disease) in 22 patients (59%). Among African Americans, there was a 36% response rate in patients who had received previous taxanes in the metastatic setting; all responders were refractory to prior taxanes. Exploratory biomarker analysis shows a trend for the strongest clinical benefit occurring in patients with LAR and/or desmoplastic stromal gene expression signatures1.

The combination of CB-839 and paclitaxel has been well tolerated to date, with adverse events that have been primarily low grade and reversible. Consistent with the previous report, there was one case of dose-limiting, recurrent grade 3 neutropenia at the 400 mg dose level, which led to a reduction in the dose of paclitaxel for that patient. The most frequent adverse event ≥ Grade 3 was neutropenia (27%). A low rate of ≥ Grade 3 peripheral neuropathy (4.2%) was observed despite 88% of the patients having prior taxane exposure. 1Lehmann et al., J Clin Invest 2011; Chen et al, Cancer Inform 2012; Jovanovic et al BMC Cancer 2017; Saleh et al, Cancer Research 2017

About CB-839 Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents