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Amgen And Xencor Announce Strategic Collaboration In Cancer Immunotherapy And Inflammation

On September 16, 2015 Amgen (NASDAQ:AMGN) and Xencor, Inc. (Xencor) (NASDAQ:XNCR) reported that the two companies have entered into a research and license agreement to develop and commercialize novel therapeutics in the areas of cancer immunotherapy and inflammation (Press release, Amgen, SEP 16, 2015, View Source [SID:1234507476]). The research collaboration brings together Amgen’s capabilities in target discovery and protein therapeutics with Xencor’s XmAb bispecific technology platform.

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The collaboration includes molecular engineering by Xencor and the preclinical development of bispecific molecules for five programs proposed by Amgen, leveraging XmAb bispecific Fc domains to make half-life extended T cell engagers and dual targeting bispecific antibodies. The agreement also includes a preclinical bispecific T cell engager program directed at CD38 and CD3 for multiple myeloma.

Amgen will be fully responsible for preclinical and clinical development and commercialization worldwide. Under the terms of the agreement, Xencor will receive a $45 million upfront payment and up to $1.7 billion in clinical, regulatory and sales milestone payments in total for the six programs. Xencor is eligible to receive mid to high single-digit royalties for candidates directed against Amgen’s targets, and high single to low double-digit royalties for Xencor’s CD38 bispecific T cell engager.

"We are pleased to be joining forces with Xencor to expand our immuno-oncology and inflammation position by leveraging Amgen’s antibodies and Xencor’s bispecific antibody platform," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We are especially excited about the T cell engaging bispecific antibody directed against CD38, which complements Amgen’s BiTE platform, while growing our hematology and oncology portfolio that includes two bispecific T cell engager antibodies, BLINCYTO (blinatumomab) and AMG 330, as well as Kyprolis (carfilzomib) for relapsed multiple myeloma."

Bispecific technologies seek to engineer monoclonal antibodies to bind two unique drug targets, as opposed to traditional antibodies designed to bind to a single antigen target. This approach represents a powerful opportunity in immuno-oncology to simultaneously engage immune cells and tumor cells to localize anti-tumor immune activity where it is needed most.

"Amgen, which has pioneered the use of bispecific antibodies, has chosen to access our XmAb bispecific technology for its robustness, long half-life, and the plug and play ease-of-development of our platform," said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. "This opportunity expands the reach of our technology with a partner that has proven experience in bispecifics and immuno-oncology. Xencor will continue to focus on its internal programs including its immuno-oncology XmAb bispecifics, XmAb14045 in acute myeloid leukemia and XmAb13676 in B-cell malignancies, which are expected to enter clinical development in 2016."

About Xencor’s XmAb Bispecific Technology
As opposed to traditional monoclonal antibodies that target and bind to a single antigen, bispecific antibodies are designed to elicit multiple biological effects that require simultaneous binding to two different antigen targets. Xencor’s XmAb bispecific Fc domain technology is designed to maintain full-length antibody properties in a bispecific antibody, potentially enabling favorable in vivo half-life and simplified manufacturing.

Efforts at bispecific antibody design are typically frustrated by poor molecular stability, difficulties in production and short in vivo half-life. Xencor has engineered a series of Fc domain variants that spontaneously form stable, heterodimeric bispecific antibodies and that can be made and purified with standard antibody production methods. These bispecific Fc domains are used to generate a broad array of novel drug candidates in a range of molecule formats.

Xencor’s initial bispecific programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3 binding domain). These bispecific antibodies activate T cells at the site of the tumor for highly potent killing of malignant cells. The XmAb Fc domain format allows Xencor to tune the potency of the T-cell killing, potentially improving the tolerability of tumor immunotherapy. Xencor plans to begin clinical testing for two internal programs, XmAb14045 and XmAb13676, in 2016.

Geron Announces Initiation of Janssen Phase 2 Clinical Trial of Imetelstat in Myelofibrosis

On September 16, 2015 Geron Corporation (Nasdaq:GERN) reported the dosing of the first patient in a Phase 2 clinical trial to evaluate imetelstat in patients with myelofibrosis (MF) (Press release, Geron, SEP 16, 2015, View Source [SID:1234507475]). This clinical trial, also referred to as the IMbarkTM study, is being conducted by Janssen Biotech, Inc. (Janssen), under the terms of the exclusive worldwide imetelstat license and collaboration agreement between the companies.

Phase 2 Clinical Trial Design

The purpose of the Phase 2 clinical trial is to assess the efficacy, safety and tolerability of two dose levels of single-agent imetelstat in patients with MF. The trial is designed to enroll approximately 200 patients (approximately 100 patients per dosing arm) with DIPSS intermediate-2 or high risk MF who have relapsed after or are refractory to Janus Kinase (JAK) inhibitor treatment. At the time of enrollment, patients must have measurable splenomegaly and symptoms of MF. Patients will be assigned randomly on a blinded basis on a 1:1 ratio to one of two dosing arms – 9.4 mg/kg every three weeks or 4.7 mg/kg every three weeks. Dose reductions for adverse events are allowed and will follow protocol-specified algorithms. An interim review of data from the trial is planned after approximately 20 patients per arm have been randomized and followed for at least 12 weeks, in order to assess the adequacy of one or both of the initial dosing arms. As a result of this interim review, one or both dosing arms could continue as planned, be stopped or modified, or alternative doses could be selected.

The co-primary efficacy endpoints for the trial are spleen response rate and symptom response rate. Spleen response rate is defined as the percentage of patients who achieve ≥ 35% reduction in spleen volume from baseline at the Week 24 visit, as measured by imaging scans and assessed at a central imaging facility and by an Independent Review Committee. Symptom response rate is defined as the percentage of patients who have ≥ 50% reduction in Total Symptom Scores from baseline at the Week 24 visit, based on patient-reported outcomes on a modified Myelofibrosis Symptom Assessment Form version 2.0 electronic diary. The primary efficacy analysis of the co-primary endpoints will occur after all treated patients have been followed for at least 24 weeks.

Secondary efficacy endpoints include the number of patients achieving complete remission (CR) or partial remission (PR), clinical improvement (CI), and anemia, spleen and symptom responses as assessed using the modified 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. These secondary endpoints will be assessed at the time of the primary efficacy analysis. Exploratory endpoints include cytogenetic and molecular responses, as well as leukemia-free survival.

Safety outcomes will be monitored throughout the trial and will include enhanced data collection and reporting for adverse events of interest, including hepatobiliary-associated laboratory findings and hepatic adverse events.

Multiple medical centers across North America, Europe and Asia are planned to participate in the trial. For more information about the IMbarkTM study being conducted by Janssen, please visit View Source

About Imetelstat

Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound, discovered by Geron, is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Preliminary clinical data suggest imetelstat has disease-modifying activity by inhibiting the progenitor cells of the malignant clone associated with hematologic malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies conducted to date include fatigue, gastrointestinal symptoms and cytopenias. Patients in these studies also experienced elevated liver enzymes, which resolved to normal or baseline in the majority of patients followed after imetelstat treatment was withdrawn. Imetelstat has not been approved for marketing by any regulatory authority.

Foundation Medicine Launches Precision Medicine Exchange Consortium™ (PMEC) to Advance the Integration of Molecular Information in Clinical Oncology and Accelerate Adoption of Precision Care

On September 15, 2015 Foundation Medicine, Inc. (NASDAQ:FMI) reported the launch of its precision medicine partner program, Precision Medicine Exchange Consortium (PMEC), to facilitate data exchange, advance research, and support education and applications of precision medicine in oncology and molecular pathology (Press release, Foundation Medicine, SEP 15, 2015, View Source [SID:1234507471]). PMEC brings together oncology thought leaders from academic medical centers, regional hospital systems, and community oncology networks, initially located in the U.S. and to be expanded internationally, who share a vision for utilizing precision medicine as a means for improving clinical outcomes in oncology treatment. The consortium intends to realize this vision through a collaborative exchange of molecular information and clinical outcomes data, and through a broader integration of comprehensive genomic profiling in cancer treatment.

Founding members of PMEC include The Cleveland Clinic’s Taussig Cancer Institute, Hackensack University Medical Center, The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Sidney Kimmel Cancer Center at Thomas Jefferson University, UC Davis Health Comprehensive Cancer Center, the University of North Carolina Lineberger Comprehensive Cancer Center, and Vanderbilt-Ingram Cancer Center and The Wake Forest Baptist Comprehensive Cancer Center.

"Progress in cancer care will be achieved by breaking down the information silos that exist in healthcare and collaborating towards clinically robust and relevant data exchange," said Brian Bolwell, MD, chairman of the Cleveland Clinic Cancer Institute and founding member of PMEC. "We applaud Foundation Medicine and our partner institutions in PMEC for their innovative thinking, for valuing the exchange of information, and for taking a leadership role to effect a positive change for our patients with cancer."

PMEC is being established on the guiding principles of innovation, education and the exchange of highly validated molecular information and outcomes data to improve cancer care. PMEC members will have access to a suite of innovative information tools and programs tailored to fit the needs of the individual cancer centers who are members of PMEC.

A selection of these planned offerings include:

access to a shared data exchange platform of de-identified, matched clinical outcomes and genomic data contributed by Foundation Medicine and PMEC members to support research and clinical innovation;
access to clinical research programs that integrate comprehensive genomic profiling to improve cancer care; and
programs to support the advancement of precision medicine and molecular oncology through training, education and streamlined member services.
Additionally, PMEC members can elect to participate in best practices exchanges, where members will have the opportunity to share ideas advancing precision medicine.

"The promise of precision medicine rests on these national and international initiatives, including PMEC, which enable investigators to share crucial data. Only through that data sharing can we understand the implications of genomics for patient care," said Mary Zutter, M.D., assistant vice chancellor for Integrative Diagnostics at Vanderbilt University Medical Center.

"The Precision Medicine Exchange Consortium is being developed as the most comprehensive program of its kind and will align innovators in cancer care around molecular information and clinical data curation and exchange," said Vincent A. Miller, M.D., chief medical officer at Foundation Medicine. "Collectively, PMEC is poised to fuel innovation, support cancer research and extend valuable information and education in a way that heretofore has not happened within the cancer community. We’re proud to be launching this initiative with so many thought leaders across a broad spectrum of cancer institutions and practices. We’re actively seeking new members who share PMEC’s vision, and we welcome conversations with additional cancer centers, data and informatics organizations and payers who embrace the opportunity to collaborate for the betterment of cancer care."

Foundation Medicine Expands Molecular Information Decision Support Offerings with GeneKit™, a Genomic Solutions Portal for Pathologists

On September 15, 2015 Foundation Medicine, Inc. (NASDAQ:FMI) reported the expansion of its suite of molecular information-based products with GeneKitTM, a genomics solutions portal for pathologists (Press release, Foundation Medicine, SEP 15, 2015, View Source [SID:1234507470]). Uniquely differentiated by the power of FoundationCORETM, Foundation Medicine’s ever-growing comprehensive cancer genomics knowledgebase of more than 50,000 genomic profiles, GeneKit facilitates the interpretation of genomic data generated by pathologists from targeted next generation sequencing (NGS) and "hot spot" assays. This integration will help pathologists to more effectively support clinical diagnosis and treatment strategies via the rapid interpretation and efficient reporting of genomic information to oncology care teams.

"To ensure that molecular information is used to inform therapeutic decisions and improve patient care, we are offering pathologists a sophisticated clinical interpretation system. GeneKit will allow pathologists to assess a patient’s specific tumor alterations against a knowledgebase of curated genomic variants, relevant scientific research, targeted therapy and clinical trial information, enabling the creation of actionable reports in a timely fashion for care teams," said David J. Daly, chief commercial officer of Foundation Medicine. "Today, a large number of institutions use manual interpretation procedures that can be incredibly arduous, technical and time-consuming. GeneKit overcomes these challenges of manual reporting and furnishes pathologists with highly relevant clinical and scientific data for the betterment of patient care."

Since hotspot panels are most widely used in pathology laboratories, GeneKit has been designed to seamlessly integrate into a pathologist’s standard workflow. GeneKit differs from other pathology reporting tools because of the following key features:

Integrates with any NGS assay that interrogates the variant status of up to 50 cancer-related genes that are known to be involved in the development, progression and/or treatment of cancers;

Relies upon FoundationCORE, Foundation Medicine’s knowledgebase of comprehensive genomic cancer information;
Efficiently and rapidly organizes and reports information on up to 50 genes using data from FoundationCORE, as well the customer’s proprietary data;

Easily integrates with other IT systems;

Offers a user-friendly interface that gives pathologists customized reporting options; and,

Provides a reflex option to Foundation Medicine’s comprehensive genomic profiling assays, FoundationOne and FoundationOne Heme.

GeneKit is a cloud-based software solution and is a component of Foundation Medicine’s molecular information-based suite of decision support solutions. GeneKit complements Interactive Cancer Explorer (ICE 2) with PatientMatchTM, the company’s innovative physician-facing decision support portal. Together, GeneKit and ICE 2 provide an unparalleled offering of molecular information-based solutions that empower cancer care teams to make informed diagnostic and therapeutic care choices based on the unique genomic drivers of each person’s cancer.

Cancer Research UK launches three new funding schemes for cancer doctors

On September 15, 2015 Cancer Research UK reported it is launching three new funding schemes to support the careers of cancer doctors researching new ways to prevent, diagnose and treat the disease (Press release, Cancer Research UK, SEP 15, 2015, View Source [SID:1234507469]).

Over the next few years, the charity’s Clinical Careers Committee hopes to fund twice as many fellowships as were previously available. And three schemes will be available for clinicians at different stages of their careers.

The Postdoctoral Research Bursary is available to clinicians to carry out research while completing speciality medical training. This bursary covers research costs for up to two years but does not cover salary.

The Clinician Scientist Fellowship is available to researchers with no previous post-doctoral fellowship experience. It provides the successful candidate’s salary and research costs for up to five years.

And the Advanced Clinician Scientist Fellowship is available to researchers with more than three years post-doctoral research experience. This fellowship provides up to five years funding for the successful candidate’s salary, the salary of another post-doctoral researcher and an assistant or technician in addition to equipment and running costs.

Dr Karen Noble, head of research training and fellowships at Cancer Research UK, said: "We’ve listened to the needs of the community and we’re tailoring our funding accordingly. These new schemes will allow us to support talented clinicians and help to advance research into new cancer treatments.

"Clinical research is the key to finding out if a new approach to cancer treatment works well – and is safe – in patients. It also helps us discover which treatments or strategies work best for certain types of cancer or groups of patients."

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: "Finding the next generation of clinical research leaders is one of our highest priorities at Cancer Research UK. People who can turn our amazing discoveries into things that will help patients in the clinic are vital to our future. We’re excited to further invest in the best clinical research taking place in the UK."