A Targeted Agent for Triple-Negative Breast Cancer

Glycoprotein NMB (gpNMB) is a transmembrane protein and tumor-associated antigen that is expressed at higher levels in certain malignancies than in normal tissues. Glembatumumab vedotin (CDX-011) is an antibody-drug conjugate consisting of a fully human IgG2 monoclonal antibody against gpNMB linked to the microtubule inhibitor monomethyl auristatin E (MMAE). By targeting and binding to cells overexpressing gpNMB, the antibody is internalized, allowing for intracellular release of the cytotoxic MMAE.

A prior phase I/II trial of CDX-011 for refractory advanced breast cancer demonstrated an acceptable toxicity profile and an objective response rate (ORR) of 12% (NEJM JW Oncol Hematol Nov 2014 and J Clin Oncol 2014; 32:3619). In the subset of patients with triple-negative breast cancer (TNBC), the ORR was 20%, and progression-free survival (PFS) was 4.1 months; in TNBC patients with gpNMB-expressing tumors the ORR was 25%, and the PFS was 5.1 months. Now, investigators have conducted an industry-supported, randomized phase II trial (EMERGE) of CDX-011 versus investigator choice of chemotherapy (IC) in 124 refractory breast cancer patients with tumors overexpressing gpNMB (defined as ≥5% of malignant epithelial or stromal cells with any expression).

ORR was similar overall for patients receiving CDX-011 or IC (6% and 7%, respectively) and for those with gpNMB-expressing tumors (12% for both). ORR was higher with CDX-011 versus IC in patients with ≥25% of tumor cells expressing gpNMB (30% vs. 9%) as well as in TNBC patients (18% vs. 0%) and TNBC patients with overexpression of gpNMB (40% vs. 0%). Dose reduction occurred in 25% of patients in both treatment arms. The most common CDX-011 toxicities were rash, fatigue, nausea, neutropenia, and neuropathy.

The attraction of targeted therapy with an antibody delivery system is that it directs the cytotoxic agent preferentially to the malignant cell population, potentially enhancing efficacy and minimizing systemic toxicity. The use of ado-trastuzumab emtansine for HER2-positive breast cancer demonstrates the success of this approach (NEJM JW Oncol Hematol Sep 2014 and J Clin Oncol 2014; 32:2750). The signal that CDX-011 is active in TNBC is exciting, but the observations from this study are based on very small numbers of patients. A larger, pivotal phase II trial (METRIC) is under way to more fully investigate this compound in TNBC.

Yardley D et al. EMERGE: A randomized phase II study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB–expressing breast cancer. J Clin Oncol 2015 Apr 6; [e-pub]. (http://dx.doi.org/10.1200/JCO.2014.56.2959)

ROS1 rearrangements occur in approximately 1% of patients with NSCLC

The Promising Therapeutic Strategy against ALKoma and ROS1-positive Tumors

It has recently been identified that crizotinib significantly inhibits the tumor cells with ALK-fusion genes or ROS1-rearranged driver genes which encode constitutive tyrosine kinase receptors. The emerging concept of lung cancer stem cells (CSCs) arises a question of the relationship between CSCs and ROS1 gene rearrangement.

Lung non-small cell cancers are likely to develop due to the fusion genes characterized by EML4-ALK, which suggests the importance of fusion genes in tumorigenesis in the same way as chronic myeloid leukemia (CML) with Philadelphia chromosome derived from t(9;22).

On the other hand, EGFR signal pathway is hyper-activated in lung cancer cells or head and neck squamous cancers. EGFR and CD44 variant (CD44v) expression shows the inverse pattern, and furthermore, CD44v-positive CSCs are refractory to reactive oxygen species (ROS)-induced cellular senescence and apoptosis. It remains to be known the way crizonitib relatively inhibits which sub-population of tumor cells.”

Content Source: Originally posted in “Cancer Targets & Therapeutics Society” LinkedIn group by Jean Plante

Citation: http://www.nejm.org/doi/full/10.1056/NEJMoa1406766

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Apollo Hospitals & Saarum Innovations launch Sapien Biosciences

Welcome to Sapienbio Blog

This article originally appeared in 2013

Joint Venture to create a world-class human bio-bank and personalized medicine company, first of its kind in India to enableinnovative research & clinical applications

Hyderabad, September 23, 2013:

Apollo Hospitals with Saarum Innovations, launched its joint venture ‘Sapien Biosciences’ today at Hyderabad to create aworld-class bio-bank and personalized medicine company. The bio-bank will comprise of collections of high-quality, ethically-consented and anonymized human samplesalong with associated medical & sample-level data across various diseases e.g., cancer, cardiovascular and diabetes. This will enable cutting-edge life sciences research and support the discovery & development of novel biomarkers, diagnostics & personalized medicine applications.Sapien plans tocollaborate with healthcare enterprises and drug discovery companies globally to study disease epidemiology, validate new diagnostics, identify new drug targets and evaluate new drugs.

Sapien has exclusive access to the entire Apollo network for its bio-banking needs but expects to partner with additional research-oriented hospitals and clinics for their personalized medicine and bio-banking needs. Further Sapien has entered into an alliance with Apollo Hospitals that allows Sapien to front-end Apollo’s personalized medicine initiatives. This allows Sapien to bring novel cutting-edge diagnostics to Apollo, either on its own or in collaboration with best-of-breed institutions world-wide thereby enabling world-class healthcare and improving patient outcomes.

Speaking on the occasion, Ms. Shobana Kamineni, Executive Director, New Initiatives, Apollo Hospitals, said, “This is a proud moment for us at Apollo to be a part of this landmark initiative in the history of Indian Health care. Apollo Hospitals has long had a vision of creating Asia’s largest bio-bank which is being realized in partnership with Saarum Innovations. Sapien will help fulfill our vision of delivering better clinical outcomes through bench-to-bedside innovation. This alliance is a further validation of Apollo’s commitment to research-driven health care.”

Speaking on the occasion Mr. Sreevatsa Natarajan, Co-founder & CEO, Sapien Biosciences said “Saarum Innovations is proud to be associated with a healthcare pioneer & leader like Apollo Hospitals. Apollo’s passion for world-class healthcare combined with Saarum Innovations’ proven research expertise will bridge healthcare & life-sciences and enable cutting-edge research & diagnostics applications.”

Speaking on the occasion, Mr. Seemant Jauhari, CEO of AHERF said, “Apollo, through the Apollo Health Education & Research Foundation (AHERF), is spearheading a vibrant portfolio of innovative projects that will enable effective and affordable technologies for better treatment outcomes. Bio-banking & personalized medicine was one such initiative which is being realized with the launch of Sapien Biosciences.

Sapien Biosciences also announces the launch of its first & novel personalized medicine test,‘myPLATELET, which determines patients’ response to their blood-thinning medicationand supports decision-making by their cardiologists to personalize therapy for better outcomes. This is the only test in India that combines both genetic and platelet function response to enable tailored anti-platelet therapy for each patient.

Speaking on the occasion Dr. Jugnu Jain, Co-founder and CSO, Sapien Biosciences said “Sapien’s novel myPLATELET test offers more complete assessment of a patient’s platelet response than existing tests and enables informed clinical decision-making thus exemplifying Sapien’s approach to personalized medicine innovation.”

About Saarum Innovations

Saarum Innovations has been set-up with the vision of utilizing human tissues, primary cells and stem cells to better understand disease biology, develop novel biomarkers and diagnostics, discover novel drug targets and drugs therapeutics that translate into better clinical successes. It is co-founded by a team of three seasoned life sciences R&D professionals,Sreevatsa Natarajan, Prithi Rajan and Jugnu Jain who collectively have over 60 years of global R&D experience.

Sapien Biosciences is managed by the Saarum Innovations team with Sreevatsa Natarajan as the Co-founder & CEO, Jugnu Jain as the Co-Founder & CSO, and Prithi Rajan as the Co-Founder & Executive Director.For more information about Sapien Biosciences, please refer www.sapienbio.com

About Apollo Hospitals

In 1983, Dr Prathap C Reddy, the architect of Indian healthcare, launched the first corporate hospital in India. An integrated healthcare company, the Apollo Hospitals Group has over 8,500 beds across 50 hospitals, more than 1200 pharmacies and 100 diagnostic clinics, medical business process outsourcing services, health insurance services, and clinical research divisions with a focus on epidemiological studies, stem cell research and genetic research. To develop talent for the burgeoning need of superior healthcare delivery, the Apollo Hospitals Group has 11 nursing and hospital management colleges. These accomplishments have earned Apollo Hospitals Group accolades such as the Centre of Excellence from the Government of India and recognition from the Joint Commission International (seven of our hospitals are JCI accredited). In a rare honor, the Government of India issued a commemorative stamp in recognition of Apollo’s contribution, the first for a health care organization. Apollo, for over 27 years, has continuously excelled and maintained leadership in medical innovation, world-class clinical services and cutting edge research. Our hospitals are consistently ranked amongst the best hospitals globally for advanced medical services. For more information visit www.apollohospitals.com

Apollo Hospitals set to integrate clinical genomics as part of its personalized medicine initiatives

Note: This article originally appeared in September, 2013

Sapien Biosciences, an Apollo subsidiary, to spearhead the introduction of cutting-edge genomic testing across the Apollo network

Apollo Hospitals today announced the introduction of several genomic tests as part of its personalized medicine initiative. The introduction of these tests, over the next few months, shall be spearheaded by the Apollo Hospitals subsidiary, Sapien Biosciences.

Sapien was launched in Dec 2012 with the vision of being a world-class biobank and personalizedmedicine company that will bring novel diagnostics to Apollo, either on its own or in collaboration with best-of-breed institutions world-wide thereby improving patient outcomes. Previously Apollo, through Sapien, had launched – India’s first, a personalized test that combines assessment of a patients’ genotype and their platelet function to allow the physician to personalize anti-platelet therapy..
Genomic testing involves analyses of patient genomes and translating insights gained from these analyses to develop better healthcare interventions by way of better prognostic tools for improved disease screening and prevention strategies, better diagnostic tests for optimization of clinical care and better theranostic tests for personalization of treatment.

Sapien has been working with multiple genetic testing providers in India over the last few months to develop and customize these tests for introduction at Apollo. The first of these tests, to be launched shortly, shall be a clinical genomics panel for oncology that is designed to identify the mutations that drive cancer initiation and progression. Insights obtained from this test will enable prediction of patients’ response to their medication allowing the physician to tailor treatment to the patients’ genomic profile. Along with the cancer genomic panels, we will also be launching other panels that will enable differential diagnosis of certain heritable eye and cardiovascular diseases. Such panels will be especially helpful in identifying specific gene mutations in affected individuals. This information can in turn be used to screen unaffected members of their family for early detection and management.

We shall also be introducing, genetic testing within the preventive healthcare context under careful physician supervision and with appropriate genetic counseling support. Apollo has pioneered the preventive healthcare revolution in India and has, to-date, performed over 8.5 million preventive health checks. The advent of advanced genomic analytical techniques has enabled screening for genetic predisposition to various diseases. In this context, tests that identify an individual’s risk for diseases of high relevance in the Indian population (such as cardiovascular, diabetes and obesity) could make a significant clinical impact. Further genetic tests planned for roll-out include single gene panels for specific cancers (such as BRCA1/2, etc.), other disease-specific genetic testing panels (such as diabetes, autism etc.), pharmacogenetic panels (for assessment of response to specific drugs) and peri-natal diagnosis of genetic disorders.

Speaking on the occasion, Dr. Prathap C. Reddy, Chairman, Apollo Hospitals, said, “At Apollo, we believe, that such genetic tests, that are increasingly being adopted world-wide, will have a major impact on the delivery of quality clinical care and we are planning to integrate them into our clinical practice, in a manner consistent with global best practices. I am excited about the comprehensive strategy put together by Sapien to introduce genomic testing at Apollo and I look forward to the successful launch of these tests.”

Speaking on the occasion, Ms. Sangita Reddy, Executive Director, Apollo Hospitals, said, “Apollo has been a trend-setter in healthcare, pioneering the concept of preventive health checks in 1983 and the concept of Personalized Health Checks (PHCs) in 2013. Going forward, we are excited that these PHCs will include an optional genetic test to assess an individual’s risk factors for diabetes, obesity and cardiovascular disorders. Such tests will allow our clinicians to personalize their patients’ health-check follow-up and assess risk factors that can potentially impact their long-term health outcomes.”

Speaking on the occasion Mr. Sreevatsa Natarajan, Co-founder & CEO, Sapien Biosciences said “The comprehensive roadmap developed by Sapien anticipates the launch of various genetic tests over the course of the next few months across the Apollo network, in partnership with key collaborators. At Sapien, we have a highly qualified, internationally experienced team that will play a major role in the systematic roll-out and integration of genomic testing and other cutting-edge diagnostic tests at Apollo. Eventually, Sapien and Apollo’s vision shall be crystallized as centers for personalized medicine across the Apollo network”

Speaking on the occasion Dr. Jugnu Jain, Co-founder and CSO, Sapien Biosciences said “Our experience with genetics allows us to critically evaluate literature and customize tests for Indian patients for optimal clinical benefit, consistent with global best practices and patient privacy norms. Over time, we expect to have a large database of genotype-phenotype correlation for Indian patients that will allow identification and quantification of genetic risk factors, akin to a ‘Framingham Score’, for cardiovascular diseases, diabetes and cancer.”

Speaking on the occasion, Mr. Seemant Jauhari, CEO, Research & Innovations, Apollo Hospitals said, “Pushing new frontiers through healthcare innovation is a key driver at Apollo. Apollo has deliberated introducing genetic testing in a responsible and effective manner. We intend to integrate these tests into the clinical practice at our hospitals with active participation from our physicians in prescribing and interpreting test results within the context of the patients’ overall clinical profile. Further, we are considering creating a comprehensive genetic counseling course as part of Apollo’s initiatives in medical education.”

Sapien Biosciences Inaugural Launch Videos

Apollo Hospitals & Saarum Innovations Launch Sapien Biosciences

Dr. Jugnu Jain Sapien Biosciences Co-Founder & Chief Scientific Officer

Sreevastsa Natarajan Sapien Biosciences Co-Founder & Chief Scientific Officer

Shobana Kamineni Apollo Hospitals Enterprise New Initiatives Executive Director

Dr. Hariprasad Apollo Hospitals Enterprise Central Region CEO