Medical World News

[Preciouslife1]

THE BRAVE NEW WORLD OF CANCER IMMUNOTHERAPY

http://noblelsp.com/news/cancer-immunotherapy-sector-review


On the surface it may seem that the progress in immunotherapy of cancer has predominantly occurred in the last few years. It is true that the most significant regulatory approvals, immune checkpoint inhibitors, came in the last year and the first checkpoint inhibitor was approved in 2011.

However, success in cancer immunotherapy is built on decades of diligent and innovative research and development, and numerous academic and corporate clinical trial failures. Past failures and the step by step incremental successes, so typical of biomedical research, have now catalyzed a new direction. In cancer immunotherapy drug development, we may have failed forward towards success.

The regulatory approvals of Bristol-Myers Squibb's (BMY) Yervoy (ipilimumab, CTLA-4 inhibitor) in March 2011 and Opdivo (nivolumab, PD-1 inhibitor) in December 2014; and Merck's (MRK) Keytruda (pembrolizumab, PD-1 inhibitor) in September 2014 are pioneering immune checkpoint inhibitor based immunotherapies that have meaningfully changed metastatic melanoma treatment. Opdiva has since been approved for advanced squamous non-small cell lung cancer, and Keytruda may follow soon. Potentially, this may be just the tip of the iceberg. The developing immunotherapy pipeline looks robust, with novel approaches such as Chimeric Antigen Receptor (CAR) T cells, novel checkpoint inhibitors, cytokine modulators, novel T cell co-stimulators, and bi-specific/tri-specific antibodies amongst other approaches. Recently, a bi-specific antibody developed by Amgen (AMGN) (Blincyto, blinatumomab) that targets CD19 on B-cells and CD3 on T cells was approved for acute lymphocytic leukemia (ALL). Furthermore, the prospect of enhancing tumor response rates with patient-specific predictive biomarkers, combination approaches with different immunotherapy agents as well as combination with conventional treatment regimens (radiation, chemotherapy, and signaling pathway inhibitors) is welcome news for patients, clinicians, and all stakeholders in the oncology community.

A new and nuanced understanding of the interaction between tumors and the host immune response and the complexities in the tumor microenvironment has been critical in immunotherapy drug development. Reversing the immune-suppression that tumors exert on the host immune system, as opposed to exclusively targeting immune stimulatory pathways or mutated signaling pathways or the cytotoxic destruction of tumors, has been the difference (with immune checkpoint inhibitors). However, response rates still need to improve and complementary combination approaches to checkpoint inhibitors may be the next advance. Combination approaches with immune checkpoint inhibitors are in development with T cell co-stimulators (OX40, CD27, 41BB, GITR, TNFRSF25), with engineered Listeria monocytogenes immunotherapy, with local delivery of immunomodulatory cytokines such as IL-12 and a host of other combinations. Novel immune checkpoint inhibitors targeting Indoleamine (2,3)-dioxygenase (IDO), phosphatidylserine and CD47 on macrophages are in development as well and could be studied in combination with PD-1. In addition, the next generation of improved CAR-T cell and novel innate immunity targeting CAR-NK cell technologies are in the pipeline. CAR-NK cells harness the potential of Natural Killer cells (NK cells). NK-cells, unlike T cells, are not antigen restricted and have the added virtue of connecting innate with adaptive immunity.

Strong interest by Big Pharma and the investor community in immunotherapy this time around is a reflection of a deeper understanding of tumor biology, the mechanisms underlying tumor evasion of the immune system, understanding molecular heterogeneity within tumors, selection of the right patient population and last, but not the least, parallel innovation in molecular biology techniques and research & development tools such as next generation sequencing, single cell analysis, bioinformatics amongst others.

Besides interest by Big Pharma, successful IPOs and follow-on financings for Juno (JUNO), Adaptimmune (ADAP), Kite (KITE), Affimed (AFMD), Bluebird (BLUE), Bellicum (BLCM), Aduro (ADRO) and NantKwest (NK) amongst others, shows prolonged investor appetite for immunotherapy at emerging biotechnology companies. Notable is the biggest biotech IPO in at least the last decade, NantKwest (formerly Conkwest) that reached $2.6B in market capitalization on its public markets debut. NantKwest (NK) develops off the shelf NK cell based immunotherapies.

Authored by: Rahul Jasuja, PhD, Managing Director, Biotechnology Research

Download the Industry Research Report

Download the full newsletter including Transaction Activity • NLSP Overview • Stock Performance here:

Cancer immunotherapy sector REVIEW | Q3 2015 ...... THANK YOU TO HUTSCHI