A Global TB Research Network

In mid-2008, Vertex announced the formation of a global collaboration aimed at advancing early-stage research into new approaches for the treatment of tuberculosis. Tuberculosis (TB), a life-threatening infectious disease, continues to be a growing world health problem. New treatments are urgently needed to shorten therapy and to target persistent infections. To address this need, Vertex established a network that brings together Vertex’s history of scientific excellence in infectious diseases drug discovery with additional chemistry and early biology expertise from academic institutions, infectious diseases hospitals, and technologically advanced contract research organizations from across the world. This network model enables a greater flow of ideas and facilitates the development of new, more innovative approaches to tuberculosis drug discovery.

To date, Vertex has engaged the commitment of multiple TB research organizations and over 60 researchers around the globe. As part of the network, Dr. Robert Husson and a team of scientists at Children’s Hospital Boston, are identifying and validating new drug targets and pathways involved in kinase pathways and bacterial physiology. Further, Vertex has entered into a research collaboration with Dr. Lee-Ann Allen of the Department of Inflammation and Immunity at the University of Iowa to develop high throughput assays that will enable the team to gain a better understanding of how Mycobacterium tuberculosis (Mtb) subverts killing by the infected macrophage. Vertex is also working with Dr. Michael Cynamon at the Veteran’s Administration Medical Center in Syracuse, New York to develop improved animal models that can be used to more rapidly identify and optimize lead molecules and drug candidates than currently used methods.

Outside the U.S., the Institute of Medicinal Biotechnology (IMB) of the Chinese Academy of Medical Sciences in Beijing will bring together several institutes in China, each having expertise in either target-based drug discovery and screening, medicinal chemistry and lead optimization, pharmacokinetics and pharmacodynamics, as well as clinical management of tuberculosis and archiving patient isolates of unique local Mtb strains, and several advanced preclinical models for TB drug testing. They will also leverage their expertise in natural product chemistry to develop new weapons that may help kill multi-drug resistant Mtb strains and shorten the therapeutic regimen. Vertex has also established a dedicated medicinal chemistry, pharmacokinetics, and bioassays unit at ChemPartner in Shanghai, China.

Vertex continues to build its network of strategic research alliances with the goal of developing multiple drug discovery programs in parallel.

A New Approach to Early Research

Can protein folding research point the way towards new ways to treat Huntington’s disease? Working together to explore this possibility, CHDI Foundation and Vertex hope to discover the tools that may help answer that question.

CHDI Foundation is a non-profit biotech committed to finding therapeutics that will delay or slow the progression of Huntington’s disease – a familial disorder that causes brain cells to fail and die. Our collaboration with CHDI, which began in June 2008, is aimed at developing assays for use in discovering novel compounds that may benefit individuals with this disease.

Protein folding aberrations involved in Huntington’s disease are also believed to be associated with other neurological diseases. The information gained from this collaboration may provide insight to new approaches for treating Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis (ALS). See press release for more information.

Lighting the Way to Drug Discovery and Development

How can the brightest light source in the world help to advance our drug discovery and development programs? In collaboration with Diamond Light Source, a scientific facility in South Oxfordshire, UK, we hope to shed new light on the atomic details of how novel drugs bind to proteins involved in human diseases.

The Diamond Light Source is a scientific tool that generates intensely focused synchrotron light in the form of X-rays. It is the largest scientific facility to be built in the UK for 40 years and is located just three miles from Vertex’s UK research center. Vertex established its collaboration with Diamond Light Source in May 2008 and is the first industrial user of the synchrotron technology. We believe that our work with Diamond Light Source will be central to the continued progress in our understanding of biological processes that enable innovative drug design. By utilizing these state of the art technologies, Vertex will continue to be at the cutting edge of science and drug discovery.

Mapping Responses with Proteomics

Does treatment success have a telltale protein signature? We have teamed up with Caprion, a privately held company based in Montreal, Canada to find out. Caprion specializes in studying protein expression in blood and tissue samples to identify specific protein targets and biomarkers that are associated with a range of diseases. Using Caprion’s CellCarta platform, we’re tracking protein markers that may predict, very early on in therapy, which patients will successfully respond to treatment.

We began collaborating with Caprion in March of 2006. We expanded our collaboration early in 2007 to provide more comprehensive evaluation of relevant protein targets and biomarkers in diseases of interest to us. We believe that the information we gain in this collaboration may help us to identify the most appropriate patients for enrollment in clinical trials, and ultimately help physicians make better treatment choices in clinical practice.

Seeing Safety in the Lab

Is it possible to know the safety profile of some drugs before they are dosed in patients? Our collaboration with CeeTox, a privately held company in Kalamazoo, Michigan, may provide an answer. CeeTox has developed a proprietary series of in vitro screens to help determine important characteristics of candidate molecules — including safety and pharmacokinetics—at the earliest stages of drug discovery.

We began collaborating with CeeTox in 2006. Incorporating CeeTox’s technology into our drug discovery efforts is helping us to select the best compounds for clinical testing, as well as to select initial doses for evaluation in clinical trials.

Finding Common Ground in Cancer

The United Kingdom Biotechnology and Biological Sciences Research Council (BBSRC) provides £200 million to support 7,000 scientists and graduate students in the UK. Major goals of the BBSRC are to provide unique research training opportunities for students and, to bring academia and industry together to advance science and medicine.

In mid-2006, a prestigious BBSRC Ph.D. studentship was awarded to Vertex and the University of Portsmouth, to study the role of growth factors and other proteins involved in cell proliferation and cancer. This project uses a new technology partly developed by University of Portsmouth Professor Ian Cree, who is co-supervising the project with scientists at Vertex. Through this collaboration, a University of Portsmouth graduate student will use novel approaches to assess growth mechanisms in human cancers.

A Pioneering Experiment

In 2007, we began an experiment with the Department of Biology at the Massachusetts Institute of Technology (MIT), just down the street from Vertex’s Cambridge, MA headquarters. As part of this collaboration, Vertex will each year sponsor two graduate students in the Department of Biology who will have access to mentoring from industry scientists. These students will graduate as Vertex Scholars from MIT.

The goal: a new level of cooperation between industry and academia that may spawn research breakthroughs and medical innovation.