Centella Therapeutics Licenses Novel New Drug Designed to Enhance the Effectiveness of Cancer Treatment

PALO ALTO, Calif. and AUCKLAND, New Zealand, May 24, 2011 /PRNewswire/ -- Centella Therapeutics, Inc., a subsidiary of Varian Medical Systems, Inc. (NYSE: VAR), and Auckland UniServices Ltd. of Auckland, New Zealand, today announced that they have entered into a licensing agreement granting Centella exclusive rights to CEN-209, a novel investigational drug designed to enhance the effectiveness of radiotherapy and chemotherapy when treating solid tumors that are hypoxic—or oxygen-starved—and therefore resistant to standard forms of radiotherapy and chemotherapy.

CEN-209 is selectively activated in areas of low oxygen often found within solid tumors.  These areas develop within tumors due to their rapid growth, which impairs the blood vessels bringing nutrients and oxygen, resulting in hypoxia.  

"Hypoxic tumors are generally resistant to radiotherapy and to chemotherapy, and there is no effective treatment for such tumors today," says Thorsten Melcher, PhD, President of Centella Therapeutics.  "Hypoxia occurs in most types of solid tumors, but not necessarily in every patient with a given tumor type. For example, in lung cancer patients, roughly 50 percent of tumors have hypoxic regions.(1)  In the future, successful treatment of hypoxic tumors will likely require identifying affected patients and giving them a hypoxia-specific drug, like CEN-209, in addition to standard treatment."(2)

Radiotherapy works by damaging tumor cells' DNA, but only in well-oxygenated areas, whereas CEN-209 is designed to 'switch on' and damage the DNA only of hypoxic cells, leaving other cells alone," Melcher adds.  "Thus, the two treatment approaches have the potential to complement each other, and CEN-209 is specifically designed to be preferentially used in combination with radiotherapy."

Professor William Wilson and Associate Professor Michael Hay, along with other researchers from the Auckland Cancer Society Research Centre (ACSRC) in Auckland, New Zealand, identified and characterized CEN-209 under the name SN30000. This work is the culmination of a ten year research program initiated under a U.S. National Cancer Institute grant to Professor J. Martin Brown, PhD, professor of radiation oncology and radiation biology at Stanford University and Professors Wilson and William Denny at the ACSRC.

According to Wilson, CEN-209 was created by improving upon tirapazamine (TPZ), another substance that showed early promise in attacking hypoxic cells but did not significantly improve patient outcomes, in part because TPZ does not penetrate deeply enough into solid tumors to be effective.  

"TPZ had only a limited ability to reach hypoxic cells, which are generally the cells furthest away from blood vessels," said Wilson.  "Drs. Kevin Hicks and Frederik Pruijn used sophisticated computer modeling techniques to validate a predictive model of drug transport within tumors," he added, referring to colleagues at the University of Auckland who collaborated on the research.(3)  

"The computer models of drug transport developed in-house at ACSRC allowed the synthetic chemists to test their design theories through computer simulations, which considerably shortened the discovery process," commented Hay.  "We believe CEN-209 improves on previous agents in this class in terms of its ability to penetrate tumors, and this is reflected by its improved activity in animals when combined with long or short courses of radiotherapy," noted Wilson.(4) "Building on the ACSRC data, we look forward to seeing how well CEN-209 performs in humans," said Melcher.

Finding Hypoxia in a Tumor

In addition to CEN-209, Centella plans to develop CEN-109, an investigational positron emission tomography (PET) imaging agent that is designed to identify tumors with hypoxic areas.(5)

"CEN-109 has undergone Phase I clinical testing at the University of Pennsylvania and the University of Turku in Finland (under the name 18F-EF5), and is being evaluated in Phase II trials at several clinical centers," Melcher says.  "Our hope is to see CEN-109 approved and labeled for use in identifying patients with hypoxic tumors who would benefit from CEN-209 as an adjunct to their chemotherapy or radiotherapy regimens.  We also envision clinicians using CEN-109, if approved, to evaluate the effectiveness of CEN-209 treatments.  We hope to show that this personalized medicine approach will improve treatment outcomes for patients with hypoxic tumors."

About Centella Therapeutics

Centella Therapeutics, Inc. is a wholly owned subsidiary of Varian Medical Systems, Inc. (Varian). Varian, headquartered globally in Palo Alto, California, is the world's leading manufacturer of medical devices and software for treating cancer and other medical conditions with radiotherapy. Centella, which was previously known as Centella biotechnologies, inc., is a dedicated enterprise focused on discovery and development of cancer treatments at the intersection of radiotherapy and pharmaceutical therapeutics.   Centella's mission is to develop a portfolio of drugs with a focus on enhancing the effectiveness of radiotherapy, making Centella the first Radiation Oncology Biotechnology company.

About the Auckland Cancer Society Research Centre

Since its inception in 1956, the Auckland Cancer Society Research Centre (ACSRC), which is managed jointly by The University of Auckland and the Cancer Society Auckland, has published nearly 1,000 papers in international scientific and medical journals, and filed more than 100 patent applications for new anti-cancer drugs. In that time, the centre has developed eight cancer drugs which have gone into clinical trials. The ACSRC has the distinction of being the first laboratory in the Southern Hemisphere to discover, trial and bring an anti-cancer drug into clinical use.

About Auckland UniServices Ltd.

Auckland UniServices Limited is the largest research and development company of its kind in Australasia, and a wholly owned company of The University of Auckland. UniServices manages the University's intellectual property and is responsible for all research-based consultancy partnerships, commercialisation, and contract education. By connecting its clients with the University's brightest academic minds, UniServices provides commercial organisations the innovative technologies they seek, and governments the national programmes they need. In this agreement, UniServices acted on behalf of the Auckland Cancer Society Research Centre (ACSRC), an operating unit of The University.

(1) Le QT et al.  An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clin Cancer Res. 2006;12(5):1507-14.

(2) Wilson WR and Hay MP.  Targeting hypoxia in cancer therapy.  Nature Reviews Cancer AOP, published online 24th May 2011; doi:10.1038/nrc3064.

(3) Hicks KO et al.  Use of three-dimensional tissue cultures to model extravascular transport and predict in vivo activity of hypoxia-targeted anticancer drugs. J Natl Cancer Inst. 2006 ;98(16):1118-28.

(4) Hicks KO et al.  Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors. Clin Cancer Res. 2010;16(20):4946-57.

(5) Komar G et al.  18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer.  J Nucl Med. 2008; 49(12):1944-51.

SOURCE Varian Medical Systems, Inc.