Small but mighty
October 2011
by David Hutton  |  Email the author


LAUSANNE, Switzerland—Debiopharm and cancer drug firm Ascenta Therapeutics have reached an exclusive license agreement for the development and commercialization of Ascenta's Phase I stage candidate AT-406.  
AT-406 is an orally available small molecule that is designed to neutralize major inhibitors of apoptosis. AT-406 was discovered in the laboratory of Dr. Shaomeng Wang at the University of Michigan. Clinical trials with AT-101 are ongoing in the United States and Europe. Phase I and Phase II trials evaluating AT-101 as single-agent therapy have already demonstrated cytoreductive activity in several cancers, including chronic lymphocytic leukemia, non-Hodgkin lymphoma and prostate cancer. Phase II trials evaluating AT-101 in combination with chemotherapy and/or radiotherapy have also been carried out in a number of cancers including hormone-refractory prostate cancer, non-small cell lung cancer, B-cell malignancies, small cell lung cancer, glioma and esophageal cancer.  
Debiopharm will designate the molecule Debio 1143. The molecule is designed to block the activity of a number of IAPs including XIAP, c-IAP1, c-IAP2 and ML-IAP. Dr. Rolland-Yves Mauvernay, president and founder of Debiopharm, says it should be possible to combine Debio 1143 with other pro-apoptotic agents, which could potentially bring huge benefits to patients by enhancing the efficiency of the treatment.

Evasion of apoptosis is a hallmark of cancer, enabling cancer cells to live indefinitely and grow uncontrollably. Most current cancer therapies, including chemotherapeutic agents, radiation and immunotherapy, work by inducing apoptosis. However, because of molecular alterations in the apoptotic pathways, many cancer cells are resistant or develop resistance to these agents. A promising new direction for drug development involves targeting apoptotic pathways directly to induce cell death and/or restore sensitivity to other treatments.  
According to Maurice Wagner, director of corporate affairs and communications for Debiopharm Group, the timeline to develop the small-molecule IAP inhibitor may be hard to gauge at this stage, as Phase I clinical trials have yet to be completed.  
"In any event, we will proceed as quickly as we can, whilst observing all safety standards," he says. "As is our business model, we will not commercialize the drug ourselves, but license it out in due time to a company that can sell and market it internationally. The out-licensing partner will be selected at a later stage."
Looking forward, Wagner says as the company proceeds with development, it will set objectives to reach.  
"We will in particular design carefully clinical studies in cancers with high medical needs," he explains. "Our success will depend upon whether we can reach our objectives.  In the short term, successes might be related to preclinical synergistic activity of Debio 1143 and other anti-cancer agents, and most importantly, obtaining encouraging clinical data from the ongoing Phase I study. The long-term success will depend upon our finding a good combination in the clinics, such as a combination that will prove therapeutically superior to the standard of care."  
According to Wagner, the company has worked with Ascenta in the past few years, but this is the first time that the two companies have entered into a partnership with each other.  
Wagner says there were two factors that led Debiopharm to target Ascenta as a collaborator for this effort: "We saw the expertise of Ascenta in the field of apoptosis, and the quality of the relationship that we could establish with the Ascenta team," he says.  
Mel Sorensen, president and CEO of Ascenta, says Debiopharm proved to be an attractive collaborator because of its commitment to and expertise in the development of medicines to help cancer patients.
Code: E101106

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