QUÉBEC CITY—In a move that illustrates Aeterna Zentaris Inc.'s strategy of pursuing a more personalized healthcare approach with its therapeutic candidate AEZS-108, the late-stage drug development company has announced a collaborative study with the diagnostics division of Almac around the company's doxorubicin luteinizing hormone-releasing hormone (LHRH) targeted conjugate compound.
Aeterna Zentaris, which specializes in oncology and endocrine therapy, says that the study is aimed at determining LHRH receptor expression through the development of a companion diagnostic tool. Selection for treatment with AEZS-108 is determined on the basis of LHRH receptor expression, currently measured immunohistochemically. In humans, LHRH receptors are expressed in ovarian, endometrial, breast, bladder, prostate and pancreatic tumors. AEZS-108 is currently in Phase II trials for advanced LHRH receptor-positive ovarian and endometrial cancer.
Almac was the collaborator of choice in this instance in part because the company has proven experience in the development and validation of companion diagnostic tools and potential biomarkers in cancer indications, says Dr. Juergen Engel, president and CEO of Aeterna Zentaris.
"This state-of-the-art companion diagnostic tool will allow us to develop improved methods of selecting the most appropriate patients to be treated with AEZS-108 in order to enhance the efficiency of our clinical trials and help us with the future successful development of AEZS-108 in a number of different LHRH-expressing cancers," he says.
Another reason for choosing Almac is that its people have an extensive knowledge of the molecular basis of cancer, "especially from the aspect of biomarker discovery combined as part of the clinical trial process," according to GinetteVallières, investor relations coordinator for Aeterna Zentaris, who adds that Almac has had extensive and successful collaborations with several of the major companies involved in the discovery and development of oncologic agents.
Paul Harkin, president and managing director of Almac Diagnostics, calls the project "exciting" and says that "the plan to develop a companion diagnostic for AEZS-108 shows Aeterna Zentaris' clear commitment to personalized medicine, which will provide this compound with the best opportunity for success."
The joint venture with Almac is Aeterna Zentaris' first in the field of cancer diagnostics, says Vallières, but Almac has also recently provided some preliminary help with solorel, designated AEZS-130.
"For a small company such as ours, this is an exciting beginning of our collaboration with them and we look forward to studying the results from our joint endeavors," Vallières says. "These will determine if and how we will work on other projects in the future. Given the rather extensive pipeline of innovative products we have, we are excited to be working with Almac as described and we look forward to a successful future."
AEZS-130 is being pursued as a potential diagnostic for growth hormone deficiency in the field of endocrinology, Vallières notes, adding, "In addition to the therapeutic field being different, in this instance, we are developing the diagnostic first and this will be followed by therapeutic exploration—in this case, with the same agent rather than a companion product. The possible indications could involve any or all of those in which patients are capable of producing growth hormone, but for whatever reason, they are failing to do so. One of the first indications we will explore with solorel is cancer cachexia."
Aeterna Zentaris notes that at the recent American Society of Clinical Oncology (ASCO) meeting in Chicago, it presented encouraging data on AEZS-108—the agent it is currently working with Almac on—in patients with advanced ovarian cancer, and Vallières notes that the company has also submitted very encouraging data from patients with advanced endometrial cancer, which may be presented before the year's end.
It was at oncology meetings such as ASCO's over the past couple years, in addition to those of the American Association for Cancer Research (AACR), that Aeterna Zentaris and Almac came to know each other, Vallières recalls, "followed by direct specific discussions. We found their dealings with companies such as AstraZeneca, Lilly and Pfizer to be reassuring. But more importantly, their attention to our specific needs as a small—but science-driven—company, was impressive to us."
The test to be developed with Almac will provide the data on sensitivity, specificity, negative predictive value, positive predictive value and hazard ratio to demonstrate the clinical potential of the targeting mechanism that is designed into AEZS-108.
"With these exciting trial data in hand and with studies about to start in patients with advanced bladder cancer and hormone refractory prostate cancer, the time is ripe to develop a robust, accurate and reproducible method for determining LHRH receptor positivity," Vallières states. "We expect these data will help in patient selection for clinical trial participation, evaluation of responses and contribute overall to the regulatory submission and eventual reimbursement decisions."
