BioWorld International Correspondent

LONDON - Alizyme plc is pondering the pathway for onward progression of ATL-104 after reporting positive results in a Phase IIa trial in oral mucositis induced by chemotherapy.

The proof-of-concept trial was in patients with hematological cancers undergoing chemotherapy followed by bone marrow transplant, and the company is weighing whether to proceed to a Phase III in that indication, or to carry out a Phase IIb trial in patients with solid tumors.

At present, Kepivance, produced by Amgen Inc., of Thousand Oaks, Calif., is the only registered treatment for mucositis in hematological cancers.

There is no marketed therapy for mucositis in solid tumors, though Amgen is working on expanding the Kepivance label in that direction. Saforis, from MGI Pharma Inc., of Minneapolis, has completed a Phase III trial in breast cancer, and two other U.S. companies, RxKinetix Inc. and Serenex Inc., have products in Phase II.

"We have demonstrated a reduction in the duration of mucositis by a number of different criteria. The next step will be discussions with the regulators and sharing the data with potential partners," Richard Palmer, CEO, said during an analysts’ meeting.

"We could go forward in bone marrow transplant. At the same time, there are many solid tumors in which mucositis can be chemotherapy dose-limiting. Certainly, the [favorable] regulatory climate in terms of this area of severe unmet needs should be tapped into," he said.

The trial compared the effect of three doses of ATL-104 and placebo on the incidence, duration and severity of mucositis. Patients were treated for three days before and three days after chemotherapy. Fifty-two out of an initial 64 patients went through to the end of the trial.

The duration of mucositis was consistently reduced across all treated groups, with a shorter mean duration at all doses compared to placebo on both the World Health Organization Oral Mucositis scale and the Western Consortium for Cancer Nursing Research scale.

The number of days when a patient was unable to take solids by mouth was reduced also, to an average of 2.5 days for the three treated groups, compared to 6.5 days for the placebo group.

"We got the same conclusion from the two different [scales]; there was a reduction of mucositis in the treated arms, accompanied by a reduction in the duration of pain, ulceration and inability to take solids," Palmer said.

"There was no appreciable difference in adverse events over chemotherapy alone, so we have achieved the objective of getting proof of concept in a study of sufficient size and diversity," he said.

ATL-104 has been sitting in Cambridge, UK-based Alizyme’s portfolio for a while, but the company has held back from investing in its development in favor of three other products that it considered lower risk.

"The problem is the basic science is not well understood, and although there is a large unmet medical need, there is a great deal of complexity," Palmer said.

ATL-104, a lectin protein manufactured by a recombinant process, is administered as a mouthwash that is rinsed for 30 seconds and then swallowed.

That differentiates it from Kepivance, a recombinant form of human keratinocyte growth factor, which is injected. ATL-104 is expected to act in the gut, as well as the mouth, though Palmer said patients receive so many agents as standard care to control the effects of mucositis in the gut that he does not expect to show any benefit in the trial.

As ATL-104 works by stimulating cell proliferation in the epithelium, Alizyme needs to demonstrate it does not stimulate tumor cells, too. Palmer said it is a large molecule, and tests showed none of it reached the bloodstream.

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