Study will evaluate firm’s fusion protein therapeutic in Phase II.

Children’s Oncology Group (COG) and Apeiron Biologics have decided to jointly investigate the company’s APN301 in a Phase II study in pediatric neuroblastoma. The drug is a recombinant fusion protein consisting of the humanized anti-GD2 mAb hu14.18 fused to the cytokine interleukin-2 (IL2).

During the new clinical trial APN301 will be administered together with GM-CSF and isotretinoin to children with refractory or relapsed neuroblastoma. “This agent has demonstrated potent antitumor effects in preclinical work and has shown clinical antitumor activity in our recently completed Phase II trial,” notes Paul Sondel, M.D., Ph.D., who will be the principal investigator and study co-chair.

“This next study is designed to provide even greater antitumor activity, to better understand the mechanisms of this activity and identify the characteristics of children most likely to respond,” Dr. Sondel explains. The study is scheduled to start in the third quarter of 2011 and will be conducted in hospitals across the U.S. and Canada.

The design of this trial is based on a recently concluded study with an anti-GD2 mAb performed by COG in which clinical activity was shown. Peter C. Adamson, M.D., chair of the Children´s Oncology Group, adds, “Being able to leverage immunotherapy is a primary strategic initiative in our efforts to improve the outcome for patients with high-risk neuroblastoma.”

Apeiron took over development of APN301 from Merck KGaA this February. It works by recognizing the GD2 disialoganglioside, which is strongly expressed on virtually all cases of human neuroblastoma as well as on several other human cancer types (including melanoma, small cell lung carcinoma, osteosarcoma, and soft-tissue sarcoma), according to the company.

IL2 has been tested extensively in clinical cancer trials and is approved as an immune activator with documented antitumor effects in certain cancers. In patients, hu14.18-IL2 localizes to GD2-positive tumor cells via the antibody component. The fused IL2 is designed to stimulate the patient’s immune system against the tumor by activation of both NK and T cells, whereas the Fc portion of the antibody is designed to trigger tumor cell killing by ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent cytotoxicity).

Apeiron has another clinical-stage neuroblastoma candidate called APN311. It is a monoclonal chimeric antibody targeting the GD2 antigen on neuroblastoma cells. The company is partnering with the Children’s Cancer Research Institute and SIOPEN on a randomized Phase III trial in Europe in patients with high-risk neuroblastoma and minimal residual disease.

Besides these two neuroblastoma candidates, Apeiron has three more clinical programs. APN311 is also in Phase II testing against melanoma. Also in Phase II is APN201, a liposomal formulation of recombinant human superoxide dismutase, for the prevention or treatment of skin damage due to radiation therapy in cancer.

Earliest in the clinical pipeline is APN01, which GlaxoSmithKline exclusively licensed for £11 million in February 2010. It expects to commence a Phase II study with this recombinant human angiotensin converting enzyme 2 in acute respiratory distress syndrome.

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