A French connection in oncology

Innate Pharma describes cutaneous T cell lymphoma therapeutic in scientific journal Cancer Research

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MARSEILLE, France—Targeted toward developing first-in-class therapeutic antibodies for cancer and inflammatory diseases, Innate Pharma S.A. has announced that a peer-reviewed scientific article describing IPH4102 and the results of preclinical efficacy studies to combat cutaneous T cell lymphoma (CTCL), was published online in Cancer Research, a journal of the American Association for Cancer Research.
The next step is a Phase 1 clinical trial in advanced CTCL patients that is scheduled to start in 2015.
The monoclonal antibody, which reportedly has shown potent efficacy in preclinical studies of advanced CTCL, was described in the article titled “IPH4102, a humanized KIR3DL2 antibody with potent activity against cutaneous T cell lymphoma.”
“There are 5,000 to 7,000 patients diagnosed with CTCL each year in the G7 [nations],” Laure-Hélène Mercier, director of investor relations at Innate Pharma, tells DDNews. “IPH4102 received an orphan drug designation in Europe for advanced CTCL. We are working on IPH4102 on an international basis.”
EMA’s Orphan Medicinal Product Designation is designed to promote the development of drugs that may provide significant benefit to patients suffering from rare, life-threatening diseases. In addition to 10 years of market exclusivity in case of approval, the designation also provides special incentives for sponsors, including eligibility for protocol assistance and possible exemptions or reductions in certain regulatory fees during development or at the time of application for marketing approval.
Journal article corresponding authors Helene Sicard of Innate Pharma, and Anne Marie-Cardine of Hôpital Saint-Louis in Paris, wrote in the journal article abstract: “Advanced cutaneous T cell lymphoma (CTCL) remains an unmet medical need, which lacks effective targeted therapies. In this study, we report the development of IPH4102, a humanized monoclonal antibody that targets the immune receptor KIR3DL2, which is widely expressed on CTCL cells but few normal immune cells.”
Potent antitumor properties of IPH4102 “were documented in allogeneic human CTCL cells and a mouse model of KIR3DL2+ disease,” the abstract states. “IPH4102 antitumor activity was mediated by antibody-dependent cell cytotoxicity and phagocytosis. IPH4102 improved survival and reduced tumor growth in mice inoculated with KIR3DL2+ tumors. Ex-vivo efficacy was further evaluated in primary Sézary patient cells, sorted natural killer-based autologous assays and direct spiking into Sézary patient peripheral blood mononuclear cells.”
In these settings, IPH4102 “selectively and efficiently killed primary Sézary cells, including at unfavorable effector-to-target ratios,” the abstract concludes.
“Together, our results offer preclinical proof of concept for the clinical development of IPH4102 to treat patients with advanced CTCL,” Mercier says.
Prof. Martine Bagot, head of the Dermatology Department at Hôpital Saint-Louis and study co-author, echoes Mercier’s sentiments that the data so far represent proof of concept for clinical development of IPH4102, and calls KIR3DL2 “one of the most relevant tumor antigens of cutaneous T cell lymphoma.”
CTCLs constitute a group of non-Hodgkin lymphomas (NHLs) of the skin, accounting for about 4 percent of all NHLs, said Mercier. The overall annual age-adjusted incidence of CTCL is approximately six cases per one million.
CTCLs are cancers of the T lymphocytes (a type of white blood cell) that mainly affect the skin but can also involve the blood, lymph nodes and/or internal organs in patients with advanced disease.
While there are many types of CTCL, the two main subtypes are mycosis fungoides (MF) and Sézary syndrome (SS). Initial signs of MF include skin patches, plaques or tumor nodules, the company states. SS is a type of CTCL that affects both the skin and the blood.
Patients with SS may experience severe itching and are at increased risk for infections, according to researchers. MF and SS are more often diagnosed in men than in women and usually are first diagnosed in people between the ages of 50 and 60 years, although these cancers can be found in younger people.
“The type of treatment prescribed for patients who have MF or SS is based on a number of factors, including the patient’s health, age and disease stage,” Mercier states. “Early-stage MF usually responds well to skin-directed therapies such as phototherapy, radiation, topical chemotherapy or corticosteroid skin creams.”
Treatment for patients with advanced stages of MF or SS generally requires systemic therapies, including biologic or immune therapies, histone deacetylase inhibitors, conventional chemotherapeutic agents or combinations of these agents.
Although research is under way to determine a cause for CTCL, at this time no definitive factor or factors have been found. Studies have thus far failed to prove an inherited genetic connection to the disease or establish links to chemical exposure, the environment, pesticides, infectious agents, radiation or occupations.
Other than allogeneic stem cell transplantation, there are no current, reliably curative therapies for MF and SS, although many effective treatments are available to manage the symptoms of the disease.
Some patients are able to achieve long-term remissions (the absence of disease) with treatment, Innate Pharma reports. In addition to the treatments available for CTCL, clinical studies investigating new agents are underway.
The market for monoclonal antibodies, such as IPH4102, is in constant progression, the company states. Assessed at $18 billion in 2006, the total monoclonal antibody market reached $40 billion in 2010, according to Innate Pharma. Between 2010 and 2016, the average annual growth rate should exceed 8 percent, which makes it the most dynamic segment of the drug market, the company says.

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