First-in-class treatment for acute leukemia

December 08, 2009

EUREKA project E! 3172 NKSTIM has produced a new potential drug to stimulate cancer patients' own 'natural killer' cells to attack and eliminate cancer cells; currently undergoing clinical testing in patients with leukaemia or myeloma. Existing knowledge of how transplanted bone marrow cells eradicate tumours gave the foundation for designing the new drug. Providing the remaining clinical trials are successful, the drug will offer the first real treatment option for older people with acute myeloid leukaemia, whose age precludes them from bone marrow transplantation. It also promises improved options for treating other types of cancer, such as multiple myeloma and lymphoma.

Myeloid leukaemia is characterised by rapid growth of abnormal white blood cells in the bone marrow, and it may exist in acute (AML) or chronic (CML) forms. AML is more prevalent among older people, where it is virtually incurable; progressing rapidly and only 10% of patients survive more than 5 years. The best treatment for leukaemia is bone marrow transplantation, which provides fresh donor-derived immune cells. One type of these - the 'natural killer' (NK) cells - release cytotoxic substances that can destroy abnormal, cancerous white blood cells without affecting the normal blood cells. The effectiveness of NK cells in various types of cancer has been reported in both mice and humans. The problem is that bone marrow transplantation is not available to elderly patients, because their general health status rarely supports the very arduous transplantation procedures.

To avoid the need for bone marrow transplantation, the NKSTIM project set out to design and generate a drug that would stimulate the patients' own NK cells. The project brought together the biotechnology skills of the French SME, Innate Pharma, with Novo Nordisk, a large biopharmaceutical manufacturer from Denmark. The project defined the type of molecule needed, used a rational and highly targeted approach to generate it, and developed the methodology to validate it.

Stimulating the patient's own immune response

At the start of the project in 2003, Innate Pharma had already identified a new generation of protein molecules able to stimulate NK cells through their specific receptors, unaffected by the activity of cancerous or infected cells which would normally suppress an immune response. On this basis, Innate Pharma and Novo Nordisk set out to discover candidate therapeutic molecules suitable for administration to humans.

A few suitable proteins were selected and taken through initial drug characterisation. The most promising candidate was identified and Novo Nordisk then supported the regulatory evaluation, pre-clinical and Phase I clinical trials for safety and dose testing. By the end of the EUREKA sponsorship (at the end of 2006), the Danish company had produced the drug in a form that could be administered to patients for safety and efficacy evaluation in Phase I and II trials. Innate Pharma is now continuing the trials toward market authorisation; anticipated to be within 6 years.

Fast and promising development

The identification of the new potential drug was very fast. "We did not need to look at many alternative candidates," says Nicolai Wagtmann, Vice President at Novo Nordisk, who led the project through the discovery phase. "This was not a traditional massive drug screen, but quite the opposite. We started from an understanding of the disease and the biological mechanism effective in transplantation, the precise molecule in the body that we wanted to modify, and a clear idea of how that had to be done."

As well as testing the potential new drug as a treatment for acute myeloid leukaemia, it is being examined for activity against the chronic form of the disease and it may also have applications in treatment of other forms of cancer, e.g. lymphoma and melanoma. Nicolai Wagtmann comments: "I think it has the potential to make a big difference in the treatment of AML. In fact the European Medicines Agency has designated AML an orphan disease as there is a big medical need and no other treatment available." For AML treatment, the new drug is anticipated to achieve the same result as marrow bone transplantations - 50-70% of patients surviving and improving.

Although there are already other therapies for chronic myeloid leukaemia, there is still a need for better treatment options. When one of the main existing treatments for CML was introduced, it quickly reached a market of over $1 billion a year. There are about the same number of patients with AML and CML in the western world, so the market for a new effective cancer treatment is very promising.

Fruitful partnership

This particularly successful EUREKA project built on the complementary skills of the small innovative and dynamic biotech company and the larger pharmaceutical company, with its technology base and experience of clinical drug development. The project was financially supportive to Innate Pharma; particularly important in the early stages by enabling investigative work that would otherwise not have been possible from the start. This generated a momentum and early progress that helped win further investment from Novo Nordisk - during the collaboration, Novo Nordisk became a main investor in Innate Pharma.

The Danish company benefited through sharing Innate Pharma's early concept, and by gaining access to Innate Pharma's patents on the strategic approach to the drug design. This was critical to the project and laid the foundation for a larger series of patent applications filed by the two companies in collaboration. The French company's patent platform and technical competences were complemented by drug-discovery and clinical skills from the Danish partner.
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EUREKA

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