Positive Results of Clinical Phase I/II Trial on Pharmexa's HER-2 DNA Autovac Breast Cancer Product


HOERSHOLM, Denmark, Dec. 12, 2002 (PRIMEZONE) - Pharmexa A/S (Other OTC:PMXAY) (Copenhagen:PHARMX) discloses very promising results from a phase I/II clinical trial on the HER-2 DNA AutoVac(TM) product at the San Antonio Breast Cancer Symposium in the USA, where healthcare professionals from all over the world meet to exchange ideas and gather information on the latest research and development within the treatment of breast cancer.

The phase I/II results show that:

 -- The product is safe and well tolerated at all three dose levels

 -- The product is capable of inducing HER-2 specific cytotoxic T-cells

 -- In addition, there are several indications that the HER-2 DNA
    AutoVac(TM) has anti-tumor activity even in these severely diseased
    metastatic breast cancer patients

 -- The results fully support proceeding into a phase II trial, which
    is now being planned.

HER-2 DNA AutoVac(TM) is a therapeutic DNA vaccine that Pharmexa is developing for the treatment of patients with HER-2 positive metastatic breast cancer. Pharmexa's AutoVac(TM) technology bypasses immunological tolerance by generating cellular and humoral immune responses against selected self-proteins that are pathologically associated with diseases, such as HER-2 in breast cancer. HER-2 is over-expressed in 20-30% of breast cancers and over-expression is related to poor prognosis. In animal models immunisation with HER-2 DNA AutoVac(TM) induced HER-2 specific cytotoxic T-cells (CTLs) and modest antibody responses, resulting in significant, protective anti-tumor immunity.

Pharmexa has now finalised a phase I/II trial carried out in U.K. and Denmark in 27 women with metastatic breast cancer whose tumors over-expressed HER-2. The objectives were to evaluate the safety of the vaccine, to evaluate the ability of the vaccine to bypass tolerance for the self-protein HER-2 by raising cellular and/or humoral immune responses and to assess the evidence of anti-tumor activity of the vaccine associated to such a response.

The conclusion from the study was that active immunotherapy with up to five repeated doses of HER-2 DNA AutoVac(TM) is safe and well tolerated at all three dose levels examined, and is capable of inducing HER-2 specific cytotoxic T-cells and antibodies in patients with HER-2 positive metastatic breast cancer. Last but not least, even in this small sample size trial, there were several indications that HER-2 DNA AutoVac(TM) had anti-tumor activity associated to the T-cell responses in these severely diseased metastatic breast cancer patients. Transient but significant tumor regression was observed in two patients, as measured by changes in metastatic lesions in the liver and in a lymph node, respectively. Stable disease was observed in another two patients, in whom the duration of the response was considered of significant duration in one of the cases, a patient with lytic bone metastasis at study entry.

Based on these results, Pharmexa will now proceed into a clinical phase II trial that is designed and powered to primarily determine the clinical benefit of the vaccine and to further demonstrate its safety and immunogenicity.

The AutoVac(TM) technology can be applied both as a protein vaccine and as a DNA vaccine dependent on what type of immune response is desired. The immune response induced by a DNA AutoVac(TM) vaccine will mainly consist of activated cytotoxic T-lymphocytes (CTLs or "killer cells") responding to the specific self-antigen. The immune response induced by a protein AutoVac(TM) vaccine is mainly characterised by polycloncal antibodies that will cross-react against the unmodified self-antigens. Passive monoclonal antibody therapy (Herceptin) directed against HER-2 has clearly proven that anti-tumor antibodies can be effective in inhibiting tumor growth and prolonging survival, suggesting that elicitation of a humoral response would be an important property of an optimal HER-2 vaccine. Furthermore, there is scientific evidence that both humoral and cellular immune mechanisms are needed for the complete eradication of tumors.

Thus, for future development exciting options exist with HER-2 DNA AutoVac(TM). It could be an option to combine HER-2 DNA AutoVac(TM) with e.g. Herceptin or with the HER-2 Protein AutoVac(TM) vaccine, whereby both humoral and cellular immune responses would be achieved. Future trials may demonstrate whether such a combination is associated with even greater tumor response and survival benefit.

Stockwise Resume:

Pharmexa reports very promising results from a phase I/II trials on the HER-2 DNA AutoVac(TM) product against breast cancer. Plans to proceed into a phase II trial is now underway.

Note to editors:

Pharmexa A/S is a leading company in the field of active immunotherapy for the treatment of serious chronic diseases. Pharmexa's proprietary AutoVac(TM) technology platform is broadly applicable, but the company has focused its resources on a number of cancer forms and chronic inflammatory diseases, with research and development programs targeted towards breast cancer, rheumatoid arthritis and bone degeneration. Collaborative agreements include Schering-Plough, H. Lundbeck and NeuroSearch.

For further information please call Noonan Russo Presence on +44-20-7726 4452.