Norwood Immunology gears up for US clinical trials

Norwood Immunology (AIM:NIM) is almost ready to take its GnRH analogue technology, designed to 'reboot' the immune system, into US clinical trials, having just completed a Phase II protocol with US partner TAP Pharmaceuticals.

But the company -- a subsidiary of Melbourne-based Norwood Abbey [ASX:NAL, NASDAQ:NABYF] -- looks likely to end the year on London's Alternative Investment Market close to where it began. It is currently trading close to its July issue price of 38 pence (AUD$0.96).

An Investigational New Drug (IND) submission, to be sponsored and filed by TAP, is being prepared for the US trials. If this is approved, the company expects them to commence in the first quarter of 2005.

Norwood Immunology's first human clinical trial -- an Australian trial in cancer bone marrow transplantation, is now fully enrolled with 100 patients. Results are expected at the end of 2005.

The company is also about to start pre-clinical trials with researchers at the MD Anderson Cancer Centre in the US, to investigate whether GnRH analogues can enhance patient responses to a melanoma cancer vaccine.

Rebuilding immunity in cancer patients is the focus of work by Assoc Prof Richard Boyd, of Monash University, Norwood Immunology's chief scientific officer, who is also director of immunology at the Australian Stem Cell Centre.

Boyd's research began with investigating how to regenerate T-cells in HIV/AIDS patients, and it translates well into cancer patients. In treating cancer, particularly cancer of the blood, chemotherapy and radiation target the cancer cells, but they also target the thymus and bone marrow, destroying immune cells. Recovery of the immune system post-chemotherapy is very important to a patient's survival.

The thymus receives haematopoietic stem cells or progenitor cells via the blood from the bone marrow, and transforms them into T-cells, re-releasing them into the blood. However, as an individual gets older, particularly after puberty, the thymus reduces in size and this correlates with a decrease in immune system function.

In looking at why the thymus deteriorates with age, Boyd's team established one fact: sex steroid hormones (oestrogen and testosterone) suppress the immune system.

Boyd's team found that in castrated mice the thymus returns to the size it was at birth after two weeks. "The T-cells it produced gave two-year-old mice the immune response of four-week-old mice," said Boyd.

His team then identified thymus stem cells and used them to generate an ex vivo thymus.

In this work, which was published in Nature Immunology in 2002, they purified progenitor cells or stem cells from the thymus of a mouse embryo and transplanted them under the kidney capsule in nude mice (these mice lack a thymus and therefore cannot generate mature T cells).

These animals grew a thymus that produced mature T-cells. Boyd said the researchers were now pursuing the same result in humans.

They are now working on temporarily blocking the sex steroid hormones with gonadotropin releasing hormone (GnRH) analogues.

In a clinical trial, held in Melbourne, Boyd's team found that by temporarily shutting down the sex steroids with the GnRH analogue, the production of new T-cells was boosted. Individuals who took part in the trial had already been receiving such sex steroid therapy, what Boyd calls "chemical castration", for breast cancer, endometriosis, prostate cancer, etc -- diseases that are all fed by oestrogen or testosterone.

Because GnRH analogues -- marketed as Lupron -- have been used for prostate and breast cancer since 1985, safety and tolerability studies were not necessary, enabling the team to move directly into Phase II placebo-controlled trials. In prostate cancer patients, for example, 60 to 80 per cent showed good evidence of new T-cells and increased thymic activity.

"We also found that an important part of the process was that the bone marrow worked better," Boyd said.

All 100 patients enrolled in the Australian clinical trial have lymphoma or leukaemia, and will receive a bone marrow transplant in clinics at the Peter MacCallum Cancer Centre and the Alfred Hospital in Melbourne. They will have their immune systems monitored for more than a year, along with the effects of chemotherapy and autologous haematopoietic stem cell transplants.