Nine million dollar hit for Adelaide biotech Bresatec: leukaemia drug hormone research data from IMVS bombs
In 1993, the E21R molecule had been licensed to Bresatec (later BresGen) from Medvet Science, commercial arm of the South Australian government’s Institute of Medical and Veterinary Science (IMVS), that oversaw the Hanson Centre for Cancer Research where professors Angel Lopez and Mathew Vadas had identified the GM-CSF protein (granulocyte-macrophage colony-stimulating factor), a growth hormone that regulated blood cells, helping fight infection.
BresaGen, the Adelaide biotechnology company, was hit in 2002 by a $9 million shock that contributed to sinking the company a few years later.
The $9 million was around the amount spent on E21R, a molecule touted to be the “first of a whole new class of cancer drugs” but that turned out to be based on flawed data. In 1993, E21R had been licensed to Bresatec (later BresGen) from Medvet Science, the commercial arm of the South Australian government’s Institute of Medical and Veterinary Science (IMVS), that oversaw the Hanson Centre for Cancer Research where the research scientists professors Angel Lopez and Mathew Vadas had identified the GM-CSF protein (granulocyte-macrophage colony-stimulating factor), a growth hormone that regulated blood cells helping fight infection.
The professors suggested rejigging amino acids in the protein might stop cancers dead by blocking the action of GM-CSF. The first experiment a year later, adding the rejigged E21R to cultured cancer cells, apparently proving their theory. In 1993, Bresatec (later Bresagen) was exclusively licensed to produce the hormone, securing regulatory approvals and marketing it, with the IMVS receiving a royalty. To take E21R to Phase 1 clinical trials, the Australian government funded a three-year R&D Start grant worth $2.6 million, with Bresatec matching that dollar for dollar.
In 1999, Drs Vadas, Lopez and professor Peter Rathjen, chairman of BresGen’s scientific advisory board, were interviewed on Australian Broadcasting Corporation science show Quantum. They told how, with BresaGen on side for the project, E21R was tested on mice, then baboons, before Des Norris became one of the first six people – each with advanced cancer –to trial the drug. Norris’s tumour had stabilised.
The timing of the Quantum interview was ideal, with BresaGen having floated as a company only one month earlier, in 1999. The Phase I trials in 1998 showed E21R to be highly effective against certain acute myeloid leukaemias and certain solid tumours, including breast cancer, and initial efficacy trials in humans for E21R from 1999 were announced as successful. This had 19 patients receiving a daily injection of E21R for 10 days.
Phase II was planned to begin in 2000 when BresaGen signed a deal with the the giant British Biotech for a E21R global marketing and licensing agreement and clinical studies to get approval for it to treat acute myeloid leukaemia in Europe and North America, starting with a Phase II clinical study, expected to start in 2001. BresaGen would make materials for clinical trials and commercial supply, but built a new plant, and British Biotech would pay up to US$7 million when E21R was developed and approved.
In 2002, the European Commission designated E21R as having orphan drug status2 to treat juvenile myelomonocytic leukaemia. But in July 2002, BresaGen announced it would suspend the Phase II trials in acute myeloid leukaemia with E21R because an independent pre-clinical study failed to support the previous high incidence of cell killing. British Biotech had been unable to duplicate preclinical trial results (from a postdoctoral researcher) published by IMVS, Medvet and professor Angel Lopez of the Hanson Centre for Cancer Research.
Several weeks later, BresaGen Ltd and British Biotech (later dissolved as company) ended their agreement. Bresagen medical director and haemotologist Chris Juttner also revisited his doubts about how E21R worked. In July 2003, BresaGen started a $7 million legal claim in the supreme court against the South Australian government because of alleged malfeasance by its IMVS.
After a delayed hearing, the matter was settled by a $900,000 payment to BresaGen but, by that stage, the company had been pushed into administration.
