BioWorld International Correspondent
LONDON - Protherics plc agreed to buy CoVaccine BV's novel adjuvant in a deal valued at €1.1 million (US$1.4 million), allowing it to go ahead with reformatting its vaccine against hypertension.
In preclinical models, adding CoVaccine's adjuvant resulted in a 10-fold higher level of antibody production against angiotensin - a peptide hormone involved in regulating blood pressure - than in the formulation used by Protherics in its positive Phase IIa study. Protherics will pay for the adjuvant with 295,413 shares on signing, and a further 590,826 on reaching two development milestones. Utrecht-based CoVaccine is entitled to single-digit royalties on sales.
The company now is commencing GMP manufacture of the adjuvant and vaccine, allowing it to start a Phase IIa study of the new formulation in the second half of 2007. The aim will be to confirm the increase in anti-angiotensin antibodies, over the levels observed in the previous Phase IIa trial and to establish that it leads to a reduction in blood pressure.
Compliance is a major issue with existing treatments for hypertension. London-based Protherics hopes to get a long-lasting effect so that the vaccine can be administered infrequently. "We are not a high blood pressure company," Andrew Heath, company CEO, told an analysts' meeting. "It's a complicated area, and trials are expensive, but we think we have a major opportunity with this adjuvant. We want good Phase II data to enable us to license [the vaccine] on."
Protherics also is pressing ahead with process scale-up and manufacturing Phase III trial supplies of CytoFab, its treatment for sepsis, which was licensed to AstraZeneca plc in December 2005. The deal is worth £195 million (US$340 million) in up-front and milestone payments, and in addition, Protherics will receive 20 percent of sales and be paid for manufacturing.
AstraZeneca made an up-front payment of £16.3 million that now is being deployed to develop manufacturing. That will include building up the sheep flock in Australia where the raw material, a polyclonal antibody, comes from.
Heath said the number of sheep required will depend on the antibody titers each generates. "We estimate we will need 10,000 to 15,000 sheep to serve a $1 billion-upward market. In the past, we have had flocks of up to 11,000, so we see the scale-up in terms of sheep as well within our capabilities."
The alliance with AstraZeneca "has got off to a great start," Heath said. Protherics has hired an alliance manager, John Doyle. "The project is completely on track; we are building serum inventory in Australia and scaling up manufacture in Wales. Material for Phase III will be available in 2007."
Meanwhile, Protherics is awaiting marketing approval in Europe for Voraxaze, for the toxic side effects of methotrexate therapy in cancer and expects to file a BLA with the FDA in the second half of this year. The company has started trials to support an extension of the label from acute use to repeat use as an adjunct to methotrexate therapy. Heath noted that toxic side effects often mean methotrexate treatments have to be delayed, or patients given lower than optimal doses.
"The next six to 18 months are going to be a pretty busy time with the BLA submission of Voraxaze in the U.S.; European and U.S approval for Voraxaze in 2007; milestones from AstraZeneca in 2007 [and] the rebirth of the angiotensin vaccine," Heath said.