BioWorld International Correspondent
NatImmune A/S licensed its lead project, recombinant human mannan-binding lectin (rhMBL), in development for prevention of severe infection in MBL-deficient individuals undergoing chemotherapy, to Enzon Pharmaceuticals Inc. for an up-front payment of $10 million, plus undisclosed development, regulatory and sales milestones, as well as royalties on eventual product sales.
NatImmune, of Copenhagen, Denmark, retains marketing rights for the Nordic region and also has retained rights to develop rhMBL for topical, non-systemic indications. Enzon, of Bridgewater, N.J., obtained exclusive rights for all other territories and will be responsible for further development and manufacturing of the plasma protein, which plays a key role in one of three complement activation pathways.
By binding to mannose residues on the surface of invading pathogens, it activates MBL-associated serine proteases, which then trigger further steps in the protective complement cascade.
"We think that the rights we're giving to Enzon - they have a really good chance of pursuing those [successfully]. They obviously have more financial muscle than we have," said Martin Bonde, CEO of NatImmune.
The compound has blockbuster potential. According to NatImmune's figures, about 170,000 cancer patients would be eligible to receive rhMBL therapy every year, at a cost of $2,000 per course of chemotherapy.
About 30 percent of the general population have sub-optimal levels of MBL due either to a homozygous or heterozygous phenotype. Those become vulnerable to acquiring severe infections when their adaptive immune system is weakened by chemotherapy or by immunosuppressive therapy to prevent organ transplant rejection. Bonde said that the 10 percent of the general population who have a homozygous MBL deficiency have a 70 percent chance of contracting a severe infection during a liver transplant, whereas wild-type individuals have only a 10 percent risk.
A Phase I trial of rhMBL in 28 MBL-deficient volunteers indicated that the replacement therapy was safe and offered an attractive pharmacokinetic profile, NatImmune said.
The recombinant protein has several potential applications to topical indications. NatImmune initially plans to explore its potential in MBL-deficient women with recurrent vaginal candidiasis.
"That is a pretty good niche for us to continue MBL development," Bonde said. The company has established a collaboration with Cornell University to pursue a clinical development program in that indication.
"We hope to start that next year," Bonde said. Protection of burn wounds and diabetic ulcers represent two other topical indications the company might explore.
NatImmune, which was established in 2000 by Alan Ezekowitz, professor of pediatrics at Harvard Medical School in Boston, and Jens Jensenius, professor of immunology at Aarhus University in Denmark, has raised $35 million to date. It has two other projects in preclinical development. It has a collaboration with Affitech AS, of Oslo, Norway, based on developing antibodies to the CaCOU-1 tumor antigen. It also is developing a treatment for prevention of ischemic reperfusion injury caused by complement activation, by blocking MBL-associated serine protease 2. The company plans to out-license that project at an early stage, Bonde said, as its main focus is on oncology. It also is looking to in-license additional oncology projects.
