DUBLIN – Pfizer Inc. has given Bioinvent International AB an end-of-year boost, in the form of an immuno-oncology deal with a potential value in excess of $500 million. The deal is very much of the jam-tomorrow variety, however. Lund, Sweden-based Bioinvent is getting $10 million initially, including an equity investment of $6 million plus $4 million as an upfront payment and early research funding.

Even if the full value of the deal is unlikely to be realized – it is contingent on Bioinvent coming up with five antibodies that go all the way to commercialization – investors were buoyed by the news. The company's shares (STOCKHOLM:BINV) gained 31.5 percent to close Wednesday at SEK2.63 (US$0.29). The agreement represents significant validation of the company's First platform, which identifies both novel targets and antibodies that act on them through functional screening of large antibody libraries against clinical material from patients and healthy volunteers.

"For us, the initial cash coming through the door is not unimportant," CEO Michael Oredsson said. It boosts the company's balance sheet by about 50 percent – it exited the third quarter with SEK196 million (US$21.1 million). The deal terms include preclinical as well as clinical milestones. Bioinvent would also earn double-digit royalties on eventual product sales.

The deal came about through "active outreach to a limited number of companies," Oredsson said. That included Pfizer's biotech unit in South San Francisco, which it built around its 2006 acquisition of Rinat Neuroscience Corp. The focus of the deal will be on probing the biology of tumor-associated myeloid cells (Tmacs) in order to find novel targets and antibodies that could have clinical relevance.

"Obviously, this is a very early stage discovery deal. In fact we haven't even started the program yet," Bioinvent chief scientific officer Björn Frendéus told BioWorld Today. But the deal is "testament" to the scientific and technical capabilities Bioinvent has built up over the last five years, he added.

The First approach involves increasingly detailed analyses of the binding properties of antibodies that recognize target structures uniquely expressed by disease tissue, combined with additional studies in complex animal models. "It's not easy to predict just from looking at a target how an antibody is going to work and how effective it's going to be," Frendéus said. The approach is unbiased – it throws up previously discovered as well as novel biology. "We actually don't circumvent that. We get that too," he said. "It kind of validates the approach. There's no magic to it." Although the company has patented aspects of the approach, its capabilities, in large part, are based on its know-how.

Immuno-oncology is, of course, a crowded area, but the main focus to date has been on targets associated with adaptive immunity, particularly T-cells. TMACs encompass a range of innate effector cells, including macrophages, monocytes, granulocytes, myeloid-derived suppressor cells and dendritic cells, all of which influence the tumor microenvironment as well. It is still an emerging field. "Understanding has significantly improved over the last five years or so, but I think it's still very early stage. There's still much more to be learned," Frendéus said.

Others with activity in this space include Basel, Switzerland-based Roche Holding AG, which is conducting a phase I trial in cancer of emactuzumab (RG7175), which targets colony-stimulating factor 1 receptor (CSF-1R), in combination with RG7876, an antibody-based CD40 agonist. Cambridge, Mass.-based Jounce Therapeutics, Inc., is in preclinical development with multiple programs that target innate immune effectors.

For Bioinvent, the deal is a positive way to close out the year, following a significant clinical setback earlier this month. It terminated a phase II trial in multiple myeloma of BI-505 soon after the FDA had placed a clinical hold on the study, because of an adverse cardiopulmonary event in one patient. BI-505, an antibody that binds Intercellular Adhesion Molecule 1 (ICAM-1), had been in development for myeloma patients undergoing autologous hematopoietic cell transplantation with high-dose melphalan.

"The '505 antibody was isolated using a very blunt version of what we have today," Frendéus said. The rationale for the trial was based on the antibody's role in harnessing a macrophage attack on myeloma cells. The program has been shelved indefinitely – even if the adverse event has not been conclusively linked to the antibody. "What we are doing is analyzing what actually happened," Oredsson said.

Meanwhile, two other clinical programs are ongoing. BI-1206, which inhibits CD32b, an immunosuppressive protein that is over-expressed in lymphoma, is undergoing a phase I/II trial in the UK in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia. Initial data are expected in 2018. TB-403, an antibody targeting anti-placental growth factor, is undergoing a U.S. phase I/II trial in medulloblastoma. Bioinvent is co-developing the drug with Oncurious NV, of Leuven, Belgium.