DUBLIN – Immunos Therapeutics AG raised CHF15 million (US$15.2 million) in a series A round to move a novel immuno-oncology platform designed to turn cold tumors hot into early clinical development.
The company is exploiting what is a pathological immune recognition mechanism in patients with autoimmune disease in order to jumpstart an immune response in cancer patients. At the core of its technology is a series of open conformers, which comprise free heavy chains derived from human leukocyte antigens (HLAs). Those molecules are not associated with either HLA beta chains or with antigenic peptides, and they have unique immune recognition properties, being capable of binding to lymphocyte immunoglobulin-like receptor 2 (LILRB2) and LILRB4, which are expressed on a diverse range of myeloid cells associated with an immunosuppressive milieu, as well as to inhibitory killer immunoglobulin-like receptors, expressed by natural killer (NK) cells.
Schlieren, Switzerland-based Immunos has built up a preclinical pipeline of three such conformers, which were originally isolated from patients with autoimmune disease or infection. "Each of these is associated with a different autoimmune disease or infection," CEO Sean Smith told BioWorld. "They're naturally occurring." The basic idea is to “transplant” an overactive immune response that occurs in patients with autoimmune disease and in some patients with infection to cancer patients whose tumors evoke an immunosuppressive milieu.
Its lead molecule, IOSH-2, comprises two copies of an HLA-B57 open conformer fused to human immunoglobulin G4 (IgG4) Fc domains. Preclinical studies in mouse models of colon cancer, pancreatic cancer and melanoma indicate that it promotes a shift in the tumor microenvironment from an immunosuppressive M2 macrophage phenotype to an M1 phenotype, which is associated with a more favorable outcome. It also reduces the influx of myeloid-derived suppressor cells, increases the ratio of cytotoxic CD8 T cells to regulatory T cells and increases NK cell infiltration.
"The money we raised recently will support the build-out of our management team and completion of our phase Ia and phase Ib studies," Smith said. A first-in-man study is still about two years away. The agent is being lined up for both solid and liquid cancers. Immunos is some way behind other contenders in that field, but it claims an advantage in the multitasking nature of its molecules, each of which can enact a broad shift in the tumor's inflammatory milieu. Their origin may also be an advantage. "These are human proteins, which have physiological affinities," Smith said.
Several recent transactions validate its general approach, Smith said. Even though Celgene Corp. (now part of New-York-based Bristol-Myers Squibb Co. ) terminated most of its involvement with Cambridge, Mass.-based Jounce Therapeutics Inc., earlier this year, at the same time it paid $50 million up front and could pay another $480 million in milestones to take forward JTX-8064, an LILRB2 inhibitor. Immune-Onc Therapeutics, Inc., of Palo Alto, Calif., raised $33 million in series B funding last year to take forward IO-202, an LILRB4 blocker, in acute myeloid leukemia. Merck & Co. Inc., of Kenilworth, N.J., is in early clinical development with MK-4830, an LILRB2 inhibitor.
Immunos was spun out of Basel and Zurich universities in 2014 but did not become operationally independent until 2017, when it closed a CHF2.3 million seed round. Its founders are its chief scientific officer, Osiris Marroquin Belaunzaran, an experienced product development scientist, and its chief medical officer, Christoph Renner, who is professor of immunology at the University of Basel. Smith came on board in 2017, following a 15-year career at Merck where he held various management, commercial and business development roles across all major territories.
The current round was co-led by Biomedpartners and Pfizer Ventures, with additional participation from Redalpine, Schroder Adveq, Wille Finance AG, Bernina Bioinvest Ltd., as well as from undisclosed new and existing private investors. In conjunction with the fundraising, Immunos has added four new members to its board: Markus Hosang, of Biomedpartners; Michael Baran, of Pfizer Ventures; company chairman Reinhard Ambros, the former head of the Novartis Venture Fund; and Daniel Vasella, the former chairman and CEO of Basel-based Novartis AG.