OncoOne Advancing Novel Immunotherapies to Clinic Targeting the oxidized Macrophage migration Inhibitory Factor (oxMIF)
Noe JT and Mitchell RA, MIF Dependent Control of Tumor Immunity, Frontiers in Immunology, 11:609948, 2020, reprinted with permission
OncoOne, a Vienna, Austria based preclinical stage biotech company, has figured out how to drug an important yet “undruggable” target pivotal to our innate and adaptive immune response, the macrophage migration inhibitory factor, or MIF. MIF has been well characterized for over 50 years as a proinflammatory cytokine implicated in acute and chronic inflammatory conditions. In cancer, MIF is associated with high tumor burden, increased metastatic potential, and poor prognosis by driving pro-proliferative cell signaling, inhibiting cellular apoptosis and by exerting immunomodulatory activities in the tumor microenvironment which contribute to immune evasive and immune tolerant tumor phenotypes. OncoOne’s founders discovered that at sites of inflammation – such as an arthritic joint, and asthmatic lung, or a solid tumor -- MIF aggregates and undergoes a confirmational change, becoming the disease-related isoform of MIF, named by OncoOne’s founders oxidized MIF or oxMIF. By targeting oxMIF, OncoOne’s therapies counter regulate pro-tumorigenic and pro-inflammatory activities of MIF which will be tested clinically with the goal of improving patient outcomes.
New advances in cancer immunotherapy with therapies such as KEYTRUDA®, OPDIVO®, and YERVOY® have led to remarkable improvements in the outcomes of many cancer patients with solid tumors. Yet challenges remain in optimizing the tumor microenvironment to provide more patients durable responses to these immunotherapies. Based on over 40 years of collective MIF expertise, OncoOne believes that their novel oxMIF therapies will be readily combinable with current standard of care treatment regimens and have the potential to establish new standards for therapeutic outcomes in both solid tumors as well as autoimmune disorders.
OncoOne has four new molecular entities advancing to the clinic: ON203 is a bioengineered oxMIF mAb designed to have antibody-dependent cellular cytotoxicity or ADCC. Parallel with this therapeutic, OncoOne is developing a radioimmunoconjugate companion diagnostic (ON102) designed to provide a non-invasive approach to highlight oxMIF-rich tumors. OncoOne also has a bispecific mAb (ON-01) targeting oxMIF and CD3, plus another novel oxMIF mAb (ON-04) for inflammatory conditions such as ulcerative colitis and Crohn’s disease, psoriasis, and refractory asthma in its pipeline.
In the past few months, OncoOne has established a US office focused on partnerships, collaborations, and investor relations based in the biotech hub of Boston. OncoOne has also recently announced a partnership with GenScript who will serve as OncoOne’s contract manufacturer to produce clinical drug substance for upcoming clinical trials. In 2022, OncoOne plans to file two INDs and remains on track for phase I human studies of their lead oxMIF therapeutics, ON102 and ON203, to begin in 1Q 2023 for patients with solid tumors.