“The risk of a colectomy and a colostomy by age 20 for such a patient as my daughter is unacceptably high.” “I have a daughter who was diagnosed with ulcerative colitis at age 10,” she says. It’s more about the pathways that may manifest in certain organ systems.”Īnother motivation, Harler confides, is more personal. “Autoimmune disease is almost system agnostic.

“If there is an organizing principle, it’s around the pathways,” Harler continues. She remarks, “The wealth of knowledge that has been generated over the past two to three decades is breathtaking.” Diseases that may differ dramatically from one another, and even from patient to patient, often share the same inflammatory pathways, and they often present similar targets for potential therapies. For example, she is motivated by scientific curiosity. IGM Biosciences is eligible to receive potentially over $6 billion in aggregate development, regulatory, and commercial milestones.Īlthough the commercial potential of IgM antibodies is exciting, Harler has additional motivations. This partner, Sanofi, will pay IGM Biosciences $150 million upfront to collaborate in the creation, development, manufacture, and commercialization of IgM antibody agonists against three oncology targets and three immunology/inflammation targets. IGM Biosciences recently announced that its technology attracted an enthusiastic development partner. She adds that pentameric antibodies could be produced that would be capable of neutralizing targets “that, frankly, were not accessible through more conventional IgG-based therapy.” “I see a very rich field of validated targets that we can strongly consider,” Harler declares. More sites to bind ligands means more inflammatory cytokines neutralized per antibody-and not just cytokines like TNF-a. “It equates to the difference between trying to pick something up with two fingers versus. “We graphed highly specific IgG binding sites onto an IgM molecule,” Harler says. To make the most of IgG antibody specificity and IgM antibody potency, IGM Biosciences tried an unusual approach. IgG antibodies, however, have just two antigen-binding sites, whereas IgM antibodies have ten. The drug is used to treat arthritis, Crohn’s disease, ulcerative colitis, and psoriasis. For example, AbbVie developed adalimumab (Humira), a recombinant monoclonal IgG antibody, to neutralize the inflammatory cytokine tumor necrosis factor alpha (TNF-a). It has already been harnessed by several drug developers. The specificity of IgG is a major strength. When faced with a pathogen, the immune system first produces nonspecific (but potent) IgM antibodies, and then, later, highly pathogen-specific IgG antibodies. Currently, IGM Biosciences has a drug pipeline that includes candidates for treating cancer, infectious disease, and autoimmune and inflammatory diseases. Besides exploiting IgM avidity, the company also works to enhance affinity, the natural binding strength of each individual IgM binding unit. The IgM antibody’s avidity advantage inspired IGM Biosciences to create an IgM antibody platform to develop IgM-based therapeutics. Consequently, the IgM antibody can bind to more targets, boosting its overall binding power, or avidity. Whereas the IgG antibody has two binding sites, the IgM antibody has ten binding sites. Essentially, Harler’s unit is combining the strengths of IgM antibodies and IgG antibodies to inactivate pro-inflammatory cytokines and dampen inflammatory signals more effectively. A wider reach and a tighter graspĪt IGM Biosciences, Mary Beth Harler, MD, is president of IGM autoimmunity and inflammation, a business unit tasked with realizing the potential of the company’s IgM antibody technology platform. Still, drug developers are showing that if they can get the lay of the land, they can head inflammation off at the pass. Indeed, they can activate and resolve inflammatory processes in varied ways in different tissues and diseases. However, inflammatory pathways are intricate. Conceivably, well-targeted drugs could have multiple indications. Some developers are excited that disparate inflammatory conditions appear to share pathways and present the same targets. To stage even more targeted deployments, drug developers are exploiting the latest research about inflammatory pathways. These medications are proving valuable in a range of applications, but there’s still room for improvement. Besides steroidal and nonsteroidal anti-inflammatories, there are now small-molecule drugs (such as Janus kinase inhibitors) and biologics (such as monoclonal antibodies against pro-inflammatory molecules).

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