Immunome, based in Exton, Pa., recently published preclinical data for an IL-38 blocking antibody. These data will underscore the company’s first Investigational New Drug (IND) application in oncology, which it plans to make within the next few months.
Matthew Robinson, PhD, Immunome’s Chief Technology Officer, took time to speak with BioBuzz about the company’s technology platform, this year’s big strategic partnership with AbbVie, and where the company is headed.
The company was founded and is chaired by Scott Dessain, MD, PhD, who is a faculty member at the Lankenau Institute for Medical Research. Robinson says Dessain was working to understand why researchers couldn’t make a stable human B-cell hybridoma. Hybridomas are cultures of hybrid cells that are the result of the fusion of B cells and myeloma cells, which are used to develop monoclonal antibodies.
“Prior to Scott’s work in Bob Weinberg’s laboratory at MIT, people could make a B-cell hybridoma, but that hybridoma would very rapidly lose expression of the antibody, essentially making it useless. Scott’s work identified a way of modifying a fusion partner that enabled the production of stable human B-cell hybridomas. And that really is the core technology that underlies what we do at Immunome and has really enabled us to address drug development in the cancer space,” Robinson said.
At the most basic level, Immunome uses cancer patients’ own immune systems — specifically, memory B cells — to help identify antibodies and new antibody targets. This is different from a more typical approach of focusing on a specific protein believed to be important on cancer cells and looking for antibodies that attack it.
Robinson said, “We want to be able to use the human immune system to show us what important targets are, and in the case of oncology, to really try and understand what the important targets are that the immune system is seeing. And once we’ve identified those, how can we underwrite a therapeutic hypothesis around those targets to develop drugs?”
The company’s research so far has come up with some surprises, facilitating what Robinson calls an “unbiased approach” with a “very robust screening paradigm.”
As an example, the company will take a tumor from a patient and isolate B cells from the tumor or out of the draining lymph node. The B cells, the company believes, are enriched for the B cells producing antibodies against the tumor. “So when we start out, we’re fishing from a stocked pond, in that sense,” Robinson said, “we look in that enriched population, we make very large libraries of hybridomas, thousands and thousands of human hybridomas out of an individual patient.”
Robinson describes enormous figures, citing that from a single tumor they can place 20,000 spots of the enriched lysate of the tumor onto a microscope slide, and then place 5,000 antibodies in quadruplicate onto those 20,000 spots, one antibody per spot.
“That allows us to ask the question: Do any of those 5,000 antibodies from that patient bind to that particular tumor? And we can do 100 different tumors at a time.”
By screening the antibodies this way, Robinson said, straight out of the patient or a mouse model, “We’re able to essentially capture the repertoire that was on the membranes of those tumor cells right as they were in a native tumor microenvironment. And the data that we’re generating suggests that patients’ immune systems are seeing really interesting targets. And we’ve been able to identify well over 70 targets at this point in time.”
They originally expected the targets would be scattered across the cell biology landscape. “That’s not the case,” Robinson said. “It really looks like patients are fighting back against specific cellular processes. We’re seeing a lot of targets against proteins that are thought to be involved in receptor trafficking or membrane dynamics or the formation of exosomes, which the tumors use to modify their microenvironment. “
Robinson added, “It’s really giving us some neat insight not only into the targets, but also potentially into some interesting biology that the tumor cells are using to help regulate their environment.”
Immunome’s technology platform caught the attention of one of the big players in immunotherapy, AbbVie. In January 2023, the two companies inked a global collaboration and option deal for the discovery of up to 10 novel antibody-target pairs for three undisclosed tumor types. Under the terms of the deal, Immunome granted AbbVie the option to acquire worldwide rights for up to 10 novel target-antibody pairs. AbbVie paid an upfront fee of $30 million. Immunome is eligible for additional platform access payments of up to $70 million if AbbVie decides it wants Immunome to continue using its Discovery Engine. Immunome is also eligible for development and first commercial sales milestones up to $120 million per target.
“AbbVie really understood and recognized what we were able to identify, the types of targets that we’re able to identify with our platform and interrogating how the immune response is fighting back against these tumors,” Robinson said.
And in February, Immunome formed an Antibody-Drug Conjugate and T Cell Redirection Advisory Board, appointing John Lambert, PhD and Anthony Tolcher, MD. Lambert is the former Chief Scientific Officer of ImmunoGen and an ADC expert. Tolcher is the Founder and Director of Clinical Research at NEXT Oncology.
Robinson describes the formation of this new board as a “refinement” of their approach, rather than an expansion. But as the company’s understanding of the new targets and the antibodies they’re developing, Immunome believes the advisory board will help provide guidance on prioritizing those targets for use in ADCs and TCR modalities.
The most recent news about the preclinical publication of an antibody targeting IL-38 is also a good example, Robinson said, “of the unexpected nature of some of the targets we have identified from our patients. In this case, we isolated an antibody from a head-and-neck cancer patient. Their immune system made a high-affinity antibody against IL-38, a cytokine. When we first identified this antibody out of the patient, there was very little known in the literature around its role in biology, and most of that focused on autoimmune disease and inflammation.”
However, their research found that tumors, especially tumors of squamous, or epithelial origin, have co-opted the mechanism. “So IL-38’s role is normally to dampen or shut down an immune response or that inflammatory response,” Robinson said. “These tumors appear to have co-opted that anti-inflammatory response to essentially shut down anti-tumor immunity inside the tumors. Tumors of squamous origin in particular overexpress IL-38 to very high levels.”
In this head-and-neck cancer patient, it looked as if their immune system was fighting back against these mechanisms and allowing anti-tumor immunity to reignite, Robin says. “What we have done is developed an antibody that binds to, and blocks IL-38 function. And we believe that by binding to and blocking IL-38 function in these patients, we’ll be able to reignite the immune system.”
Robinson notes that one important distinction from the well-known checkpoint inhibitors against PD-1 or PD-L1 is those are part of the adaptive immune response. IL-38 appears to work at an earlier level in what is called the innate immune response. “And getting the innate immune response activated is what’s important for lighting the fuse of the adaptive response,” Robinson said. “So we believe if you can overcome these high levels of IL-38 that appear to be in some of these squamous tumors, that will help the innate immune system go on and elaborate a fulsome and active response as well.”
This molecule is part of the company’s own pipeline, separate from the AbbVie deal. Immunome is currently working on an IND for the IL-38 antibody to submit to regulators within the next few months.
