Novartis has thrown its weight behind a “Cinderella antibody,” leading a 30.8 million pound sterling ($40.9 million) series B round that positions Epsilogen to try to create “a brand new category of pharmaceutical within within cancer.”
London-based Epsilogen’s primary focus is an immunoglobulin E (IgE) antibody that targets the folate receptor alpha antigen. While researchers discovered IgE antibodies in 1966, and biologics pioneers considered them at the birth of the biotech industry, Epsilogen claims its candidate is the world’s first IgE antibody to enter the clinic.
Epsilogen CEO Tim Wilson, who coined the term “Cinderella antibody,” framed the near-total dominance of IgG antibodies up to this point as a result of “folklore problems with IgE” that have “prevented people paying attention” to recent advances in understanding of the potential benefits of the antibodies.
“At the start, we did have a bit of an uphill struggle in persuading people that an IgE would be safe and readily manufacturable,” Wilson said. “If you talk to people in the pharma industry who go back to the 1980s, they'll tend to say ‘we thought about IgE way back when and we were worried about anaphylaxis and we were worried about manufacturing’. Well, we've answered those two questions.”
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The anaphylaxis worry stems from the fact IgE antibodies drive the allergic immune response. In a trial of 24 solid tumor patients who were free from concomitant medications or comorbidities increasing risk of anaphylaxis, Epsilogen saw one case of the severe immune reaction. The patient was treated successfully for anaphylaxis with adrenaline.
Epsilogen emerged from the trial with a way to screen out patients who are at higher risk of anaphylaxis. The patient who had the severe immune reactions was the only one of the 24 subjects who was positive on the basophil activation test at baseline.
The worry about the manufacturability of IgE antibodies reflects the fact the molecules are bigger and more heavily glycosylated than IgG antibodies. While Epsilogen is still operating at fairly small scales, its initial manufacturing runs are encouraging, with several CDMOs producing more than 90 different IgEs at expression levels comparable with IgGs.
If, as Wilson believes, Epsilogen’s early clinical and manufacturing data clear the historical barriers to IgEs, that leaves one big outstanding question: Why use IgEs over tried-and-tested IgG antibodies?
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The case for using IgE antibodies rests on data generated in recent years, notably by Sophia Karagiannis’ laboratory at King's College London. Karagiannis, Ph.D., a scientific founder of Epsilogen, and other researchers have shed light on the role of IgE antibodies and their relevance for oncology. IgE antibodies stimulate myeloid lineage cell responses, in particular macrophages and monocytes, to remove parasites. Applied to cancer, that mechanism could turn the immune system against solid tumors.
“We are changing the tropism of an immunoreactive warrior class of cells. When you stick something on their cell membrane that says, ‘I will bind to folate receptor alpha,’ they will seek it out. That's what they're there to do. It doesn't matter whether it’s a schistosome or a breast cancer cell,” Wilson said.
Novartis Venture Fund sees promise in the idea, teaming up with new investors 3B Future Health Fund, British Patient Capital, Schroders Capital and Caribou Property along with existing backers Epidarex Capital and ALSA Ventures to pump 30.8 million pounds into Epsilogen. The money will fund a phase 1b clinical trial that will test MOv18 IgE in platinum-resistant ovarian cancer patients, a population in whom standard of care has an objective response rate of 10% to 12%.
“If we can beat that number significantly, we're in good shape,” Wilson said. “We hope to establish clinical proof of concept. If we get that, I expect the industry will realize that we have a brand new category of pharmaceutical within cancer.”