Two years ago, researchers from South Korea’s Ajou University and Orum Therapeutics showed that their cell-penetrating antibody blocked RAS activity in mice, safely targeting a mutation long thought to be “undruggable.” Orum has been exploring different applications for its antibody tech since then, and now it’s picked up $30 million to fuel that work.
Based on the research of co-founder Yong-Sung Kim, Ph.D., of Ajou University, Orum’s platform creates antibodies that go where other antibodies can’t to target proteins that small molecules and other antibodies cannot.
“Undruggable targets, such as RAS, are located inside the cell, but they don’t have an appropriate target for small molecules,” Orum CEO Sung Joo Lee, Ph.D., told FierceBiotech. These intracellular proteins are hard to target with small molecules, because they don’t have obvious binding pockets on their surface. And antibodies tend to be a nonstarter, because they’re too big to get inside the cells.
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“What Orum is doing about that is delivering antibodies into the cells so they can bind pocketless, undruggable targets within the cytoplasm. This opens up a huge target space for antibody therapies,” Lee said.
Orum’s platform, dubbed Oromab, builds antibodies that bind to cell-specific receptors and then are taken up into the cell through a process called endocytosis. The antibodies hitch a ride in a membrane-bound “bubble” called an endosome into the cell’s interior. Instead of going all the way to the lysosome—an organelle that contains enzymes to break down waste and foreign bodies—the antibodies get off early, entering the cytosol, or cellular fluid.
Orum drew its series B from IMM Investment, Smilegate Investment, KTB Network and Stassets Investment as well as from its existing backers InterVest and KB Investment/Solidus Investment. The capital will go toward expanding the repertoire of its antibody platform Oromab and building out its R&D labs in Boston and Daejeon, South Korea.
In addition to delivering an antibody for a therapeutic effect—like it’s doing with RAS—Orum is looking at attaching payloads such as enzymes or oligonucleotides to the antibodies and using the antibodies to degrade disease-causing proteins.
“We have a handful of other projects besides RAS, but we’ve been on RAS since the publication [of the mouse study in the journal Nature],” Lee said. “We’ve been trying different approaches using a cell-penetrating antibody, delivering cargo and so on, so we know when our molecule goes to the clinic, we will have something that has a big chance to benefit cancer patients.”
Orum reckons its antibody may have an advantage over other RAS-targeting treatments currently in the clinic including Amgen’s AMG 510, the first KRAS inhibitor to post clinical data.
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“The inhibitors in the clinic focus on G12C mutations [of the RAS gene]. The cysteine mutation is a good mutation for a covalent small molecule inhibitor. But out molecule is more of a pan-RAS inhibitor, so we can address mutations that are not G12C … We could address unmet medical needs not currently addressed by the RAS inhibitors in the clinic,” Lee said.
In addition to working on its in-house pipeline, Orum is looking for partners to realize the full potential of its technology. Cancer is an obvious focus, but so is rare disease.
“We can’t do this alone. We’ve been talking with a few pharma partners, but we are actively looking for partnerships that could advance the platform in rare diease, oligonucleotides, or even gene editing. I think that kind of collaboration would be necessary to work on a huge problem like drugging the undruggable,” Lee said.