Checkpoint inhibitors transformed cancer treatment, bringing to patients immunotherapies now widely used to treat a range of tumors. But there are different types of checkpoints that interact with the immune system, and the scope of this drug research is expanding. Valora Therapeutics focuses on sugar molecules found all over cells and a particular mechanism that regulates them. The preclinical startup emerged from stealth on Wednesday with $30 million to advance its research.
One way that cells communicate with the immune system is through glycans, sugar molecules found on the surfaces of all cells. The presence of these molecules are a key way that the body distinguishes foreign cells from cells that belong to the body. Communication happens as glycans displayed on one cell are recognized by lectins, proteins on other cells that bind to glycans. But in some diseases, this communication is dysregulated. In cancer, that can mean tumors send signals that suppress the immune system. In autoimmune disease, the signaling can lead to excessive immune cell activity.
San Diego-based Valora targets the glyco-immune checkpoint, a regulatory pathway in which glycans interact with lectins, said Miguel Garcia-Guzman, the startup’s co-founder and CEO. Valora’s drugs are engineered antibodies. The antibody component provides the targeting ability for the therapy, just like currently available therapeutic antibodies. But Valora brings additional functionality with a domain that directly binds to glycans, blocking their interaction with lectins. Valora calls these drugs antibody-lectin chimeras, or AbLecs.
“In the case of cancer, we try to reduce the glyco-immune checkpoint so the immune system becomes active again,” Garcia-Guzman said. “In the case of autoimmune disease, we do the contrary.”
Valora’s science is based on the research of Carolyn Bertozzi, the Stanford University professor credited with inventing bioorthogonal chemistry, chemical reactions that happen in living systems without interfering with native biochemical processes. Applications of this chemistry include drug targeting, and Bertozzi’s work in this field was recognized with the 2022 Nobel Prize in Chemistry.
Garcia-Guzman’s experience includes posts at Vertex Pharmaceuticals and Rakuten Medical, a cancer drug developer that he founded. He learned about AbLecs from a pre-print that was published in 2022, and he reached out to Bertozzi to discuss forming a company around the science. Valora was founded in 2023 with a license to Bertozzi’s Stanford research. Bertozzi is a scientific co-founder of the startup. The other scientific co-founder is Jessica Stark, an MIT professor of biological engineering and chemical engineering whose postdoctoral research in Bertozzi’s lab focused on identifying and targeting glycans that act as immune checkpoints for cancer.
Garcia-Guzman said the importance of the glyco-immune checkpoint in cancer and autoimmune disease has gained recognition in the last decade. But there are many glycans, and it’s difficult to modulate the ones that are unknown. He added that he was drawn to the AbLec technology because this approach is both simple and powerful in the way that it addresses the pathological signaling that you want to modulate.
There are other companies pursuing glycobiology drug research. GlycoMimetics was developing small molecule drugs that block certain lectins. Lead program uproleselan, an experimental treatment for acute myeloid leukemia, hit a setback over the summer when the FDA said it needed another study. That program’s future is now uncertain as GlycoMimetics is serving as a vehicle for Crescent Biopharma to go public via a reverse merger. Meanwhile, Palleon Pharmaceuticals is another glycobiology company based on Bertozzi’s research. The Waltham, Massachusetts-based biotech is developing drugs that edit glycans as a way to treat cancers and autoimmune disease. Palleon recently reported Phase 1/2 data demonstrating proof of mechanism in cancer.
Garcia-Guzman said Valora’s new funding will enable the startup to develop in phases. The first phase is platform exploration and optimization with a broad range of AbLec molecules that use different antibodies and lectins. This work will be applied to both cancer and autoimmune disease. The next phase will be prioritizing the mechanisms most promising for therapeutic development. After that, the company will work to toward the preclinical research that could support an investigational new drug application. Garcia-Guzman said Valora is not currently looking for partnerships with large pharmaceutical companies, but the broad potential applications of the company’s technology may lead to such alliances in the future.
Valora’s $30 million seed round was co-led by Avalon BioVentures, Bregua Corporation, and TigerGene. Alexandria Ventures and Correlation Ventures also participated. The startup is based at Avalon’s accelerator in San Diego.
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