Palleon Pharmaceuticals, Inc.

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. Consumer / Employer Health Executives on Digital Transformation in Healthcare Hear executives from Quantum Health, Surescripts, EY, Clinical Architecture and Personify Health share their views on digital transformation in healthcare. By MedCity News “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. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health 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.

– Safety, proof of mechanism and early antitumor activity was demonstrated for E-602 in combination with cemiplimab in patients with PD-(L)1-resistant solid tumors – E-602, a first-in-class human sialidase enzyme therapeutic developed from Palleon’s EAGLE platform is designed to restore antitumor immunity by degrading immunosuppressive sialoglycans on hypersialylated tumors and immune cells WALTHAM, MA, USA I November 08, 2024 I Palleon Pharmaceuticals , a clinical-stage company pioneering glyco-immunology drug development to treat autoimmune diseases and cancer, today announced results from the Phase 1/2 GLIMMER-01 trial of E-602, its first-in-class human sialidase enzyme therapeutic , in combination with PD-1 inhibitor cemiplimab (Libtayo ® ) in patients with PD-(L)1-resistant solid tumors. The results will be shared in both rapid oral and poster presentations on Saturday, November 9 at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting in Houston, Texas. In the Phase 1/2 study, 21 patients with anti-PD(L)-1-resistant melanoma, non-small cell lung cancer and esophagogastric junction cancer, defined according to the SITC consensus definition for resistance to immunotherapy, were treated with E-602 in combination with cemiplimab. All patients were assessed for tumor sialoglycan levels and characterized as having hypersialylation or not. The combination was generally well-tolerated, with no dose-limiting toxicities observed. Patients with tumor hypersialylation trended toward better clinical outcomes compared to those lacking hypersialylation, including a confirmed partial response achieved in one anti-PD-1 resistant melanoma patient, and disease stabilization achieved in another six patients. All patients lacking hypersialylation showed disease progression. In addition, paired tumor biopsies from patients with hypersialylation showed tumor desialylation and immune modulation in tumors, however, tumor desialylation only lasted 2-3 days with weekly dosing. These findings provide the first proof of mechanism for glycan editing as a novel therapeutic approach to modulating the immune system. “The proof of mechanism and antitumor responses observed with E-602 as a combination therapy for patients with solid tumors further validate the therapeutic potential of targeting glyco-immunology to regulate the immune response in treating cancer and autoimmune diseases,” said Li Peng, Ph.D., Chief Scientific Officer of Palleon Pharmaceuticals. “We look forward to applying E-602 to treat diseases that align with its pharmacological characteristics, and advancing our next-generation EAGLE molecules that have a longer half-life sialidase and a tumor-targeting moiety to address the unmet needs of cancer patients.” “E602 is the first candidate in a brand new class of therapeutics designed to modulate the immune system by targeting glyco-immunology. Palleon is building a rich pipeline of first-in-class drug candidates with the potential to improve and extend the lives of patients with diseases characterized by immune dysfunction, including cancer and autoimmunity,” added Jim Broderick, M.D., CEO and Founder of Palleon. The study results will be available for viewing on the Palleon Publications section of the Education Hub page of Palleon’s website following the official presentation on November 9. About Palleon Pharmaceuticals Palleon Pharmaceuticals is the leading biotechnology company developing drugs that harness glyco-immunology to treat cancer and autoimmune diseases. The company’s proprietary platforms enable new target discovery, patient selection, and the development of novel therapeutics for devastating diseases characterized by immune system dysfunction. The groundbreaking discoveries of Palleon Co-Founder and Nobel laureate Carolyn Bertozzi enabled development of the company’s EAGLE glycan editing therapeutic platform. www.palleonpharma.com SOURCE: Palleon Pharmaceuticals

WALTHAM, Mass.--( BUSINESS WIRE )-- Palleon Pharmaceuticals , a clinical-stage company pioneering glyco-immunology drug development to treat autoimmune diseases and cancer, today announced results from the Phase 1/2 GLIMMER-01 trial of E-602, its first-in-class human sialidase enzyme therapeutic , in combination with PD-1 inhibitor cemiplimab (Libtayo ® ) in patients with PD-(L)1-resistant solid tumors. The results will be shared in both rapid oral and poster presentations on Saturday, November 9 at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting in Houston, Texas. In the Phase 1/2 study, 21 patients with anti-PD(L)-1-resistant melanoma, non-small cell lung cancer and esophagogastric junction cancer, defined according to the SITC consensus definition for resistance to immunotherapy, were treated with E-602 in combination with cemiplimab. All patients were assessed for tumor sialoglycan levels and characterized as having hypersialylation or not. The combination was generally well-tolerated, with no dose-limiting toxicities observed. Patients with tumor hypersialylation trended toward better clinical outcomes compared to those lacking hypersialylation, including a confirmed partial response achieved in one anti-PD-1 resistant melanoma patient, and disease stabilization achieved in another six patients. All patients lacking hypersialylation showed disease progression. In addition, paired tumor biopsies from patients with hypersialylation showed tumor desialylation and immune modulation in tumors, however, tumor desialylation only lasted 2-3 days with weekly dosing. These findings provide the first proof of mechanism for glycan editing as a novel therapeutic approach to modulating the immune system. “The proof of mechanism and antitumor responses observed with E-602 as a combination therapy for patients with solid tumors further validate the therapeutic potential of targeting glyco-immunology to regulate the immune response in treating cancer and autoimmune diseases,” said Li Peng, Ph.D., Chief Scientific Officer of Palleon Pharmaceuticals. “We look forward to applying E-602 to treat diseases that align with its pharmacological characteristics, and advancing our next-generation EAGLE molecules that have a longer half-life sialidase and a tumor-targeting moiety to address the unmet needs of cancer patients.” “E602 is the first candidate in a brand new class of therapeutics designed to modulate the immune system by targeting glyco-immunology. Palleon is building a rich pipeline of first-in-class drug candidates with the potential to improve and extend the lives of patients with diseases characterized by immune dysfunction, including cancer and autoimmunity,” added Jim Broderick, M.D., CEO and Founder of Palleon. The study results will be available for viewing on the Palleon Publications section of the Education Hub page of Palleon’s website following the official presentation on November 9. About Palleon Pharmaceuticals Palleon Pharmaceuticals is the leading biotechnology company developing drugs that harness glyco-immunology to treat cancer and autoimmune diseases. The company’s proprietary platforms enable new target discovery, patient selection, and the development of novel therapeutics for devastating diseases characterized by immune system dysfunction. The groundbreaking discoveries of Palleon Co-Founder and Nobel laureate Carolyn Bertozzi enabled development of the company’s EAGLE glycan editing therapeutic platform. www.palleonpharma.com