Gain Therapeutics Presents DDR2 Allosteric Inhibitors Data at EORTC-NCI-AACR Symposium

Gain Therapeutics, Inc. (Nasdaq: GANX), a clinical-stage biotechnology company at the forefront of developing next-generation allosteric small molecule therapies, has recently presented promising research at the 36th EORTC-NCI-AACR (ENA) Symposium on molecular targets and cancer therapeutics. This symposium, held from October 23-25, 2024, in Barcelona, Spain, showcased significant advancements in targeting discoidin domain receptor 2 (DDR2) using the company's innovative Magellan drug discovery platform.

The presentation, led by Sara Cano-Crespo, Ph.D., Senior Scientist of Biology at Gain, focused on identifying allosteric inhibitors aimed at DDR2. The poster, titled “Identification of allosteric inhibitors targeting Discoidin Domain Receptor 2 (DDR2),” highlighted the process from virtual screening to experimental validation that resulted in the discovery of GT-03842 and several analogues. These findings are pivotal as DDR2, when bound to collagen, undergoes autophosphorylation, which activates downstream signaling pathways implicated in cancer progression, including metastasis and resistance to immunotherapy.

Joanne Taylor, Ph.D., Senior Vice President of Research at Gain, emphasized the importance of this discovery, noting that targeting DDR2 with allosteric small molecule inhibitors validates the efficacy of the Magellan platform. This approach holds promise for developing novel therapies for malignancies driven by DDR2.

GT-03842 stands out due to its ability to inhibit DDR2 phosphorylation without interfering with the kinase domain. This property suggests that GT-03842 might circumvent resistance mechanisms typically associated with traditional kinase inhibitors. Moreover, this specificity could translate to enhanced safety profiles and selectivity in therapeutic applications.

Experimental investigations demonstrated that GT-03842 and its analogues effectively hinder DDR2 phosphorylation in a dose-dependent manner. These findings were validated using an AlphaLISA-based phosphorylation assay with HEK293 cells overexpressing DDR2. Additionally, in a metastatic breast cancer model, GT-03842 significantly reduced DDR2 phosphorylation, underscoring its potential in oncology.

DDR2 phosphorylation is linked to various cancers and plays a crucial role in tumor proliferation, migration, invasion, epithelial-mesenchymal transition, and metastasis. By targeting these pathways, GT-03842 may offer a new therapeutic avenue for treating cancers where DDR2 signaling is a key driver.

The poster detailing these findings is available on the Science and Technology section of Gain Therapeutics' website.

Gain Therapeutics, Inc. is a pioneering entity in the realm of clinical-stage biotechnology, specializing in the discovery and development of allosteric therapies. The company's lead drug candidate, GT-02287, is currently undergoing evaluation for the treatment of Parkinson’s disease, with or without a GBA1 mutation. Early phase studies demonstrated promising safety, tolerability, and effective engagement with the target enzyme GCase in the central nervous system.

Gain’s unique approach leverages the Magellan™ platform, facilitating the discovery of novel small molecule modulators that can either restore or disrupt protein function. This platform has the potential to accelerate drug discovery, opening doors to novel treatments for a range of challenging conditions, including neurodegenerative diseases, rare genetic disorders, and cancer.

The advancements presented at the ENA Symposium reflect Gain Therapeutics' commitment to harnessing innovative approaches in drug discovery. By focusing on allosteric modulation, the company is poised to make significant strides in developing therapies that address unmet medical needs in oncology and beyond.