Summary                      

IPG6620 is an innovative, first-in-class, pre-clinical small-molecule antagonist of the LPAR5 receptor. It is being developed with a unique dual-purpose strategy designed to address two significant unmet needs in oncology simultaneously. Firstly, it aims to treat Chemotherapy-Induced Peripheral Neuropathy (CIPN), a common and debilitating side effect of cancer treatment with a high unmet medical need. Secondly, it is anticipated to enhance the efficacy of antitumor medicines by reversing immunosuppression within the tumor microenvironment. By targeting a novel pathway that links nerve pain and immune function, IPG6620 represents a mechanistically distinct strategy with the potential to both improve patients' quality of life and boost the effectiveness of their cancer therapy.

Mechanism of Action

IPG6620's novel dual activity stems from its targeted inhibition of the LPAR5 receptor, which is highly expressed in key cells for both neuropathy and immunity.

￭  For Neuropathic Pain (CIPN): LPAR5 is highly expressed in dorsal root ganglion (DRG) neurons and microglia. Nerve injury from chemotherapy leads to an upregulation of LPAR5's endogenous ligand, causing activation of these cells and a pro-inflammatory response. This cascade disrupts the normal function of the DRG and is a key driver of neuropathic pain. By blocking LPAR5, IPG6620 is anticipated to reduce this neuro-inflammatory signaling, thereby alleviating the symptoms of CIPN.

￭  For Immuno-Oncology: The LPAR5 receptor is also highly expressed on CD8+ T cells. The tumor microenvironment is known to boost the expression of the LPAR5 ligand, which in turn prevents the activation, proliferation, and tumor-killing function of these critical immune cells. By antagonizing LPAR5, IPG6620 is expected to enhance the function of CD8+ T cells, helping to overcome tumor-induced immunosuppression and acting as a potential therapeutic agent in combination with antitumor medicines.

Key Differentiation

￭ Novel Dual Mechanism: IPG6620 is uniquely positioned to not only treat a severe side effect of chemotherapy (CIPN) but also to potentially overcome a key mechanism of tumor immune evasion. This creates a powerful synergy where a single agent can improve both tolerability and efficacy of cancer treatment.

￭ First-in-Class Target: LPAR5 is a novel target in this space, offering a mechanistically distinct strategy from current CIPN treatments (e.g., duloxetine, gabapentin), which are often repurposed and have limited efficacy.

￭ Addressing a High Unmet Need: CIPN remains a major challenge with unsatisfactory treatment options. Clinical guidances recommends only duloxetine as a first-line agent, and its use is limited by side effects and incomplete response. IPG6620 could offer a more effective and better-tolerated alternative.

￭ Broad Therapeutic Potential: Beyond CIPN, the mechanism of IPG6620 suggests potential applications in other neuropathic pain conditions, such as diabetic neuropathy and postherpetic neuralgia, thereby expanding its potential market.

Current Development & Status

￭ IPG6620 is in the pre-clinical phase. We are advancing the IND-enabling studies.