ImmunoMet Therapeutics, Inc.

HOUSTON--(BUSINESS WIRE)--ImmunoMet Therapeutics, Inc., a clinical stage biotechnology company targeting metabolism to develop novel anti-cancer and anti-fibrotic therapies, today announces that the first patient has been dosed in the single-arm Phase 1b trial of IM156 in combination with gemcitabine and nab-paclitaxel as frontline therapy in patients with advanced pancreatic cancer. The study is led by Shubham Pant, MD, Professor in Department of Gastrointestinal (GI) Medical Oncology and Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. This clinical trial evaluates the potential of IM156 in combination with gemcitabine and nab-paclitaxel to address resistance and improve patient outcomes. The trial includes a dose escalation phase followed by an expansion phase, treating a total of approximately 25 patients with advanced pancreatic cancer. The primary endpoint is to evaluate the safety and tolerability of the combination. Exploratory efficacy endpoints include objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using RECIST v1.1 criteria. “Pancreatic cancer continues to be defined by high unmet need, morbidity, and mortality. There is substantial evidence that differential cancer cell metabolism, and oxidative phosphorylation (OxPhos) in particular, plays a key role in the development of resistance to current therapies. We are hopeful that this potentially best-in-class OxPhos inhibitor can improve outcomes for these patients,” said Dean Welsch, CEO of ImmunoMet Therapeutics. Additional information about the trial, which is recruiting patients, can be found on clinicaltrials.gov using the identifier NCT05497778. ImmunoMet is also pleased to announce that it has received Orphan Drug Designation status for IM156 in patients with pancreatic cancer and closed a Series C-1 financing in October 2022. ImmunoMet continues to investigate additional indications where emerging data implicate OxPhos inhibition will demonstrate anti-tumor effects. About IM156 IM156 is a Protein Complex 1 (PC1) inhibitor that targets the oxidative phosphorylation (OXPHOS) pathway that is required to drive tumor growth and proliferation in some tumors. IM156, ImmunoMet’s lead drug candidate, is solely owned by ImmunoMet and is currently in development for the treatment of selected cancers. About ImmunoMet Therapeutics ImmunoMet is a clinical stage biotechnology company targeting metabolism for the treatment of selected cancers and fibrotic diseases. ImmunoMet’s lead molecule, IM156, is the first PC1 inhibitor to complete Phase 1 with good tolerability. In addition to IM156, ImmunoMet owns a large library of biguanides with the potential for development, internally or with partners, for multiple indications. The company was founded in 2015, is headquartered in JLABS @ TMC in Houston and has raised $34M to date. For more information about the company, please visit www.immunomet.com.

HOUSTON, TX, USA I November 17, 2022 I ImmunoMet Therapeutics, Inc., a clinical stage biotechnology company targeting metabolism to develop novel anti-cancer and anti-fibrotic therapies, today announces that the first patient has been dosed in the single-arm Phase 1b trial of IM156 in combination with gemcitabine and nab-paclitaxel as frontline therapy in patients with advanced pancreatic cancer. The study is led by Shubham Pant, MD, Professor in Department of Gastrointestinal (GI) Medical Oncology and Associate Professor, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. This clinical trial evaluates the potential of IM156 in combination with gemcitabine and nab-paclitaxel to address resistance and improve patient outcomes. The trial includes a dose escalation phase followed by an expansion phase, treating a total of approximately 25 patients with advanced pancreatic cancer. The primary endpoint is to evaluate the safety and tolerability of the combination. Exploratory efficacy endpoints include objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using RECIST v1.1 criteria. “Pancreatic cancer continues to be defined by high unmet need, morbidity, and mortality. There is substantial evidence that differential cancer cell metabolism, and oxidative phosphorylation (OxPhos) in particular, plays a key role in the development of resistance to current therapies. We are hopeful that this potentially best-in-class OxPhos inhibitor can improve outcomes for these patients,” said Dean Welsch, CEO of ImmunoMet Therapeutics. Additional information about the trial, which is recruiting patients, can be found on clinicaltrials.gov using the identifier NCT05497778. ImmunoMet is also pleased to announce that it has received Orphan Drug Designation status for IM156 in patients with pancreatic cancer and closed a Series C-1 financing in October 2022. ImmunoMet continues to investigate additional indications where emerging data implicate OxPhos inhibition will demonstrate anti-tumor effects. About IM156 IM156 is a Protein Complex 1 (PC1) inhibitor that targets the oxidative phosphorylation (OXPHOS) pathway that is required to drive tumor growth and proliferation in some tumors. IM156, ImmunoMet’s lead drug candidate, is solely owned by ImmunoMet and is currently in development for the treatment of selected cancers. About ImmunoMet Therapeutics ImmunoMet is a clinical stage biotechnology company targeting metabolism for the treatment of selected cancers and fibrotic diseases. ImmunoMet’s lead molecule, IM156, is the first PC1 inhibitor to complete Phase 1 with good tolerability. In addition to IM156, ImmunoMet owns a large library of biguanides with the potential for development, internally or with partners, for multiple indications. The company was founded in 2015, is headquartered in JLABS @ TMC in Houston and has raised $34M to date. For more information about the company, please visit www.immunomet.com . SOURCE: ImmunoMet Therapeutics

A new study focused on the immune system's Th17 cells suggests that the shape and function of their mitochondria (the powerhouse of cells) is important in autoimmune and inflammatory disorders, such as multiple sclerosis. A new study focused on the immune system's Th17 cells suggests that the shape and function of their mitochondria (the powerhouse of cells) is important in autoimmune and inflammatory disorders, such as multiple sclerosis. T helper 17 (Th17) cells are a type of CD4+ T immune cell, which collectively help make antibodies, activate enemy-eating cells and recruit more soldiers to the battlefront. The research, led by Erika Pearce, Ph.D., at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center, suggests that learning how mitochondria impact Th17 cells is key to understanding how to control them. The study, published Sept. 28 in the journal Nature, identifies several avenues for trying to influence the behavior of these important cells, with the goal of dampening their autoimmune activity. When a T cell is first exposed to an enemy, it responds to signals from the enemy and the environment to become one of several types of specialized T cells, each armed with distinct functions in the immune response. While all T helper cell subtypes are crucial to the body's fight against foreigners, their imbalance can also cause disease, including type 1 diabetes, asthma, allergies and chronic inflammation. "If we could control T cells, we could arguably control many, if not most, infections, autoimmunities and cancers," says Pearce, the study's senior author and a Johns Hopkins Bloomberg Distinguished Professor in the Department of Oncology and the Department of Biochemistry and Molecular Biology. The study began when researchers in Pearce's laboratory, which was then at the Max Planck Institute in Freiburg, Germany, noticed a trait peculiar to Th17 cells. Among three main T effector cell types, only Th17 cells had elongated mitochondria; that is, their inner powerplants were fused together into larger structures. "That was strange because elongated mitochondria are usually seen in resting cells and not in activated cells," says first author Francesc Baixauli, Ph.D., a former postdoctoral fellow at the Max Planck Institute. The researchers knew that the OPA1 gene regulates mitochondrial fusion, so they deleted it in Th17 cells and found that their mitochondria reverted to a more fragmented size and shape. However, the cells also stopped doing their main job -- producing the signaling molecule interleukin-17 (IL-17). To confirm this result in an organism, the researchers deleted the OPA1 gene in mice and promoted a disease in these animals that models human multiple sclerosis, which is driven by their Th17 cells. With OPA1 deleted, not only did their cells stop making IL-17, but their disease symptoms abated. Wondering how OPA1 deletion stopped the production of IL-17, the team first thought that the cells' mitochondria simply weren't producing enough energy. However, they found that OPA1 deletion did not affect energy production, and that OPA1 was crucial to the production of IL-17 regardless of whether the cells' metabolic activity was high or low. Then, they found that a central biochemical process occurring in the mitochondria had been altered, causing the buildup of a metabolite known to influence DNA and the transcriptional program of the cell. "That molecule was dampening the ability of the cell to read its DNA, and consequently IL-17 was no longer produced," says Baixauli. To identify the connection between these responses and OPA1 deletion, the researchers compared proteins produced by normal Th17 cells and those without OPA1. In cells missing OPA1, they found a large increase in the activated form of the protein LKB1, which is a metabolic sensor that regulates cellular metabolism, cell division and mitochondrial function. When they deleted both OPA1 and LKB1 from cells, IL-17 production was restored, and the mitochondrial processes returned to normal. "We think that LKB1 senses mitochondrial stress and alters the mitochondria's biochemical reactions appropriately, which affects the production of IL-17," says Pearce. "We now have a short list of molecules known to influence this key aspect of Th17 function, which can be the tipping point between its helpful and harmful roles. Our future research will continue to explore these relationships so that we can hopefully one day therapeutically modify them." Other researchers were Klara Piletic, Daniel J. Puleston, Matteo Villa, Cameron S. Field, Lea J. Flachsmann, Andrea Quintana, Nisha Rana, Joy Edwards-Hicks, Mai Matsushita, Michal A. Stanczak, Katarzyna M. Grzes, Agnieszka M. Kabat, Mario Fabri, George Caputa, Beth Kelly, Mauro Corrado, Yaarub Musa, Katarzyna J. Duda, Gerhard Mittler, David O'Sullivan, Thomas Jenuwein and Joerg M. Buescher at the Max Planck Institute, and Hiromi Sesaki, Edward J. Pearce and David E. Sanin at The Johns Hopkins University. The research was supported by the Max Planck Society, the Leibniz Prize, the National Institutes of Health (R01AI156274 and R35GM144103), The Johns Hopkins University and a Bloomberg Distinguished Professorship, a Marie Sklodowska-Curie Actions individual fellowship, a Sir Henry Wellcome fellowship and an Alexander von Humboldt postdoctoral fellowship. Erika Pearce is a member of the ImmunoMet Therapeutics Scientific Advisory Board, and Erika Pearce and Edward Pearce are founders and scientific advisers to Rheos Medicines.