Ingenol Mebutate

EMERYVILLE, Calif.--(BUSINESS WIRE)-- Eureka Therapeutics Inc., a clinical-stage biotechnology company developing novel T-cell therapies to treat solid tumors, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to ET140203 for the treatment of hepatoblastoma (HB), a rare childhood tumor in the liver that typically occurs in children under the age of 5. “We are pleased to receive ODD for ET140203 following the FDA’s earlier grant of Fast Track Designation (FTD) and Rare Pediatric Disease Designation (RPDD) designations to ET140203 for the treatment of HB,” said Dr. Cheng Liu, President and CEO of Eureka Therapeutics. “These designations highlight the significant unmet medical need for better pediatric liver cancer treatment options.” Eureka is currently recruiting patients in three Phase I/II clinical trials to investigate the safety and potential efficacy of ARTEMIS® T cells that have been engineered to target specific liver cancer antigens. The ARYA-1 (adult) and ARYA-2 (pediatric) studies use ET140203 ARTEMIS T cells directed with a TCR mimic antibody to target an alpha fetoprotein (AFP)-peptide/HLA-A2 complex found on liver cancer cells. The ARYA-3 study uses ECT204 T cells to target the Glypican 3 (GPC3) protein expressed on the surface of liver cancer cells. FDA Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug status provides benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees and seven years of post-approval marketing exclusivity. Patients, caregivers and health care professionals interested in Eureka’s clinical trials and technology can find more information by visiting eurekaconnectme.com. About ARYA-2 Trial and ET140203 The ARYA-2 study is an open-label, dose escalation, multi-center, Phase I/II clinical trial designed to assess the safety/tolerability and preliminary efficacy of ET140203 T-cells in pediatric subjects who are AFP-positive/HLA-A2-positive and have relapsed/refractory hepatoblastoma (HB), hepatocellular malignant neoplasm, not otherwise specified (HCN-NOS), or hepatocellular carcinoma (HCC). Additional information about Eureka’s Phase I/II study may be found at ClinicalTrials.gov, using Identifier NCT: NCT04634357. ET140203 is an investigational therapy during which a patient’s T cells are collected, engineered to express Eureka’s proprietary ARTEMIS® cell receptor and infused back into the patient. Engineered ET140203 T cells express a TCR-mimic antibody to target an alpha fetoprotein (AFP)-peptide/HLA-A2 complex on liver cancer cells. In addition, ET140203 ARTEMIS® T cells also incorporate Eureka’s proprietary tumor infiltration technology demonstrating enhanced ability to infiltrate solid tumors in animal models, potentially leading to improved efficacy in patients. About Eureka Therapeutics, Inc. Eureka Therapeutics, Inc. is a privately held clinical-stage biotechnology company focused on developing novel T cell therapies to treat cancers. Its core technology centers around its proprietary ARTEMIS® cell receptor platform and E-ALPHA® antibody discovery platform for the discovery and development of potentially safer and more effective T cell therapies for the treatment of solid tumors and hematologic malignancies. The company currently has two clinical programs, ET140203 (ARYA1 and ARYA2) and ECT204 (ARYA3), in Phase I/II US trials in patients with advanced liver cancer. Eureka Therapeutics, Inc. is headquartered in the San Francisco Bay Area. For more information on Eureka, please visit .

Evommune team/courtesy of Evommune Evommune’s novel human tissue-based assay system is proving to be a key differentiator as the company develops therapies to control chronic inflammation in autoimmune diseases. “Working with human tissue puts us closer to the target and yields a model that is much more predictive of outcomes in the human immune system,” said Luis Peña, CEO of Evommune, in an interview with BioSpace. “Skin has all of the cell types that are needed to induce specific inflammatory pathways,” said Eugene Bauer, M.D., CMO of Evommune. The company’s human tissue model is an ex vivo system that uses living skin from human donors, allowing the model to reflect all the immune responses that occur across various tissues in the body that drive inflammation. Consequently, in this context, it is more robust, predictive and relevant than animal modeling. This most closely mimics a “real-time” look at immune pathways and how to find the best way to target and modify inflammation. The miniaturized technology enables hundreds of assays to be conducted to study both systemic and topical therapies. Evolving Immunology In seeking to evolve immune therapy, Evommune is looking at the following opportunities in treating patients: early intervention in their disease state, improving efficacy, increasing response rates in patients and enhancing safety. “Autoimmune diseases are, in fact, systemic inflammatory conditions that are often associated with serious co-morbidities including infections, cardiovascular events, renal disease and mental health issues, making early intervention and preventing disease progression extremely important,” Peña said. “The entire body is in an accelerated immune-response mode. So, we are trying to modulate the immune system to dial down some of these responses. “Existing therapeutics have improved our ability to treat inflammatory conditions, but in most diseases, they still only elicit a response in about half the patients treated and achieve a great response rate in only one-third of those,” he continued. “Creating medicines that have better efficacy and that induce remission is the goal for us.” Improving the safety pro drugs that treat autoimmune diseases could make a meaningful impact in this space. “We want to develop therapies that improve patients’ quality of life without putting them at risk for other factors,” Peña said. Evommune’s senior leadership and scientific teams are primed to do just that. Throughout their careers, they have helped bring more than 25 medicines to patients in need. As Peña noted, “the combination of scientific insights, drug development expertise and building companies makes this team a unique group.” Accomplished Team of Experts A testament to this is that Peña and Bauer were co-founders of Dermira, which Eli Lilly acquired for $1.1 billion to get the rights to lebrikizumab. The two had originally helped acquire this asset from Genentech, despite the drug having failed in prior Phase III trials for a different indication. “We saw that lebrikizumab had promise in atopic dermatitis. We believed lebrikizumab had been under-dosed in previous atopic dermatitis trials, mostly because of a focus on asthma,” Peña explained. “We adjusted the dose in a Phase II atopic dermatitis program and delivered strong data. Lilly bought us because of that drug and since then, lebrikizumab has had great data from their Phase III studies. We believe lebrikizumab will become a significant therapy for atopic dermatitis and the team at Evommune had the vision to make that happen,” he said. Before Dermira, Bauer was president and CMO of Peplin, Inc. (acquired by LEO Pharma) and shepherded Picato® through a global submission, which included the FDA and resulted in an approval for actinic keratosis. Additionally, the Evommune development team has been responsible for multiple new drug applications or biologics license applications, several investigational new drug applications and numerous other interactions with regulators, including four global clinical development programs. “That combination of intimate knowledge of both immunology and drug development is what separates Evommune from other companies in terms of our ability to move these novel therapies forward,” Peña said. Evommune is committed to this promise with the ongoing expansion of the team, including new management positions across R&D, CMC, legal, strategy and finance who also bring a wealth of diverse drug discovery and development expertise. A Multifaceted Pipeline Evommune currently has four programs in the pipeline. "The goal for all of our programs is to be best in class,” Peña said. “EVO101 for atopic dermatitis is an IRAK4 inhibitor, which is a very novel target.” A randomized, blinded, placebo-controlled Phase IIa clinical trial for patients with mild-to-moderate atopic dermatitis was initiated in Q3 2022. “We define ‘mild-to-moderate’ atopic dermatitis as affecting between 4 and 12% of an individual’s body surface area. For perspective, the palm of your hand is 1%,” Bauer elaborated. “Study participants will apply a 0.1% cream to the lesions twice daily for eight weeks.” Results will be scored using the eczema area severity index (EASI), which measures redness, scaling and thickness of lesions, as well as the extent and severity of the disease. In EVO101’s development work, Evommune’s human tissue model enabled researchers to recapitulate disease pathology and inflammatory mediators of atopic dermatitis. “Adding low-, mid- and high-potency topical steroids (current standard-of-care therapeutics) to the human tissue model provided a control set of efficacy data – a baseline by which we could then compare the performance of EVO101,” Bauer explained. EVO101, at the dosage being used for patients in the clinical trial, lowered inflammation levels to those comparable with doses of ultra-high potency steroids, but with high selectivity. “We believe this could become an alternative to standard-of-care therapies for atopic dermatitis,” Bauer said, that may be used to treat both adult and pediatric patients. “In addition, we now have a development stage program that could potentially be a ground-breaking oral therapy for mast cell-mediated diseases,” he said. “EVO756 is a completely novel compound that will target the treatment of mast cell-mediated diseases and inflammatory itch,” Peña said. EVO756 targets MRGPRX2, a receptor that exists on mast cells and peripheral neurons and regulates mast cell degranulation. EVO756 is targeted for the treatment of mast cell-mediated disorders with highly prevalent populations such as chronic spontaneous urticaria, interstitial cystitis and hereditary alpha-tryptasemia. In addition, preclinical data have shown that itch can be completely eliminated in mice: knocking out that receptor made it impossible to induce itch. “For patients with inflammatory diseases, itch can be severe and have a significant, negative impact on a patient’s quality of life. We think EVO756 could be a great oral therapy, that can act quickly to relieve itch,” Peña continued. Another program, EVO390, is in development for the treatment of mild-to-moderate psoriasis in the hope of slowing or halting disease progression. This therapeutic agent targets RORγt and has the potential to be best-in-class and the agent of choice for these patients. It may also serve as an adjunct therapy in more severe cases. “We believe it could be a broadly used therapy for psoriasis,” Peña added. “Our fourth program, currently in discovery, targets protein kinase C (PKC) theta,” Peña continued. The company has identified several potent molecules that may have broad anti-inflammatory activity, highly targeted to T-effector cell inhibition and T-regulatory cell activation. This may have utility across a number of inflammatory conditions such as rheumatoid arthritis, IBD, atopic dermatitis and psoriasis. In addition, because it is highly targeted, it has the potential to be safer than the JAK inhibitors and other systemic anti-inflammatory agents. “As a company, we understand the importance of working on multiple targets and managing a portfolio of compounds. This approach provides the opportunity to work on different agents, impact many diseases and make a difference in patients’ lives,” Peña said. The company’s discovery engine is working to identify new targets so the team can extend its therapeutic impact.