Cardiotoxicity

SEOUL, South Korea, Oct. 24, 2024 /PRNewswire/ -- J INTS BIO, a pioneering biopharmaceutical company, has unveiled promising interim results from the Phase 1/2 clinical trial of its novel 4th-generation EGFR Tyrosine Kinase Inhibitor (TKI), JIN-A02, aimed at EGFR-mutated non-small cell lung cancer (NSCLC) patients who developed resistance and progressive diseases despite treatments. The data was presented at this year's edition of ENA (EORTC-NCI-AACR) Symposium, held in Barcelona, Spain, from October 23-25, 2024, drawing significant attention from the global oncology community. Continue Reading Ethan Seah, Vice President of J INTS BIO, is giving a poster presentation on the Phase 1/2 study of its novel oral 4th generation EGFR-TKI ‘JIN-A02’ at the ENA (EORTC-NCI-AACR) Symposium. JIN-A02: A Next-Generation Therapeutic Targeting Resistance to 3rd-Generation EGFR-TKIs Mutations in the epidermal growth factor receptor (EGFR) is a key driver in the pathogenesis of NSCLC, with 3rd Generation EGFR-TKIs like osimertinib serving as the cornerstone of treatment. Unfortunately, eventually resistance to this treatment will occur, leading to cancer relapse and disease progression. JIN-A02, developed by J INTS BIO, is the 4th-generation EGFR-TKI specifically designed to address this. By targeting both the original mutations and those acquired subsequently as a result of cancer treatments, it offers a therapeutic solution for these patients. The ongoing Phase 1/2 clinical trial evaluates JIN-A02 in patients with advanced or metastatic NSCLC who have developed resistance and disease progression after 3rd-generation EGFR-TKIs use. The study consist of 3 parts: dose escalation (Part A), dose exploration (Part B), and dose expansion (Part C). The data generated so far in Part A has been encouraging with a good safety profile and early efficacy signals, underscoring JIN-A02's position as a novel treatment for EGFR-TKI-resistant NSCLC. J INTS BIO said, "New treatment are urgently needed for lung cancer patients whose disease has worsened or relapsed after treatment with 3rd-generation EGFR-TKI. JIN-A02 is potentially one such treatment option that can bring hope to patients world wide." Study Design and Interim Results: To date, the Part A of the study has enrolled 16 patients who received increasing doses of JIN-A02, starting with a low dose of 12.5mg daily to 150 mg daily, with the primary objective of determining the maximum tolerated dose (MTD). This Part also look at safety, pharmacokinetics, and anti-tumor activity as secondary objectives. Doses higher than 150mg are currently being studied in this Part. Key Interim Findings: Safety: JIN-A02 demonstrated a very favorable tolerability across all dose levels studied so far, with no dose-limiting toxicities (DLTs) observed up to 150mg daily. There has been no myelosuppression and more importantly, no adverse events commonly associated with EGFR TKI such as rash, diarrhea and cardiotoxicity and this despite tumor reduction already being observed. This is the reason higher doses are being studied. Efficacy: Tumor control were reported early in this study at lower doses. The first instance occurring at a relative low dose of 50mg. In this cohort, Partial Response of the lung lesions with stable disease in brain metastases was reported. Another Partial Response of the lung lesions was reported in the next cohort of 100mg, in a patient with similar primary EGFR mutation. These findings highlight JIN-A02's potency as a therapeutic agent, even in patients with progressive diseases and who were heavily treated prior to entering this study. Central Nervous System (CNS): Of interest is JIN-A02 activity against brain metastases, a potentially fatal complication of progressive lung disease. Reduction in the brain metastases was first reported with JIN-A02 in the 100mg Cohort, although stable disease was reported in the 50mg Cohort. These results points to JIN-A02 not only penetrating the tough Blood-Brain Barrier, but also exerting its anti-tumor effects. Progression to Subsequent Trial Phases: Once we have the final doses to be used in Phase 2, the dose-expansion part of the study (Part B) will begin, and two doses will be selected and studied in bigger groups of patient to verify its safety, pharmacokinetics, and anti-tumor activity. Part B is essential for the selection of the final dose level to be used in Phase 2 or Part C of this study. In this final part (Part C), we will investigate JIN-A02 in specific patient populations who are stratified by EGFR mutation subtypes and the presence of CNS metastases. Part C is critical for generating a bigger dataset on the drug's therapeutic potential across distinct NSCLC patient groups for regulatory approval purposes. Implications for Future Therapeutic Development Professor Byeong Cheol Cho of Severance Hospital's Division of Medical Oncology, South Korea, commented on the significance of these findings, stating, "JIN-A02's demonstrated efficacy against both lung and its associated CNS disease underscores its potential as a groundbreaking treatment for patients with EGFR-TKI-resistant NSCLC, including and especially those with brain metastases." JIN-A02's ability to effectively target CNS lesions represents a notable advancement and as a 4th generation EGFR-TKI, offers hope for patients with very limited options as a result of progression after 3rd-generation TKIs use. Next Steps in Clinical Development: J INTS BIO is fully committed to accelerating the clinical development of JIN-A02. And as the clinical study continues to enroll patients ahead of schedule, JIN-A02, is poised to shape the treatment landscape of NSCLC and to offer hope to lung cancer patients worldwide. SOURCE J INTS BIO WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

People with chronic myeloid leukemia, a simmering cancer of the bone marrow, are often treated with one of several targeted drugs that, over the past two decades, have helped to substantially prolong survival from the disease.Study results revealed Friday suggest that Scemblix, the newest of those therapies, can be both safer and more effective, potentially supporting wider use of it as an initial treatment. The results are from a late-stage clinical trial run by Scemblixs maker, Novartis, and will be presented at the American Society of Clinical Oncologys annual meeting.In the trial, dubbed ASC4FIRST, Scemblix led to treatment responses in significantly more participants than did other targeted drugs, which included the mainstay therapy Gleevec as well as more recently introduced medicines. Additionally, more people given Novartis drug experienced whats called a deep molecular response, which over time can be considered a remission and allow treatment to be stopped.Study researchers also reported markedly favorable safety and tolerability for Scemblix, compared to Gleevec and the other so-called kinase inhibitors it was tested against.This combination of potency and safety may enable more patients to achieve treatment-free remission, the ultimate goal of CML therapy, said Timothy Hughes, the lead author of the ASC4FIRST study and an oncologist at the University of Adelaide, Australia, in a statement provided by ASCO.Scemblix is already approved in the U.S. and elsewhere for CML thats previously been treated with two or more kinase inhibitors. Based on the results of the ASC4FIRST trial, which Novartis in January said succeeded, the drugmaker has submitted for U.S. approval in people newly diagnosed with CML.If approved in the first-line setting, Scemblix would join Gleevec and three other kinase inhibitors that are currently available as first-line CML treatments. Their arrival in the 2000s and 2010s helped to triple the five-year survival rate for the disease, to roughly 70% among people diagnosed between 2012 and 2018, according to ASCO.Yet people with CML still cycle through different therapies, typically because their cancer develops resistance to treatment or side effects become intolerable.Patients with chronic myeloid leukemia often have to be on treatment for a very prolonged period, and more than 40% of patients who are newly diagnosed with CML fail to achieve the major molecular response after a year of treatment, said Oreofe Odejide, a medical oncologist at the Dana-Farber Cancer Institute, in a press conference held Wednesday under a publishing embargo. And then [some] also have to switch treatments because of adverse events.Fridays results indicate Scemblix may help on both fronts.The drug works differently than other kinase inhibitors approved before it, targeting a certain pocket on a mutant protein that drives CML proliferation. This difference might make Scemblix more selective in its binding and therefore less toxic, according to Jorge Cortes, director of the Georgia Cancer Center and an ASC4FIRST study investigator.Novartis designed its trial to compare Scemblix to available kinase inhibitors selected by participants treating physicians. Just over 400 adults with recently diagnosed, chronic-phase CML were enrolled and randomized to receive either Scemblix or the selected kinase inhibitor. (Along with Gleevec, approved first-line kinase inhibitors include the drugs Sprycel, Tasigna and Bosulif.)Results showed that, after 48 weeks, 68% of patients given Scemblix achieved a major molecular response, versus 49% of those on other kinase inhibitors. This laboratory measure looks at levels of mutant protein in the body. A major response means that levels are less than or equal to 0.1% on a so-called International Scale.Major molecular response predicts for better event-free survival, said Cortes, at the ASCO press conference. But probably more important is that it's a good predictor for the deep molecular responses in the long term, particularly the sustained deep molecular responses that make the patients eligible for considering treatment discontinuation.Nearly two-fifths of Scemblix-treated patients met the threshold for those deep molecular responses in the trial, compared to 21% of those on the other kinase inhibitors.Novartis also designed ASC4FIRST with a twist. Before patients were randomized to either the Scemblix or control groups, their physicians chose whether they would get Gleevec, which is typically used with older individuals, or one of the more potent, second-generation kinase inhibitors. For the main study analysis, Novartis then compared patients selected to receive Gleevec but randomized to Scemblix, to those who were randomized to the control group.Here, too, Scemblix outperformed. Major molecular responses were observed in 69% of Gleevec-selected patients who received Scemblix, versus 40% who went on to get one of the control drugs. This comparison was a main objective of the study.Patients were similarly grouped prior to randomization by whether they were selected for a second-generation kinase inhibitor, but the study wasnt powered to detect a statistical difference on that score.Its common for newer drugs to offer better efficacy or safety. But its rarer that theyre both safer and more potent. In ASC4FIRST, Scemblix was associated with lower rates of study discontinuation, dose adjustment or treatment interruptions than the comparator kinase inhibitors. And there were fewer side effects classified as medically significant with Scemblix than with either Gleevec or the second-generation drugs. The most common adverse events were low platelet and neutrophil counts.In its current labeling, Scemblix carries cautions about the risk of pancreatic toxicity, hypertension and cardiovascular toxicity.Scemblix has a nice balance of efficacy and tolerability, said Odejide. This is really poised to potentially change the management of first-line treatment of chronic myeloid leukemia.Researchers will continue to follow patients through 96 weeks, testing whether earlier molecular responses lead to better outcomes. Other studies will test progression-free survival or overall survival.For Novartis, the results position the company to extend a legacy in CML treatment. Gleevec, which had roots in the Swiss firm Ciba-Geigy, became a top-seller for Novartis, which also later developed Tasigna. Executives hope Scemblix can find similar commercial success.Our goal is to make this, over time, the leading CML treatment in the world, said Novartis CEO Vas Narasimhan on a recent earnings call. He added that Novartis has long patent protection on the medicine, which also may not be eligible for drug price negotiations in the U.S. since CML is a rare form of cancer. '

Preclinical Pro DLX-001 Promotes Robust Neuroplastic Effects with Rapid and Durable Antidepressant Effects Novel Neuroplastogen Continues to Be Well-Tolerated After Single and Multidose Administration Data Presented at SOBP and ASCP Annual Meetings BEDFORD, Mass.--(BUSINESS WIRE)-- Delix Therapeutics, a clinical-stage neuroscience company developing novel neuroplasticity-promoting therapeutics for psychiatric and neurological disorders, today announced additional data from an ongoing Phase 1 trial evaluating DLX-001, a novel neuroplastogen, demonstrating evidence of brain activity in healthy volunteers without producing psychotomimetic, dissociative or hallucinogenic effects. The Company also announced preclinical data showing the effects of DLX-001 on antidepressant, structural, and functional plasticity assays. These data were presented at the 2024 Society of Biological Psychiatry (SOBP) Annual Meeting from May 9-11 in Austin, Texas and will also be presented at the 2024 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting from May 28–31 in Miami Beach, Florida. “Building on interim results presented at ACNP in December, we are encouraged by DLX-001’s favorable safety and tolerability pro date, as well as time- and dose-dependent effects observed on quantitative EEG,” said Aaron Koenig, MD, Chief Medical Officer of Delix Therapeutics. “These results, coupled with a continued lack of hallucinogenic, psychotomimetic, or dissociative effects as we approach the end of this first-in-human study, reinforce our belief that DLX-001 has the potential to address significant unmet needs for patients suffering from MDD and related disorders.” DLX-001, A Novel Neuroplastogen, Produces Rapid Time- and Dose-Dependent Increases in Delta and Theta Power on Quantitative EEG (qEEG) Lead Author: Aaron Koenig, M.D. Session Date: Thursday, May 9 Session Time: 5:30-7:30pm CT A three-part Phase 1 study will enroll over 100 healthy volunteers at the Center for Human Drug Research (CHDR) in The Netherlands, with the primary objectives of assessing safety, pharmacokinetics (PK), and markers of brain activity. Part A is a randomized, double-blind, placebo-controlled single ascending dose (SAD) study of DLX-001. Part B is an open-label crossover design study to investigate the effect of food on the PK of DLX-001. Part C is a randomized, double-blind, placebo-controlled multiple ascending dose (MAD) study in which participants receive multiple oral doses of either DLX-001 or placebo over 7 days. Key Findings DLX-001 has demonstrated a favorable safety and tolerability pro date, with no serious adverse events. No psychotomimetic, hallucinatory, or dissociative effects have been observed, as reflected by no change over time on a robust battery of assessments. Time and dose-dependent changes measured by resting-state quantitative electroencephalography (qEEG), paired with consistently measurable concentrations of compound in the cerebrospinal fluid (CSF), support brain penetration and the presence of target engagement with DLX-001. The qEEG pattern of DLX-001 in healthy volunteers is characterized by increases in slow wave (delta and theta) activity consistent with the pattern observed with ketamine and Electro-Convulsive Therapy (ECT). The maximum tolerated dose for DLX-001 has not yet been reached, and the study remains in progress. Along with these additional Phase 1 data, Delix presented preclinical data characterizing DLX-001’s neuroplastic and therapeutic effects, including comparative data marking the beneficial efficacy of DLX-001 against ketamine, psilocybin, DMT, and differentiating from these compounds due to a lack of hallucinogenic liability. Preclinical Pharmacology of DLX-001, a Novel Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases Lead Author: Kurt Rasmussen, Ph.D. Session Date: Saturday, May 11 Session Time: 12:30–2:30pm CT DLX-001 was examined in a series of in vitro, ex vivo, and in vivo assays relevant to neuroplasticity and major depressive disorder (MDD). Key Findings In PK studies, DLX-001 was shown to be orally bioavailable and brain penetrant. In vitro studies demonstrate robust increases in neurite length and branching, increasing neuronal complexity. Ex vivo, DLX-001 demonstrated robust effects on both structural and functional neuroplasticity after a single dose. The magnitude of these effects was on par with first generation compounds including ketamine, psilocybin, and DMT and were seen at doses relevant to the behavioral effects of each of these compounds. DLX-001 exhibited both rapid—within 24-hours, and enduring—up to 14 days, antidepressant-like activity after a single dose in multiple behavioral models. In studies relevant to cardiotoxicity and hallucinations, no signal was identified for DLX-001. About DLX-001 DLX-001 is a novel, non-hallucinogenic, and non-dissociative isotryptamine neuroplastogen currently undergoing initial human testing to treat those diagnosed with major depressive disorder (MDD) and other associated neuropsychiatric conditions. Preclinical data show that in efficacious doses, DLX-001 increased dendritic spine density in rat brain PFC layer-V pyramidal neurons and had rapid and enduring antidepressant-like effects after a single dose. Recent phase 1 data found DLX-001 to be well tolerated, with no serious adverse events reported and robust signs of target engagement. In addition, researchers did not observe significant abnormalities among crucial safety indicators, including vital signs, electrocardiogram (ECG) readings, and laboratory analysis. About Neuroplastogens Neuroplastogens are a novel class of potentially disease-modifying therapeutics for psychiatric and neurological conditions. These compounds promote rapid and sustained neuroplasticity in select neural circuits resulting in fast-acting therapeutic effects. Neuroplastogens are novel chemical entities inspired by compounds that are proving to be beneficial across a range of therapeutic areas including mood, anxiety, cognitive, and neurodegenerative disorders in addition to other synaptopathies. Leveraging our phenotypic drug discovery engine to generate distinct compounds, Delix seeks to bring to market a pipeline of neuroplastogens that will be the faster, stronger, and more effective therapies of the future. About Delix Therapeutics Delix Therapeutics is a clinical-stage neuroscience company focused on harnessing the power of novel neuroplasticity-promoting therapeutics to better treat patients struggling with difficult-to-treat neuropsychiatric and neurological disorders. The company's compounds are easily manufactured small molecules capable of rapidly inducing structural and functional neural changes in targeted areas of the brain. Through its novel Neuroplastogen Platform, Delix is pioneering a new class of fast-acting outpatient pharmacotherapies and rapidly advancing through preclinical and clinical development to bring patients FDA-approved, take-home medicines that will serve several unmet needs and enhance the psychiatric treatment paradigm for patients and providers.