ITK

DZD8586 study results in B-cell non-Hodgkin lymphomas (B-NHLs) were selected for oral and poster presentations. The analysis in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after covalent or non-covalent BTK inhibitors and BTK degraders was selected for oral presentation Dizal will also present results from the ongoing Phase I/II study of DZD6008, a 4th generation EGFR TKI with full BBB penetration, in advanced EGFR mutation positive (EGFRm) non-small cell lung cancer (NSCLC) SHANGHAI, April 24, 2025 /PRNewswire/ -- Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, announced today that the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting will feature the latest study results from the company's investigational drugs DZD8586 and DZD6008 in B-cell non-Hodgkin lymphomas (B-NHLs) and non-small cell lung cancer (NSCLC). The oral presentation includes results in B-NHLs from a pooled safety and efficacy analysis of two phase I/Ⅱ studies of DZD8586 in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients with prior treatment of covalent and/or non-covalent BTK Inhibitors as well as BTK degraders. While early clinical data showed encouraging anti-tumor activities from BTK degraders in CLL/SLL patients, resistance mutations to both BTK inhibitors and degraders have already been reported, and degrader-related toxicities may affect long-term clinical application. Data from Phase I/II studies of DZD8586 in CLL/SLL, presented at the 66th American Society of Hematology (ASH) Annual Meeting, showed that 94.4% of patients achieved tumor shrinkage at ≥50 mg QD. Significant tumor responses were also observed in other B-NHLs, including diffuse large B-cell lymphoma (DLBCL). Preliminary results from the ongoing phase Ⅱ study of DZD8586 monotherapy in patients with relapsed/refractory DLBCL will be presented at this ASCO meeting. Dizal will also present Phase I/II data of DZD6008, a 4th generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with full blood–brain barrier (BBB) penetration, in advanced EGFR mutation positive (EGFRm) NSCLC patients who failed prior 3rd generation EGFR TKI treatment. Lung cancer is a leading cause of brain metastases (BMs), with 10-20% of patients with NSCLC presenting with BMs at diagnosis and 25-50% developing them over the course of their disease. NSCLC patients whose disease progressed after 3rd generation EGFR TKI treatment often develop CNS metastasis and exhibit acquired EGFR resistance mutations. Preclinical data shows that DZD6008 demonstrates good safety and efficacy in NSCLC patients with brain metastases who had failed 3rd generation EGFR TKI therapy or multiple lines of pre-treatments. "We are honored that our study results have been selected for oral presentations at ASCO for three consecutive years. Our presence at this congress highlights our commitment to addressing global unmet medical needs in hematological malignancies and lung cancer," said Xiaolin Zhang, PhD, CEO of Dizal. "We look forward to sharing positive clinical data of our novel medicines, which have the potential to bring clinical benefit to patients with limited treatment options." Dizal presentation details during ASCO 2025 ： About DZD8586 DZD8586 is a first-in-class, non-covalent, LYN/BTK dual inhibitor with full blood-brain barrier (BBB) penetration, designed as a potential treatment option for B-cell non-Hodgkin lymphoma (B-NHL). While Bruton's Tyrosine Kinase (BTK) inhibitors have been approved for the treatment of B-NHL, resistance can arise through two major mechanisms: the BTK C481X mutation and BTK-independent BCR signaling pathway activation. Currently, there is no targeted therapy available to address both resistance mechanisms, posing an urgent clinical challenge. Although BTK degraders have shown encouraging efficacy in early clinical studies, mutation-related resistance has been reported, and degrader-related toxicities may affect long-term clinical application. DZD8586 has high selectivity against other TEC family kinases (TEC, ITK, TXK and BMX). By targeting BTK and LYN, it blocks both BTK-dependent and -independent BCR-signaling pathways, effectively inhibiting tumor growth of B-NHLs in cell lines and in animal models. Phase I clinical trial suggests that DZD8586 exhibits favorable PK properties, good central nervous system (CNS) permeability, complete blockade of BCR signaling, and encouraging anti-tumor efficacy with good safety and tolerability in patients with B-NHL. About DZD6008 DZD6008 is a novel, highly selective, full-BBB penetrant EGFR TKI, designed as a potential treatment option for advanced EGFR mutation positive (EGFRm) NSCLC. Non-small cell lung cancer is the leading cause of cancer death in the world. Epidermal growth factor receptor (EGFR) gene is one of the most common driver genes for NSCLC. Multiple agents can be used to treat patients with EGFR mutated NSCLC who develop resistance to EGFR tyrosine kinase inhibitors (TKIs), but the clinical outcome was not satisfactory. Brain metastases (BM) are a leading cause of death and disease progression for NSCLC. Approximately 23%-30% of NSCLC patients are synchronous BM at their initial diagnosis. Previous studies reported that the 3-year cumulative rate of BMs ranges from 29.4% to 60.3% in patients with mutated EGFR. Currently, the clinical benefits of existing treatments for third-generation EGFR TKI-resistant NSCLC are limited and DZD6008 is expected to fill the unmet medical needs. DZD6008 effectively inhibits EGFR-mutated tumor growth in cell lines and in animal models. Previous clinical studies have validated the design concept of the molecule and suggest that DZD6008 demonstrates good safety and efficacy in NSCLC patients with brain metastases who had failed third-generation EGFR TKI therapy or multiple lines of pre-treatments. About Dizal Dizal is a biopharmaceutical company, dedicated to the discovery, development and commercialization of differentiated therapeutics for the treatment of cancer and immunological diseases. The company aims to develop first-in-class and groundbreaking new medicines, and further address unmet medical needs worldwide. Deeply rooted in translational science and molecular design, it has established an internationally competitive portfolio with two leading assets in global pivotal studies, both of which have already been launched in China. To learn more about Dizal, please visit , or follow us on Linkedin or X. Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", and "intend" and similar expressions, as they relate to Dizal, are intended to identify certain forward-looking statements. Dizal does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections, and understandings of the management of Dizal with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties, and other factors, some of which are beyond Dizal's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Dizal's competitive environment, and political, economic, legal, and social conditions. Dizal, the Directors, and the employees of Dizal assume (a) no obligation to correct or update the forward-looking statements contained on this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turnout to be incorrect. Contacts Investor Relations: [email protected] Business Development: [email protected] Media Contact: [email protected] SOURCE Dizal Pharmaceutical WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

March 20, 2025 -- Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, today announced that additional data from the Company’s Phase 1/1b clinical trial of soquelitinib for the treatment of patients with T cell lymphoma (TCL) is being presented at the 16th Annual T-Cell Lymphoma Forum taking place March 20-22, 2025 in San Diego, CA. “The data from the Phase 1/1b clinical trial of soquelitinib in patients with T cell lymphoma continues to demonstrate strong indications of anti-tumor activity in a significant number of patients,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “We are encouraged by the high complete response, prolonged median progression free survival and high rate of 18-month progression free survival, which all appear superior to standard of care agents such as belinostat and pralatrexate. In addition, analysis of patient blood samples at baseline and on treatment show that soquelitinib reduces T cell exhaustion, which may allow for improved T cell function and anti-tumor immunity. Supported by this data, our registrational Phase 3 trial of soquelitinib is enrolling patients with relapsed peripheral T cell lymphoma at multiple sites in the U.S., Canada and Australia, along with our Phase 1 trial in atopic dermatitis that is anticipated to deliver data in the second quarter 2025.” The soquelitinib data from the Phase 1/1b clinical trial of soquelitinib for TCL will be presented by John Reneau, MD, PhD, Assistant Professor in the College of Medicine and The Ohio State University Comprehensive Cancer Center. Dr. Reneau is a hematologist who specializes in treating patients with lymphoma and an investigator in the trial. The details of Dr. Reneau’s presentations are as follows: Oral Presentation Title: Selective ITK Inhibition for Treatment of PTCL Time: 4:50 – 5:10 pm PT on March 20, 2025 Poster Presentation Abstract Title: Soquelitinib, a Selective ITK Inhibitor for Treatment of T Cell Lymphomas: Results of Ph1 trial Reveal Novel Mechanisms of Action A total of 25 patients were enrolled in the Phase 1/1b trial at the optimum 200 mg two-times a day dose and would have met the eligibility criteria for the ongoing registrational Phase 3 clinical trial based on ≥1 and ≤3 prior therapies, including 23 evaluable patients. For the 23 evaluable patients: Objective responses (complete response, CR, plus partial response, PR) were seen in nine patients (39%), including six CRs (26%) and three PRs. The median duration of response (DOR) for the nine patients with objective response by Lugano criteria was 17.2 months. Three patients continue on therapy at 25+ months, 18+ months and 14+ months. Kaplan Meier estimated median progression free survival (PFS) was 6.2 months. At 18-month follow-up, the PFS rate was 30%, which compares favorably to 18-month PFS of 1 2 Peripheral blood samples were collected from patients both prior to the initiation of soquelitinib therapy and during the course of treatment. These samples were analyzed for markers of T cell exhaustion in normal T cells. The results indicated that the majority of patients exhibited a reduction in T cell exhaustion markers on both CD4+ and CD8+ cells after 21 days of treatment. T cell exhaustion is a state in which T cells exhibit diminished functionality due to prolonged exposure to antigens. Soquelitinib was well-tolerated, with no new safety signals, drug interruptions or dose reductions. Based on the results from the Phase 1/1b trial, Corvus is enrolling patients in a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed Peripheral T cell lymphoma (PTCL) at multiple sites. This randomized controlled trial is anticipated to enroll a total of 150 patients with relapsed PTCL and is evaluating soquelitinib versus physicians’ choice of either belinostat or pralatrexate. The primary endpoint of the trial is PFS. There are no FDA fully approved agents for the treatment of relapsed PTCL and the FDA has granted soquelitinib Orphan Drug Designation for the treatment of T cell lymphoma and Fast Track designation for treatment of adult patients with relapsed or refractory PTCL after at least 2 lines of systemic therapy. Peripheral T cell lymphoma (PTCL) is a heterogeneous group of malignancies accounting for about 10% of non-Hodgkin’s lymphomas (NHL) in western populations, reaching 20% to 25% of NHL in some parts of Asia and South America. The most common subtypes are PTCL-not otherwise specified (PTCL-NOS) and T follicular helper cell lymphoma. Initial therapy for these diseases is typically combination chemotherapy; however, approximately 75% of patients either do not respond or relapse within the first two years. Patients in relapse are treated with various chemotherapy agents but have poor overall outcomes with median progression-free survival in the 3 to 4 month range and overall median survival of 6 to 12 months. There are no approved drugs in relapsed PTCL based on randomized trials. PTCL is a disease of mature helper T cells that express ITK (interleukin-2-inducible T cell kinase), often containing numerous genetic mutations and frequently associated with viral infection. Most often the malignant cells of PTCL express a Th2 phenotype. Soquelitinib (formerly CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. Soquelitinib has been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of their secreted cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases. Recent studies have demonstrated that ITK controls a switch between the differentiation of Th17 proinflammatory cells and T regulatory suppressor cells. Inhibition of ITK leads to a shift toward T regulatory cell differentiation which has the potential to suppress autoimmune and inflammatory reactions. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company is conducting a registrational Phase 3 clinical trial (NCT06561048) of soquelitinib in patients with relapsed PTCL. Soquelitinib is also being investigated in a randomized placebo-controlled Phase 1 clinical trial in patients with atopic dermatitis and a Phase 2 clinical trial in patients with autoimmune lymphoproliferative syndrome (ALPS), a rare genetic disease. A recent publication describing the chemistry, enzymology and biology of soquelitinib appeared in NPJ Drug Discovery in December 2024 and is available online at the Nature website and on the Publications and Presentations page of the Corvus website. Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancers and immune diseases. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit www.corvuspharma.com. 1 O’Connor O. et. al. J. Clin Onc 33:2492, 2015 2 O’Connor O. et. al. J. Clin Onc 29:1182, 2011 The content above comes from the network. if any infringement, please contact us to modify.

Trial for this rare genetic disease to be conducted by NIH/NIAID in partnership with Corvus ITK inhibition intended to address dysregulation of T cells that causes ALPS and has been shown to be effective at treating the disease in preclinical models March 12, 2025 -- Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, today announced that the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), has initiated a Phase 2 clinical trial of soquelitinib for the treatment of patients with autoimmune lymphoproliferative syndrome (ALPS), a rare genetic disease. The lead investigator of the trial is V. Koneti Rao, MD, FRCPA, Senior Research Physician, Primary Immune Deficiency Clinic (ALPS Clinic) at NIH Clinical Center. Dr. Rao previously presented preclinical data supporting the potential of soquelitinib in patients with ALPS. Other trial sites include Children’s Hospital of Philadelphia and Texas Children’s Cancer and Hematology Center. “Developing safe and effective targeted treatments to address ALPS and related disorders is a priority at the NIAID since this condition was first discovered in NIAID in the early 1990s,” said Dr. Rao. “ALPS typically begins to manifest by age two and most patients live into adulthood with burdensome symptoms often related to refractory autoimmune cytopenias (low blood counts). This requires ongoing surveillance and the risk for potentially fatal conditions such as infection, hemorrhage and malignant lymphoma. We look forward to investigating the potential of ITK inhibition with soquelitinib to improve immune system balance and reduce the buildup of dysfunctional T cells in lymph nodes and spleens and autoantibodies that drive the disease.” ALPS is most often caused by a mutation in the gene for the Fas protein, which spans the cell membrane and helps facilitate apoptosis, or programmed cell death. When this protein is missing or defective, T cells can build up and disrupt the immune system, leading to potentially debilitating symptoms and an increased risk for developing serious health conditions, including autoimmune diseases and lymphoma. There currently is no cure for ALPS and the disorder is managed by a variety of empirical methods aimed at addressing pathological changes caused by the disease, such low blood-cell counts (cytopenias), excessive lymphocyte production (lymphoproliferation), enlarged spleen or lymph nodes, and lymphoma. Treatments may include corticosteroids such as prednisone and other immunosuppressive medications to modulate the immune system, or cancer therapies to address lymphoma. “We are excited to expand the potential of ITK inhibition to address people with ALPS, which is a serious genetic disease that begins in childhood and gets worse due to progression during young adulthood and lacks good treatment options,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “There is compelling preclinical evidence that soquelitinib may address the immune dysregulation in T cells that is a hallmark of the disease. It also bridges the biology of T cell lymphomas and autoimmunity, highlighting the role that ITK inhibition may play in restoring immune balance in lymphoma and immune disease. This adds to our conviction for the potential of soquelitinib as we continue to enroll patients in our registrational Phase 3 trial in PTCL and Phase 1 trial in atopic dermatitis.” The Phase 2 clinical trial (NCT06730126) is designed to enroll up to 30 patients aged 16 or older with confirmed ALPS-FAS based on genetic testing. Two dosing cohorts will be studied. The patients will receive soquelitinib doses of 200 mg or 400 mg twice per day for a period of up to 360 days. The primary endpoint of the trial is efficacy determined by reductions in splenomegaly and lymph node volumes as measured by computed tomography (CT) or positron emission tomography/computed tomography (PET/CT). Improvements in cytopenias will be assessed by complete blood count (CBC). Cytopenias are caused by autoantibodies as well as splenic sequestration that may lead to destruction of red blood cells, platelets and/or neutrophils leading to anemia, thrombocytopenia or neutropenia. Improvements in cytopenias can improve quality of life and overall health, and they also serve as a valuable biomarker associated with ALPS disease activity. Secondary endpoints include safety and tolerability. This is the third indication under clinical development for soquelitinib, which is also in a registrational Phase 3 trial for peripheral T cell lymphoma (PTCL) and a Phase 1 trial for atopic dermatitis (AD). Corvus also plans to initiate a Phase 1 clinical trial of soquelitinib in patients with solid tumors in the second quarter 2025. ALPS is a rare genetic disease inherited as a germline autosomal dominant pattern or due to somatic mosaicism affecting children that manifests with lymphadenopathy, splenomegaly, cytopenias (low blood counts) and autoimmunity. The disease is caused by a mutation in the Fas gene, which provides instructions for making a signaling protein involved in the induction of apoptosis to get rid of redundant lymphocytes. The mutation results in immune dysregulation due to accumulation abnormally high levels of “double negative” T cells (CD4 and CD8 double negative), which infiltrate the blood, spleen and lymphoid tissues. Fas signaling is regulated by ITK and T cell receptor signaling and patients with ALPS have an imbalance in this regulation resulting in a failure of T cells to undergo apoptosis and an accumulation of abnormal T cells. Soquelitinib (formerly CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. Soquelitinib has been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of their secreted cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases. Recent studies have demonstrated that ITK controls a switch between the differentiation of Th17 proinflammatory cells and T regulatory suppressor cells. Inhibition of ITK leads to a shift toward T regulatory cell differentiation which has the potential to suppress autoimmune and inflammatory reactions. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company has initiated a registrational Phase 3 clinical trial (NCT06561048) of soquelitinib in patients with relapsed PTCL. Soquelitinib is also being investigated in a randomized placebo-controlled phase 1 clinical trial in patients with atopic dermatitis. A recent publication describing the chemistry, enzymology and biology of soquelitinib appeared in npj Drug Discovery in December 2024 and is available online at the Nature website and on the Publications and Presentations page of the Corvus website. Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancer and immune diseases. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Its other clinical-stage candidates are being developed for a variety of cancer indications. The content above comes from the network. if any infringement, please contact us to modify.