Adult Acute Myeloblastic Leukemia

June 06, 2024 -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has initiated Phase I clinical trial of its menin inhibitor HMPL-506 in patients with hematological malignancies in China. The first patient received their first dose on May 31, 2024. This is a Phase I, multicenter, open-label clinical study to evaluate the safety, pharmacokinetics and efficacy of HMPL-506 in patients with hematological malignancies. The study is divided into two phases, a dose escalation phase and a dose expansion phase. The study is expected to enroll at least 60 patients. The lead principal investigators are Dr. Jianxiang Wang and Dr. Hui Wei of Chinese Academy of Medical Sciences Blood Diseases Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT06387082. HMPL-506 is a novel, investigational, selective small molecule inhibitor for oral administration targeting the menin protein. The menin protein is a scaffold protein that controls gene expression and cell signaling. Mixed-lineage leukemia (“MLL”, also known as KMT2A) rearrangement and nucleophosmin 1 (“NPM1”) mutation play key roles in acute myeloid leukemia (“AML”). MLL-rearranged AML accounts for approximately 5% of adult AML and NPM1-mutant AML accounts for approximately 30% of AML.1,2,3 Current research has demonstrated that the inhibition of menin-MLL interaction is a feasible therapeutic strategy in MLL-rearranged and/or NPM1-mutant AML.4,5,6,7 Currently there is no menin inhibitor approved worldwide. HUTCHMED currently retains all rights to HMPL-506 worldwide. According to the National Cancer Institute (NCІ), there will be approximately 20,380 new cases of AML in the U.S. in 2023 and the five-year relative survival rate is 31.7%.8 There were an estimated 19,700 new cases of AML in China in 2018 and is estimated to reach 24,200 in China in 2030.9 HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three oncology drugs marketed in China, the first of which is also marketed in the U.S. For more information, please visit: www.hutch-med.com or follow us on LinkedIn. 1Ibrahim S, Estey EH, Pierce S, et al. 11q23 abnormalities in patients with acute myelogenous leukemia and myelodysplastic syndrome as detected by molecular and cytogenetic analyses. Am J Clin Pathol, 2000, 114(5):793-7. 2Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood, 2010,116(3):354-65. 3Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352(3):254-66. 4Krivtsov AV, Evans K, Gadrey JY, et al. A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. Cancer Cell 2019;36:660–73 e11. 5Uckelmann HJ, Kim SM, Wong EM, et al. Therapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia. Science 2020;367:586–90. 6Borkin D, He S, Miao H, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell 2015;27:589–602. 7Klossowski S, Miao H, Kempinska K, et al. Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J Clin Invest 2020;130:981–97. 8National Cancer Institute – seer.cancer.gov/statfacts/html/amyl.html. 9Lin J, Yao D, Qian J, et al. ІDH1 and ІDH2 mutation analysis in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol. 2012;91(4):519-525. doi:10.1007/s00277-011-1352-7. The content above comes from the network. if any infringement, please contact us to modify.

Funding will be utilized to conduct clinical trial to discover possible immunotherapy treatments for specific cancer patient populations PHILADELPHIA , June 28, 2023 /PRNewswire/ -- Children's Hospital of Philadelphia (CHOP) announced today it has received $1 million from Pediatric Cancer Foundation, an organization that has been raising funds for research since 1970 to support doctors and hospitals in an effort to eradicate childhood cancer. The grant will help to fund a planned first-in-human phase 1 clinical trial led by Sarah K. Tasian, MD, which will use a new immunotherapy to target the FLT3 receptor protein in high-risk pediatric leukemias. Chemotherapy fails many patients with high-risk leukemias, particularly infants with acute lymphoblastic leukemia (ALL) and children with acute myeloid leukemia (AML) with high-risk genetic alterations who have poor long-term survival. Recent CAR T-cell therapies targeting the CD19 protein on ALL cells have been very effective in overcoming chemotherapy resistance and can now cure many children with relapsed ALL. However, some leukemias have learned to outsmart these therapies in various ways. One problem is that infant and childhood ALL with KMT2A genetic rearrangements are more likely to change into AML after CD19 CAR T-cell immunotherapy, which usually makes them incurable. To date, it has been challenging to develop successful immunotherapies for pediatric AML. To address this problem, CHOP's collaborative research team, led by Dr. Tasian and her colleague Dr. Terry Fry at Children's Hospital Colorado, developed and tested a new CAR T-cell immunotherapy targeting an alternative protein called FLT3 that occurs at high levels in a type of AML and in infant ALL. In the laboratory, FLT3 CAR T cells were very effective at attacking and killing both AML and ALL cells in both in vitro and in vivo models of the disease. Remarkably, FLT3 CAR T cells eradicated both KMT2A-rearragned ALL and ALL that had turned into fatal AML after CD19 CAR T-cell treatment of the patient. "Based upon our promising lab results, we aim to test FLT3 CAR T cells in pediatric patients through a first-in-human/child phase 1 clinical trial," said Sarah K. Tasian, MD, a pediatric oncologist and Chief of the Hematologic Malignancies Program at CHOP. "Our research team has a strong track record of bench-to-bedside translation of CAR T cells for high-risk pediatric leukemias and is uniquely poised to undertake this challenge. Because of the funding provided by Pediatric Cancer Foundation, we can now work to translate our FLT3 CAR T-cell immunotherapy from promising results in the laboratory to the clinic. We hope that this clinical trial will have significant potential to credential a promising new immunotherapy against a shared target in two major types of high-risk childhood leukemias." "For the past decade, CHOP has been a recognized leader in the development of CAR-T cell therapy for use in pediatric cancers," said Cheryl Rosen, Medical Liaison of Pediatric Cancer Foundation. "Pediatric Cancer Foundation is proud to partner with Dr. Sarah Tasian and CHOP to enable these promising laboratory results for treating both AML and ALL to be tested in a clinical trial. We hope that, together, we can significantly improve the survival rates of infants and children battling these cancers." The Cancer Immunotherapy Program at CHOP has revolutionized the care and the cure of children with relapsed/refractory B-cell ALL via its pioneering investigation of CD19-targeted killer T cells (CART19) that led to first-in-child FDA approval of the tisagenlecleucel cell therapy product in 2017. The program has continued to change and set new paradigms through investigation of additional CAR T cell therapies for children with B-cell ALL or lymphoma, AML, T-ALL, and neuroblastoma. To find out more information visit, chop.edu/centers-programs/cancer-immunotherapy-program. About Children's Hospital of Philadelphia  A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as an inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit .   CONTACT:  Kaitlyn Tivenan  Children's Hospital of Philadelphia  610-618-0542  [email protected] SOURCE Children's Hospital of Philadelphia

- Clinical data support safety and tolerability profile of FHD-286, a highly potent, - selective, allosteric, oral, small molecule inhibitor of BRG1/BRM - Clinical activity observed in late-line metastatic uveal melanoma includes nine patients with stable disease and one patient with a confirmed partial response - Foghorn does not plan to advance FHD-286 in uveal melanoma - Foghorn anticipates initiating a FHD-286 combination study in relapsed/refractory AML during the third quarter of 2023 CAMBRIDGE, Mass., June 28, 2023 (GLOBE NEWSWIRE) -- Foghorn® Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious disease by correcting abnormal gene expression, today announced data from the Phase 1 dose escalation safety study of FHD-286 in metastatic uveal melanoma (mUM). These data reinforce the safety and tolerability profile of FHD-286. At this time, the company does not plan to advance FHD-286 in uveal melanoma.“The clinical data further support the safety and tolerability of FHD-286 and build on the previously disclosed AML/MDS data. In the study, nine patients had stable disease and one patient had a durable partial response,” said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. “However, Foghorn does not plan to pursue this indication on its own. We plan to initiate dosing the FHD-286 combination study in relapsed/refractory AML during the third quarter of 2023 and continue to invest in our promising pre-clinical programs such as Selective-BRM, CBP, EP300, and ARID1B.”FHD-286 Phase 1 Dose Escalation Study Data in Metastatic Uveal Melanoma The trial evaluated 73 metastatic uveal melanoma patients who had been treated with a median of two prior therapies across nine different cohorts. The doses evaluated included four continuous daily doses: 2.5mg (n=2), 5.0mg (n=12), 7.5mg (n=17), and 10.0mg (n=9); and five intermittent 1 week on/1 week off dose cohorts: 10.0mg (n=10), 15.0mg (n=9), 17.5mg (n=3), 20.0mg (n=5), and 22.5mg (n=6). Clinical data seen in the Phase 1 dose escalation study reinforced the safety and tolerability profile of FHD-286. The most common treatment-related adverse events were dysgeusia, fatigue, AST increase, nausea/vomiting, dry mouth, and rash. The most common treatment-related grade 3 events or higher included anemia, asthenia, ALP increase, hypokalemia, muscular weakness, and rash. Forty-seven of the 73 patients on study had target lesions for evaluation. One patient had a durable partial response and remained on treatment for over 16 months, and nine patients had stable disease. Tumor reductions in target lesions were also observed in eight patients. The clinical activity seen in the study was further supported by reductions in circulating tumor DNA (ctDNA). Preliminary data on immune modulation markers in the tumor microenvironment also support a combination path forward with checkpoint inhibitors. The Company plans to present the full results at a future scientific meeting. Foghorn plans to dose the first patient in a Phase 1 study of FHD-286 in combination with decitabine or cytarabine in relapsed and/or refractory AML patients in the third quarter of 2023. About FHD-286 FHD-286 is a highly potent, selective, allosteric and orally available, small-molecule, enzymatic inhibitor of BRG1 (SMARCA4) and BRM (SMARCA2), two highly similar proteins that are the ATPases, or the catalytic engines of the BAF complex, one of the key regulators within the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors. FHD-286 is being developed for relapsed and/or refractory AML, and the company plans to commence a Phase 1 study, in combination with decitabine or cytarabine, in the third quarter of 2023. About Uveal Melanoma Uveal (intraocular) melanoma is a rare eye cancer that forms from cells that make melanin in the iris, ciliary body, and choroid, and is the most common eye cancer in adults. It is diagnosed in about 2,000 adults every year in the United States and occurs most often in lightly pigmented individuals with a median age of 55 years, however, it can occur in all races and at any age. UM metastasizes in approximately 50% of cases, leading to very poor prognosis. This press release refers to data gathered on an ongoing basis from our open-label Phase 1 trial in FHD-286 for uveal melanoma. About AML Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States. About Foghorn Therapeutics Foghorn® Therapeutics is discovering and developing a novel class of medicines targeting genetically determined dependencies within the chromatin regulatory system. Through its proprietary scalable Gene Traffic Control® platform, Foghorn is systematically studying, identifying and validating potential drug targets within the chromatin regulatory system. The Company is developing multiple product candidates in oncology. Visit our website at www.foghorntx.com for more information on the company, and follow us on Twitter and LinkedIn. Forward-Looking Statements This press release contains “forward-looking statements.” Forward-looking statements include statements regarding the Company’s clinical trials, including its Phase 1 study of FHD-286 in combination with decitabine or cytarabine in relapsed and/or refractory AML patients, product candidates and research efforts and other statements identified by words such as “could,” “may,” “might,” “will,” “likely,” “anticipates,” “intends,” “plans,” “seeks,” “believes,” “estimates,” “expects,” “continues,” “projects” and similar references to future periods. Forward-looking statements are based on our current expectations and assumptions regarding capital market conditions, our business, the economy and other future conditions. Because forward-looking statements relate to the future, by their nature, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. As a result, actual results may differ materially from those contemplated by the forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include regional, national or global political, economic, business, competitive, market and regulatory conditions, including risks relating to our clinical trials and other factors set forth under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022 and subsequent Quarterly Reports on Form 10-Q, as filed with the Securities and Exchange Commission. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Contact: Ben Strain, Foghorn Therapeutics Inc. (Media and Investors)bstrain@foghorntx.com Karin Hellsvik, Foghorn Therapeutics Inc. (Media)khellsvik@foghorntx.com