更新于：2024-04-01

Acute myeloid leukemia with multilineage dysplasia

急性髓细胞白血病伴多系发育不良

更新于：2024-04-01

基本信息

别名

AML with Multilineage Dysplasia、AML with multilineage dysplasia、AML with myelodysplasia-related features

+ [9]

简介

An acute myeloid leukemia arising de novo and not as a result of treatment. It is characterized by the presence of myelodysplastic features in at least 50% of the cells of at least two hematopoietic cell lines. Patients often present with severe cytopenia.

关联

项与急性髓细胞白血病伴多系发育不良相关的临床试验

NCT04869683 / RecruitingN/AIIT

Biocollection in Patients With Myelodysplastic Syndrome (P-MDS)

Myelodysplastic syndromes (MDS) are chronic myeloid hemopathies characterized by ineffective hematopoiesis (with peripheral cytopenias) and which contrast with a marrow of normal richness. MDS is considered one of the four most common blood diseases. The incidence is estimated at 4,059 cases / year in 2012 with an average age of 78 years in men and 81 years in women (INCA report, Cancers in France in 2015). The incidence increases with lengthening of the lifespan. The main risk of MDS is transformation to acute leukemia in 30 to 40% of cases. Treatment options depend on clinical, hematologic and chromosomal abnormalities. The prognosis is considered to be at low or high risk of developing acute leukemia. This distinction will therefore have an impact on the therapeutic solution (s). MDS exhibit clinical, morphological and genetic heterogeneity. It is therefore necessary to form subgroups of patients to better understand the physiopathogenesis of this pathology. The constitution of a biocollection will make it possible to search for clinical and biological prognostic markers in order to identify patients progressing to acute myeloid leukemia.

开始日期2022-10-19

申办/合作机构

University Hospital of Brest

NCT04802161 / Recruiting临床2期IIT

Randomized Phase 2 Study of Daunorubicin and Cytarabine Liposome + Pomalidomide Versus Daunorubicin and Cytarabine Liposome in Newly Diagnosed AML With MDS-Related Changes

This phase II trial studies the effect of adding pomalidomide to usual chemotherapy treatment (daunorubicin and cytarabine liposome) in treating patients with newly diagnosed acute leukemia with myelodysplastic syndrome-related changes. Pomalidomide may stop the growth of blood vessels, stimulate the immune system, and kill cancer cells. Chemotherapy drugs, such as daunorubicin and cytarabine liposome, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding pomalidomide to chemotherapy treatment with daunorubicin and cytarabine liposome may be effective in improving some treatment outcomes in patients with newly diagnosed acute leukemia with myelodysplastic syndrome-related changes.

开始日期2022-08-24

申办/合作机构

National Cancer Institute

NCT03047993 / Completed临床1/2期IIT

Phase Ib/II Study of the Glutaminase Inhibitor CB-839 in Combination With Azacitidine in Patients With Advanced Myelodysplastic Syndrome

This phase I/II trial studies the side effects of glutaminase inhibitor CB-839 in combination with azacitidine in treating patients with myelodysplastic syndrome that has spread to other places in the body. Glutaminase inhibitor CB-839 and azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

开始日期2017-11-15

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与急性髓细胞白血病伴多系发育不良相关的临床结果

登录后查看更多信息

100 项与急性髓细胞白血病伴多系发育不良相关的转化医学

登录后查看更多信息

0 项与急性髓细胞白血病伴多系发育不良相关的专利（医药）

登录后查看更多信息

221

项与急性髓细胞白血病伴多系发育不良相关的文献（医药）

2024-02-08·Clinical and experimental medicine

The clinical outcomes of haploidentical stem cell transplantation (haplo-HSCT) for patients with therapy-related myelodysplastic syndrome: comparable to de novo myelodysplastic syndrome.

Article

作者: Feifei Tang ; Yunqi Wang ; Yu Wang ; Jian Jin ; Wei Han ; Yuhong Chen ; Chenhua Yan ; Lanping Xu ; Xiaohui Zhang ; Xiaojun Huang

Therapy-related myelodysplastic syndrome (t-MDS) is defined as a complication in patients with cancer following exposure to chemotherapy and/or radiotherapy and has an inferior outcome compared with de novo myelodysplastic syndrome (de novo MDS). This study aimed to estimate and compare the clinical outcomes of haploidentical stem cell transplantation (haplo-HSCT) for t-MDS and de novo MDS. We retrospectively analyzed 96 patients with MDS who received haplo-HSCT between January 2015 and December 2021. Eleven patients with t-MDS and 85 patients with de novo MDS were matched using the case-pair method in a 1:8 ratio with the following pairing criteria: (1) sex, (2) age (± 5 years), (3) year of haplo-HSCT (± 2 years), and (4) blast cell counts (≥ 5% or not). The 3-year overall survival and disease-free survival after haplo-HSCT for t-MDS versus de novo MDS patients were 72.7% versus 75.1% (P = 0.99) and 54.5% versus 67.0% (P = 0.50), respectively. The 3-year cumulative incidence of relapse was 36.4% versus 15.5% (P = 0.08), respectively. In multivariate analysis, there was no difference in relapse between t-MDS and de novo MDS. The 3-year cumulative non-relapse mortality rates were 9.1% versus 17.6% (P = 0.45), respectively. This study confirmed the comparable clinical outcomes of haplo-HSCT on the prognosis of t-MDS and de novo MDS.

2023-06-28·Bulletin du cancer

Therapy-related myelodysplastic syndromes in the genomics era.

Review

作者: Aline Renneville ; Elsa Bernard ; Jean-Baptiste Micol

Therapy-related myelodysplastic syndromes (t-MDS) represent a heterogeneous group of malignancies that arise as a late complication of prior exposure to chemotherapy and/or radiotherapy administered for a primary condition. T-MDS account for approximately 20% of all MDS and are characterized by resistance to current treatment strategies and poor prognosis. Our understanding of t-MDS pathogenesis has considerably improved over the last 5 years with the availability of deep sequencing technologies. T-MDS development is now considered as a multifactorial process resulting from complex interactions between an underlying germline genetic susceptibility, the stepwise acquisition of somatic mutations in hematopoietic stem cells, the clonal selection pressure exerted by cytotoxic therapies, and alterations of the bone marrow microenvironment. The survival of patients with t-MDS is generally poor. This can be explained by both patient-related factors including poor performance status and less tolerance to treatment and disease-related factors, such as the presence of chemoresistant clones, high-risk cytogenetic alterations and molecular features (e.g. high frequency of TP53 mutations). Around 50% of t-MDS patients are classified as high/very high risk based on IPSS-R or IPSS-M scores, versus 30% in de novo MDS. Long-term survival is only achieved in a minority of t-MDS patients who receive allogeneic stem cell transplantation, but the development of novel drugs may open new therapeutic opportunities, especially in unfit patients. Further investigations are needed to improve the identification of patients at higher risk of developing t-MDS and determine whether primary disease treatment can be modified to prevent the occurrence of t-MDS.

2023-03-17·Leukemia

Therapy-related MDS dissected based on primary disease and treatment-a nationwide perspective.

Article

作者: Daniel Moreno Berggren ; Hege Garelius ; Petter Willner Hjelm ; Lars Nilsson ; Bengt Rasmussen ; Caroline E Weibull ; Mats Lambe ; Sören Lehmann ; Eva Hellström-Lindberg ; Martin Jädersten ; Elisabeth Ejerblad

In this population-based study, we aimed to characterize and compare subgroups of therapy-related Myelodysplastic syndromes (t-MDS) and define the implications of type of previous treatment and primary disease. We combined data from MDS patients, diagnosed between 2009 and 2017 (n = 2705), in the nationwide Swedish MDS register, with several health registers. Furthermore, using matched population controls, we investigated the prevalence of antecedent malignancies in MDS patients in comparison with the general population. This first ever nationwide study on t-MDS confirms a shorter median survival for t-MDS compared to de novo MDS (15.8 months vs 31.1 months, p < 0.001). T-MDS patients previously treated with radiation only had disease characteristics with a striking resemblance to de novo-MDS, in sharp contrast to patients treated with chemotherapy who had a significantly higher risk profile. IPSS-R and the WHO classification differentiated t-MDS into different risk groups. As compared with controls, MDS patients had a six-fold increased prevalence of a previous hematological malignancy but only a 34% increased prevalence of a previous solid tumor. T-MDS patients with a previous hematological malignancy had a dismal prognosis, due both to mortality related to their primary disease and to high-risk MDS.

项与急性髓细胞白血病伴多系发育不良相关的新闻（医药）

2024-03-07

·GlobeNewswire-Health Care

Foghorn Therapeutics Provides Financial Update for 2023 and 2024 Strategic Outlook

• Dose escalation in FHD-286 combination study in AML continues to progress; clinical data anticipated in the second half of 2024 • FHD-909, a first-in-class BRM selective inhibitor, selected for clinical development by partner Lilly; preclinical data to be presented at AACR with IND planned for the second quarter, primary target patient population in non-small cell lung cancer • Selective CBP and EP300 degrader preclinical data to be presented at AACR; IND-enabling studies for CBP degrader program planned to begin by end of 2024 • Foghorn anticipates at least six new INDs targeting significant oncology patient populations over the next four years, reflecting the continued productivity of its precision medicine platform • Cash, cash equivalents, and marketable securities of $234.1 million, as of December 31, 2023, provide cash runway into the first half of 2026 CAMBRIDGE, Mass., March 07, 2024 (GLOBE NEWSWIRE) -- Foghorn® Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, today provided a financial update and corporate outlook in conjunction with the Company’s 10-K filing for the year ending December 31, 2023. With an initial focus in oncology, Foghorn’s Gene Traffic Control® Platform and resulting broad pipeline have the potential to transform the lives of people with a wide spectrum of diseases. “The research and clinical advances we made in 2023 set the stage for Foghorn to deliver significant value with the potential for several differentiated, high-impact medicines in 2024 and beyond,” said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. “In 2023 we initiated a combination study with FHD-286 in AML, with data anticipated in the second half of 2024. Based on the mutation-agnostic differentiation effect observed in our single-agent escalation study, we believe FHD-286 has the potential to be a first-in-class broad-based differentiation therapeutic in AML. We are also making progress with our selective BRM program with FHD-909, a first-in-class BRM selective inhibitor, selected for clinical development by partner Lilly. The IND is planned for the second quarter of 2024, with an initial focus in non-small cell lung cancer. Finally, we are excited by the preclinical efficacy and safety data for our CBP and EP300 selective degrader programs and target IND-enabling studies for CBP by the end of the year. Our cash position remains strong with runway into the first half of 2026.” Key Recent Updates and Upcoming Milestones FHD-286. FHD-286 is a potent, selective inhibitor of the BRG1 and BRM subunits of the BAF chromatin remodeling complex where dependency on BRG1/BRM is well-established preclinically with multiple tumor types, including acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS), non-small cell lung cancer (NSCLC) and prostate cancer. AML Update. Foghorn commenced a Phase 1 study of FHD-286 in combination with decitabine or low-dose cytarabine (LDAC) in relapsed and/or refractory AML patients, with the first patient dosed during the third quarter of 2023. Dose escalation is ongoing, and the first clinical data are expected in the second half of 2024.TKI Resistance. Recently published data, along with Foghorn’s work, suggest that FHD-286 may play an important role in overcoming resistance in EGFR/KRAS tumors. The Company is conducting preclinical work to further explore the opportunity and expects data in the second quarter of 2024. Differentiated Pipeline Advancement. Foghorn continues to expand its platform and pipeline. The Company anticipates the potential for six new investigational new drug (IND) applications in the next four years. The Company continues to progress programs for multiple targets that include chromatin remodeling complexes, transcription factors, helicases, and other chromatin-related factors. These targets include selective BRM and wholly owned programs including CBP, EP300, and ARID1B, as well as other undisclosed targets, which combined could address more than 20 tumor types impacting more than 500,000 new patients annually. Selective CBP and Selective EP300 programs. Foghorn is presenting new preclinical data for its CBP and EP300 selective degrader programs at the 2024 AACR Annual Meeting, April 5-10, 2024. CBP selective degraders have shown significant tumor growth inhibition in a colorectal cancer in vivo model. Antiproliferative effects were also observed for numerous cancer cell lines, including colorectal, gastric and bladder cancers.EP300 selective degraders have shown potent cellular antiproliferation and in vivo tumor growth inhibition in an AR+ enzalutamide prostate in vivo model.At preclinical efficacious doses, neither the CBP nor the EP300 selective degraders cause thrombocytopenia, a commonly observed safety liability for dual CBP/EP300 inhibitors. Lilly Collaboration. Foghorn is engaged in a strategic collaboration with Lilly and continues to advance the BRM selective inhibitor and degrader programs along with other undisclosed programs. In the first quarter of 2024, Lilly selected FHD-909, a first-in-class oral BRM selective inhibitor, for clinical development. Lilly plans to file an IND for FHD-909 in the second quarter of 2024. The primary target patient population is BRG1-mutated NSCLC.Selective BRM inhibition has been a sought-after objective in cancer research for many years. A variety of tumor types, including NSCLC, are known to have mutations in BRG1, which we believe make them dependent on BRM activity for their survival. Selective blocking of BRM activity is considered a promising strategy for causing tumor cell death while sparing healthy cells.Preclinical data will be presented in 2024, including at AACR with a poster presentation on April 8. In December 2021, Foghorn announced a strategic collaboration with Lilly to create novel oncology medicines. The collaboration includes a co-development and co-commercialization agreement for Foghorn’s Selective BRM oncology program and an additional undisclosed oncology target. In addition, the collaboration includes three discovery programs using Foghorn’s proprietary Gene Traffic Control platform. Full Year 2023 Financial Highlights Collaboration Revenues. Collaboration revenues were $34.2 million for the year ended December 31, 2023, compared to $19.2 million for the year ended December 31, 2022. The increase year-over-year was primarily driven by revenue recognized under the Merck collaboration due to the termination of the agreement and the subsequent recognition of the remaining deferred revenue.Research and Development Expenses. Research and development expenses were $109.7 million for the year ended December 31, 2023, compared to $105.6 million for the year ended December 31, 2022. This increase was primarily due to costs associated with continued investment in R&D personnel, platform, and other early-stage research, partially offset by a decrease in spend on FHD-286 and FHD-609.General and Administrative Expenses. General and administrative expenses were $32.4 million for the year ended December 31, 2023, compared to $30.7 million for the year ended December 31, 2022. This increase was primarily due to an increase in investments to support the growing business, which included increases in personnel-related costs and stock-based compensation expense.Net Loss. Net loss was $98.4 million for the year ended December 31, 2023, compared to a net loss of $108.9 million for the year ended December 31, 2022.Cash, cash equivalents and marketable securities. As of December 31, 2023, the Company had $234.1 million in cash, cash equivalents and marketable securities, providing cash runway into the first half of 2026. 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. About AMLAdult 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 FHD-909FHD-909 (a.k.a. LY4050784) is a highly potent, allosteric and orally available small molecule that selectively inhibits the ATPase activity of BRM (SMARCA2) over its closely related paralog BRG1 (SMARCA4), two proteins that are the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, tumors with mutations in BRG1 rely on BRM for BAF function. FHD-909 has shown significant anti-tumor activity across multiple BRG1-mutant lung tumors. About Foghorn TherapeuticsFoghorn® 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 X (formerly Twitter) and LinkedIn.Forward-Looking StatementsThis press release contains “forward-looking statements.” Forward-looking statements include statements regarding the Company’s clinical trials, 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, 2023, 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. Condensed Consolidated Balance Sheets(In thousands) Dec. 31, 2023 Dec. 31, 2022Cash, cash equivalents and marketable securities$234,057 $345,798Collaboration receivable — —All other assets 51,859 59,085Total assets$285,916 $404,883Deferred revenue, total$302,665 $336,820All other liabilities 60,441 67,951Total liabilities 363,106 404,771Total stockholders’ equity (77,190) 112Total liabilities and stockholders’ equity$285,916 $404,883 Condensed Consolidated Statements of Operations(In thousands, except share and per share amounts) Twelve Months Ended December 31, 2023 2022 Collaboration revenue$34,155 $19,228 Operating expenses: Research and development 109,689 105,618 General and administrative 32,372 30,747 Total operating expenses 142,061 136,365 Loss from operations (107,906) (117,137)Total other income, net 13,706 8,255 Loss before income taxes (94,200) (108,882)Provision for income taxes (4,226) — Net loss$(98,426) $(108,882)Net loss per share attributable to common stockholders—basic and diluted$(2.34) $(2.62)Weighted average common shares outstanding—basic and diluted 41,974,484 41,591,433 Contacts:Greg Dearborn, Foghorn Therapeutics Inc. (Investors) gdearborn@foghorntx.com Karin Hellsvik, Foghorn Therapeutics Inc. (Investors and Media) khellsvik@foghorntx.com Adam Silverstein, ScientPR (Media) adam@scientpr.com Peter Kelleher, LifeSci Advisors (Investors) pkelleher@lifesciadvisors.com

临床1期财报AACR会议

2024-01-21

·动脉网

超20家机构押注、哈佛遗传学大佬领衔，这家公司已开启“返老还童” 密码【衰老标志物检测】

1990年，联合国大会通过决议，指定10月1日为国际老年人日，以呼吁公众关注老龄化问题。31年后，长寿补充剂研发商Novos在2021年的国际老年人日宣布完成351万美元的Pre-种子轮融资。由美国一家专注种子轮和早期发展的风投公司Resolute Ventures领投、专注于长寿领域投资的机构Longevitytech.fund和Arkitekt Ventures、Awesome People Ventures以及20家机构投资者和知名企业家跟投。Novos成立于2018年，总部位于美国旧金山。公司通过提供测试人体衰老速度产品和抗衰产品实现减少衰老的影响并延长健康寿命的目标。该公司推进了Novos的测衰产品NOVOS Age以及2个抗衰产品——NOVOS Core和NOVOS Boost的发展和商业化进程。目前，公司的三款产品已全部上市销售，并且部分使用人群反馈取得了积极的抗衰效果。 “抗衰达人”创立、“当代基因组学教父”支持Chris Mirabile是Novos的创始人兼CEO，是一位连续创业者和长寿专家，同时也是一位将延长健康寿命理念和实践融入20多年生活中的“抗衰达人”。Chris Mirabile通过改善饮食、坚持运动和健康睡眠等生活方式并服用长寿补充剂后，39.2岁的他通过表观遗传时钟测试后得到的生理年龄结果为27.9岁，衰老速度减缓了近31%。16岁时，Chris Mirabile因脑肿瘤突发癫痫，险些失去生命。幸存下来后，他开始对健康衰老充满热情，希望通过更科学的方式让自己“更健康、更长寿”。因此，基于健康衰老的理念和十多年衰老研究，Chris Mirabile和专门研究衰老的Kris Verburgh博士共同创立了Novos，以通过科学方法帮助消费者驾驭实现提高健康水平和延长寿命的目标。Novos成功创立后，Chris Mirabile和Kris Verburgh招募了一系列衰老研究专家和技术专家，组建了一个包括哈佛大学、麻省理工学院、利物浦大学和华盛顿大学等知名院校的生物化学家、遗传学家和教授科学在内的顾问委员会。其中就包括衰老领域资深科学家和连续创业者、“当代基因组学教父”George Church。George Church是一位久负盛名的“全才科学家”。他是人类遗传学和生物技术领域的权威科学家，以在基因组测序、基因编辑、合成生物学，以及神经科学的科研贡献而享誉全球。同时，George Church是个人基因组学和合成生物学的开创者。1984 年，他开发出了世界上第一个直接基因组测序方法，并参与启动人类基因组计划以及个人基因组计划。两年后，他加入哈佛医学院担任遗传学系教授，是哈佛大学/麻省理工学院HST联合研究所教授。其诸多突破性创新成果也成为Editas Medicine、 Gen9bio等近50家生物技术公司的基础。近年来，这位世界级的科学家也重点关注抗衰老研究，多个关于衰老的前沿皆有George Church的身影。他希望开发创新抗衰老基因疗法，以逆转衰老并治疗与衰老相关的各种疾病，延长人类健康寿命。因此，在2018年，George Church与他人联合创立了抗衰老基因疗法公司Rejuvenate Bio，以研发逆转年龄的基因疗法。除George Church外，Novos的科学顾问委员会还包括索尔克生物研究所（Salk Institute for Biological Studies）研究员Pamela Maher博士、哈佛医学院J Pedro de Magalhaes博士以及麻省理工学院Matt Kaeberlein博士等人。科学顾问委员会部分成员图源：Novos官网不仅测生理年龄也测衰老速度NOVOS Age是Novos推出的生理年龄检测产品，能够通过单次血液检测人体的衰老速度、生理年龄和端粒长度三个衰老相关指标。用户购买该产品后，使用指定设备采集个人血液样本，并将样本邮寄到Novos实验室，大约4周后即可得到检测结果。NOVOS Age产品示例图源：Novos官网值得一提的是，NOVOS Age采用的是第三代DunedinPACE衰老时钟。DunedinPACE由哥伦比亚大学和杜克大学生物钟科学家创造并于2021年推出，是一种基于 DNA甲基化的衰老生物标志物的检测衰老速度时钟。该时钟不仅可对某个年龄段内的衰老速度进行精准评估，实现衰老的可视化，还可预测与衰老和年龄相关的疾病的患病风险1。目前DunedinPACE已被30多所实验室的45多种出版物验证了可行性，其推出时被称为“预测衰老的最新标准”，也被称为继DNAm GrimAge、DNAm PhenoAge、Horvath、Hannum四个衰老时钟之后的第三代衰老时钟。此外，与以上4个衰老时钟相比，DunedinPACE显示出更高的灵敏度和可靠性。研究团队针对不同衰老时钟做了一项比较研究试验，在183名患者的两次DNA样本测试结果中，DunedinPACE得出的ICC（组内相关系数，Interclass Correlation Coefficient）分数为0.90，其余4个时钟的则在0.6—0.78范围内。关于衰老检测结果，研究团队将DunedinPACE在试验中所测量得到的衰老速度缩放至平均值1，即每个时间年1个生物年。例如，如果测试结果为0.90，则意味着衰老速度比平均速度慢10%，而1.05则意味着衰老速度比平均速度快5%。其次，如果数值<1，表明衰老速度较慢，死亡和年龄相关的疾病的风险也将降低54%；如果数值>1且数值越高，表明衰老速度较快，该部分个体在未来7年内的死亡风险预计增加56%。除通过DunedinPACE测量衰老速度外，Novos还与哈佛大学的科学家达成合作，通过血液样本对用户进行表观遗传学测试，以揭示用户的生物年龄和端粒长度。最后将三项检测结果结合起来，综合评估用户的衰老水平和整体健康水平。一次性针对12个衰老特征用户使用NOVOS Age进行测试后，Novos随后会将一份长达55页的NOVOS年龄报告发送给用户。该报告包含用户整体衰老和健康水平的检测结果和可能存在的疾病风险，公司的医生团队也据此提出改善衰老速率和提升健康水平的方法。其中，在营养补充剂方面就包括Novos推出的2款抗衰产品——NOVOS Core和NOVOS Boost。NOVOS Core是一种长寿补充剂，旨在减缓个体衰老速度。它包含α-酮戊二酸钙、非瑟酮、甘氨酸等12种抗衰成分，每袋产品中含有6.9g混合抗衰成分，这一含量是目前其他补充剂的10倍。Novos称NOVOS Core由多位长寿专家和医生经过多次科学测试开发，并在一项针对约40人的研究中验证了该产品的有效性。NOVOS Boost是一种补充胶囊，由NMN（β-烟酰胺单核苷酸）一种成分制成。Novos声称，每一粒NOVOS Boost中NMN含量高达99%，不含人工色素、防腐剂或添加剂等杂质。据悉，NOVOS Core和NOVOS Boost正在近435项研究中进行测验。Novos团队表示，该组合是目前为数不多的使用多种成分针对线粒体功能障碍、细胞衰老、蛋白质稳态丧失等12种经过科学验证的衰老特征的抗衰产品。目前，Novos已公布的研究成果也证明了NOVOS Core和NOVOS Boost的抗衰效果。例如，在2022年2月—8月，Novos开展了一项案例研究，该研究纳入了12名年龄在39—76岁之间的参与者，包括6名男性和6名女性。开始前，他们使用NOVOS Age测试衰老水平，而后六个月内每天服用NOVOS Core和NOVOS Boost。参与者被要求除非有医疗必要，否则不要对生活方式做出任何重大改变，其中，一名男性参与者因不遵守规定而退出。六个月后，11名受试者再次进行NOVOS Age测试。结果显示，参与者的生物衰老速度在统计学上显著降低，其中8名（73%）的衰老速度降低幅度超出了测试的误差范围，平均百分比变化为-6.1%。美国第三方实验室Ichor Life Sciences也针对该组合产品做了研究，其公布的结果表明，该组合可在多种剂量范围内防止DNA损伤。而由英国纽卡斯尔大学衰老研究实验室进行的一项研究则发现，Novos产品的多种成分组合具有抑制衰老的作用，但不会影响正常的非衰老细胞2。每月106美元，普通人也能“返老还童”？近年来，科技巨头、世界首富纷纷扎堆投资抗衰领域，以期找到实现“返老还童”甚至“长生不老”的办法。例如，美国硅谷富豪布莱恩·约翰逊（Bryan Johnson），他以8亿美元将自己创立的支付处理公司Braintree卖给eBay，随后将资金投入到“返老还童”的计划中。2021年至今，Bryan Johnson每年花费约200万美元，由30名医生组成的专业团队进行专业服务，每天精准摄入1977卡路里，服用数十粒药物和营养素补充剂，定期检查各器官和组织的情况。如此持续2年多后，实际年龄为45岁的Bryan Johnson生理年龄减少了19.65%，衰老速度为0.72。看到自身抗衰的显著效果后，Bryan Johnson和Oliver Zolman博士在2023年推出了一个在线长寿排行榜——“返老还童奥运会（Rejuvenation Olympics）”。该榜单分为两个，分别是“相对变化排行榜”和“绝对排行榜”，任何人都可在Rejuvenation Olympics上分享抗衰成果和抗衰方案。Bryan Johnson在两个榜单中排名分别是第7名和第六名。但是，以Bryan Johnson为代表的巨头富豪们的抗衰方法往往建立在大量金钱的基础上，他们拥有的资源远超普通人，Rejuvenation Olympics上难见普通人的身影。不过，今年就有一位普通女性朱莉·吉布森·克拉克（Julie Gibson Clark）在一众富人中脱颖而出。她在Rejuvenation Olympics“相对变化排行榜”上排名第8，仅次于Bryan Johnson；而在“绝对排行榜”中位列第2，远超Bryan Johnson。 Rejuvenation Olympics榜单排名图源：Rejuvenation Olympics与Bryan Johnson动辄200万美元/年不同，Julie Gibson Clark自称年收入不到10万美元，每个月最大的健康支出是27美元健身房会员费用和79美元补剂订阅费用3。通过坚持锻炼、健康饮食和冥想，实际年龄55岁的Julie Gibson Clark生理年龄减少了27.62%，衰老速度仅为0.665，这意味着，每过一年，Julie Gibson Clark的生理年龄仅增加0.665岁。其中，Julie Gibson Clark正是使用NOVOS Age检测其衰老水平并服用Novos的产品，在“相对变化排行榜”中，前10位参与者中有2位所用的抗衰产品和方法出自Novos，Chris Mirabile服用的长寿补充剂也是自家公司产品。如此看来，Novos的产品似乎为普通人实现“返老还童”提供了另一种相对便宜且极可能实现的方式。不过，目前Novos及其大部分抗衰赛道公司的产品都未经过美国食品和药物管理局的评估，也尚未有任何一种衰老生物标志物获得美国监管机构批准用于临床应用。不同个体需谨慎选择，看起来行之有效的抗衰方式可能并不会对所有人都有针对性效果，甚至可能会产生“背道而驰”的负面影响，加速衰老。衰老是一个复杂的生理过程，各种关于衰老生物标志物的指标可能会随时波动发生变化。目前，科学家们正在努力探索关于衰老的秘密，希望能够选出能够明确反映衰老及其调控过程的衰老生物标志物。随着研究的深入，不日或将产生新一代衰老检测产品。参考资料：1. Daniel W Belsky, Avshalom Caspi, David L Corcoran, Karen Sugden, Richie Poulton, Louise Arseneault, Andrea Baccarelli, Kartik Chamarti, Xu Gao, Eilis Hannon, Hona Lee Harrington, Renate Houts, Meeraj Kothari, Dayoon Kwon, Jonathan Mill, Joel Schwartz, Pantel Vokonas, Cuicui Wang, Benjamin S Williams, Terrie E Moffitt (2022) DunedinPACE, a DNA methylation biomarker of the pace of aging eLife 11:e73420.2. New studies show NOVOS' ingredient combinations help to maintain healthy DNA and support the body to deal with senescent cells.https://www.prnewswire.com/news/novos/3. Wealthy men are spending millions to lower their biological ages and live longer. These women are beating them with cheaper solutions.https://fortune.com/well/2023/11/04/longevity-women-biohackers-diet-exercise-bryan-johnson/文|冯汝梅微信|echo822207添加时请注明：姓名-公司-职位网站、公众号等转载请联系授权：Rekkiiie近期推荐声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。动脉网，未来医疗服务平台

医药出海

2024-01-08

·GlobeNewswire-Health Care

Foghorn Therapeutics Highlights Clinical Program Updates and Research Progress and Provides Strategic Objectives for 2024

- FHD-286 combination study in AML continues to progress in the clinic with data anticipated in the second half of 2024; preclinical combination data with FHD-286 and tyrosine kinase inhibitors (TKIs) in EGFR/KRAS resistance anticipated by the second quarter of 2024 - BRM selective inhibitor and degrader programs advancing in partnership with Loxo@Lilly - Preclinical efficacy and safety demonstrated with selective EP300 and CBP programs; additional preclinical data anticipated in the second quarter of 2024; targeting IND enabling studies for CBP before end of 2024 - Foghorn anticipates at least six new INDs targeting significant oncology patient populations over the next four years, reflecting the continued productivity of its precision medicine platform - Cash, cash equivalents, and marketable securities of $259.9 million, as of September 30, 2023, provides cash runway into the first half of 2026 CAMBRIDGE, Mass., Jan. 08, 2024 (GLOBE NEWSWIRE) -- Foghorn® Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, today announced its strategic objectives for 2024. “We enter 2024 with several important milestones ahead of us. We anticipate data from our Phase 1 combination study of FHD-286 in AML in the second half of the year and look forward to continued progress with our unique pipeline, including our BRM selective inhibitor and degrader programs in collaboration with Loxo@Lilly,” said Adrian Gottschalk, President and Chief Executive Officer. “We have made significant progress with our preclinical programs, including our selective EP300, CBP and ARID1B degrader programs and are getting ready to share more preclinical data in the first half of the year. This will also include preclinical combination data of FHD-286 with tyrosine kinase inhibitors of EGFR and KRAS. Over the next four years, we anticipate the filing of at least six new INDs, reflecting the productivity of our precision medicine platform. This is all supported by our cash and equivalents position of approximately $259.9 million as of September 30, 2023.” FHD-286. FHD-286 is a potent, selective inhibitor of the BRG1 and BRM subunits of the BAF chromatin remodeling complex where dependency on BRG1/BRM is well-established preclinically with multiple tumor types, including acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS), non–small cell lung cancer (NSCLC) and prostate cancer. AML Update. Foghorn commenced a Phase 1 study of FHD-286 in combination with decitabine or low-dose cytarabine (LDAC) in relapsed and/or refractory AML patients, with the first patient dosed during the third quarter of 2023. The first clinical data are expected in the second half of 2024.TKI Resistance. Recently published data, along with Foghorn’s work, suggest that FHD-286 may play an important role in overcoming resistance in EGFR/KRAS tumors. The company is conducting preclinical work to further explore the opportunity. Differentiated Pipeline Advancement. Foghorn continues to expand its platform and pipeline. The Company anticipates the potential for six new investigational new drug (IND) applications in the next four years. The Company continues to progress programs for multiple targets that include chromatin remodeling complexes, transcription factors, helicases and other chromatin-related factors. These targets include selective BRM* and wholly owned programs including CBP, EP300, and ARID1B, as well as other undisclosed targets, which combined could address more than 20 tumor types impacting more than 500,000 new patients annually. Selective EP300 and Selective CBP programs. Foghorn presented new preclinical data for its EP300 and CBP selective degrader programs at Hanson Wade’s 6th Annual Targeted Protein Degradation Summit on October 31, 2023. EP300 selective degraders showed potent cellular antiproliferation and in vivo tumor growth inhibition in an AR+ enzalutamide prostate in vivo model.CBP selective degraders demonstrated significant tumor growth inhibition in a colorectal cancer in vivo model. Antiproliferative effects were also observed for numerous cancer cell lines, including colorectal, gastric and bladder cancers.At preclinical efficacious doses, neither the EP300 nor the CBP selective degraders caused thrombocytopenia, a commonly observed safety liability for dual CBP/EP300 inhibitors.Additional preclinical data will be presented in the first half of 2024. *Loxo@Lilly Collaboration. Foghorn is engaged in a strategic collaboration with Loxo@Lilly and continues to advance the BRM selective inhibitor and degrader programs along with other undisclosed programs.Strong Balance Sheet and Cash Runway. As of September 30, 2023, the Company had $259.9 million in cash, cash equivalents and marketable securities providing cash runway into the first half of 2026. 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 X (formerly Twitter) and LinkedIn. Forward-Looking Statements This press release contains “forward-looking statements.” Forward-looking statements are 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, including statements regarding potential combination trials involving FHD-286, the progress of our Loxo@Lilly collaboration, and our proprietary pre-clinical programs. 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, 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. Contacts: Karin Hellsvik, Foghorn Therapeutics Inc. (Media)khellsvik@foghorntx.com Greg Dearborn, Foghorn Therapeutics Inc. (Investors)gdearborn@foghorntx.com Michael Lampe, ScientPR (Media)michael@scientpr.com Peter Kelleher, LifeSci Advisors (Investors)pkelleher@lifesciadvisors.com

临床1期