排名前五的靶点	数量

EZH2(组蛋白赖氨酸甲基化酶EZH2)	4
KDM1A(赖氨酸特异性组蛋白脱甲基酶-1)	2
p300-CBP transcription factors(p300-CBP转录因子)	2
BET(溴结构域和超末端结构蛋白家族)	1
BRD4(溴结构域蛋白-4)	1

关联

项与 Constellation Pharmaceuticals, Inc. 相关的药物

Ruxolitinib Phosphate

磷酸芦可替尼

靶点

JAK1 x JAK2

作用机制

JAK1抑制剂 [+1]

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2011-11-16

Pelabresib

靶点

BET

作用机制

BET抑制剂

在研机构

Constellation Pharmaceuticals, Inc. [+1]

原研机构

Constellation Pharmaceuticals, Inc.

在研适应症

血液肿瘤 [+10]

非在研适应症

多发性骨髓瘤

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期-

Tulmimetostat

靶点

EZH1 x EZH2

作用机制

EZH1抑制剂 [+1]

在研机构

Constellation Pharmaceuticals, Inc. [+2]

原研机构

Constellation Pharmaceuticals, Inc.

在研适应症

淋巴瘤 [+12]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期-

项与 Constellation Pharmaceuticals, Inc. 相关的临床试验

NCT06401356 / Recruiting临床3期

An Open-Label, Multicenter, Extension Study for Patients Previously Enrolled in Studies with Pelabresib

The purpose of this study is to provide continued access to treatment with pelabresib for patients who previously received pelabresib in a parent study and to continue collecting safety and efficacy information. By collecting efficacy information, the study team monitors if pelabresib helps the patient with their disease. Additionally, survival follow-up data will be collected. Survival follow-up collects information on the patient's leukemia-free survival and overall survival status (life span) during and after the treatment is ended. If a patient stopped pelabresib treatment on the parent study for any other reason than participation in this study, they will not receive further pelabresib treatment, but they can enter the study for survival-follow up only.

开始日期2024-08-13

申办/合作机构

Constellation Pharmaceuticals, Inc.

ISRCTN10750305 / Completed临床1期

Phase I trial Quotient Code: QSC207682. The full scientific title will be published within 30 months after the end of the trial

开始日期2022-11-16

申办/合作机构

Constellation Pharmaceuticals, Inc.

NCT05391022 / Completed临床1期

A Phase 1, 2-Part Study to Evaluate the Effect of Food on Pharmacokinetics of Pelabresib (CPI-0610) and the Effect of Pelabresib on QTc in Patients With Advanced Malignancies

Phase 1 2-part study to evaluate the effect of food on pharmacokinetics of pelabresib (CPI-0610) and the effect of pelabresib on QTc in patients with advanced malignancies

开始日期2021-07-20

申办/合作机构

Constellation Pharmaceuticals, Inc.

100 项与 Constellation Pharmaceuticals, Inc. 相关的临床结果

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0 项与 Constellation Pharmaceuticals, Inc. 相关的专利（医药）

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项与 Constellation Pharmaceuticals, Inc. 相关的文献（医药）

2024-08-01·CANCER RESEARCH

Comprehensive Target Engagement by the EZH2 Inhibitor Tulmimetostat Allows for Targeting of ARID1A Mutant Cancers

Article

作者: Adams, Elizabeth J. ; Khanna, Avinash ; Sun, Kaiming ; Côté, Alexandre ; Meyer, Rosana ; Arora, Shilpi ; Taimi, Mohammed ; Truong, Jennifer ; Cui, Jike ; Stuckey, Jacob I. ; Lakhani, Nehal J. ; Cantone, Nico ; Cummings, Richard T. ; Levell, Julian ; Devitt, Michael ; Zhao, Feng ; Mertz, Jennifer A. ; Wang, Jing ; Chen, Zehua ; Duska, Linda ; Trojer, Patrick ; Keller, Patricia J. ; Gehling, Victor ; Rippley, Ronda ; Yu, Ziyang ; Wu, Rentian ; Rasco, Drew ; Gutierrez, Martin

Abstract:

Recurrent somatic mutations in the BRG1/BRM-associated factor (BAF) chromatin remodeling complex subunit ARID1A occur frequently in advanced urothelial, endometrial, and ovarian clear cell carcinomas, creating an alternative chromatin state that may be exploited therapeutically. The histone methyltransferase EZH2 has been previously identified as targetable vulnerability in the context of ARID1A mutations. In this study, we describe the discovery of tulmimetostat, an orally available, clinical stage EZH2 inhibitor, and it elucidates the aspects of its application potential in ARID1A mutant tumors. Tulmimetostat administration achieved efficacy in multiple ARID1A mutant bladder, ovarian, and endometrial tumor models and improved cisplatin response in chemotherapy-resistant models. Consistent with its comprehensive and durable level of target coverage, tulmimetostat demonstrated greater efficacy than other PRC2-targeted inhibitors at comparable or lower exposures in a bladder cancer xenograft mouse model. Tulmimetostat mediated extensive changes in gene expression, in addition to a profound reduction in global H3K27me3 levels in tumors. Phase I clinical pharmacokinetic and pharmacodynamic data indicated that tulmimetostat exhibits durable exposure and profound target engagement. Importantly, a tulmimetostat controlled gene expression signature identified in whole blood from a cohort of 32 patients with cancer correlated with tulmimetostat exposure, representing a pharmacodynamic marker for the assessment of target coverage for PRC2-targeted agents in the clinic. Collectively, these data suggest that tulmimetostat has the potential to achieve clinical benefit in solid tumors as a monotherapy but also in combination with chemotherapeutic agents, and may be beneficial in various indications with recurrent ARID1A mutations.Significance: The EZH2 inhibitor tulmimetostat achieves comprehensive target inhibition in ARID1A mutant solid tumor models and cancer patients that can be assessed with a pharmacodynamic gene signature in peripheral blood.

2024-03-20·Leukemia & lymphoma

Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies

Article

作者: Fathi, Amir T. ; Colak, Gozde ; Fusco, Andrea ; Harb, Wael A. ; Mangan, James K. ; Stein, Eytan M.

Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24-400 mg capsule or 225-275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.CLINICAL TRIAL REGISTRATION: NCT02158858.

2023-09-26·Blood advances

Matching-adjusted indirect comparison of the pelabresib-ruxolitinib combination vs JAKi monotherapy in myelofibrosis.

Article

作者: Kremyanskaya, Marina ; Vannucchi, Alessandro M ; Harrison, Claire ; Colak, Gozde ; Verstovsek, Srdan ; Dey, Debarshi ; Gupta, Vikas ; Rampal, Raajit K ; Kiladjian, Jean-Jacques ; Talpaz, Moshe ; Mascarenhas, John

Janus kinase inhibitors (JAKis) ruxolitinib, fedratinib, and pacritinib are the current standard of care in symptomatic myelofibrosis (MF). However, progressive disease and toxicities frequently lead to JAKi discontinuation. Preclinical data indicate that combining JAK and bromodomain and extraterminal (BET) domain inhibition leads to overlapping effects in MF. Pelabresib (CPI-0610), an oral, small-molecule BET1,2 inhibitor (BETi), in combination with ruxolitinib showed improvements in spleen volume reduction (SVR35) and total symptom score reduction (TSS50) from baseline in the phase 2 MANIFEST study (NCT02158858) in patients with MF. Given the absence of a head-to-head clinical comparison between JAKi monotherapy and JAKi with BETi combination therapy, we performed an unanchored matching-adjusted indirect comparison analysis to adjust for differences between studies and allow for the comparison of SVR35, TSS50, and TSS measured at several timepoints in arm 3 of MANIFEST (pelabresib with ruxolitinib in JAKi treatment-naive patients with MF), with data from the following JAKi monotherapy studies in JAKi treatment-naive patients: COMFORT-I and COMFORT-II (ruxolitinib), SIMPLIFY-1 (ruxolitinib and momelotinib), and JAKARTA (fedratinib). Response rate ratios >1 were observed for pelabresib with ruxolitinib vs all comparators for SVR35 and TSS50 at week 24. Improvements in TSS were observed as early as week 12 and were durable. These results indicate that pelabresib with ruxolitinib may have a potentially higher efficacy than JAKi monotherapy in JAKi treatment-naive MF.

项与 Constellation Pharmaceuticals, Inc. 相关的新闻（医药）

2024-10-10

·PipelineReview

Novo Holdings Launches Portfolio Company Booster Therapeutics to Advance New Class of Small Molecule Proteasome Activator Therapeutics

Booster Therapeutics raises $15 million seed financing led by Apollo Health Ventures and Novo Holdings Booster Therapeutics’ proteasome activation approach designed to achieve wider degradation of harmful proteins than current targeted protein degraders Harmful protein accumulation implicated in range of complex diseases also linked to proteasome dysfunction COPENHAGEN, Denmark I October 10, 2024 I Novo Holdings, a leading global life sciences investor, today announced the launch of Booster Therapeutics (Booster / the Company), a biotechnology company developing a new class of proteasome activator medicines to treat neurodegenerative and other diseases. The launch is accompanied by a $15 million seed financing round led by Apollo Health Ventures and Novo Holdings. Novo Holdings will play a central role in helping to further build Booster in its next phase of growth, bringing hands-on operational expertise, strategic guidance and helping the Company access a larger network of talent. Novo Holdings will further leverage the expertise in its group of entrepreneurs-in-residence, as well as the Seed Lab wet-lab capabilities in Copenhagen, Denmark. Proteasomes play an important role in the clearing of dysfunctional proteins. Booster is leading a new field of protein degradation via small molecules that activate and restore the function of 20S proteasomes. These proteasomes naturally and directly recognise and degrade a wide range of misfolded or otherwise damaged proteins in contrast to conventional protein degradation therapeutics, which only degrade one target protein at a time. Activation of the 20S proteasome can remove a wide range of disease-causing proteins and thus address more complex diseases caused by multiple concurrent proteinopathies. With a vision of a multi-disease pipeline, Booster will initially focus on major neurodegenerative diseases such as Parkinson’s and Alzheimer’s. This group of diseases generally carries a tremendous burden of disease for patients, families and the healthcare system due to their progressive and severe nature and a lack of disease-modifying therapeutics. Booster was founded by the pioneering work of Dr. Diogo Feleciano and University of California Irvine Professor Dr. Darci Trader, as part of the company creation efforts of Apollo Health Ventures. The Company was built on the idea that small molecules could be used to trigger natural proteasome processes. Their DGRADX™ platform, which was conceived in Prof. Trader’s laboratory, combines proprietary methods for automated high-throughput screening with advanced structural and computational tools to develop Booster’s novel proteasome activator compounds. “Proteasome activation is a truly novel concept because it can potentially transform how we address some of the most multi-factorial diseases. Booster’s deep expertise in proteasome biology means it is well positioned to deliver on first-in-class medicines and expand the protein degradation landscape to more comprehensively address protein dysfunction and impact more disease areas,” said Dr. João Ribas, Principal at Novo Holdings, Seed Investments and Interim Chief Business Officer and Board Member, Booster Therapeutics. “We’re excited to join efforts with Apollo and the Booster team in order to take this novel therapeutic concept forward for the benefit of patients.” The Company and corporate strategy will be led by Dr. Diogo Feleciano as Chief Scientific Officer and Dr. João Ribas as interim Chief Business Officer. Dr. Patrick Trojer, Co-Founder of Constellation Pharmaceuticals and current Chief Executive Officer & President of TRIANA Biomedicines will serve as Chair of Booster’s Board of Directors. About Booster Therapeutics Booster Therapeutics is pioneering a new class of medicines that activate the cell’s natural quality control machinery to treat a range of complex indications. Booster’s small molecule therapeutics, discovered through the DGRADX™ platform, are designed to directly boost the activity of 20S proteasomes to restore the body’s ability to clear disease-causing proteins. The Company is developing a multi-disease pipeline, with an initial focus on neurodegenerative diseases associated with impaired proteasome function such as Parkinson’s disease and Alzheimer’s disease. Booster is based in Berlin, Germany. For more information, visit www.boostertx.com About Novo Holdings A/S Novo Holdings is a holding and investment company that is responsible for managing the assets and the wealth of the Novo Nordisk Foundation. The purpose of Novo Holdings is to improve people’s health and the sustainability of society and the planet by generating attractive long-term returns on the assets of the Novo Nordisk Foundation. Wholly owned by the Novo Nordisk Foundation, Novo Holdings is the controlling shareholder of Novo Nordisk A/S and Novonesis A/S and manages an investment portfolio with a long-term return perspective. Novo Holdings is a world-leading life sciences investor. Through its Seed, Venture, Growth, Principal Investments, Planetary Health Investments and Asia teams, Novo Holdings invests directly in life science companies at all stages of development. In addition, it manages a broad portfolio of Capital Investments, including equities, bonds, fixed income, real estate, and infrastructure assets. As of year-end 2023, Novo Holdings had total assets of EUR 149 billion. www.novoholdings.dk SOURCE: Novo Holdings

蛋白降解靶向嵌合体

2024-10-03

·同写意

下一个十亿美元分子！BET三期数据公布有望成为骨髓纤维化一线疗法

临床3期并购临床2期临床成功临床结果

2024-09-26

·GlobeNewswire-Health Care

EnnoDC unveils the next generation of dendritic cell-targeting immunotherapies supported by new leadership and an evolved strategy

PRESS RELEASE EnnoDC unveils the next generation of dendritic cell-targeting immunotherapies supported by new leadership and an evolved strategy Versatile new technology featuring an antibody fused with an antigen, harnesses the power of immunotherapy and vaccines by stimulating dendritic cells through CD40 to deliver a targeted and effective immune response for cancer and infectious diseasesNew approach aims to reduce harmful side effects and optimize the immune system's ability to detect, combat, and prevent cancer and infectious diseases Dr. Jean-Paul Kress, former Chief Executive Officer of MorphoSys, joins as Board Chairman; Christophe Hubert, industry veteran and entrepreneur joins as Chief Executive Officer; with co-founder Prof. Yves Levy, as Chief Medical and Scientific Officer and Dr. Hatem Azim joining as Chief Medical Officer Oncology Paris, France, 26 September 2024 – EnnoDC (or “the Company”), a clinical-stage biotech company pioneering the development of first-in-class dendritic cell-targeting immunotherapies, unveils today its promising pipeline of preclinical and clinical-stage programs for cancer and infectious diseases. EnnoDC’s technology, developed by the Vaccine Research Institute (VRI) of Inserm (French National Institute for health and Medical Research) and its spin-off LinKinVax, combines an antibody fused with an antigen to stimulate Dendritic Cells (DCs) through CD40 and deliver a targeted and effective immune response. The technology has already entered clinical development in the field of infectious diseases. EnnoDC is now extending the use of its technology to expand its portfolio of immunotherapies to fight cancers. EnnoDC is one of the innovative projects selected and supported by the Paris Saclay Cancer Cluster, whose mission is to accelerate the development of innovation in oncology. Immunotherapies, which enable a patient’s immune system to recognize and target cancer cells, have made a significant difference to cancer patients over the last decade. However, many patients fail to mount a robust and durable immune response, resistance can develop, and immune-related adverse events and systemic toxicity can be severe. DCs are crucial for the development of immune memory to identify and eliminate threats such as viruses and cancer. They form the basis of EnnoDC’s first-in-class immunotherapy platform by directly targeting DCs through a unique anti-CD40 antibody fused with tumor-specific or a pathogenic antigen, driving a highly specific immune response. EnnoDC’s evolution is accompanied by a change of leadership with the appointment of Christophe Hubert as the new Chief Executive Officer. Christophe is an international business executive and biotech entrepreneur, with over 25 years’ experience in the pharmaceutical and biotech industry. He previously served as SVP of Asia Merck and was the founder of three biotech companies. Christophe Hubert, Chief Executive Officer of EnnoDC, commented: “I am honored to lead the team at EnnoDC as it pioneers the development of the next generation of immunotherapies for cancer and infectious diseases. This is a fantastic opportunity to translate some of the best research within the immunotherapy space into meaningful change for patients.” Dr Jean-Paul Kress has joined EnnoDC as its Chairman of the Board and brings over 25 years of experience driving transformative change in the biotech and pharmaceutical industries. As the former CEO of MorphyoSys, he has completed two significant transactions: the acquisition of Constellation Pharmaceuticals in 2021 and the acquisition of MorphoSys by Novartis in 2024. Dr. Jean-Paul Kress, Chairman of EnnoDC added: “My time at MorphoSys has given me a deep appreciation of the complexities and challenges of developing effective treatments for cancer. EnnoDC’s new technology at the forefront of medicine drew me to the role of Chairman as I see great promise in the scientific approach which has already shown promise in the clinic. I look forward to working with the Board and management.” Dr Hatem Azim has also joined EnnoDC as the Chief Medical Officer Oncology and is an expert in cancer and drug development. His previous research focused on breast cancer and early drug development, with his contributions shaping international guidelines. This new clinical oncology expertise will be particularly useful with EnnoDC’s additional focus on developing immunotherapies for cancer. Pr. Yves Lévy, co-founder, Chief Medical and Scientific Officer at EnnoDC concluded: “Clinical progress and technological development over the last ten years in the fields of infectious diseases and cancer in an academic laboratory like the Vaccine Research Institute (VRI), supported by its supervisory authorities, is a source of great pride for all researchers. However, challenges remain immense and we are aware of this. The environment and resources provided by EnnoDC will be essential to succeed for the benefit of patients.” EnnoDC has an extensive pipeline of clinical and preclinical stage assets in HPV-induced cancers, prostate cancer and in infectious diseases. A Phase I/II clinical trial with CD40.HVac is currently running in 24 HPV16+ oropharyngeal cancer patients at Gustave Roussy Cancer Campus and Curie Institute in France. EnnoDC is planning to initiate in Q2 2025 a Phase IIb in HPV16+ oropharyngeal cancer patients and is planning a pre-IND filing for a Phase I/IIa trial in prostate cancer early 2027. A Phase I/IIa clinical trial for a prophylactic COVID-19 vaccine is ongoing and a Phase I clinical trial with a HIV vaccine has been completed. * EnnoDC is the trading name of LinKinVax Europe SAS. -Ends- For more information please contact: EnnoDC Christophe Hubert, CEOinfo@EnnoDC.com ICR Consilium Ashley Tapp / Jonathan Edwards / Kumail Waljee EnnoDC@consilium-comms.comTel: +44 (0) 20 3709 5700 About EnnoDC EnnoDC, the trading name of LinKinVax, is a clinical-stage biotech company pioneering the development of first-in-class Dendritic Cell (DC)-targeting immunotherapies. Through our versatile DC-targeting immunotherapy platform we are developing CD40-specific monoclonal antibodies fused with pathogenic antigens to induce a highly specific, safe, broad, and long-lasting immune response to combat diseases like cancer and infectious diseases. The Company currently has three active clinical trials in various stages of clinical development, addressing oncology and infectious disease indications. Its lead asset, CD40HVac is currently in a Phase I/IIa clinical trial for HPV16+ oropharyngeal cancer patients. EnnoDC is a spin out from the Vaccine Research Institute (VRI), an institute of INSERM (the French National Institute of Health and Medical Research) and is supported by longstanding investors and internationally renowned key opinion leaders who contribute their expertise in the clinical development of EnnoDC’s assets and help explore the expansive therapeutic potential of its innovative platform. Find out more online at: http://www.EnnoDC.com Follow us on X and LinkedIn

临床1期疫苗高管变更免疫疗法并购

100 项与 Constellation Pharmaceuticals, Inc. 相关的药物交易

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100 项与 Constellation Pharmaceuticals, Inc. 相关的转化医学

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药物(靶点)	适应症	全球最高研发状态

Pelabresib ( BET )	原发性骨髓纤维化更多	临床3期
Tulmimetostat ( EZH1 x EZH2 )	晚期恶性实体瘤更多	临床1/2期
磷酸芦可替尼 ( JAK1 x JAK2 )	骨髓增生异常综合征更多	临床1/2期
CPI-482 ( KDM1A )	原发性骨髓纤维化更多	临床前
CPI-1328 ( EZH2 )	MSI 癌症更多	临床前