Completion of IND-enabling studies required for first-in-human studies of a novel oral therapeutic agent for treating pulmonary fibrosis
完成用于治疗肺纤维化的新型口服治疗剂的首次人体研究所需的 IND 授权研究
基本信息
- 批准号:10384244
- 负责人:
- 金额:$ 100.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-05 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffinityAnimal ModelCardiovascular systemCessation of lifeChronicCicatrixClinicalClinical ResearchCollagenComplexDataDiseaseDisease ProgressionDoseDrug KineticsEnzyme PrecursorsEnzymesEpithelialEtiologyExtracellular MatrixFailureFibrinolysisFibronectinsFibrosisGene FamilyHeart DiseasesHemostatic functionHumanHuman GeneticsHydrophobicityImpaired wound healingInflammationInjuryInterstitial Lung DiseasesInvestigational DrugsInvestigational New Drug ApplicationKidney DiseasesLeadLungLung diseasesLung fibrogenesisMacaca fascicularisMedicalModelingMonoclonal AntibodiesMusNatural ProductsNeuraxisOralOrganPatientsPharmaceutical PreparationsPharmacologic SubstancePharmacologyPhasePhase I Clinical TrialsPhysiologicalPhysiologyPirfenidonePlasmaPlasminPlasminogenPlasminogen ActivatorPlasminogen Activator Inhibitor 1Plasminogen Activator InteractionPlasminogen InactivatorsPlayProcessPulmonary FibrosisResolutionRespiratory FailureRoleSERPINE1 geneSafetySerine Proteinase InhibitorsSerpinsSpecificitySyndromeSystemSystemic SclerodermaTelemetryTherapeuticTherapeutic AgentsTissuesToxic effectToxicokineticsToxicologyUrokinaseVitronectincofactorcommercializationdrug candidatefibrotic lung diseasefirst-in-humanhigh throughput screeningidiopathic pulmonary fibrosisin vivoinhibitorinnovationinterestmembermortalitymouse modelnintedanibnovelnovel therapeuticspre-clinicalpreclinical studyprogramspulmonary functionrepairedskin disordersmall moleculesmall molecule inhibitorsuccesstherapeutic targetwound healing
项目摘要
MDI Therapeutics is an early-stage pharmaceutical company developing a new class of small molecule inhibitors
of plasminogen activator inhibitor-type 1 (PAI-1) (gene: SerpinE1) for the treatment of fibroproliferative diseases.
Fibrosis is defined by the excessive accumulation of components of the extracellular matrix (ECM), such as
collagen and fibronectin, in and around inflamed or damaged tissue, which can lead to permanent scarring,
organ malfunction and, ultimately, death. Nearly 45% of all deaths in the developed world are attributed to some
type of chronic fibroproliferative disease. In patients with acute and chronic fibrotic lung disease there is a marked
induction of PAI-1. PAI-1 is best understood for its role regulating fibrinolysis and wound healing by inhibiting the
tissue-type (tPA) and urokinase-type (uPA) plasminogen activators, which convert the zymogen plasminogen to
the active enzyme plasmin. The role of PAI-1 as a primary regulator of wound healing, including in the lung, is
consistent with its critical regulatory role in fibrosis. Wound healing is a natural repair process after injury that
consists of overlapping stages, including hemostasis, inflammation, proliferation and matrix synthesis, and finally
resolution. Disruption of this ordered process can result in impaired wound healing, leading to persistent
inflammation and/or matrix synthesis and ultimately to a fibrotic syndrome. PAI-1, as a primary regulator of wound
healing has been shown to impact all stages of wound healing, and accordingly to play a causal role in pulmonary
fibrogenesis. MDI Therapeutics has developed a highly effective, orally active, small molecule inhibitor of PAI-1,
MDI-2517, with demonstrated efficacy in multiple models of pulmonary fibrosis. The studies proposes here will
provide critical IND-enabling data for this novel therapeutic necessary for filing an Investigational New Drug (IND)
application prior to conducting first-in-human Phase 1 clinical studies of the first-in-class PAI-1 inhibitor (MDI-
2517) for the treatment of pulmonary fibrosis. Specific milestones include completion of key GLP safety
pharmacology, pharmacokinetics and toxicology studies required for submission of an Investigational New Drug
(IND) application for MDI-2517. The successful completion of these milestones will significantly advance this
program toward commercialization by providing data necessary for the start of human Phase 1 clinical trials.
MDI Therapeutics 是一家早期制药公司,开发新型小分子抑制剂
纤溶酶原激活剂抑制剂 1 型 (PAI-1)(基因:SerpinE1)用于治疗纤维增生性疾病。
纤维化的定义是细胞外基质 (ECM) 成分的过度积累,例如
发炎或受损组织内部和周围的胶原蛋白和纤连蛋白,可能导致永久性疤痕,
器官功能障碍,最终导致死亡。发达国家近 45% 的死亡归因于某些疾病
慢性纤维增生性疾病的类型。在患有急性和慢性纤维化肺病的患者中,存在明显的
PAI-1的诱导。 PAI-1 因其通过抑制纤维蛋白溶解和伤口愈合的调节作用而被人们所熟知。
组织型(tPA)和尿激酶型(uPA)纤溶酶原激活剂,将酶原纤溶酶原转化为
活性酶纤溶酶。 PAI-1 作为伤口愈合(包括肺部)的主要调节剂的作用是
与其在纤维化中的关键调节作用一致。伤口愈合是受伤后的自然修复过程
由重叠的阶段组成,包括止血、炎症、增殖和基质合成,最后
解决。破坏这一有序过程可能会导致伤口愈合受损,从而导致持续的伤口愈合。
炎症和/或基质合成,最终导致纤维化综合征。 PAI-1,作为伤口的主要调节剂
愈合已被证明会影响伤口愈合的所有阶段,因此在肺损伤中发挥因果作用
纤维发生。 MDI Therapeutics 开发了一种高效、口服活性的 PAI-1 小分子抑制剂,
MDI-2517,在多种肺纤维化模型中已被证明有效。这里的研究建议将
为这种新型疗法提供提交研究性新药 (IND) 所需的关键 IND 启用数据
在进行首创 PAI-1 抑制剂(MDI-
第2517章)用于治疗肺纤维化。具体里程碑包括完成关键的 GLP 安全性
提交研究性新药所需的药理学、药代动力学和毒理学研究
MDI-2517 的 (IND) 申请。这些里程碑的成功完成将显着推进这一进程
通过提供启动人体一期临床试验所需的数据来实现商业化。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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James Craig Hartman其他文献
James Craig Hartman的其他文献
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{{ truncateString('James Craig Hartman', 18)}}的其他基金
Completion of IND-enabling studies required for first-in-human studies of a novel oral therapeutic agent for treating pulmonary fibrosis
完成用于治疗肺纤维化的新型口服治疗剂的首次人体研究所需的 IND 授权研究
- 批准号:
10584585 - 财政年份:2022
- 资助金额:
$ 100.06万 - 项目类别:
Development of a small molecule inhibitor of PAI-1 for the treatment of diffuse cutaneous systemic sclerosis
开发用于治疗弥漫性皮肤系统性硬化症的 PAI-1 小分子抑制剂
- 批准号:
9909794 - 财政年份:2018
- 资助金额:
$ 100.06万 - 项目类别:
Development of a small molecule inhibitor of PAI-1 for the treatment of diffuse cutaneous systemic sclerosis
开发用于治疗弥漫性皮肤系统性硬化症的 PAI-1 小分子抑制剂
- 批准号:
10004564 - 财政年份:2018
- 资助金额:
$ 100.06万 - 项目类别:
Development of a small molecule inhibitor of PAI-1 for the treatment of diffuse cutaneous systemic sclerosis
开发用于治疗弥漫性皮肤系统性硬化症的 PAI-1 小分子抑制剂
- 批准号:
9619126 - 财政年份:2018
- 资助金额:
$ 100.06万 - 项目类别:
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