Aerosolized Chemically Modified Tetracycline Nanoformulation for the Treatment of Acute Respiratory Distress Syndrome
雾化化学修饰四环素纳米制剂治疗急性呼吸窘迫综合征
基本信息
- 批准号:10602896
- 负责人:
- 金额:$ 42.67万
- 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:2022-12-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AIDS with Kaposi&aposs sarcomaAccountingAcneAcute Lung InjuryAcute Respiratory Distress SyndromeAdultAgreementAlveolarAmericanAnimal ModelAnimalsAreaAuthorization documentationBiodistributionBiotechnologyCenters for Disease Control and Prevention (U.S.)Cessation of lifeChemicalsChronicClinicalClinical ResearchClinical TreatmentClinical TrialsComplexComplicationDataDermatologyDevelopmentDiffuseDiseaseDisease ProgressionDisparateDisseminated Malignant NeoplasmDoseDrug KineticsEtiologyExtracorporeal Membrane OxygenationFDA approvedFamily suidaeFormulationGliomaGoalsHospital MortalityHospitalsHumanHydrophobicityHypoxiaImmuneIncidenceInduction of neuromuscular blockadeInflammationInflammatoryIntensive CareInternationalInterventionIntubationInvestigational DrugsKnowledgeLicensingLungMarketingMatrix MetalloproteinasesMechanical ventilationMediatingMedicalMedical emergencyMethodsModalityModelingMorbidity - disease rateMusOncologyOralOutcomePathologicPathway interactionsPatientsPeriodontitisPeriostatPharmaceutical PreparationsPharmacologic SubstancePhasePreventionProne PositionPublic HealthPublishingRattusRecurrenceRefractoryResearchResearch PersonnelRespiratory distressRiskRosaceaSafetyScheduleSepsisSeptic ShockSeverity of illnessSheepSmall Business Technology Transfer ResearchSupportive careTetracyclinesTherapeuticTherapeutic InterventionTherapy trialTissuesToxic effectWorkaerosolizedauthorityclinical applicationclinical developmentcommercial applicationcommercializationcytokine release syndromedesigndrug candidatedrug developmentefficacy evaluationefficacy studyendothelial dysfunctionexperimental studyforgingimprovedimproved outcomelung injurymortalitynanoformulationnovelpharmacokinetics and pharmacodynamicspre-Investigational New Drug meetingpreclinical developmentpreclinical efficacypreventrepositorysafety studysepsis induced ARDSseptic patientsside effectsystemic inflammatory responsesystemic toxicitytherapeutically effectiveventilation
项目摘要
PROJECT SUMMARY/ABSTRACT
CMTx Biotech is a drug development company working to rescue, develop and commercialize a proprietary
clinical-stage drug candidate, incyclinide (CMT-3 / COL-3), for the treatment of sepsis patients at risk of acute
respiratory distress syndrome (ARDS). According to the U.S. Centers for Disease Control (CDC), at least 1.7
million American adults develop sepsis annually, resulting in nearly 270,000 deaths. Sepsis accounts for more
than 50% of hospital deaths, and mortality increases dramatically with greater disease severity: 10–20% for
sepsis, 20–40% for severe sepsis, and 40–80% for septic shock. Sepsis is a medical emergency characterized
by severe immune dysregulation with a very complex immunopathogenesis. ARDS is a devastating complication
of severe sepsis, both with similar underlying mechanisms characterized by inflammation and endothelial
dysfunction. Sepsis is the leading cause of ARDS and accounts for 32% of the etiology of the condition.
Approximately 6-7% of sepsis patients rapidly progress to ARDS, which is associated with a significantly
increased risk of in-hospital mortality. There is currently no specific treatment for sepsis-induced ARDS.
Moreover, researchers have not yet elucidated the multifactorial mechanisms by which sepsis induces ARDS,
or why the inflammatory cytokine storm eventually induces diffuse alveolar damage and severe hypoxia. Though
advances in treatment modalities have improved the outcome over recent decades, including lung protective
ventilation, prone positioning, use of neuromuscular blockade, and extracorporeal membrane oxygenation, the
mortality rate still remains high. There remains a critical unmet need for the development of safe and efficacious
therapeutics to prevent the onset of sepsis-induced ARDS, protect against lung injury and improve survival.
CMTx Biotech is working to develop and commercialize a novel and proprietary nanoformulation of incyclinide
(nCMT-3) that can be aerosolized, and which can be delivered to specifically target the lung and treat sepsis-
induced ARDS while limiting systemic toxicity. Incyclinide is a clinical-stage, non-antibiotic, chemically-modified
tetracycline that belongs to a class of pleiotropic matrix metalloproteinase (MMP) modulators which inhibit
pathologically-excessive collagenolysis and resolve systemic inflammation. Importantly, the safety of incyclinide
has already been demonstrated in Investigational New Drug (IND)-enabling studies, and incyclinide has been
evaluated in a number of human clinical trials for the treatment of diseases as disparate as AIDS-related Kaposi’s
sarcoma, recurrent high-grade gliomas, refractory metastatic cancer, acne, rosacea and periodontitis. Published
pre-clinical efficacy studies have shown that systemic administration of incyclinide prevents the development of
ARDS and septic shock, and improves survival in several chronic insidious onset animal models of ARDS across
several species, including mice, rats, pigs, and sheep. Our long-term goal is to obtain regulatory approval from
the FDA and comparable international regulatory authorities to market aerosolized nCMT-3 for the treatment and
prevention of sepsis-induced ARDS. We strongly anticipate that nCMT-3 will inhibit disease progression, mitigate
acute lung injury and respiratory distress, reduce the need for intensive care and intubation, and improve clinical
outcomes for sepsis patients, including overall survival. Our specific aims are (a) to determine the
pharmacokinetics, biodistribution, and safety of aerosolized nCMT-3 in mechanically ventilated pigs with healthy
lungs, (b) to demonstrate the efficacy of aerosolized nCMT-3 in reducing the incidence and mortality of sepsis-
mediated ARDS in a high-fidelity, clinically applicable porcine sepsis-induced ARDS model, and (c) to
demonstrate the efficacy of aerosolized nCMT-3 at reducing local and systemic inflammation. Successful
completion of these studies will allow CMTx Biotech to advance nCMT-3 towards human clinical trials for the
treatment of ARDS patients.
项目总结/文摘
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)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Michaela Christina Kollisch-Singule其他文献
Michaela Christina Kollisch-Singule的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Michaela Christina Kollisch-Singule', 18)}}的其他基金
Novel Small Molecule Drug Candidate for the Prevention of Bronchopulmonary Dysplasia
预防支气管肺发育不良的新型小分子候选药物
- 批准号:
10698418 - 财政年份:2023
- 资助金额:
$ 42.67万 - 项目类别:
Shape Memory Polymer Foams for Hemorrhage Control in Traumatic Wounds
用于控制外伤出血的形状记忆聚合物泡沫
- 批准号:
10638377 - 财政年份:2023
- 资助金额:
$ 42.67万 - 项目类别:
相似海外基金
The antitumor effect of histone deacetylase inhibitor against multidrug-resistant Ewing' s sarcoma cells
组蛋白脱乙酰酶抑制剂对多重耐药尤文氏肉瘤细胞的抗肿瘤作用
- 批准号:
21791409 - 财政年份:2009
- 资助金额:
$ 42.67万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
NON-HUMAN PRIMATE MODEL OF KAPOSI?S SARCOMA-ASSOCIATED HERPESVIRUS INFECTION
卡波西肉瘤相关疱疹病毒感染的非人灵长类动物模型
- 批准号:
7715514 - 财政年份:2008
- 资助金额:
$ 42.67万 - 项目类别:
Role of viral microRNAs in Kaposi´s Sarcoma-associated Herpesvirus (KSHV) infection and KSHV-associated Disease
病毒 microRNA 在卡波西肉瘤相关疱疹病毒 (KSHV) 感染和 KSHV 相关疾病中的作用
- 批准号:
37904962 - 财政年份:2007
- 资助金额:
$ 42.67万 - 项目类别:
Research Grants
KAPOSI?S SARCOMA-ASSOCIATED HERPESVIRUS GENE EXPRESSION
卡波西肉瘤相关疱疹病毒基因表达
- 批准号:
7349564 - 财政年份:2006
- 资助金额:
$ 42.67万 - 项目类别:
KAPOSI?S SARCOMA-ASSOCIATED HERPESVIRUS K1 SIGNALOSOME
卡波西肉瘤相关疱疹病毒 K1 信号体
- 批准号:
7349565 - 财政年份:2006
- 资助金额:
$ 42.67万 - 项目类别: