Novel small molecules for protection against doxorubicin cardiotoxicity in TNBC

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43HL147726-01A1
Agency Tracking Number: R43HL147726
Amount: $375,001.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NHLBI
Solicitation Number: PA18-574
Timeline
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-09-19
Award End Date (Contract End Date): 2020-08-31
Small Business Information
11575 SORRENTO VALLEY RD STE 210, San Diego, CA, 92121-1320
DUNS: 620623764
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: N
Principal Investigator
 CATHY SWINDLEHURST
 (858) 350-8826
 cswindlehurst@novomedix.com
Business Contact
 CATHY SWINDLEHURST
Phone: (858) 350-8826
Email: cswindlehurst@novomedix.com
Research Institution
N/A
Abstract
Project SummaryThe overall goal of this program is to discover and develop a first in class small molecule that provides cardioprotective and beneficial anti tumor effects with standard of care chemotherapies for the treatment of triple negative breast cancerTNBCOne inwomen in the United States will develop invasive breast cancer during her lifetimeBreast cancer is the most commonly diagnosed cancer in women worldwide and one of the leading causes of cancer death among women of all races and ethnicities in the U SOvernew cases of breast cancer are projected to be diagnosed in the U Sinand overpeople in the U Sare estimated to die this year from this devastating diseaseApproximatelyof all breast cancers are categorized as triple negative breast cancer due to the lack of expression of the estrogen receptorERprogesterone receptorPRand human epidermal growth factor receptor typeHERUnlike other forms of breast cancerno targeted therapy exists for TNBCSystemic chemotherapy is usually the first line of treatmenthowevercurrently available regimens often fail to control advanced TNBCAnthracyclines like doxorubicinDOXAdriamycinare a leading modality for treating breast cancer patients due to their superior clinical efficacyUnfortunatelytreatment with DOX is associated with a dose dependent delayed and progressive cardiomyopathy often observed years after cessation of treatmentThe leading cause of death in breast cancer survivors is cardiovascular diseasewhich is often caused by the very treatments that once saved their livesAdditionallymany cancer patients have pre existing heart disease that could be exacerbated by chemotherapyNovoMedix has discovered novel small molecule allosteric AMPK agonists that are also strong mTORCinhibitorsthese are concerted biological properties not found in existing therapeutics and thus represent a new promising treatment that will provide protection against DOX induced cardiomyopathy while maintaining or enhancing anti tumor activity in TNBCNovoMedix s lead compounds have demonstrated anti canceralone and in combination with DOXanti fibroticand cardioprotectiveagainst DOX induced cardiotoxicityproperties with an excellent preclinical safety profileConsistent with thisthese novel compounds have exhibited remarkable safety and efficacy when administered orally in independent animal models of TNBC and pulmonary and cardiac fibrosisThe Phase I goal is demonstration of proof of concept that NovoMedix s lead compounds reduce DOXinduced cardiotoxicity in TNBC while maintaining or enhancing efficacyThe specific aims for this Phase I proposal arei confirm safety and PK properties in combination with DOXmechanism of cardioprotection studiesandprevention of DOX induced cardiotoxicity in a xenograft model of TNBC Project NarrativeThe goal of this program is to discover and ultimately commercialize novelsmall molecules for coadminstration with anthracyclinese gDoxorubicinDOXAdriamycinto improve clinical outcome for the treatment of triple negative breast cancerTNBCby significantly decreasing long term cardiotoxicity related mortalitya leading cause of death in breast cancer survivorsThese novel orally available small molecules have demonstrated anti canceralone and in combination with DOXanti fibroticand cardioprotectiveagainst DOX induced cardiotoxicityproperties with an excellent preclinical safety profileThe selected clinical candidate will be poised to have significant impact in the treatment of TNBC by maintaining or enhancing the efficacy of anthracycline therapy while mitigating long term cardiotoxicity

* Information listed above is at the time of submission. *

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