Zenopharm, LLC — Department of Health and Human Services SBIR Phase II: 102

Description

Project Summary Fulvestrant is the only FDA approved selective estrogen receptor downregulatorSERDindicated for advanced metastatic breast cancer that has progressed after or during tamoxifen or aromatase inhibitorAItreatmentIn July and Augustfulvestrant was approved as a first line endocrine agent for breast cancer patients by the European Medicines AgencyEMAand US FDArespectivelyHoweverthe drug is not orally bioavailableits high dose monthly regimen ofmg as an intramuscular injection had limited drug exposure and ER turnover in patientsThe low bioavailability of fulvestrant and its slow action presents clinical challenges because endocrine resistant tumors require a significantly higher SERD exposure which is insufficient in the fulvestrant treatmentAs a resultthe clinical response rate to fulvestrant in the advanced metastatic setting remains belowIn the first line settingan oral SERD with greater drug exposure and faster action would bring immediate clinical benefits to patients in numbers that far exceed those who are treated with fulvestrant only as a second line regimenThusan urgent need exists for an orally bioavailable SERD that offers first line therapy advantages over other endocrine regimens and higher clinical response rates in the second line setting or beyondAdvances in oral SERDs development have been so far confined to nonsteroidal moleculesand all non steroidal SERD candidates have yet to be advanced to phase II clinical trialsZenopharmandapos s lead compoundZBwill be the first oral steroidal SERD to enter clinical trials if we are successful in securing the funds to complete the proposed IND enabling studiesZBhas shown promising preclinical data in bioavailabilityefficacyand toxicologyIf clinically provenZBwill bring substantial clinical benefits to advancedmetastatic breast cancer patients both as a first line endocrine therapy and as ER targeting treatment for recurring diseases after SERM and or AI therapyTo bring this promising oral SERD candidate to clinical trials we propose to complete remaining FDA required studies both in the CMCChemistryManufacturingand Controland Toxicology categoryIn Specific AimZenopharm will collaborate with Avista Pharma Solutionsa GMP manufacturer on a fee for service basis to optimize process scale up and manufactureg of the API for GLP toxicity studiesand preparekg GMP batch of API for clinical studiesIn Specific AimZenopharm will collaborate with Covance to implement the nonclinical development plan following the ICH Sguidance for the Nonclinical Evaluation for Anticancer PharmaceuticalsThe IND enabling studies will be conducted to ensure approval for the First in Human study and support the confirmation clinical Proof of Concept studyCompletion of the above proposed work will allow Zenopharm to prepare and file an IND application for ZBto be tested in the clinic for safetytolerabilityand pharmacokinetic studiesIt will also enable the company to secure funds from venture capital firms to conduct the phaseclinical trial Project Narrative Fulvestrant is currently the only FDA approved selective estrogen receptor downregulatorSERDindicated for breast cancer progressing after previous endocrine therapy and as a first line endocrine agent for metastatic and locally advanced breast cancerThe major limitation of fulvestrant stems from its well known poor bioavailability and the standard intramuscular route of administrationwhich could be addressed by the availability of an orally bioavailablemore efficacious SERDZenopharm has recently developed ZBan orally bioavailable SERD that demonstrated superior bioavailabilitypharmacokinetic profilesand efficacy in multiple breast tumor modelsCompared to fulvestrantZBafforded overfold higher plasma drug concentration in animals at lower dosageZenopharm was awarded an SBIR phasegrant to initiate key preclinical studies to further demonstrate the feasibility of developing ZBfor first in human trialsIn the phaseapplication we propose to complete all IND enabling studies in order to obtain approval from FDA to conduct clinical trialsThe proposed work includes manufacture of the API for GLP toxicology studies and GMP drug substance and product for clinical useAt the conclusion of this SBIR phase grantZenopharm will be able to file an Investigational New Drug application for ZBto test safetytolerabilityand pharmacokinetics in humans