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ZyVersa Therapeutics(ZVSA) - 2024 Q4 - Annual Report
ZVSAZyVersa Therapeutics(ZVSA)2025-03-27 13:05

Clinical Development - VAR 200 is in clinical development for the treatment of focal segmental glomerulosclerosis (FSGS), with plans to initiate a small Phase 2a trial in patients with diabetic kidney disease in H1-2025[20] - IC 100, targeting obesity with metabolic complications, is nearing completion of preclinical development, with a planned IND submission in H2-2025[21] - The company aims to expand its product portfolio by developing multiple indications for VAR 200 and IC 100, including Alport Syndrome and diabetic kidney disease for VAR 200, and Alzheimer's and Parkinson's diseases for IC 100[36] - Preclinical studies for IC 100 are underway in Alzheimer's and Parkinson's diseases, with plans to initiate IND-enabling studies in diet-induced obesity[21] - The company is preparing to initiate two IND-enabling preclinical studies with IC 100 in DIO obesity models, comparing its effects to semaglutide[65] Market Opportunity - Approximately 40,000 people in the United States are affected by FSGS, with 40-60% of patients progressing to end-stage kidney disease within 10-20 years[25] - The economic burden of chronic kidney disease (CKD) in the United States was approximately 130billionin2018,highlightingtheneedforeffectivetherapies[22]−TheU.S.prevalenceofdiabetickidneydiseaseisupto12million,highlightingasignificantmarketopportunityforrenaltherapies[100]−Theglobalrenaldrugmarketisprojectedtogrowfrom130 billion in 2018, highlighting the need for effective therapies[22] - The U.S. prevalence of diabetic kidney disease is up to 12 million, highlighting a significant market opportunity for renal therapies[100] - The global renal drug market is projected to grow from 17.71 billion in 2024 to 30.3billionby2034,drivenbyrisingobesityanddiabetesrates[98]−Theglobalanti−inflammatorybiologicsmarketisvaluedat30.3 billion by 2034, driven by rising obesity and diabetes rates[98] - The global anti-inflammatory biologics market is valued at 104.81 billion in 2024 and projected to reach 185.51billionby2034,drivenbychronicinflammatorydiseases[102]MechanismofActionandEfficacy−VAR200′smechanismofactioninvolvesmediatingcholesteroleffluxtopreserverenalstructureandfunction,potentiallyreducingproteinuriaanddelayingtheneedfordialysis[40]−VAR200demonstratedasignificantreductionincholesterollevelsintherenalcortexofFSGSmice,leadingtoanotabledecreaseinproteinuria(albumin/creatinineratio)comparedtountreatedmice[46]−IntheAdriamycin−inducedFSGSmodel,VAR200treatmentresultedinasignificantreductioninmesangialexpansionandproteinuria,aswellaslowerbloodureanitrogen(BUN)levelscomparedtountreatedmice[49]−VAR200significantlyreducedrenalneutrallipid,cholesterolester,andcholesterolcrystalaccumulationinAlportSyndromemice,correlatingwithimprovedrenalfunctionandreducedproteinuria[54][56]−Indiabetickidneydiseasemodels,VAR200treatmentledtoasignificantreductionintotalcholesterolandrenaldamage,withstatisticallysignificantdecreasesinproteinuriaobservedfrom3monthsonward[61]−IC100showeda55185.51 billion by 2034, driven by chronic inflammatory diseases[102] Mechanism of Action and Efficacy - VAR 200's mechanism of action involves mediating cholesterol efflux to preserve renal structure and function, potentially reducing proteinuria and delaying the need for dialysis[40] - VAR 200 demonstrated a significant reduction in cholesterol levels in the renal cortex of FSGS mice, leading to a notable decrease in proteinuria (albumin/creatinine ratio) compared to untreated mice[46] - In the Adriamycin-induced FSGS model, VAR 200 treatment resulted in a significant reduction in mesangial expansion and proteinuria, as well as lower blood urea nitrogen (BUN) levels compared to untreated mice[49] - VAR 200 significantly reduced renal neutral lipid, cholesterol ester, and cholesterol crystal accumulation in Alport Syndrome mice, correlating with improved renal function and reduced proteinuria[54][56] - In diabetic kidney disease models, VAR 200 treatment led to a significant reduction in total cholesterol and renal damage, with statistically significant decreases in proteinuria observed from 3 months onward[61] - IC 100 showed a 55% reduction in retinal ASC speck formation in retinopathy models, indicating its potential to alleviate retinal inflammation and structural damage[82] - In stroke-related cardiovascular injury models, IC 100 administration resulted in significant reductions in IL-1β levels and improved cardiac function post-stroke[77] - IC 100 treatment in MS models delayed disease onset and improved functionality, evidenced by reduced activated microglial cells in the spinal cord[91] Regulatory and Compliance - The FDA is expected to adopt recommendations from the Parasol project, which identified proteinuria reduction as a surrogate endpoint for FSGS drug approval, based on data from over 1,600 patients[98] - The FDA regulates drug products and requires extensive data demonstrating quality, safety, and efficacy before a new drug can be marketed, which involves significant time and financial resources[129] - The FDA may require substantial post-approval testing and surveillance, including Phase IV clinical trials, to monitor product safety or efficacy after approval[155] - The FDA requires a user fee payment exceeding 2.5 million for each NDA or BLA submission, as of fiscal year 2019[145] - The FDA may issue a complete response letter if the NDA or BLA is not ready for approval, which may require additional clinical data or trials[151] Financial and Operational Challenges - The company is a development stage entity with no revenues and limited operating history, which may affect its business prospects[199] - The company has never been profitable, with an accumulated net loss of approximately 179 million as of December 31, 2024, and has not generated any revenue from product sales[208] - The company will need substantial additional capital to develop and commercialize its product candidates, particularly VAR 200 and IC 100, and has no commitments for additional financing[213] - The company expects to incur increased expenses as it continues clinical development for VAR 200 and preclinical development for IC 100, leading to continued net losses and negative cash flows[208] - The company is dependent on the successful development, regulatory approval, and commercialization of its product candidates, facing significant competition if approved[200] Intellectual Property - The company has an exclusive, sublicensable, worldwide license for 2-hydroxypropyl-beta-cyclodextrin (2HPβCD) for treating kidney disease, with 4 issued U.S. patents and 12 foreign granted or allowed applications, expected to last until at least 2033[125] - The patent portfolio for IC 100 includes 5 patent families with 6 issued U.S. patents and 14 foreign granted patents, with a term until at least December 2037[126] - The company has no patents or patent applications outside of those connected to the L&F or InflamaCORE License Agreements, and there is no guarantee that the validity of these patents will be upheld if challenged[127] Strategic Partnerships - The company has entered into a License Agreement with L&F Research, involving an upfront fee of 200,000 and potential milestone payments up to 21.5millionforVAR200development[106]−ThecompanyhasasublicenseagreementwithInflamaCOREforIC100,withanupfrontfeeof21.5 million for VAR 200 development[106] - The company has a sublicense agreement with InflamaCORE for IC 100, with an upfront fee of 346,321.08 and potential milestone payments up to $22.5 million[114] Workforce and Corporate Structure - The company has seven full-time employees as of December 31, 2024, and maintains good relations with its workforce[194] - The company was incorporated on March 17, 2021, and changed its name to ZyVersa Therapeutics, Inc. on December 12, 2022, following a business combination[195] Risks and Uncertainties - The company may face litigation risks and potential liabilities that could harm its professional reputation and financial condition[200] - The company is subject to extensive domestic and foreign regulations, which may impose significant costs and compliance requirements[200] - The company may not be able to continue as a going concern without additional funding, raising doubts about its ability to sustain operations[210] - The company must navigate complex healthcare reforms and pricing pressures that could affect its ability to sell products profitably[182] - The COVID-19 pandemic has adversely affected operating results, with future impacts depending on external factors beyond the company's control[218]