Erectile dysfunction (ED) affects about 18 million men in the U.S. and is estimated to affect 322 million menworldwide by 2025. ED can have a profound negative impact on quality of life and well-being and is oftenassociated with anxiety and depression. ED also represents a significant economic burden, with over $4 billionspent in 2017 in the U.S. ED is a common consequence of diseases that affect the microvasculature and nervoustissue, including common chronic diseases such as hypertension, dyslipidemia, and diabetes, and a frequentside effect of prostate cancer treatment. Currently available ED treatments are moderately effective at best, havehigh discontinuation rates, and address only the symptoms, not the underlying causes. To address the needfor novel treatments for ED, Evincis Bio is developing a regenerative gene therapy based on stromalcell"derived factor"1 (SDF-1) mRNA. SDF-1 is a highly conserved chemokine that regulates an endogenousrepair pathway used by many tissues throughout the body, such as the heart, brain, muscle, and vasculature.Often upregulated following injury, SDF-1 signaling leads to stem cell migration to the injury site. SDF-1 binds toits receptor CXCR4 on resident tissues, including nerves, muscle, and vasculature, inducing angiogenesis,neurogenesis, anti-apoptotic pathways, and upregulating the expression of growth factors. Evincis hasdemonstrated that SDF-1 penile injections improve erectile function in a rat model of ED. Thisimprovement was associated with increased major pelvic ganglion (MPG) neurons, decreased penile fibrosis,and increased growth factor expression in penile tissues. SDF-1 penile injections were shown to upregulate theexpression of stem cell-associated genes in the MPG and erectile tissue. Evincis has also demonstrated thefeasibility of targeted mRNA-based gene expression in penile tissues. In fact, mRNA technology is beingutilized by several current COVID-19 vaccines. In this Phase I project, Evincis will conduct in vitro and in vivodosing, efficacy, and safety studies to support further clinical research. This will be accomplished through thefollowing specific aims: 1) Screen engineered mRNA candidates in vitro for expression efficiency and cytotoxicity;2) Determine EVI-200 dosage, expression duration, and safety in vivo; and 3) Perform efficacy and cancer safetystudies in vivo. These studies will support further Phase II work, in which Evincis will expand the preclinicaltesting to additional disease states, investigate different nucleic acid carriers, perform pharmacokinetic andtoxicology studies, and initiate the GMP setup necessary to support an IND application and start a Phase I clinicaltrial. Evincis will pursue approval as a biologic, resulting in a product J-code and stand-alone reimbursement forthe in-office procedure. If successful, EVI-200 will be the first therapy specifically designed to treat theunderlying causes of ED due to injury of nerve, muscle, and vascular tissue, and potentially provide acure for millions of individuals. This project will also serve as a proof-of-concept for EVI-200 as an mRNA-based regenerative therapy for other conditions, such as urinary incontinence.
Public Health Relevance Statement: Narrative
Erectile dysfunction (ED) is a significant and often-overlooked public health challenge with a profound negative
impact on quality of life and well-being, and for which currently available treatments are moderately effective at
best, have high discontinuation rates, and address only the symptoms, not the underlying causes. Evincis Bio is
developing EVI-200, a regenerative gene therapy based on stromal cell"derived factor"1 (SDF-1), a chemokine
that regulates an endogenous repair pathway used by many tissues throughout the body and that activates stem
cell migration to the injury site, promoting healing. If successful, EVI-200 will be the first therapy specifically
designed to treat underlying the causes of ED due to injury of nerve, muscle, and vascular tissue, with the
potential to provide a cure for millions of Americans.
Project Terms: Adipose tissue ; Fatty Tissue ; adipose ; white adipose tissue ; yellow adipose tissue ; Adrenergic alpha-Antagonists ; Adrenergic alpha-Blockers ; Adrenergic alpha-Receptor Blockaders ; Adrenergic α-Antagonists ; Adrenergic α-Blockers ; alpha adrenergic blockade ; alpha antiadrenergic agent ; alpha blocker ; alpha-Adrenergic Blocking Agents ; α blocker ; Affect ; inhibitor/antagonist ; inhibitor ; Anxiety ; Blood Platelets ; Marrow platelet ; Platelets ; Thrombocytes ; Blood Vessels ; vascular ; Brain ; Brain Nervous System ; Encephalon ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Cardiovascular Agents ; Cardiovascular Drugs ; Chronic Disease ; Chronic Illness ; chronic disorder ; Clinical Research ; Clinical Study ; Mental Depression ; depression ; Diabetes Mellitus ; diabetes ; Disease ; Disorder ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Investigational Drugs ; Investigational New Drugs ; Engineering ; Fibrosis ; Ganglia ; Neural Ganglion ; Gene Expression ; gene therapy ; DNA Therapy ; Gene Transfer Clinical ; Genetic Intervention ; gene-based therapy ; genetic therapy ; genomic therapy ; Genes ; Heart ; Heart Diseases ; Cardiac Diseases ; Cardiac Disorders ; heart disorder ; Hypertension ; Vascular Hypertensive Disease ; Vascular Hypertensive Disorder ; high blood pressure ; hyperpiesia ; hyperpiesis ; hypertensive disease ; In Vitro ; Injection of therapeutic agent ; injection therapy ; Insurance ; Maintenance ; men ; men's ; Muscle ; Muscle Tissue ; muscular ; Nerve ; Nerve Tissue ; Nervous Tissue ; Neurons ; Nerve Cells ; Nerve Unit ; Neural Cell ; Neurocyte ; neuronal ; Nitrates ; NO3- ; nitrate ; Nucleic Acids ; Patients ; Pelvis ; Pelvic ; Pelvic Region ; Penile Prosthesis ; Artificial Penis ; Penile Implant ; Penis Prosthesis ; penis ; Personal Satisfaction ; well-being ; wellbeing ; Drug Kinetics ; Pharmacokinetics ; Pharmacology ; phosphoric diester hydrolase ; Phosphodiesterases ; Plasma ; Blood Plasma ; Plasma Serum ; Reticuloendothelial System, Serum, Plasma ; Porifera ; Sponges ; Proteins ; Public Health ; Quality of life ; QOL ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Messenger RNA ; mRNA ; Safety ; Signal Transduction ; Cell Communication and Signaling ; Cell Signaling ; Intracellular Communication and Signaling ; Signal Transduction Systems ; Signaling ; biological signal transduction ; Standardization ; stem cells ; Progenitor Cells ; Technology ; Tissues ; Body Tissues ; Toxicology ; Translating ; Treatment Protocols ; Treatment Regimen ; Treatment Schedule ; Urinary Incontinence ; Vacuum ; Vasodilator Agents ; Vasodilating Agent ; Vasodilator Drugs ; Vasodilators ; Work ; nerve injury ; neural injury ; Investigational New Drug Application ; Injury ; injuries ; base ; dosage ; improved ; Procedures ; Site ; repaired ; repair ; Phase ; Biological ; Series ; Stromal Cell-Derived Factor 1 ; CXCL12 protein ; Chemokine (C-X-C Motif) Ligand 12 ; Pre-B Cell Growth Stimulating Factor ; SDF-1 ; SDF-1alpha ; Sdf1 protein ; hIRH ; stromal cell-derived factor-1alpha ; Individual ; Dyslipidemias ; Erectile dysfunction ; uptake ; CXCR4 Receptors ; C-X-C Chemokine Receptor Type 4 ; CD184 Antigen ; Chemokine (C-X-C Motif) Receptor 4 ; Chemokine, CXC Motif, Receptor 4 ; Fusin ; LESTR Receptor ; LPS-Associated Protein 3 ; Leukocyte-Derived Seven-Transmembrane Domain Receptor ; Lipopolysaccharide-Associated Protein 3 ; Neuropeptide Y Receptor Y3 ; SDF-1 Receptor ; SDF1/PBSF Receptor CXCR4 ; Spleen Seven-Transmembrane-Segment Receptor ; Stromal Cell-Derived Factor 1 Receptor ; Randomized Controlled Trials ; chemokine ; Chemotactic Cytokines ; Homologous Chemotactic Cytokines ; Intercrines ; SIS cytokines ; chemoattractant cytokine ; angiogenesis ; Oral ; Clinic ; restoration ; American ; Lytotoxicity ; cytotoxicity ; Performance ; Viagra ; novel ; Drug Interactions ; Modality ; Devices ; Coding System ; Code ; neurogenesis ; Modeling ; Early-Stage Clinical Trials ; Phase 1 Clinical Trials ; phase I protocol ; Phase I Clinical Trials ; Cialis ; Levitra ; vardenafil ; Molecular Interaction ; Binding ; Address ; Dose ; Symptoms ; Data ; Economic Burden ; pre-clinical testing ; Preclinical Testing ; in vivo ; Apoptotic ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; safety study ; Pathway interactions ; pathway ; healing ; injured ; design ; designing ; drug distribution ; Prostate Cancer therapy ; Prostate CA therapy ; prostate cancer treatment ; regenerative therapy ; regeneration based therapy ; regeneration therapy ; regenerative therapeutics ; minimally invasive ; regenerative ; clinical infrastructure ; Growth Factor ; Growth Agents ; Growth Substances ; Proteins Growth Factors ; efficacy study ; Injections ; side effect ; COVID-19 vaccine ; 2019-nCoV vaccine ; COVID19 vaccine ; SARS-CoV-2 vaccine ; SARS-CoV2 vaccine ; SARS-coronavirus-2 vaccine ; Severe Acute Respiratory Syndrome CoV 2 vaccine ; Severe acute respiratory syndrome coronavirus 2 vaccine ; corona virus disease 2019 vaccine ; coronavirus disease 2019 vaccine ; vaccine against 2019-nCov ; vaccine against SARS-CoV-2 ; vaccine against SARS-CoV2 ; vaccine against SARS-coronavirus-2 ; vaccine against Severe Acute Respiratory Syndrome CoV 2 ; vaccine against Severe acute respiratory syndrome coronavirus 2 ; vaccine for novel coronavirus ; stem cell migration ;
