SBIR-STTR Award

Symptomatic gallstone disease affects nearly 5 million people in the United States and consumes over $6.3B annually. Complications occur when gallstones move from the wide body of the gallbladder and enter the narrow system of ducts connecting the gallbladder to the small intestine. The incidence of gallstones increases with age and is higher in women and obese people. Other risk factors include pregnancy, hormone replacement therapy, rapid weight loss, diabetes, Crohn's disease, family history, older age, and prolonged fasting. As Western-style diets gain traction across the globe, the worldwide rate of gallstone disease is rising quickly in areas where surgical treatment is not always available. The most common and effective treatment for gallstone disease today is surgical removal of the gallbladder, or cholecystectomy. Unfortunately, surgery is not always an option. Patients may be unable to tolerate surgery due to comorbidities such as uncontrolled heart or lung diseases which make general anesthesia impossible or they have temporary conditions which delay surgery, for example a recent heart attack, stroke, or sepsis. The risk of a recurrent gallstone-related complication increases with waiting time and patients with a surgical contraindication or scheduling delays are subject to increasing risk of developing gallstone-related complications. Acute cholecystitis can force a decision to perform emergency surgery in these patients with very high mortality and morbidity risks. Kōli has developed a non-surgical alternative to treat gallstone disease. A small implantable filter is deployed in the gallbladder to prevent complications associated with gallstones obstructing the outlet of the organ. Kōli replaces surgery with a minimally invasive outpatient procedure designed to be safe in high risk patients, including the elderly, pregnant women, and patients with recent MI, stroke, or surgery. Kōli fits into existing referral and reimbursement patterns, would utilize conventional ultrasound and fluoroscopic techniques, and will be performed by interventional radiology, gastroenterology, or general surgery. The company's technology was developed with support from an NSF SBIR award (#1248295) and private investment. Over the past 5 years, Kōli has advanced their novel gallstone filtering system from proof-of-concept bench testing, GLP-like large animal studies, and recently completed a successful first-in-human clinical feasibility study in the Philippines. The current iteration of the Kōli system relies on sharp barbed anchors to penetrate the luminal wall of the gallbladder and hold the self-expanding filter in place. Penetrating anchors carry risks associated with perforation, scarring, and mechanical failure. Once deployed, the anchored device cannot be removed without surgery. To address these risks, Kōli has partnered with Hoowaki, LLC to integrate a novel anti-migration micro surface into our filtering system in place of barbed anchors. This approach will eliminate risks associated with the current anchors and the filtering system will be easier to manufacture, easier to deploy, and completely removable up to months after placement. This project represents the first time a micro surfaced implant will be used in the biliary system and a starting point for a number of innovative applications in gastroenterology. This Direct to Phase II award will fund advanced development of the filtering system, including incorporation of an innovative micro surface textured coating to replace the current barbed metal anchors, integration of radiopaque tantalum markers, and validation of the updated system in bench and large animal studies Completion of these activities will allow the company to begin pre-submission discussions with FDA for an early feasibility study that will form the basis of a Phase IIB application.

Public Health Relevance Statement:
Gallstones are present in up to 25% of adults. Approximately 1% to 4% of people with gallstones develop symptoms and complications such as acute cholecystitis, obstructive jaundice, or pancreatitis. Surgery is currently the only definitive solution. Unfortunately, a timely operation is not always an option. Patients may be unable to tolerate surgery due to other medical conditions and risk the chance of a recurrence while surgery is delayed. Kōli is a medical device company developing a novel implantable device to prevent recurrent obstruction in patients with gallstone disease without surgery. This Direct to Phase II award will fund advanced development of the filtering system, including incorporation of an innovative micro surface textured coating to replace the current barbed metal anchors, integration of radiopaque tantalum markers, and validation of the updated system in bench and large animal studies.

Project Terms:
Abdominal Pain; 21+ years old; Adult Human; adulthood; Adult; Affect; ages; Age; advanced age; elders; geriatric; late life; later life; older adult; older person; senior citizen; Elderly; General Anesthesia; Animals; Antibiotic Agents; Antibiotic Drugs; Miscellaneous Antibiotic; Antibiotics; Award; Bile fluid; Bile; Bile Juice; biliary tract; Bile Tract; Biliary System; Biliary Tree; Capital; Cholecystectomy; gallbladder removal; Cholelithiasis; Gallbladder Calculus; Gallbladder Stone; Gallstones; cholelith; Cholesterol; Cicatrix; Scars; comorbidity; co-morbid; co-morbidity; Complication; Crohn's disease; Crohn disease; Crohn's; Crohn's disorder; Granulomatous Enteritis; eleocolitis; regional enteritis; Diabetes Mellitus; diabetes; Emergency Situation; Emergencies; Family; Fasting; fasted; fasts; Feasibility Studies; Fluoroscopy; Gallbladder; Gall Bladder; Gallbladder / Biliar; Gallbladder/Biliary system; Gastroenterology; Heart Diseases; Cardiac Diseases; Cardiac Disorders; heart disorder; Recording of previous events; History; histories; implantable device; biomedical implant; implant device; indwelling device; Incidence; Infection; Inflammation; Small Intestines; small bowel; Investments; Obstructive Jaundice; Cholestatic Jaundice; Mechanical Jaundice; Obstructive hyperbilirubinemia; Lung diseases; Pulmonary Diseases; Pulmonary Disorder; disease of the lung; disorder of the lung; lung disorder; Medical Device; Metals; Morbidity - disease rate; Morbidity; mortality; Myocardial Infarction; Cardiac infarction; Myocardial Infarct; cardiac infarct; coronary attack; coronary infarct; coronary infarction; heart attack; heart infarct; heart infarction; Persons; Neck; Obstruction; Outpatients; Out-patients; Pancreatitis; Legal patent; Patents; Patients; Philippines; Philipines; Phillipines; Phillippines; Polyurethanes; Ostamer; Pellethane; Polyisocyanates; Pregnancy; Gestation; Pregnant Women; expectant mother; expecting mother; pregnant mothers; Privatization; Interventional radiology; Recurrence; Recurrent; Risk; Risk Factors; Safety; Stroke; Apoplexy; Brain Vascular Accident; Cerebral Stroke; Cerebrovascular Apoplexy; Cerebrovascular Stroke; brain attack; cerebral vascular accident; cerebrovascular accident; stroked; strokes; Tantalum; Ta element; Technology; Testing; Time; Tissues; Body Tissues; Traction; United States; Vomiting; Emesis; Body Weight decreased; Weight Loss; Weight Reduction; body weight loss; wt-loss; Woman; Work; Film; Schedule; Acute Cholecystitis; Organ; Procedures; Area; Surface; Chronic; Solid; Clinical; Penetration; Phase; Medical; Series; Grips; grasp; Failure; Funding; radiologist; Hormone Replacement Rx; Hormone replacement therapy; Life; programs; Mechanics; mechanic; mechanical; Texture; Pattern; Techniques; System; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Perforation; human old age (65+); 65+ years old; Aged 65 and Over; age 65 and greater; age 65 and older; aged 65 and greater; aged ≥65; old age; Performance; Histopathology; novel; Duct (organ) structure; Duct; Devices; Reporting; Patient observation; Watchful Waiting; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; Positioning Attribute; Position; Modeling; Sampling; Adverse event; Adverse Experience; Intervention; Intervention Strategies; interventional strategy; preventing; prevent; Address; Symptoms; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Update; Validation; validations; Advanced Development; designing; design; blood infection; bloodstream infection; Sepsis; Consumption; migration; innovate; innovative; innovation; Implant; prototype; commercialization; high risk; minimally invasive; common treatment; effective treatment; effective therapy; clinical practice; adverse consequence; adverse outcome; operations; operation; western-style diet; western-type diet; western diet; Wait Time; first in man; first-in-human; gallstone disease; obese individuals; obese people; obese population; obese subjects; obese person; pig model; piglet model; swine model; porcine model; ultrasound; manufacture

Symptomatic gallstone disease affects nearly 5 million people in the United States and consumes over $6.3B annually. Complications occur when gallstones move from the wide body of the gallbladder and enter the narrow system of ducts connecting the gallbladder to the small intestine. The incidence of gallstones increases with age and is higher in women and obese people. Other risk factors include pregnancy, hormone replacement therapy, rapid weight loss, diabetes, Crohn's disease, family history, older age, and prolonged fasting. As Western-style diets gain traction across the globe, the worldwide rate of gallstone disease is rising quickly in areas where surgical treatment is not always available. The most common and effective treatment for gallstone disease today is surgical removal of the gallbladder, or cholecystectomy. Unfortunately, surgery is not always an option. Patients may be unable to tolerate surgery due to comorbidities such as uncontrolled heart or lung diseases which make general anesthesia impossible or they have temporary conditions which delay surgery, for example a recent heart attack, stroke, or sepsis. The risk of a recurrent gallstone-related complication increases with waiting time and patients with a surgical contraindication or scheduling delays are subject to increasing risk of developing gallstone-related complications. Acute cholecystitis can force a decision to perform emergency surgery in these patients with very high mortality and morbidity risks. Kōli has developed a non-surgical alternative to treat gallstone disease. A small implantable filter is deployed in the gallbladder to prevent complications associated with gallstones obstructing the outlet of the organ. Kōli replaces surgery with a minimally invasive outpatient procedure designed to be safe in high risk patients, including the elderly, pregnant women, and patients with recent MI, stroke, or surgery. Kōli fits into existing referral and reimbursement patterns, would utilize conventional ultrasound and fluoroscopic techniques, and will be performed by interventional radiology, gastroenterology, or general surgery. The company's technology was developed with support from an NSF SBIR award (#1248295) and private investment. Over the past 5 years, Kōli has advanced their novel gallstone filtering system from proof-of-concept bench testing, GLP-like large animal studies, and recently completed a successful first-in-human clinical feasibility study in the Philippines. The current iteration of the Kōli system relies on sharp barbed anchors to penetrate the luminal wall of the gallbladder and hold the self-expanding filter in place. Penetrating anchors carry risks associated with perforation, scarring, and mechanical failure. Once deployed, the anchored device cannot be removed without surgery. To address these risks, Kōli has partnered with Hoowaki, LLC to integrate a novel anti-migration micro surface into our filtering system in place of barbed anchors. This approach will eliminate risks associated with the current anchors and the filtering system will be easier to manufacture, easier to deploy, and completely removable up to months after placement. This project represents the first time a micro surfaced implant will be used in the biliary system and a starting point for a number of innovative applications in gastroenterology. This Direct to Phase II award will fund advanced development of the filtering system, including incorporation of an innovative micro surface textured coating to replace the current barbed metal anchors, integration of radiopaque tantalum markers, and validation of the updated system in bench and large animal studies Completion of these activities will allow the company to begin pre-submission discussions with FDA for an early feasibility study that will form the basis of a Phase IIB application.

Public Health Relevance Statement:
Gallstones are present in up to 25% of adults. Approximately 1% to 4% of people with gallstones develop symptoms and complications such as acute cholecystitis, obstructive jaundice, or pancreatitis. Surgery is currently the only definitive solution. Unfortunately, a timely operation is not always an option. Patients may be unable to tolerate surgery due to other medical conditions and risk the chance of a recurrence while surgery is delayed. Kōli is a medical device company developing a novel implantable device to prevent recurrent obstruction in patients with gallstone disease without surgery. This Direct to Phase II award will fund advanced development of the filtering system, including incorporation of an innovative micro surface textured coating to replace the current barbed metal anchors, integration of radiopaque tantalum markers, and validation of the updated system in bench and large animal studies. Terms: <21+ years old; 65 and older; 65 or older; 65 years of age and older; 65 years of age or more; 65 years of age or older; 65+ years; 65+ years old; > 65 years; Abdominal Pain; Abscission; Acute Cholecystitis; Address; Adult; Adult Human; Advanced Development; Adverse Experience; Adverse event; Affect; Age; Aged 65 and Over; Animals; Antibiotic Agents; Antibiotic Drugs; Antibiotics; Apoplexy; Area; Award; Bile; Bile Juice; Bile Tract; Bile fluid; Biliary System; Biliary Tree; Body Tissues; Body Weight decreased; Brain Vascular Accident; Capital; Cardiac Diseases; Cardiac Disorders; Cardiac infarction; Cerebral Stroke; Cerebrovascular Apoplexy; Cerebrovascular Stroke; Cholecystectomy; Cholelithiasis; Cholestatic Jaundice; Cholesterol; Chronic; Cicatrix; Clinical; Complication; Consumption; Crohn disease; Crohn's; Crohn's disease; Crohn's disorder; Devices; Diabetes Mellitus; Duct; Duct (organ) structure; Elderly; Emergencies; Emergency Situation; Emesis; Excision; Extirpation; Failure; Family; Fasting; Feasibility Studies; Film; Fluoroscopy; Funding; Gall Bladder; Gallbladder; Gallbladder / Biliar; Gallbladder Calculus; Gallbladder Stone; Gallbladder/Biliary system; Gallstones; Gastroenterology; General Anesthesia; Gestation; Granulomatous Enteritis; Grips; Heart Diseases; Histopathology; History; Hormone Replacement Rx; Hormone replacement therapy; Implant; Incidence; Infection; Inflammation; Intervention; Intervention Strategies; Interventional radiology; Investments; Legal patent; Life; Lung Diseases; Mechanical Jaundice; Mechanics; Medical; Medical Device; Metals; Miscellaneous Antibiotic; Modeling; Morbidity; Morbidity - disease rate; Myocardial Infarct; Myocardial Infarction; Neck; Obstruction; Obstructive Jaundice; Obstructive hyperbilirubinemia; Operative Procedures; Operative Surgical Procedures; Organ; Ostamer; Out-patients; Outpatients; Pancreatitis; Patents; Patient observation; Patients; Pattern; Pellethane; Penetration; Perforation; Performance; Persons; Phase; Philipines; Philippines; Phillipines; Phillippines; Polyisocyanates; Polyurethanes; Position; Positioning Attribute; Pregnancy; Pregnant Women; Privatization; Procedures; Pulmonary Diseases; Pulmonary Disorder; Recording of previous events; Recurrence; Recurrent; Removal; Reporting; Risk; Risk Factors; SBIR; Safety; Sampling; Scars; Schedule; Sepsis; Series; Small Business Innovation Research; Small Business Innovation Research Grant; Small Intestines; Solid; Stroke; Surface; Surgical; Surgical Interventions; Surgical Procedure; Surgical Removal; Symptoms; System; Ta element; Tantalum; Techniques; Technology; Testing; Texture; Time; Tissues; Traction; United States; Update; Validation; Vomiting; Wait Time; Watchful Waiting; Weight Loss; Weight Reduction; Woman; Work; above age 65; adulthood; advanced age; adverse consequence; adverse outcome; after age 65; age 65 and greater; age 65 and older; age 65 or older; age > 65; age of 65 years onward; aged 65 and greater; aged 65+; aged ≥65; ages; biliary tract; biomedical implant; blood infection; bloodstream infection; body weight loss; brain attack; cardiac infarct; cerebral vascular accident; cerebrovascular accident; cholelith; clinical practice; co-morbid; co-morbidity; commercialization; common treatment; comorbidity; coronary attack; coronary infarct; coronary infarction; design; designing; diabetes; disease of the lung; disorder of the lung; effective therapy; effective treatment; eleocolitis; expectant mother; expecting mother; fasted; fasts; first in man; first-in-human; gallbladder removal; gallstone disease; geriatric; grasp; heart attack; heart disorder; heart infarct; heart infarction; high risk; histories; human old age (65+); implant device; implantable device; indwelling device; innovate; innovation; innovative; interventional strategy; lung disorder; manufacture; mechanic; mechanical; migration; minimally invasive; mortality; novel; obese individuals; obese people; obese person; obese population; obese subjects; old age; operation; operations; over 65 years; pig model; piglet model; porcine model; pregnant mothers; prevent; preventing; programs; prototype; radiologist; regional enteritis; resection; senior citizen; small bowel; stroked; strokes; surgery; swine model; ultrasound; validations; western diet; western-style diet; western-type diet; wt-loss; ≥65 years