Alzheimer's Disease Research Program
Alzheimer’s disease is a neurodegenerative disorder that leads to progressive memory loss and death.
We are testing Lomecel-B as a potential treatment for AD based on the hypothesis that its multiple possible MOAs can simultaneously address multiple features of AD. Preclinical studies show that MSCs can potentially reduce AD-associated brain inflammation, improve the function of blood vessels in the brain, and reduce brain damage due to AD progression, and promoteregenerative responses. We have completed a multicenter, randomized, placebo-controlled Phase 1 safety study of subjects with mild AD (n=33) designed to evaluate safety and tolerability, and to explore potential efficacy. This trial was supported by a Part the Cloud grant from the Alzheimer’s Association. Based on preliminary results, we intend to initiate a larger Phase 2 study. If successful in clinical studies, we hope that Lomecel-B may prove to be a disease-modifying therapy for AD.
Protocol ID 00-0000-01: A Phase I, Prospective, Randomized, Double-Blinded, Placebo-controlled Trial to Evaluate the Safety and Potential Efficacy of Lomecel-B Infusion Versus Placebo in Patients with Alzheimer’s Disease
o Primary Trial Objective: To evaluate the safety and tolerability of Lomecel-B.
o Exploratory Efficacy Endpoints:
o Neurocognitive tests:
• Trail Making Test A&B
• Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 11)
• Geriatric Depression Scale (GDS)
• Neuropsychological Inventory (NPI)
• University of Pennsylvania Smell Identification Test (UPSIT)
• Mini Mental State Exam (MMSE)
o Inflammatory and Alzheimer’s disease-specific biomarkers,
o Quality of life assessments
o Brain volumetry.
o Dose: Single intravenous infusion of Lomecel-B 20 million cells, Lomecel-B 100 million cells or Placebo
o Follow-up: 52 weeks post-infusion
Aging Frailty Research Program
Aging Frailty is a common geriatric condition that disproportionately increases a patient’s risk for poor clinical outcomes due to disease and injury, and is widely believed by geriatricians to ultimately be treatable. Our multinational interventional Aging Frailty clinical research program is one of the most advanced and extensive in the world for a pharmaceutical investigational product. According to various studies by leading geriatricians, Aging Frailty affects approximately 15% of individuals 65 years and older, which translates to roughly 8.1 million people in the U.S. alone. Yet, no medical treatments for Aging Frailty have been approved by the FDA, or anywhere in the world.
o U.S. Trials: We have two U.S. clinical trials ongoing in Aging Frailty subjects to assess whether Lomecel-B can improve physical function, reduce inflammation, and improve quality of life, among other endpoints, and to evaluate if Lomecel-B can be an effective vaccine adjuvant to improve immunity against influenza. Data from both frailty trials are expected in the second half of 2021.
o Japan Clinical Trial: The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) has approved a Clinical Trial Notification (CTN), which is equivalent to a U.S. IND, allowing us to sponsor an investigator-initiated Phase 2 clinical study for Aging Frailty subjects in Japan. We expect to initiate this trial in 2021.
o The Bahamas Registry Trial: We sponsor a Registry Trial in Nassau, The Bahamas, where eligible participants may receive Lomecel-B for Aging Frailty and other indications, at their own expense.
Frail individuals have an increased risk of poor clinical outcomes such as hospitalization, dependency, disability and/or death. Signs and symptoms of frailty include reduced activity, slowness, involuntary weight loss, weakness, and fatigue. Additionally, there is a connection between frailty and chronic inflammation in the body. Frail elderly patients place significant demand for healthcare services and there are no approved therapeutics for the condition.
CLINICAL TRIAL ID# NCT03169231
Protocol 001-03: A Phase 2b, Randomized, Blinded and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B Infusion in Patients With Aging Frailty
We are evaluating the safety and efficacy of Lomecel-B in Aging Frailty in a prospective 150 subject Phase 2b trial. The primary objective of this study is to determine whether intervention with Lomecel-B has a beneficial effect on functional mobility and exercise tolerance compared to placebo in patients with Aging Frailty. This trial is supported by a grant from the NIH’s National Institute on Aging.
This trial has completed enrollment and subjects are in follow-up.
o Primary Efficacy Endpoint: The change from baseline in 6-minute walk test distance compared to placebo at 180 days post-infusion.
o Other secondary efficacy endpoints:
• Physical function, mobility and upper body strength patient reported outcomes (PROs)
• Short Physical Performance Battery (SPPB), grip strength, walking speed
• Frailty status
• Tinetti Performance Oriented Mobility Assessment (POMA) score
• Fear and risk of falling
• Inflammatory biomarkers.
• Cognitive function; depression
• Sexual function
• Incidence of the following clinical outcomes: falls, fractures, admissions to healthcare facility (e.g. assisted-living facility, nursing home, long-term care facility, etc.), hospitalizations, and death.
o Dose: Single intravenous infusion of Lomecel-B 25 million cells, Lomecel-B 50 million cells, Lomecel-B 100 million cells, Lomecel-B 200 million cells, or Placebo.
o Follow-up: 52 weeks post infusion
CLINICAL TRIAL ID# NCT02982915
Protocol ID 00-0000-03: Effects of Intravenous Delivery of Lomecel-B on Vaccine-Specific Antibody Responses in Subjects with Aging Frailty: The HERA Trial
Frailty is associated with a decreased immune response, which means that your body’s ability to fight off infections decreases, and your body’s ability to respond positively to vaccination, such as the influenza vaccine, decreases. The purpose of this study is to measure the safety of treatment with Lomecel-B to improve vaccine response in patients with Aging Frailty (Phase 1 n=22; Phase 2 n=39).
o Primary Efficacy Endpoint: Change from baseline in hemagglutination inhibition (HAI) assay in Lomecel-B group compared to placebo.
o Secondary efficacy endpoints:
• Immune-response as measured by levels of influenza virus-specific antibody production given in Index Value (IV) units.
• Proportion of subjects with influenza virus-specific antibodies ≥ 1.1 IV units.
• Changes in the Geometric Mean Titer (GMT) determined by HAI assay performed against the various flu strains on this study.
• The proportion of subjects with a GMT change from baseline that is ≥ 4-fold (≥ 300%) at each time-point.
• Change in 6-Minute Walk Test (6MWT) distance from baseline and for the Lomecel-B arms versus the change in placebo.
o Exploratory Endpoints:
• T-cell & B-cell function
• Frailty status (CSHA Clinical Frailty Scale)
• Physical function (SPPB, POMA, handgrip strength)
• Patient-reported outcomes (physical function, upper body strength, sexual function)
• Prevention of illness caused by influenza
• All-cause mortality
o Dose: Single intravenous infusion of Lomecel-B 100 million cells or Placebo.
o Follow-up: 52 weeks post infusion
Metabolic Syndrome Research Program
We are conducting a sub-study of our Aging Frailty program to evaluate whether Lomecel-B may improve the symptoms of the Metabolic Syndrome, and the effects of this comorbidity on response to treatment in Aging Frailty subjects. Top-line results are expected in the second half of 2021, as we receive data from our two Aging Frailty trials.
Protocol ID 00-0002-03: Evaluation of the Safety and Efficacy of Lomecel-B in the Treatment of Aging Frailty Patients with The Metabolic Syndrome
The purpose of this study is to measure the safety of treatment with Lomecel-B in patients with the Metabolic Syndrome, and to explore the benefits of treatment on symptoms of the Syndrome.
The Metabolic Syndrome is a well-documented and insidious condition which, over the course of years to decades, leads to cardiovascular disease and type II diabetes mellitus. The Metabolic Syndrome is defined as a cluster of conditions that include high blood pressure, high blood sugar, excess body fat and abnormal cholesterol or triglyceride levels. There are no approved therapies for the Metabolic Syndrome, aside from symptomatic treatments. The incidence of this syndrome has reached epidemic proportions and is estimated to impact approximately 35% of the total U.S. population aged 18 and older, or over 80 million people.
Hypoplastic Left Heart Syndrome Research Program
HLHS is a severe congenital birth defect in which the left ventricle of the heart is either severely underdeveloped or missing. As a consequence, babies born with this condition have severely diminished systemic blood flow, which requires children to undergo a complex, three stage heart reconstruction surgery process over the course of the first 5 years of their lives. While these children can now live into adulthood, early mortality is still extremely high in this population due to right ventricle failure, which is not meant for the increased load demanded for systemic circulation. As such, there is an important unmet medical need to improve right ventricular function in these patients to improve both short-term and long-term outcomes.
We are testing Lomecel-B as a potential combinatorial therapy candidate to surgical intervention for HLHS. The scientific goal underlying this study builds on surgical advances of the past thirty years, and is intended to address remaining obstacles to improving long-term cardiac function in HLHS patients. The Phase 1 trial has completed enrollment and the subjects remain in follow up.
Protocol ID 00-0000-05: Lomecel-B Delivered During Stage II Surgery for Hypoplastic Left Heart Syndrome (ELPIS) (n=10)
o Primary Outcome Measures: Safety and feasibility of intramyocardial injection of Lomecel-B during the Stage II (BDCPA) operation for HLHS.
o Secondary Efficacy Endpoints:
• Right ventricular ejection fraction (%)
• Right ventricular end-systolic and end-diastolic volume
• Right ventricular end-diastolic diameter
• Tricuspid regurgitation
• Efficacy: Change in height (in centimeters).
o Dose: 2.5 x 105 cell/kg recipient body weight delivered intramyocardially
o Follow-up: 52 weeks post-injection
Acute Respiratory Distress Syndrome Research Program
Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that prevents enough oxygen from getting to the lungs and into the blood. People who develop ARDS often are very ill with another disease or have major injuries. The condition leads to a buildup of fluid in the air sacs which prevents enough oxygen from passing into the bloodstream. Symptoms may include difficulty breathing, low blood pressure and organ failure, rapid breathing and shortness of breath.
ARDS occurs in about 150,000 patients per year, can result in both short-term severe consequences (e.g., prolonged and expensive hospitalization, and death), and long-term debilitating consequences (e.g., severe lung fibrosis and pulmonary dysfunction). ARDS due to viral infection is particularly devastating to those with Aging Frailty, and is especially well-appreciated in the context of the COVID-19 pandemic, in which approximately 80% of deaths have occurred in people aged 65 and older. There are currently limited treatment options for ARDS beyond supportive palliative care, making ARDS a “rare disease or condition” under the FDA’s Orphan Drug Act definition, and an extremely important unmet medical need.
Protocol ID 000-06: Regenerative Medicine for COVID-19 and Flu-Elicited ARDS Using Lomecel-B (RECOVER Trial) (n=70; 35 due to COVID-19 & 35 due to Influenza Infection)
o Primary Outcome Measures:
• Safety: Incidence of treatment-emergent serious adverse events (TE-SAEs) within 4 weeks after treatment.
• Efficacy: Time to recovery of Sp02 to 90% or higher on room air (or the oxygen concentration the patient had before acute illness) after 10 minutes of spontaneous breathing.
o Secondary Efficacy Endpoints:
• Post-infection recovery and 4-week survival
• Rate of intubation and duration of intubation (when applicable).
• Time to recovery from mechanical ventilation
• Time to restore normal temperature from fever
• Sequential Organ Failure Assessment (SOFA)
• Length of hospital stay
• Serum biomarkers
• Evaluation of lymphocytopenia.
• Number of day’s alive and not requiring invasive mechanical ventilation in the first 28 days following treatment.
• Other endpoints not listed
o Dose: Up to 3 doses of Lomecel-B 100 million cells or Placebo
o Follow Up: 6 months post initial infusion