Vascarta is currently clinically focused on two conditions with great unmet medical need: Sickle Cell Disease and Osteoarthritis. The following table shows the development stage for Sickle Cell Disease and Osteoarthritis programs.
VASCARTA CLINICAL DEVELOPMENT STATUS BY HEALTH CONDITION
| Drug Candidate | Indication | Development Status | ||||
| Research | IND enabling | Phase I | Phase II | Phase III | ||
| Vasceptor® (VAS-101) | Sickle Cell Disease | |||||
| Vasceptor® (VAS-101) | Osteoarthritis | |||||
Sickle Cell Disease
Background
- Sickle Cell Disease (SCD) is the most common inherited disease that primarily affects African Americans and Hispanics in the United States. Individuals with SCD may experience serious health complications such as chronic pain, stroke, lung problems, eye problems, infections, and kidney disease, along with periodic acute pain crises.
- SCD affects about 175,000 people in the USA and 45,000 in European Union countries. The estimated life expectancy of those with sickle cell disease in the USA is more than 20 years shorter than the average expected lifespan.
- Beyond the U.S. and Europe, SCD affects millions of people throughout the world, being most common in Sub-Saharan Africa, South America, Caribbean & Central America, Saudi Arabia, India, Turkey, Greece, and Italy.
- The medical needs of many sickle cell sufferers remain unmet.
Vasceptor® shows promise in addressing limitations of currently available FDA Sickle Cell Disease therapies because it:
- Prevents/reduces sickling of red blood cells.
- Enhances tissue oxygenation.
- Relieves pain.
- Reduces systemic inflammation.
- Stabilizes red blood cells.
- Limits organ damage.
- Prophylactically prevents vaso-occlusive crisis.
- Limits oxidative damage.
- Prevents mitochondrial dysfunction.
- Prevents and reverses endothelial dysfunction.
- Enhances nitric oxide production in the vasculature.
- Does not alter hemoglobin oxygen binding properties.
- Curcumin is FDA recognized as a Generally Recognized As Safe (GRAS) ingredient.
- Safe and easy to use for patients of all ages.
Vascarta Sickle Cell Disease Research – Selected Key Findings
- An article published in the Proceedings of the National Academy of Sciences (PNAS) Nexus journal describes studies in which humanized sickle cell mice topically treated with Vasceptor® experienced reduced pain and inflammation and reduced nerve damage along with improved red blood cell stability and functionality.
- “Targeting sickle cell pathobiology and pain with novel transdermal curcumin”
- Pain is a central characteristic of SCD. As shown below in Chart C, in cold conditions, male mice treated with Vasceptor® became less sensitive to painful stimulation within 1 hour post treatment, while female mice treated with Vasceptor® (chart D) became less sensitive to painful stimulation at 14 days. In room temperature conditions, female mice treated with Vasceptor® (Chart B) became less sensitive to painful stimulation at 10 days and male mice at 14 days (Chart A).
Sickle Mice Treated With Vasceptor® Have Less Pain
(Note – “PWF” is Paw Withdrawal Frequency in response to painful stimulation – a common pain measurement)
Statistical Significance levels: *† P < 0.05; **†† P < 0.01; ***††† P < 0.001
The PNAS Nexus publication also describes that the application of Vasceptor® significantly deactivated granulated mast cells (MC), which are significant indicators of inflammation and contributors to chronic pain.
Sickle Mice Treated With Vasceptor® Have Fewer Degranulated Mast Cells (MC), Indicators of Inflammation and Contributors to Chronic Pain
Statistical Significance levels: *P < 0.05; **P < 0.01; ***P < 0.001.
Nerve damage is another characteristic of SCD. The PNAS Nexus publication further describes that application of Vasceptor® reverses nerve damage which was induced in the treated mice by applying TNF-α+hemin (T + H). As shown below, when T+H is applied, the number of nerve (neurite) connections (intersections) is greatly reduced. However, usage of Vasceptor® (“Curc”) restored the number of nerve connections, even when combined with the nerve damaging T+H.
Vasceptor® Reverses Nerve Damage in Sickle Mice
Tissue Oxygenation at Baseline (BL) and under 3 scenarios
Statistical Significance levels: ***P < 0.001; ****P < 0.0001.
An additional characteristic of SCD is that it results in lower oxygen concentration in body tissues. In a not yet published study conducted by Song Biotechnologies (data on file at Vascarta), rats received an exchange transfusion (“ET”) of human sickle blood cells designed to reduce tissue oxygenation. The oxygenation of the rat tissue was measured at baseline (“BL”) before ET, and then under 3 different scenarios.
- In the “Sham” group, no Vasceptor® was applied to rats.
- In the Pre-treatment group, Vasceptor® was applied to rats 30 minutes before ET.
- In the Treatment scenario, Vasceptor® was applied to rats at the same time as ET.
As shown below, in the Sham group, tissue oxygenation dropped substantially as predicted. When Vasceptor® was applied at the same time as the exchange transfusion, tissue oxygenation dropped, but by a lesser amount compared to the Sham group. Importantly, when Vasceptor® was prophylactically applied 30 minutes before ET, tissue oxygenation increased even beyond the levels seen before the sickle cell blood was transfused. This is a very promising finding.
Vasceptor® Improves Tissue Oxygenation in Sickle Cell Blood
Tissue Oxygenation at Baseline (BL) and under 3 scenarios
Statistical Significance is achieved when the error bars from Sham (black color) do NOT overlap with error bars in Vasceptor® treatment (blue and green colors)
Sickle Cell Disease - Pilot Phase 1 Clinical Study
- Based on the findings above and other favorable pre-clinical results, a pilot clinical trial using Vasceptor® (VAS-101) in individuals with SCD is being conducted by the Foundation for Sickle Cell Disease and Research [FSCDR (Hollywood, Florida, USA)]. Patients will be treated with VAS-101 via the topical and sublingual routes of administration. The key clinical endpoints are shown below:
Primary Study Objectives:
- To assess the safety and tolerability of VAS-101.
- To assess the effect(s) of VAS-101 on impaired blood flow dynamics, including adhesion molecule expression and erythrocyte fragility parameters.
Secondary Study Objectives:
- To evaluate the effect of VAS-101 on inflammatory markers associated with the activation of sterile inflammation over 28 days.
- To determine the mean change in red blood cell sickling kinetics and oxygen dissociation curves.
- To assess the pain-relieving benefit/opioid sparing effect of VAS-101.
Osteoarthritis
Disease Background
- Osteoarthritis is a chronic condition that causes joint pain, stiffness, and swelling. It’s the most common type of arthritis and affects the cartilage and bone in joints.
- Roughly 32.5 million U.S. adults have osteoarthritis, and about 500 million adults globally. Osteoarthritis is the leading cause of disability among U.S. adults.
- The medical needs of many osteoarthritis patients remain unsatisfied, particularly among those sensitive to the potential cardiovascular and gastrointestinal bleeding side effects of non-steroidal anti-inflammatory drugs (NSAIDs such as Ibuprofen), the liver and kidney toxicity concerns of acetaminophen, and/or the addiction and overdose concerns of opioids.
Rationale for using Vasceptor® to address Osteoarthritis –
- Curcumin is an anti-inflammatory compound often used to treat pain-related conditions, including osteoarthritis (OA). In a recent meta-analysis, it was concluded that based on the results of 23 studies and 2175 patients with knee OA, compared to a placebo, the oral administration of curcumin reduced self-reported pain as measured by the visual analogue scale pain score, and Western Ontario and McMaster Universities Arthritis Index. Moreover, compared with NSAIDs, curcumin alone and curcumin + NSAIDs (OR = 0.23, 95% CI: 0.06 to 0.9) had a reduced incidence of adverse reactions.
- Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis
- Although effectiveness against OA has been seen with curcumin taken orally, the therapeutic benefits of oral curcumin are limited due to its poor bioavailability (e.g., poorly absorbed; rapidly excreted) providing a clear rationale to topically/transdermally test Vasceptor® against OA. For example, in an unpublished study, curcumin was not detected in blood or plasma after the oral ingestion of curcumin; however, it was detected in blood for up to 6 hours after the transdermal delivery of Vasceptor®.
- Additional rationale for testing Vasceptor® include the many improvements in biomarkers of inflammation seen in rodent studies.
Vasceptor® reduces Plasma SAP, a key marker of systemic inflammation
In a published study https://pubmed.ncbi.nlm.nih.gov/38036015/, there was a significant reduction in Plasma SAP (Serum amyloid P-component), the rodent equivalent of C reactive protein for human beings, serving as a marker of systemic inflammation.
In a published study https://pubmed.ncbi.nlm.nih
.gov/38036015/, there was a significant reduction in Plasma SAP (Serum amyloid P-component – Chart A), the rodent equivalent of C reactive protein for human beings, serving as a marker of systemic inflammation.
Statistical Significance levels: *P < 0.05
In the same published study, as shown below, Vasceptor® significantly reduced inflammatory cytokines including IL-2, IL-4, IL-6, IL-17, MCP1, INF-γ, GM-CSF, and RANTES.
Vasceptor® reduces inflammation cytokines which play a role in osteoarthritis
Statistical Significance levels: *P < 0.05; **P < 0.01
Osteoarthritis - Phase 1, Randomized, Double-Blinded, Placebo-Controlled Clinical Study (60 Patients)
Primary Study Objective:
-
- To examine the safety and tolerability of applying VAS-101 or placebo on knee pain in adults with chronic knee osteoarthritis.
Secondary Study Objectives:
- To evaluate the effect of VAS-101 or placebo on:
- Knee osteoarthritis symptoms, quality of life and daily function.
- Change in the use of pain-relieving / rescue medication for knee pain.
- Type II collagen cleavage products (CTX-II).
Vasceptor® Safety & Bioavailability
STONG SAFETY
GRAS Status
Turmeric (curcumin) is generally recognized as safe by the US Food & Drug Administration as a nutritional product.
Animal Safety Study
Minipigs are frequently used in safety studies because they are similar to humans in many ways, including anatomy, physiology, and biochemistry. Moreover, Minipigs have skin that is similar to human skin, making them a good model for assessing topical products.
Vascarta’s studied the safety of its topical curcumin gel by applying it to Minipigs at two different doses for 7 consecutive days. The key conclusion from the study was that “No adverse systemic effects were noted”.
Human Safety Study
A randomized, double-blind, placebo-controlled human safety study of Vascarta’s topical/transdermal curcumin gel, formulated at higher curcumin levels than marketed products, demonstrated that it is well tolerated by healthy subjects, with no adverse effects. This safety trial was performed in accordance with ICH E6, Good Clinical Practice. The conclusion from this study was:
“Conclusion: Overall, Vascarta’s curcumin’s gel formulation demonstrated an excellent safety and tolerability profile. All adverse events were judged UNLIKELY related to the study drug by the investigator. The reported physiological data (blood pressures; brachial artery dilatation) further substantiated the safety of Vascarta’s curcumin formulation at the three (3) doses studied. Specifically, the 24-hour brachial artery dilatation results showed preliminary evidence of enhanced vascular compliance in healthy volunteers.”
BETTER BIOAVAILABILITY
Topical versus oral administration of curcumin was studied in rats:
- Probal Banerjee, Ph.D., Professor of Chemistry, Biochemistry, and Neuroscience The College of Staten Island (CUNY)
- 2 ml of curcumin administered (oral; topical)
- Custom extraction/HPLC protocol specifically designed for curcuminoids
- Pharmacokinetics in both plasma and blood cells
Results
- Orally delivered curcumin – No curcumin detectable in plasma or blood cells
- Topical/transdermal Vascarta curcumin – Curcumin still strongly available in blood cells after 6 hours
Red Blood Cell Preservation and Storage
Condition Background
- Having healthy red blood cells is essential to treating many disease conditions including anemia, sickle cell anemia, and acute injuries.
- In the United States, about 15 million red blood cell (RBC) units are transfused each year. Worldwide, about 85 million RBC units are transfused each year. It is typically a challenge to obtain enough high quality blood to meet these transfusion requirements.
Vascarta Red Blood Cell Preservation and Storage Research – Key Findings to Date
- Stored red blood cells can undergo biochemical and structural changes called storage lesions which reduce their safety, therapeutic efficacy, and circulation lifetime when transfused. Recently, scientists from the Food & Drug Administration’s Laboratory of Biochemistry and Vascular Biology at the Center for Biologics Evaluation and Research, along with colleagues from the University of California San Diego and Albert Einstein College of Medicine found that these storage lesions can be mitigated by adding Vasceptor ®to stored red blood cells.
- Scientific Reports : Biopreservation and reversal of oxidative injury during blood storage by a novel curcumin-based gel formulation
- As visualized below, this published study shows that addition of a single dose of Vasceptor® (Curcumin) to stored red blood cells reduces oxidative damage by about 50%. Note the reduction in Reactive Oxygen Species (ROS) in the 14-day curcumin group versus the 14-day control (Con) group:
Vasceptor® reduces oxidative damage in stored red blood cells
(Lower levelsre better)
- The addition of a single dose of Vasceptor® to stored red blood cells also increases ATP (adenosine triphosphate) by about 40%. ATP is crucial because not only is it the molecule which produces energy in our cells, it also helps maintain the health of our vascular system.
Vasceptor® increases beneficial ATP in stored red blood cells.
Statistical Significance levels: *P < 0.01 versus corresponding vehicle treated group
- The benefits shown by Vasceptor® in improving the health of red cells provided additional rationale for conducting human clinical testing of Vasceptor® in sickle cell disease.
Hypertension/High Blood Pressure
Disease Background
- Hypertension, also known as high blood pressure, is a chronic condition that occurs when the force of blood in your arteries is too high. It’s a common condition that can be serious if left untreated. Hypertension can increase your risk of heart disease and stroke, which are leading causes of death in the United States.
- According to the U.S. Centers for Disease Control (CDC), nearly 48% of U.S. adults had hypertension during August 2021–August 2023 (47.7%). The prevalence of hypertension increased with increasing age, with more than 70% of adults aged 60 and older having hypertension.
- The medical needs of many hypertension sufferers remain unsatisfied, since many common blood pressure medications can cause side effects like dizziness, drowsiness, headaches, nausea, fatigue, and sexual dysfunction, which can affect adherence to treatment plans.
Vascarta Hypertension Research – Key Findings to Date
- A key cause of hypertension is endothelial dysfunction, a condition where the inner lining of blood vessels (endothelium) does not function properly. Vascarta commissioned a study in which the blood vessel lining in rats was intentionally damaged causing leakage in the blood vessel. However, the application of Vasceptor® prevented the blood vessel damage and leakage:
Vasceptor® reduces blood vessel damage and leakage
- Directly measuring the blood pressure of rats treated with Vasceptor® shows a substantial reduction in blood pressure lasting for hours. If this finding ultimately holds in human beings, there would be a large benefit to reducing blood pressure without unwanted side effects.
Vasceptor® reduces blood pressure in rats hours
Anti-aging
Disease Background
- There is an increasing gap between lifespan (how long you live) and healthspan (how long you remain healthy). According to recent research, there is a 9.6 year global gap between lifespan and healthspan, meaning people on average live 9.6 years in poor health. In the U.S., this gap is the largest in the world at 12.4 years.
- There is an urgent unmet need to improve our health, both physical and mental, as we age.
Vascarta Anti-Aging Research – Key Findings to Date
- Beginning at 20 months of age (equivalent of roughly 60-65 years old for human beings), male mice were treated only twice weekly with a topically applied placebo vehicle gel or Vasceptor® for 2-3 months.
- As shown below, Vasceptor® improves multiple aspects of health span in aged mice. Specifically, Vasceptor® tended to lead to a slight, albeit non-statistically different reduction in body weight (graph A), without effects on insulin sensitivity (graph B). When assessing indicators of functional health and condition, Vasceptor® treated mice had improved coordination on balance beams of increasing difficulty, including fewer slips on easy, medium or hard difficulty beams (graph C). While grip strength was not significantly different between groups (graph D), Vasceptor® significantly improved exercise capacity during an acute treadmill challenge (graph E) and led to a notably lower frailty index (graph F). If similar improvements in frailty, balance, and exercise capacity were to be experienced in human beings, this would have profound personal and societal benefits.
Vasceptor® improves multiple aspects of health span in aged mice, improving endurance and balance, while decreasing frailty
Statistical Significance levels: *p<0.05, **p<0.01
- Consistent with the findings on improved exercise capacity, there were improvements in key cardiac biomarkers. Specifically, the p16 protein which typically increases with aged hearts was significantly lower in Vasceptor®-treated mice (graph A). Similarly, the cytokine il-1b which signifies damaging inflammation in the heart was significantly lower in Vasceptor®-treated mice (graph B).