Lexaria Bioscience Corporation (NASDAQ:LEXX) has updated investors on numerous active initiatives including progress on the hypertension investigational new drug (IND) application and other related efforts integral to launching the trial, updates on the nicotine, hormone and blood glucose studies and the grant of several new patents. Capital was raised in an early May transaction and a new Chief Financial Officer was appointed in June. Most recently, Lexaria highlighted a publication in the International Journal of Molecular Science which examined the differences in cannabidiol concentrations in women and men.
Lexaria has published eight research papers since late 2019 predominantly focused on cannabidiol (CBD) and its effect on blood pressure. A full list and summary of the articles are included in a June 22nd press release with the most recent highlight of the group a publication in the International Journal of Molecular Sciences. Its title is Differences in Plasma Cannabidiol Concentrations in Women and Men: A Randomized, Placebo-Controlled, Crossover Study.
Findings and conclusions from the Journal of Molecular Sciences article revolve around the concentration of CBD in a subject’s plasma and the bioavailability of the drug. It examined the potential therapeutic benefits of CBD in a triple-blind, placebo-controlled, crossover study in which 62 hypertensive volunteers were randomly assigned to receive DehydraTECH CBD formulation or a placebo. Concentration of CBD was found to be higher in women and correlated with proportion of adipose tissue. The difference between the sexes was attributed to higher levels of fat tissue in women compared with men and women having significantly higher fat percentages. Men’s higher metabolism also contributed to their more rapid clearance of the metabolite and lower levels of CBD according to the study.
Other findings include the absence of a statistically significant difference in CBD and CBD metabolites in subjects taking other hypertensive medication such as angiotensin-converting enzyme (ACE) inhibitors, calcium blockers or thiazide diuretics. This provides a column of support for the use of CBD in the control of hypertension using multiple mechanisms of action that complement each other.
Hypertension Study Details
Lexaria has launched four human hypertension studies that are evaluating the use of DHT-CBD in reducing blood pressure. The first human study enrolled 24 subjects and examined diastolic pressure over a three-hour period and found that the pressure was lower in those administered DHT-CBD. The second study was conducted in 16 volunteers and confirmed that DHT can reduce arterial stiffness. The fourth study began in early April 2022, enrolled 66 subjects and has now reported several data sets to investors.
Hypertension Study HYPER-H21-4
HYPER-H21-4 began enrolling in an April 2022. The 60-subject study, later increased to 66, was designed as a randomized, double blinded, placebo-controlled, cross-over study with elevated, mild or moderate hypertension. The primary endpoint was 24-hour ambulatory blood pressure. Secondary endpoints include vascular health including arterial stiffness and autonomic balance, electrocardiogram analysis, brain structure and function through MRI testing, blood biomarkers, renal and hepatic analysis, sleep quality, geriatric depression scale, perceived stress and Beck anxiety inventory. These endpoints have been the subject of several articles that have been and will be published.
Dosing began ahead of schedule and was announced as complete on July 27th. Maximum dose levels used in the study reached 5 mg/kg/day, which matches the lowest daily starting dose of CBD used in children for the approved treatment of Dravet syndrome.2 No serious adverse events were reported during the study and DHT-CBD was well tolerated. Data from the study will be used to support an Investigational New Drug (IND) application with the FDA.
Reduction in Pro-Inflammatory Biomarkers
A publication based on the data in HYPER-H21-4 identified the upregulation of several pro-inflammatory biomarkers linked to cardiovascular diseases. This includes interleukin (IL)-8, IL-10 and IL-18. IL-8 is a cytokine known for its chemotactic properties and is involved in attracting immune cells to the site of inflammation or infection. IL-8 also has pro-inflammatory effects. If prolonged, excessive IL-8 can cause various inflammatory conditions or diseases such as rheumatoid arthritis and cancer. IL-10 is a cytokine that is anti-inflammatory in nature. It suppresses the production of other inflammatory cytokines, promotes the differentiation of regulatory T cells and protects tissue from damage. IL-18, similar to IL-8, is another pro-inflammatory cytokine produced by a variety of immune cells to initiate a response against infection and inflammation. The cytokine induces the production of other inflammatory cytokines and antimicrobial peptides and activates natural killer cells.
Selecting A CRO
A contract research organization (CRO) was selected to run the Phase Ib study that is titled: A Phase 1b Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Pharmacokinetics, and Pharmacodynamics of DehydraTECH-CBD in Subjects with Stage 1 or Stage 2 Hypertension. The CRO, InClin, Inc. is a California-based provider of consulting, project management, biostatistics and other services related to managing early, mid and late-stage clinical trials. InClin has experience in a broad range of indications including cardiovascular and vascular diseases.
Chemistry, Manufacturing and Controls
Further progress was reported in a May 11th press release. Batch manufacturing of the DehydraTECH-processed cannabidiol and placebo materials is complete. A current good manufacturing practices (cGMP) manufacturer was retained to produce the materials. Next steps include filling the capsules and analytical release and stability testing to obtain quality control data necessary for the investigational new drug (IND) application.
Next steps for the hypertension program include IND submission and additional preparations for the clinical trial. If the IND is cleared by the FDA, we then expect the start of a Phase Ib study in the late third or early fourth quarter. Trial design has not yet been shared with investors; however, we expect details will emerge after IND finalization.
Lexaria’s February update on its hypertension program identified a potential novel mechanism of action. The press release highlighted the FDA’s desire to review anti-hypertensive medicines that offer complementary mechanisms. Based on observations from the HYPER-H21-4 hypertension study using DHT-CBD, CBD may stimulate the production of catestatin via its interaction with the sympatho-chromaffin system which can favorably affect hypertension and may represent a novel mechanism of action for treating hypertension.
Hypertension grabbed the spotlight in early 2023 with AstraZeneca’s (NASDAQ:AZN) bid for the recently IPOed CinCor Pharma (NASDAQ:CINC). CinCor recently provided top-line data from its Phase II study that evaluated baxdrostat in hypertension patients. Baxdrostat is a selective aldosterone synthase inhibitor shown to lower aldosterone levels without affecting cortisol. The primary endpoint of the study was not met; however, there were large reductions in systolic blood pressure. AstraZeneca saw enough promise in the data to support further trials in hypertension and chronic kidney disease. Merger and acquisition activity in the space accentuate the unmet need for effective control of hypertension and provides a healthy backdrop for further work by Lexaria in this area.
Lexaria was granted its first Canadian patent and 28th patent worldwide in late December 2022. The patent, entitled “Transdermal and/or dermal delivery of lipophilic active agents” relates to improved compositions and methods for transdermal and dermal delivery of cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC). Similar patents in other jurisdictions remain pending. Skin-based delivery is an alternative to oral and inhalation routes and can provide advantages for localized treatment and reduce systemic exposure. Lexaria’s 2018 study demonstrated improved CBD permeability using DehydraTECH compared with a control and the best performing commercial penetration enhancer.
2023 Issued Patents:
o Food and Beverage Compositions Infused with Lipophilic Active Agents and Methods of Use Thereof
o Compositions Infused with Nicotine Compounds and Methods of Use Thereof
o Pharmaceutical Compositions and Methods for Treating Hypertension
o Compositions and Methods for Treating Hypertension
o Stable Ready-to-Drink Beverage Compositions Comprising Lipophilic Active Agents
o Compositions and Methods for Enhanced Delivery of Antiviral Agents.
On May 8th, Lexaria announced a $2.0 million capital raise in a public offering which was closed on May 11th. 2,106,000 units were sold at $0.95 per unit. The units consist of one share of stock and a warrant with an exercise price of $0.95 per share offering a five-year life.
Lexaria announced its receipt of Independent Review Board (IRB) approval for its human nicotine study designated NIC-H22-1 last November. The 36-subject study was designed to be a randomized, double-blind, cross over study in cigarette smokers. The pharmacokinetic (PK) evaluation dosed each individual three times over a period of several weeks using an oral nicotine pouch. The pouch was either DHT nicotine, or competing brands On! or Zyn.
Dosing for the trial began in December 2022, and evaluated subjects with questionnaires and eight blood samples taken over the evaluation period to measure nicotine delivery to the bloodstream. Other biomarkers including blood pressure and heart rate were also taken. The goal of the study is to show whether or not DHT is able to provide better oral-tissue absorption and reduced negative experiences vs. the other participants in the study. Support for NIC-H22-1 was provided by previous animal model work demonstrating faster peak delivery of nicotine using DHT.
In May 2023, Lexaria reported dosing of the 36 patients was completed. We anticipate that partner work with large global tobacco companies will accelerate when the results of the study are made public.
Estradiol Hormone Study
Animal study HOR-A22-1 has ended demonstrating successful delivery of estradiol and its metabolite estrone using DehydraTECH. Results presented in the May 18th press release produced an average peak concentration of estradiol and estrone of 9x and 20x compared with control. Area under the curve (AUC) levels for estradiol and estrone were 15x and 125x greater than control levels. Estradiol is used to treat endometriosis, premature ovarian failure and breast cancer among other conditions. Oral estradiol is also used in women’s birth control products. Estrone is important for bone health, reproductive system development, heart health and skin health.
There are many side effects associated with the use of estradiol including breast tenderness, headache, weight gain and vaginal bleeding. This accentuates the need for delivering the minimal effective level of the hormone. The impressive bioavailability of DehydraTECH estradiol compared to control supports further work in this discipline. Furthermore, bioavailability for estradiol formulations is low, calling for new methods to improve delivery.5
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1. Source: Company press releases and Zacks analyst compilation
2. Dose is recommended to start at 2.5 mg/kg twice per day which is doubled after one week and increased to 20 mg/kg/day inappropriate circumstances. Source: Epidiolex FDA Label
3. Lexaria Biosciences Press Release May 23, 2023.
4. Source: Lexaria Press Release - Lexaria Discovers Potential Novel Mechanism From Hypertension Study HYPER-H21-4. February 21, 2023.
5. Kuhl, H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric, 2005.
6. Lexaria Press Release May 18, 2023.