RGC: Regencell Bioscience - Investigational Liquid-Formula RGC-COV19™ Shows Promise in Eliminating COVID-19 Symptoms

By Beth Senko, CFA

NASDAQ:RGC

Asia is in the throes of the omicron variant, and Hong Kong is at the center. Although Hong Kong has been successful in limiting cases in past waves, the omicron variant is so contagious that current public health measures have been inadequate. According to the New York Times, the death rate in Hong Kong in early March exceeded 25 per 100,000 residents – higher than any country currently. Unfortunately, as of March 2022, nearly 40% of Hong Kong's population is not vaccinated, and the rate is over 50% for the elderly. Vaccine skepticism plays a significant role in low vaccination rates, but so does a preference for traditional Chinese medicine (TCM) as frontline therapy.

In addition to the surges in number of cases is the problem of lingering symptoms (long-COVID). There are hundreds of millions of individuals who have been diagnosed with COVID-19 around the world, and some experience post-COVID symptoms such as extreme tiredness (fatigue), shortness of breath, problems with memory and concentration (brain fog), heart palpitations, dizziness, chest pain or tightness and joint pain, among others, which are now being classified as long-COVID symptoms.

Founded in 2014, Hong Kong-based Regencell Bioscience RGC is an early clinical stage bioscience company using traditional Chinese medicine (TCM) approach to develop standardized TCM formulas to holistically treat autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in children, and infectious diseases such as COVID.

In March 2020, Regencell's strategic partner and TCM practitioner, Mr. Sik-Kee Au, adapted his proprietary TCM cold and flu formula for use in COVID patients. The TCM practitioner subsequently treated 9 voluntary COVID-19 patients in the United States and patients showed improvements after an average of five days. Based on these promising results, Regencell formed a joint venture with Honor Epic Enterprises Limited in September 2021 to conduct further tests and commercialize Regencell's COVID treatment in ASEAN countries.

TCM and COVID-19

Traditional Chinese medicine (TCM) has been practiced continuously over 3,000 years and during that time, knowledge and modalities have evolved as a result of treatment and observation. TCM includes a range of disciplines including: herbal medicine, acupuncture, bone setting, nutritional changes, body manipulation and exercise. Herbal medicine is the most common form of TCM practiced in Hong Kong (Lam, 2001).

TCM is based on the concept of balance in Qi (or "chi"). Health arises from a balance in Qi, while disease and illness are the result of an imbalance. In allopathic medical terms, a healthy Qi implies that the physiological barriers, immune cells and molecules and other components of the immune system are functioning well.

In TCM, infectious disease progresses through four steps: defense, qi, nutrient and blood. Each step is associated with pathological changes of varying severity. (Ma et al., 2019) Treatment depends on disease stage with reducing inflammation as the primary goal.

Wei Fen is early-stage infectious disease characterized by the invasion of pathogenic factors leading to fever, mild cold, dry cough with less sputum, headache, body pain, and dry pharynx. In this stage, treatment focuses on boosting immune defenses such as nasal mucosa. Qi Fen describes the movement of pathogenic factors into the body. In Qi Fen state, the body reacts to damage from the infection, but the disease is not yet circulating through the body; patient may experience high fever, flushing, chest pain, cough, thick sputum, congestion, and GI symptoms. In Wei Fen and Qi Fen, the imbalance is located primarily in the lung, stomach, intestine and gallbladder, although in the latter part of Qi Fen, the blood circulatory system may start to be affected. The latter stages, Ying Fen and Xue Fen, arise as pathogens circulate throughout the body causing more significant disease and damage.

Although there are common underlying principles in TCM, treatment is personalized for each patient and individual practitioners may utilize different approaches to the same condition. TCM treatments aim to strengthen the resistance, protect and adjust how the body, and organs, function enabling it to overcome pathogens. In TCM, viruses do not cause an infectious disease; if the body is cured, the virus will die out.

Although COVID-19 is primarily located in the lungs, observational studies report myriad symptoms including GI distress, mental fog, fatigue, and other symptoms. Patients often report lasting psychological/neurological and cardiovascular symptoms, long after testing negative for the virus (Wang et al., 2020).

Regencell's COVID formula

Brain function relates to oxygen level required for brain to conduct normal cognitive function. For optimal function, the heart needs to be functioning normally to be able to deliver sufficient oxygen to the brain.

According to the TCM Practitioner's brain theory known as "Sik-Kee Au TCM Brain Theory®", when the heart is weakened, the heart cannot efficiently pump enough blood to circulate oxygen throughout the body. When this happens, the brain function is reduced, which results in a person experiencing fatigue, nausea, disorientation and reduced immune response.

Regardless of the COVID-19 variant, the lungs and heart are where the coronavirus does much of its damage, and such infection can set off an inflammatory immune response that ravages infected and uninfected cells alike, leading to tissue scarring and oxygen deprivation which will in turn reduce optimal brain function.

RGC-COV19TM is a natural formula designed by the TCM Practitioner to strengthen one's heart function. When one's heart is strengthen, it will increase blood flow and more oxygen will be delivered to the brain, resulting in the reduction of blood clots and regaining of optimal brain function.

Based on the Sik-Kee Au TCM Brain Theory®, this leads to more responsive cognitive function which in turn, stimulates the body's own healing mechanism to reduce COVID-19 symptoms. RGC's formula and the body's own response work together to:

• reduce and clear the mucus and phlegm from the upper respiratory system;

• dispel exterior viral pathogen via heavy sweats, urine and excrement;

• clear endogenous and liver heat;

• detox the liver, and

• improve circulation.

EARTH Efficacy Trial

From March 2020 to August 2021, Regencell set up protocols and procedures to conduct the EARTH efficacy trial in Malaysia and the United States.

EARTH was a non-blinded trial to study the efficacy of Regencell's TCM formula for COVID-19 (RCG-COV19TM) over a six-day treatment period. The study included 37 subjects age 5 to 61 with a mix of race, ethnic and socioeconomic backgrounds. Subjects were located in Malaysia (n=23) and the US (n=14). All subjects showed onset of symptoms within five days of treatment initiation and laboratory-confirmed diagnosis of COVID-19 within three days to the start of treatment. Subjects with a confirmed diagnosis of COVID-19 but who were asymptomatic, were excluded from the study.

31 subjects were fully-vaccinated, 3 were partially vaccinated and 3 were not vaccinated. All subjects who were vaccinated either received a single dose, double dose, or a combination of vaccine from Pfizer-BioNTech, Moderna, AstraZeneca, Sinovac-CoronaVac and/or Johnson & Johnson's Janssen.

Each patient received two doses of Regencell's formula (two days of treatment) and were followed for a maximum of six days. Patients in Malaysia (n=23) also took a COVID-19 Polymerase Chain Reaction test (PCR test) for COVID every two days. The COVID-19 treatment ended upon patients receiving a negative COVID test or when their symptoms were gone (except for loss or reduce of sense of smell and/or taste (Sensory Dysfunction) or occasional cough), at the end of the six-day study period.

To assess the efficacy and time to symptom improvement/resolution, patients recorded their symptoms daily on a three-point scale ranging from mild to severe. Patients were asked to log specific symptoms such as fever (including hot flashes or chills), upper respiratory issues (cough, sore throat, runny nose), lower respiratory issues (shortness of breath, chest pain or pressure), muscle aches, nausea, abdominal discomfort, and drowsiness, and to identify any other symptoms they were experiencing. On average patients reported 6 symptoms, with the highest number of symptoms reported being 14.

None of the trial subjects was hospitalized and there was no death. The efficacy of RGC-COV19TM was not affected by timing of symptom onset or underlying risk factor. Results were consistent across all ages, gender, races and ethnicity demographic among subjects.

Symptom elimination

Of the 37 subjects, 36 patients (97.3%) had all mild-to-moderate symptoms eliminated (except for Sensory Dysfunction or occasional cough) within six days. 31 of 37 patients (83.8%) reported elimination of one or more symptoms after the first treatment. On average, patients reported elimination of all symptoms (except Sensory Dysfunction and occasional cough) 3.4 days after starting treatment.

Clearing the virus - negative COVID test (Malaysia subjects)

Subjects in Malaysia also took PCR tests every other day during the study. In Malaysia, the threshold is 40, meaning a CT value of less than 40 means a person is positive while more than 40 means a person is tested negative. Of the 23 subjects, 43.5% (n=10) tested negative for COVID by the end of the study. The remaining 13 subjects reported all symptoms alleviated (excluding Sensory Dysfunction and/or occasional cough) by the end of the study, but had not completely cleared the virus by the end of the study.

By vaccination status

The study's unvaccinated subjects (n=3) reported an average of three symptoms and took approximately 2.3 days for symptoms to be eliminated. Partially vaccinated subjects (n=3) recorded symptoms eliminated at 3.3 days on average. Fully-vaccinated subjects (n=31) reported no symptoms after 3.5 days on average.

Sensory dysfunction

Sensory dysfunction (loss or reduce of sense of smell or taste) appears to linger beyond the six-day study period for many subjects. Prior to receiving treatment, 15 of 36 patients reported sensory dysfunction. Five of the subjects regained their sense of smell at the end of the six-day study, while the other ten patients reported improvement.

TCM and COVID – clinical trials

As there were no established treatments for COVID-19 in the first year of the outbreak, TCM was used early on in China as a treatment. Since then, TCM therapies have been used both alone and in combination with allopathic medicine in China. There are numerous studies on the use of TCM in COVID; however, the vast majority of studies are observational, or have small sample sizes, and will need to be verified by more rigorous studies.

Several well-designed systematic reviews have been conducted to evaluate the efficacy of TCM in COVID-19. Most reviews consider evidence from case reports, case series, and observational studies. However, a few examine randomized controlled trials (RCT) of TCM in COVID-19 as well.

Zhang et al. (2022) studied the impact of TCM when combined with chemical drugs (CD) in 18 trials with a total of 2,036 participants. Zhang considered studies that were based on China's National Health Commission "Three medicines, three prescriptions" (TMTP) regimen. The TMTP regimen consists of three patented (standardized) TCM medicines (Lian-Hua-Qing-Wen (LHQW), Jin-Hua-Qing-Gan (JHQG), and Xue-Bi-Jing (XBJ)), and three TCM prescriptions (Qing-Fei-Pai-Du (QFPD), Xuan-Fei-Bai-Du (XFBD), and Hua-Shi-Bai-Du (HSBD)). Researchers reported elimination of fever (RR, 1.49; 95% CI, 1.30 to 1.70), cough (RR, 1.72; 95% CI, 1.38 to 2.14), and fatigue (RR, 1.55; 95% CI, 1.25 to 1.93) were much better when TMTP was combined with CD, compared to CD alone. The study identified LHQW as demonstrating particular efficacy in eliminating COVID-19 symptoms as measured by both clinical and CT evaluation.

A review of 32 RCTs covering 3,177 subjects, found that TCM as an adjuvant to allopathic medicine results in significantly higher improvement compared to allopathic medicine alone. (Kumar et al., 2022). Of note, the study found that TCM improved COVID-19 symptoms more quickly, but it did not find that TCM along with allopathic medicine shortened the time to testing negative for COVID-19 at a statistically significant level. A separate study (Liu, 2022), similarly reported that TCM in combination with allopathic therapy is more beneficial than allopathic therapy alone for eliminating COVID symptoms.

Path to registration and commercialization of its ASD/ADHD treatment formula

Regencell Bioscience has a four-year timeframe to commercialize its standardized formulations and gain proprietary Chinese medicine (pCm) registration in Hong Kong. The Company has a number of tasks ahead:

• Completing its second clinical trial for ASD/ADHD and COVID, and evaluating results.

• Conducting additional clinical trials to support its proprietary formulae in ASD/ADHD and other applications.

• Obtaining patents and other forms of IP protection in Hong Kong and other markets.

• Establishing manufacturing capability and supply chain that will meet registration requirements.

• Assembling and filing documentation for pCm approval.

• Build out its marketing and distribution strategy and infrastructure.

Additional Products – ASD/ADHD TREATMENT FORMULA

Regencell Bioscience's formulation for the treatment of neurological disorders was developed by Mr. Sik-Kee Au, a TCM practitioner, who has used the formula in his practice for over 30 years to treat patients with ASD, ADHD and other neurocognitive disorders. Currently, the Company is working towards standardization and commercialization of its formula.

The formula is based on the "Sik-Kee Au TCM Brain Theory®" that ASD and ADHD stem from inadequate blood flow and creation of neurotransmitters in the developing brain. As we discuss earlier, this hypothesis is complementary to the western medicine view that ASD and ADHD are present at birth and arise from developmental differences in brain function.

Regencell Bioscience's first clinical trial was designed to establish benchmarks for treatment, dosing, adverse effects (AEs) and measuring patients' response in a systematic and repeatable way, while evaluating the effectiveness of a customized TCM formula.

As a customized formula limits the ability to produce in large quantities as compared to a standardized formula, Regencell is currently evaluating and assessing the effectiveness of a standardized TCM formula in reducing ADHD and ASD symptoms in children through a holistic approach within 3 months of treatment, in its second efficacy trial.

Conclusion

Proprietary Chinese medicine registration (pCm), the "approval" process for TCM falls under a different regulation process as compared to western treatments in Hong Kong, and Asia in general. When applying for registration of pCm in Hong Kong, applicants are required to provide sufficient documents to show safety, stability, quality and efficacy of the pCm formulae products to the Hong Kong Chinese Medicines Board. Efficacy documents include reference materials in which the claimed therapeutic functions are supported by research studies, interpretation and principle of formulating a prescription and a summary report on all the product efficacy documents.

While there is still much work to do, in our view, Regencell Bioscience is taking a thoughtful, systematic approach to developing its TCM formulae.

At its July 2021 IPO including the exercise of the over-allotment option, Regencell Bioscience raised approximately $25 million, which the Company has since utilized the funds raised to fund its second research study related to ASD/ADHD treatment, established a joint venture with Honor Epic to provide COVID treatment to patients in ASEAN countries, hiring of new talent to expand its team, in addition to working capital and other general corporate purposes.

We believe that an emphasis on conducting well-designed clinical trials that measure outcomes based on well-established assessment instruments, will provide Regencell Bioscience with a competitive advantage in terms of expertise and credibility in an industry that is moving towards higher standards for efficacy, safety and quality.

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