Mr. Greg Fenton reports

ZENTEK AND MCMASTER ANNOUNCE POSITIVE RESULTS FOR APTAMER-BASED TECHNOLOGY WITH THERAPEUTIC POTENTIAL

Further to its press release dated May 19, 2022, Zentek Ltd.'s aptamer platform under global exclusive licence from McMaster University has been successfully tested as a potential prophylactic or therapeutic for SARS-CoV-2 in preclinical animal models. In repeat trials, the aptamers developed by Dr. Yingfu Li demonstrated similar efficacy against SARS-CoV-2 when benchmarked against a commercial monoclonal antibody.

This new aptamer, based on a novel approach, was developed under the exclusive worldwide 20-year licence agreement between Dr. Li's lab at McMaster and Zentek first announced on June 17, 2021.

Preclinical trials

Dr. Li's team developed a series of aptamers with high-binding affinity with the SARS-CoV-2 spike protein. In February, 2023, the best-performing aptamer against all variants of SARS-CoV-2 was tested in vitro to assess the neutralizing of the virus by the aptamer in Vero cells. With strong results, Zentek was motivated to move into in vivo trials.

Dr. Matthew Miller, the Canada research chair in viral pandemics and the director of the Michael G. DeGroote Institute of Infectious Disease Research, designed and supervised all of the preclinical trials. The first preclinical trial included three groups of mice: (i) group A, which was a control group and received no prophylactic treatment; (ii) group B, which received a commercial monoclonal antibody that was a leading antibody for the original SARS-CoV-2 strain until it was rendered ineffective due to antigenic changes in Omicron sublineages; and (iii) group C, which received an aptamer designed by Dr. Li's team. All groups were infected with SARS-CoV-2. After four days, the mice that received the antibody and aptamer treatment had minimal weight loss while the control group had a 10-per-cent body weight decline. In addition, the viral burden of the control group was measured at 10,000 PFU (plaque-forming units) per lung. Significantly, the viral burden was undetectable in the lungs of the mice treated with the antibodies or the aptamer.

Based on these promising results, an additional trial was completed following the same procedure with a lethal challenge dose of SARS-CoV-2, where the mice were once again divided into three groups: control, antibody and aptamer treatment. The control or untreated group lost 20 per cent of their body weight after four days and all mice reached humane end points. The groups receiving either the aptamer or antibody treatment had less than a 5-per-cent reduction in body weight after the four days. The gross pathological assessment of these lungs at day 4 postinfection indicated that the aptamer, like the antibody, completely protected the lungs from any observable tissue damage. The control group's lungs, on the other hand, had evidence of significant hemorrhaging. In addition, the antibody and aptamer prophylactic provided sterilizing protection where no detectible viral titers were measurable, demonstrating similar performance between the commercial monoclonal antibody and the Dr. Li lab aptamer.

Dr. Li stated: "The binding affinity of our aptamers has translated exceptionally well to neutralizing the virus in both in vitro and more importantly in in vivo animal tests. Since the neutralization of the virus occurs because our universal spike-binding aptamer binds to the spike protein and prevents the virus from binding and infecting the ACE2 receptors, I believe this aptamer may be a potential prophylactic or therapeutic for all current and possibly future variants of SARS-CoV-2, including XBB 1.5. Having the in vivo preclinical results strongly correlating to the earlier in vitro results from my lab was not only very exciting but will be very helpful as a predictive model as we study new targets."

Dr. Miller commented: "Our lab has been at the forefront of COVID-19 research and vaccine development in Canada. Since the outbreak, we have been looking for therapeutics that are effective, safe and can be rapidly developed for current and future pandemic outbreaks. The results we observed with the Li lab aptamers are incredibly exciting. I see great potential for these aptamers to be used to develop treatments and prophylactics for other potential targets. This is a significant first step in the pathway to prevent and treat COVID disease with aptamers."

Aptamers -- safety profile

Aptamers are synthetic single-stranded DNA-type or RNA-type molecules that are built from the same building blocks of human DNA or RNA, hence offering a significant positive safety profile and have already demonstrated such safety. The 2018 article entitled "Pharmacokinetics, Pharmacodynamics, and Safety of Aptamers" by Kovacevic et al. stated that aptamers are considered to be generally safe based on multiple studies of aptamers for therapeutic use. Reference to toxicology studies and off-target side effects also led to the concluding statement that, generally, the safety of aptamers is very good.

Next steps

Given the significance of these results and based on the importance of this opportunity, a preclinical plan is being formulated for the development of a COVID-19 therapeutic/prophylactic based on the Dr. Li aptamers. Dr. Li is also working on other targets for aptamer treatments, and these are under early investigation.

Greg Fenton, chief executive officer of Zentek, commented: "The results of this testing conducted by the Miller Lab has exceeded our expectations. The potential of these aptamers to play a role in the prevention, detection and treatment of COVID and potentially other diseases is significant. Additionally, what we understand about the safety profile of aptamer-based therapeutics also derisks this project and could potentially lead to a shorter pathway to commercialization. We are currently focusing on this opportunity and the continued development of aptamers for both therapeutic and diagnostic uses, and this is now a high priority for Zentek."

Amendment to McMaster licence agreement

Pursuant to a licence agreement dated June 11, 2021, McMaster University granted to the company, for a 20-year term, a worldwide exclusive royalty-bearing licence to use and practise certain aptamer-based rapid detection technologies to detect SARS-CoV-2. Effective June 23, 2023, the licence agreement was amended to broaden the scope of the worldwide exclusive licence to apply to all aptamer and DNAzyme uses, including, but not limited to, diagnostics, therapeutics and as neutralization agents and not limited to SARS-CoV-2.

The company is not making any express or implied claims that its product has the ability to eliminate, cure or contain the COVID-19 (or SARS-CoV-2 coronavirus) at this time

About Zentek Ltd.

Zentek is an ISO 13485:2016 certified graphene technology company focused on the research, development and commercialization of graphene-based novel products seeking to give the company's commercial partners a competitive advantage by making their products better, safer and greener.

Zentek's patented technology platform ZenGuard, is shown to have 99-per-cent anti-microbial activity and to significantly increase the bacterial and viral filtration efficiency of both surgical masks and HVAC (heating, ventilation and air conditioning) systems. Zentek's ZenGuard production facility is located in Guelph, Ont. Zentek's patent-pending ZenArmor technology platform is focused on corrosion protection applications.

We seek Safe Harbor.