Two Paths to End the Pandemic but the Hybrid Approach Looks Dominant

Pfizer PFE is arguably one of the biggest leaders in COVID-19 technology, whether it’s their vaccine or their newly approved oral antiviral called Paxlovid. The groupthink is that if anyone is going to end the pandemic, PFE would be the best name to bet on. Moderna MRNA is another name, but the lack of any COVID therapeutic handicaps it. Gilead GILD pulled in great numbers initially because doctors had to use it at the time, but its viral inhibitor failed to control the pandemic. Merck’s MRK newly approved Molnupiravir is shrouded in controversy and full of restrictions. Rounding out the contenders is CytoDyn CYDY with its positive phase 3 trial design for critical patients that just got the FDA’s attention and might have a chance to take death off the table. Sitting in between all these names is Todos Medical TOMDF with the next major oral antiviral to readout expected in the coming weeks along with a diagnostic test that with early detection in the 1-3 day range could dramatically curb the contagion with accurate early detection.

Path 1: A Vaccine a Day to Keep the Pandemic Away

The political arena initially vowed to help develop therapies as well as vaccines for COVID-19, but the lion's share of the Operation Warp Speed (OWS) money went to vaccine makers. Dozens of small to medium biotech companies were vying for therapeutic solutions, but they had to go it alone. Ironically, the smallest and most poorly capitalized biotechs seemed to have developed the most novel solutions. Many haven’t seen the light of day, but a few have survived and made it into this article.

The COVID-19 pandemic should have unified mankind against the virus, instead, it became a political debate topic for the USA 2020 presidential elections. Just last year President Biden vowed to shut down the virus. Everyone is now walking back on those statements with Fauci suggesting masks could be forever, Kamala claiming that they were “not victorious” and “didn’t see Omicron coming” while placing the blame on scientific advisors. Politicians were warned that coronaviruses are highly mutagenic and can create new, dangerous variants seemingly out of nowhere and that a vaccination-only strategy might work in the short run but was doomed to failure in the long run.

Just a few months ago political pundits were blaming the continued viral outbreaks as a “pandemic of the unvaccinated” in an effort to double down on the vaccination blitzkrieg strategy, despite the well-known facts that vaccinations only reduce transmission slightly, with one study suggestion reduction by about one third. This phrase even got blowback from The Lancet about stigmatization. In August unvaccinated people were 29 times more likely to be hospitalized with COVID-19 and now the CDC stopped tracking that statistic. Washington state shows unvaccinated are 12 times more likely to be hospitalized but the trend lines are converging as a greater portion of the population experiences breakthrough infections. Now infections are reportedly through the roof with Omicron being highly transmissible and evading the immune system. The strategy to encourage more vaccinations is to push by potentially changing the definition of fully vaccinated to include a booster.

Some vaccine skeptics seem to have grasped that the coronavirus mutates, and immunity eventually wanes. Those facts suggest that vaccines can’t snuff out the virus by itself. Now treatments are in the spotlight. With the White House and health officials scrambling to find a solution in light of lawsuits filed over the vaccine mandates, they finally have no place to turn but to treatments. And by the way, this multifaceted strategy is what society has used against the flu for a long time—vaccines for those who want them, and antivirals like Roche’s RHHBY Tamiflu for those who get sick.

Path 2- Therapeutics and Antivirals

The best COVID treatments are administered early before patients really get bad and have to be intubated on a ventilator in the hospital. This basically leaves two main options: monoclonal antibodies such as those produced by Regeneron REGN and Eli Lilly LLY, and antivirals like Molnupiravir and Paxlovid from the likes of Merck and Pfizer. The monoclonal antibodies were highly effective but now there’s a big concern that they don’t work well on Omicron. It was initially unclear why they wouldn’t simply test people for the variant first, but recent CDC guidance to the testing labs prohibits them from disseminating the variant of concern to either the patient or the doctor. Without the ability to determine the Omicron variant, hospitals like Mt. Sinai were forced to suspend use of Regeneron and Lilly’s antibody infusions which no longer work on Omicron. The new case prevalence of Omicron is 73.2% but the lack of variant testing means people also don’t know if they have any potential vaccine immunity based on the variant.

The only approved antibody cocktail that is left is sotrovimab, a drug produced by Vir Biotechnology VIR and GlaxoSmithKline GSK. But the supply is limited (350,000 doses by January) and either they’ll have to be used up or testing for the specific variant will have to be done before administering the other monoclonal antibodies.

Antivirals, on the other hand, may represent a much more durable way to treat the virus. However, there are limited options that have been proven to work, with Pfizer’s Paxlovid clearly in the lead with regards to efficacy. Furthermore, monoclonal antibodies are more expensive to manufacture, store, and transport compared to small molecule drugs of those made from natural sources. Monoclonals also require intravenous infusion. Either early-stage therapeutics or antiviral treatments are needed.

Hybrid Approach - Testing / Antiviral / Vaccine Booster

Vaccines and boosters have limited utility in controlling the contagion without knowing the neutralizing antibody levels of people to determine who really has adequate protection. Only increased testing will plug this hole in the pandemic plan. Testing could also provide a more accurate picture of the true level of herd immunity because it would then include the vaccinated and the natural immunity from infections. There is also considerable community spread that has gone unchecked due to lack of testing and reliance on vaccination status. Without the government paying for free tests people choose to be tested when they are symptomatic instead of on a regular basis. Increased testing frequency could reduce community spread thereby reducing the contagion.

Breakthrough infections spread disease just as much as a new infection. People are contagious on average 10 days because there are no antivirals to give the masses to get them better quicker. Antivirals hold the promise of lowering the time a person is infectious. A key point in ending the pandemic.

Ultimate COVID-19 Possibility Stock?

Whether the reduction in contagion comes from increasing testing to control community spread, or better management of boosters, or employing antivirals to reduce the time of infectivity, all roads may lead to a company like Todos Medical.

Their testing business and nutraceutical sales are reported to be booming. Their companion diagnostic (3CL protease test called Tollotest) for early 1-3 day detection could replace PCR as a standard test. Trial results for Tollovir are coming soon. They hosted a Key Opinion Leader webinar session for Tollovir as a treatment for COVID-19. One of the KOLs, Dr. Greenberg, is a member of the COVID vaccines advisory team for the Ministry of Health in Israel. He pointed out in the video the quick approval pathway of botanical drugs. This particular piece of information has Todos investors speculating that Tollovir could be approved under an EUA in Israel to keep people safe and the economy going regardless of whether vaccines continue to work or not.

With 9.4 million people in Israel and current active cases sitting at over 7,000 per day, this may represent a very large market for Todos. The wild card is if Todos can give their drug as a prophylactic or to mild-to-moderate patients, it means a total available market (TAM) in Israel of about 7,000 patients per day before Omicron may ramp up considerably. Mild COVID-19 might not seem like a big deal but it can still result in long-COVID which is a significant, long-term negative for many people, with symptoms ranging from GI discomfort, to fatigue, dizziness, nausea, headache, tingling and numbness, and depression.

Even the mass booster strategy might lead to Todos. With mounting evidence suggesting boosters aren’t working as well as hoped, how do people know that an additional booster will actually help when the first didn’t? The answer is the cPass test, an FDA EUA approved test for determining if a person has immunity by measuring neutralizing antibodies. If the cPass test shows weak or no neutralizing capacity, a person might want to look at whether a booster will work for them.

Taking a Bite Out of the Pandemic

Tollovir and Tollovid have the same mechanisms of action as Pfizer’s Paxlovid, which is highly efficacious and is expected to generate $24 billion and $33 billion in revenue in 2022 and 2023, respectively. Todos Medical’s CEO seems extremely confident regarding all aspects of the business, especially Tollovir.

Todos only has a market capitalization of less than $70 million, but some are saying that Tollovir, its COVID-19 antiviral, has the same potential as Pfizer’s Paxlovid. In the meantime, revenues are reportedly ramping up from nutraceutical sales and testing, and the company has an impressive pipeline past COVID. For an OTC microcap biotech stock, this might be a good one to watch.

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