Todos Medical (OTCMKTS: TOMDF) today announced excellent Phase 1/2 results that appear to take dying from COVID-19 off the table. In a small clinical trial of 32 patients the company tested Tollovir in hospitalized patients. Although the treated group was small Tollovir performed very well and had zero deaths in the treated cohort versus 5 which represented a 23% mortality rate in that population. At baseline the hospitalized patients were evaluated for a key biomarker of inflammation called C-reactive protein (CRP). Both the treated and observational group had similarly high levels but 50% of the treated group experienced an over 50% reduction in CRP in the 48 – 72 hours after baseline admission versus only 10% in the observational group. A 4 fold reduction in CRP is one of the keys to quieting the cytokine storm and letting patients walk out of the hospital.
Mechanism of Action – Stopping Viral Replication
Tollovid is a 3CL protease inhibitor. The best way to describe how Tollovid works is to put it in simple terms. When the virus infects the cell it deposits its mRNA into the cytoplasm and the cell’s ribosomes which are responsible for making the cellular proteins it needs start stamping out viral proteins instead of cellular proteins to form the building blocks of the budding viruses. The very first protein stamped out is a protease and it looks like a pacman from the video game. Its sole purpose is to cut the long protein chains that the ribosome is going to make next. Proteins are made in a linear fashion but then fold on themselves like an earthworm coils into a ball. Envision the ribosomes making a nail gun cartridge. They would make the nails which represent the viral proteins together with the little piece of plastic. The nail is unusable until it is separated from the plastic. Same concept applies in the cell. Without the protease pacman-like structure cutting the proteins to the right size viral replication would come to a halt. The protease inhibitor gunks up the protease saw. This mechanism stops new viruses from being made which is why it is so critical to get treatment as quickly as possible.
The principal investigator in this trial was Dr. Ilan G. Ron who is a Clinical Professor of Oncology and Radiotherapy at Tel Aviv Medical Center Faculty & Medicine. Dr. Ron is a highly experienced researcher with over 80 scientific and medical publications in peer-reviewed journals to his credit. This means that investors can have confidence that this was a sound study geared toward proving the thesis behind the mechanism of action of the drug that it not only reduced viral load but also reduced the inflammatory response.
Oral Antiviral Contenders – Merck & Pfizer
These trial results mark a turning point in TOMDF’s trajectory because it solidifies them as a contender in the race to an oral antiviral. The field of oral antivirals is pretty crowded. The leader in clinical trial development is Merck (NYSE: MRK) with their investigational candidate Molnupiravir. This drug has been touted by many for its early efficacy data. Dr. Marc Siegel said in a Fox news interview:
“It may be the holy grail on this because it was just studied in phase two trials and it literally stopped the virus in its tracks,”
If Tollovir data was put in front of Dr. Siegel back then his comments would likely change to Tollovir is the Holy Grail instead of it may be because Molnupiravir was tested in early-stage people who didn’t get better quickly and was only designed to lower the viral load. Tollovir happens to have a cousin nutraceutical called Tollovid that lowers 3CL protease. Although interim data has not been released from the Phase 2 it is widely expected to show a reduction in viral load because after all, it’s a viral inhibitor too. This dual mechanism of action gives Tollivir an upper hand in the oral antiviral race because it’s more of a one size fits all strategy.
Molnupiravir is expected to finish up its Phase 3 in November, but still has some regulatory challenges on the safety front. The FDA has valid concerns about lingering side effects as well as the fact that Molnupiravir is mutagenic and works by introducing errors into the genetic code of the virus. This is precisely how variants get started and expanded use of the drug might actually encourage mutation. The drug is using the virus’s propensity to mutate against itself by tricking the replication machinery to pump out reproduction errors until the virally infected cell collapses. In a rush to get efficacy results, it’s unclear if MRK has been testing its patients for any mutations that might arise from using the drug. Early trial results of Molnupiravir didn’t include the Delta variant so the company also has some concerns about the Delta variant’s higher viral load and if the drug will be able to keep pace. They just announced they did lab studies that show that Molnupiravir would be effective against the Delta Variant and reiterated that it works best in early disease. Unfortunately for those hoping for a solution “works best in early disease” is code for, it’s going to be hard to prove statistical significance. They also have another phase 3 looking at the drug as a prophylactic.
Pfizer and its 3CL protease inhibitor called PF-07321332 started Phase 2/3 studies just a couple of days ago for post-exposure prophylaxis. This follows the clinical trial that started earlier this month in non-hospitalized COVID-19 patients who are at low risk of progressing to severe disease. What is clear is the efficacy of the 3CL protease inhibitor and that it acts as an effective antiviral, but what is brushed under the rug is their move to combination therapy. The International Journal of Molecular Sciences article put Pfizer’s revised combination strategy into context. It’s pretty clear that the drug works, but there are some off-target effects that might have caused PFE to sideline dose escalation as a tool to enhance efficacy. Instead, they have resorted to combination therapy with ritonavir to keep the drug in the system longer. The article concluded that
“Our study elucidated in detail the binding mechanism of the potent PF-07321332 to 3CLpro along with the low potency of lopinavir and ritonavir due to weak binding affinity demonstrated by the binding energy data. This study will be helpful for the development and optimization of more specific compounds to combat coronavirus disease.”
The verbiage “helpful for the development and optimization of more specific compounds” is code for its good, but not good enough for whatever reason. The binding affinity wasn’t good which means they need to use a higher dosage to push efficacy and their reluctance to do so means that the binding isn’t strong enough and they want to use more but they can’t so they will try to keep it in the system longer. This is a setback and takes a lot of wind out of the sails of Albert Bourla, Pfizer CEO, to dominante the COVID-19 landscape. It is a net positive for Todos Medical on many fronts.
The data announcement today was extremely exciting. The company believes this study is supportive of a EUA. This $32 million market cap company has the potential to be a unicorn within the next 6-9 months and investors are on the sidelines wondering what to think. It’s just a matter of time before investors connect the dots that Tollovid is a watered-down formulation of Tollovir, which is undergoing phase 2 clinical testing with at least an interim readout due this year but perhaps in weeks. Tollovid is a nutraceutical that can be purchased TODAY, not next year, TODAY. With a watered-down version of the 3CL protease inhibitor on the market, it’s reasonable to think that if TOMDF checks the boxes to prove efficacy that the FDA would have very few if any safety concerns.
“We are aggressively planning our expansion into new sites in Israel in order to accelerate enrollment because we believe that both the data generated in hospitalized patients and the observational study will support Emergency Use Authorization (EUA) applications in various jurisdictions.” – Gerald Commissiong, CEO Todos Medical
The other oral antivirals in the pipeline are months away from any sort of approval and there are many obstacles in their way. TOMDF simply needs to find the money to finish their clinical trial or start a pivotal Phase 2/3, and the recent raise suggests they are in good shape. In the interim, Tollovid sales as an immune supplement will continue, and as reports grow that it either preventing people from getting COVID-19 or helping people with COVID-19 valuation will funnel into the stock price. Tollovir took dying off the table in a small clinical trial, but when results come out in a larger clinical trial the stock is certainly due to jump multiple orders of magnitude. Nibbling at this name with unicorn potential is a smart move, but an even smarter move is for investors to have a bottle of this on their nightstand just in case. No other pharma name essentially allows you to try the drug and experience if it works before approval. This is truly a special opportunity stock. PFE is targeting the same receptor and it works, but you can’t get their drug except in a clinical trial. Tollovid is available NOW and this nutraceutical catalyst just needs one medical influencer to realize that this is the next leronlimab, and that could take the company to new heights.
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