Connect with us

BioPharma

CytoDyn’s Robust Platform Technology Keeps Expanding Into Breakthrough Therapy Designation Territory

Published

on

  • Leronlimab is an immunomodulator that targets many diseases
  • Multiple indications being pursued in parallel
  • Proven safety profile, novel mechanism of action, & ease of application enables quick label expansion strategy
  • Breakthrough Therapy Designation possible for cancer and Long-Haulers

CytoDyn (OTCMKTS: CYDY) has made a number of recent announcements that when examined together add up to significant progress and potential that is not reflected in the current stock price which values the company at just under $1.0 billion market cap.  Looking back over the last 12 to 18 months investors have witnessed CytoDyn move from being a one trick pony for HIV to a platform technology in cancer and a slew of other indications in the immunological category, with more in the future.  

Elements of a Platform Technology

A platform technology in drug development involves getting a therapeutic approved for one indication so that it derisks future development costs and allows for a label expansion.  Two examples of the most successful drug platform technologies are Merck’s KEYTRUDA with 31 approvals and Abbvie’s (ABBV) HUMIRA with 9.  KEYTRUDA generated $14.4 billion  and HUMIRA generated $19.8 billion in sales in 2020.  What is so fitting about these examples is leronlimab is a combination cancer drug and immunological drug, so it’s a cross between KEYTRUDA and HUMIRA.  If CYDY inks just one approval their drugs could quickly grow in magnitude because unlike MRK and ABBV who developed additional indications after the drug was approved, leronlimab’s other indications were done in parallel.  Investors seem to be sitting on the sidelines wondering which indication will hit first.  Leronlimab has 9 clinical trials on clinicaltrial.gov, 7 of which were started in 2020 including the cancer basket trial, metastatic Triple Negative Breast Cancer (mTNBC), NASH, Long-Haulers and Covid-19.  Most of these have results coming out this year.

To Find out the inside Scoop on CYDY Subscribe to Microcapdaily.com Right Now by entering your Email in the box below

CYDY


Data from Drugs.com

If CYDY gets just one indication in cancer approved then it’s possible that they could follow an even steeper trajectory in obtaining follow-on indications in cancer.  The company has said in its latest press release that

“The positive advancement confirms leronlimab will be administered with a 700 mg dosage for patients in the mTNBC trial and Basket trial for 22 solid tumor cancers, as well as compassionate use, eIND and “right-to-try” patients.”  

It’s possible that over time CYDY could get enough cancer indications to rival MRK based on them defining the mechanism of action (MOA) of the drug. HUMIRA got its first indication approved in 2002 for Rheumatoid Arthritis and has been able to get 12 approvals over 19 years.  KEYTRUDA got its first approval in 2014 and has been able to get 29 approvals in 7 years.  The next platform drug player might even be able to do it quicker.   

Multiple Cancer Indications

The most recent press release also discussed the advancement of their triple negative breast cancer trial from a Phase 1b study to a Phase 2. This is important news that has not yet been digested by the investment community.  Phase 1b studies are about gradually increasing a drug’s dose to find the optimal safe dose.  The primary endpoint for phase 1b of the CytoDyn study was maximum tolerated dose (MTD).  CYDY just announced that there were no dose limiting toxicities associated with 700 mg.  This data establishes the maximum dose that could be available in the Phase 2 trial protocol.  Investor frustration in the cancer trials seems to be centered on the slow pace of enrollment to get safety data on something that was so intuitively obvious.  It took 1.5 years to garner 9 patients in the trial.  That frustration was also part of the friction that led to the termination of Dr. Pestell for designing a suboptimal trial that was detailed in the litigation.  

In contrast to the safety portion of the trial, the primary endpoint in CYDY’s Phase 2 is expected to be progression free survival (PFS) which is the most commonly used endpoint to measure efficacy in cancer trials.  Phase 2 trials are designed to flush out if the treatment works.  Leronlimab showed paradigm changing efficacy in mice models so it is expected to translate into positive human trials. These mouse models below show virtually a stoppage of metastasis.  The lack of any tumor growth in the mice demonstrates how amazing this drug is at stopping metastasis.

 

Breast Cancer Research Article

One of the things that would be required for a breakthrough therapy designation (BTD) is an elucidation on the Mechanism of Action (MOA).  The company has developed a great video on the mechanism of action and also did a TNBC presentation to academics that showed a 62% reduction in blood vessel area (p=.013) also known as angiogenesis.  It’s really easy to spot the noticeable lack of blood vessels supporting the tumor in leronlimab treated mice.  Although there are specific drugs like Avastin that are designed to target angiogenesis this was just a byproduct of the mechanism of action.  The amazing outcome was a 87% reduction in tumor burden compared to the control.   

Screenshot – TNBC Presentation

CytoDyn is well positioned for a BTD from the FDA if the soon to be released (2 weeks) trial results from the Phase 1 measure up to expectations.  The data is expected to confirm the number of responders and stable disease rate.  In the latest shareholder update, Dr. Scott Kelly, the chairman of CytoDyn, suggested that CytoDyn will eventually transform itself into an oncology company and this data point looks like it will be extremely positive.  Any positive Phase 1b result could have a multiplier effect on valuation.  Investors need to remember that there are 22 cancers in the basket trial which opens up even more potential in the future.  The potential for an oncology platform is significant as more studies show immune modulating drugs such as CCR5 antagonists as promising therapeutic targets.

Rising NASH Leader

CYDY also recently announced enrollment of their final patient, patient #60, in their NASH trial. NASH is the unicorn of diseases for pharma companies: a large multi-billion market with millions of people affected in the US alone.  Mouse studies conducted at the Cleveland Clinic showed leronlimab effectively “inhibited fatty liver development”, a precursor to NASH.  To date no drug has been approved.  Gilead Sciences (NASDAQ: GILD), French company Genfit (NASDAQ: GNFT), Intercept Pharmaceuticals (NASDAQ: ICPT) and, recently, NGM Pharmaceuticals (NYSE: NGM) all have failed trials.   An oral CCR2/CCR5 antagonist, cenicriviroc, showed strong phase 2 results but the phase 3 trial was halted by Allergan (NYSE: AGN) due to an underwhelming inflammation effect and a strong placebo effect making available data harder to interpret.  Galectin Therapeutics (NASDAQ: GALT) is developing the only drug that demonstrated efficacy in NASH. Unfortunately a conservative Phase 3 trial design and COVID-19 delays have pushed a top line read out into 2023 which could give time for CYDY to steal the lead with their Phase 2 readout provided they get drug approval on their MOA in 2022 and a label extension.   

As an immune modulating antibody, leronlimab has a much more pronounced effect against inflammation compared to small molecule drugs such as cencriviroc or marivoroc.  Unless the FDA surprises investors with a BTD, which is very possible, most are expecting that strong Phase 2 results released before the end of 2021 will precipitate a Phase 3 in early 2022.  This advancement should increase the value of CYDY significantly given the large market potential and lack of any approved therapeutic.  As HIV patients also are more susceptible to NASH, a platform drug that addresses both is of great interest.

HIV Franchise Forming

The HIV BLA submission is also expected to be fully submitted over the next couple of months.  Putting aside the drama of the submission process, leronlimab continues to have the potential of disrupting the HIV industry given the once a week injection, high effectiveness, and strong safety profile.  Gilead Sciences HIV combo pill, Biktarvy, which grew to $7.26 billion in 2020, has a black box warning, needs to be taken daily, and is not recommended for those with severe liver or kidney impairment.  The current BLA is in combination with HAART, which is a custom designed set of therapeutics for each patient to manage the viral load.  A monotherapy trial for CCR5-tropic HIV 1 infection showed a 92% reduction in viral load and no serious adverse effects. Once the BLA is approved, CYDY has stated they plan to apply for a label expansion for monotherapy.  Given that all newly infected HIV patients and approximately 70% of existing HIV cases are CCR5-tropic, CYDY’s platform has the potential of dominating the future of HIV therapy.

But wait, there’s more!  CYDY is also looking at the HIV prevention market.  The market is currently at about $3 billion and is expected to double by the end of the decade.  Gilead’s drug, Descovy, needs to be taken daily and has a host of side effects including nausea, worsening kidney function, and fat redistribution.  Leronlimab if proved through clinical study will have significant advantages at potentially a once a month only self-administered injection.  CYDY unveiled their strategy that they are exploring the launch of a prep study in Brazil possibly by the end of year.  Given the successful clinical trials which have earned a fast track designation from the FDA, BLA approval is a question of when, not if.   Under the steady hands of Dr. Recknor, investors should have much higher confidence in the BLA being submitted in 2021 with a PFUDA date in the first half of 2022.

Expanding Pipeline 

Graft vs Host Disease (GvHD)  is on the back burner for now but will be revisited in the coming year. CYDY has already received orphan drug status for this application which provides tax credits, fee waivers, and exclusivity for seven years.  The Phase 2 trial was modified in 2020 to allow all trial participants to receive leronlimab.  The potential market is expected to be $640M in 2026.  The company had 2 compassionate use cases with stroke and both stroke patients responded well to treatment.  

COVID-19 Trial Failures or Dose Justification?

Covid is still very much in play with the Delta and other variants causing a resurgence of infections.  In the US alone infections have doubled in the last three weeks.  While many bears on the message boards have claimed the mild/moderate and severe/critical trials were failures as they didn’t meet their primary endpoint, Phase 2 trials are exploratory in nature and serve to inform Phase 3 trial design.  Even Dr. Janet Woodcock, acting head of the FDA, stated the severe/critical trial was hypothesis forming and supports additional trials. Since additional trials are continuing the results could hardly be judged a failure.

These trials did help CYDY learn more about the dosage, frequency and method of application as well as showed that leronlimab appears to work extremely well if given over a long enough period of time.  The Phase 3 Brazil trials will soon start with the cards stacked in CytoDyn’s favor.  The critical trial has IV injection, four doses over four weeks, a sufficient number of patients with 1 to 1 drug vs control, and a primary endpoint of “time to recovery”.  This trial design is practically bulletproof because all the endpoints achieved statistical relevance in the Phase 2 in the USA.  Given the continued high number of Covid cases in Brazil and 45 trial sites, the trials should fill up rapidly and interim results should be out sometime by the end of year.  If anything close to last trial results of 82% pans out for critical patients, leronlimab will become the new standard of care for those that progress to critical.  The FDA statement on leronlimab has set this up nicely as the view that leronlimab has “no clinical benefit” will change to leronlimab has “significant clinical benefit” and the FDA will be compelled to respond with approval.  Becoming the standard of care for critical and possibly severe Covid will have a significant impact on CYDY’s valuation.  An even bigger market is Long-Hauler’s.  Preliminary results of the Phase 2 study were excellent, but failed to impress the market which wants to see the full results with biomarker data.  Since the biomarker data speaks to the MOA of the drug, the release should add to their valuation and increase the potential for a big pharma partner to participate in a Phase 3.  It also opens up the potential to go after other post viral syndromes such as chronic fatigue syndrome.

Other Blockbuster Indications

Possibilities seem endless with CCR5 implicated in strokes, Alzheimer’s, Parkinson’s, Lyme disease, MS and many other diseases.  CytoDyn has a paradox of choice given the growing number of diseases that appear to have CCR5 as a potential target for therapeutics.  Leronlimab’s unparalleled binding to CCR5, ease of application, and proven safety profile puts it in a strong position to become the standard of care in many of these over a multi year horizon.  They are getting closer to getting approval than ever including many with the potential of breakthrough designation including long haulers. Just one approval will enable label expansion opportunities and off-label uses.

Financial Analysis & Risks

One of the biggest risk factors is potential dilution but the company has issued around 622 million shares while there are only 800 million authorized.  In a worst case scenario this represents 22% dilution.  In the latest Proactive video the CEO said the company has enough cash to last through the year.  In April they raised $50 million in an above market offering at $10.00.  Based on their latest 10-Q they are burning about $6.5 million per month which would give them about 8 months of burn before they run out and confirms the CEO’s statement.  Management is also facing a challenge by an activist shareholder group called Advancing Leronlimab that appears to be composed of 2 ex-directors that were let go and both sued the company. If this group does get control of the company it may impair some of the drug trial development but the company is expected to get a major readout and file their BLA for HIV before the shareholder meeting expected in October.  If the BLA is filed it is widely expected they will be granted approval given the incredible safety profile of the drug.  So any potential upheaval would likely be after the company hits major drug development milestones.

There is a risk of a Refuse to File for the BLA, but most of those points should have been addressed in the upcoming filing.  Traditionally once the BLA is accepted there is a very high probability of success.  This is one of the supporting factors for a significantly higher stock price.         

Investment Summary

A number of investors have been critical of CYDY’s placing multiple bets but in reality CYDY is building a platform drug that has the potential of surpassing HUMIRA’s revenues.  HUMIRA is the number one drug in ABBV’s portfolio by far and has helped propel Abbvie’s market cap to over $200B.  We will see CYDY’s platform strategy start to unfold over the rest of 2021 as various trial results come in.  Given the current stock price there is significantly more upside than down for the patient investor that realizes it is still all about the science. We will be updating on CYDY when more details emerge so make sure you are subscribed to Microcapdaily so you know what’s going on with CYDY.

Disclosure: we hold no position in CYDY either long or short and we have not been compensated for this article.

Continue Reading
7 Comments

7 Comments

  1. Charles

    July 20, 2021 at 1:34 am

    Excellent summary of an absurdly promising drug. Despite some missteps by the current mgmt the share price is mind-bogglingly low right now. With today’s cancer news, this stock is going to get very expensive soon.

  2. Ken Chowder

    July 20, 2021 at 3:11 am

    This article covers all the bases and shows how absurd the short position is in this drug. It also reveals how lethal the unwillingness to accept Leronlimab has been: many have died who did not have to die, and many more will. History will look back on the lack of speed in accepting and understanding the power of Leronlimab with astonishment and disgust.

  3. Sven

    July 20, 2021 at 11:58 am

    Great article. Could you also elaborate on the patent/IP situation with LL? Would that add to risk or can it be neglected as it will still take many years to full potential.

    • Tom Rieder

      July 21, 2021 at 2:33 am

      The key to the IP situation is that the BLA actually gives you 12 years of exclusive marketing protection. The patent is not as important as marketing exclusivity.

  4. Ron Tiffany

    July 20, 2021 at 12:16 pm

    Well balanced article on the future potential of leronlimab. There certainly have been a plethora of negative and inaccurate articles over recent months. Thanks for the thorough research.

    • Tom Rieder

      July 21, 2021 at 2:42 am

      LL has a bright future but it has been clouded by a massive misinformation campaign spearheaded by shorts and the Advancing Leronlimab crew. There is still tremendous risk in the stock but I characterize upside as risk. The one risk that is negligible and I hope this article brings light to the fact that the regulatory risk of approval is extremely small. This means you can almost count on an approval, but the question is when. Based on the trajectory of development it seems like a BTD is almost imminent.

  5. Tom Rieder

    July 20, 2021 at 12:36 pm

    The big thing hampering the valuation is the markets perception that the FDA is not in their corner. The FDA statement was clearly political motivated when they claimed the drug didn’t have efficacy and market participants took this at face value instead of doing their own due diligence. It is because of this statement that people believe there is no possible way the company will get a fair shake from the FDA. The new data that was released was really remarkable and no matter how politically charged the FDA seems to be this particular news cannot be swept under the rug. Once a BTD is given then market participants will flood into the name realizing that the FDA wasn’t partisan and simply wanted more data.

Leave a Reply

Your email address will not be published. Required fields are marked *

BioPharma

BioXyTran Inc (OTCMKTS: BIXT) Crushes Primary Endpoint, Expected to Achieve Unicorn Status in New Year

Published

on

Last month, BioXyTran Inc (OTCMKTS: BIXT) achieved a once-in-a-decade type event with their announcement of a perfect phase 2 clinical trial outcome with a 100% response rate by day 7.  Only when Gilead (NASDAQ: GILD) announced results of their Hepatitis C treatment in May 2013, which became a cure for HCV, did a trial last achieve a perfect response rate status and then increased the company’s market value by $80 billion in the process. Most investors familiar with BioXyTran know the company for its oxygenation drug, BXT-025, which has massive potential across many medical indications, including ischemic stroke. However, fewer investors are just as familiar with the company’s prowess in infectious diseases, specifically with antivirals.  The question on investors’ minds is how an obscure oxygen carrier company turned into a potential pandemic-ending therapeutic company. The answer is that the therapy wasn’t a repurposed drug; it was developed from scratch.

During the pandemic’s start, the company made a hard pivot into COVID-19, where a predominant number of biotechs shifted toward COVID-19 treatments. Clinical trials in chronic diseases slowed to a halt while healthcare facilities focused solely on the pandemic. The company’s deep expertise in carbohydrate chemistry presented a unique opportunity to do what nobody else was doing—design a carbohydrate-based antiviral for COVID-19 that might act as an entry inhibitor instead of blocking viral replication from the inside. The idea’s genesis started in March 2020, when the focus of the world’s researchers was on getting a compromised immune system to respond better and faster to clear the viral infection. The oral version of the antiviral they developed, ProLectin-M, is an unconventional antiviral since it doesn’t interfere at the intracellular level; instead, it blocks viral docking of the virus to the target cell by binding to galectins and a conserved site on the spike protein. Most antivirals work inside the cell, but this works outside the cell as an entry inhibitor.

Overcoming Adversity – David vs. Goliath Struggle

The company successfully jumped through hurdles that other companies did not have placed in their path. They were one of 38 companies suspended by the SEC in a blanket of COVID-19 enforcement action that temporarily suspended the company and effectively forced them to reregister the company in order to achieve trading status via a 15c211 filing. To survive, the company had to raise money as essentially a private company and negotiate with debtors they were in default to. They found the backing of a private equity firm and high-net-worth individuals and went through an almost 2-year process in order to regain trading status while cleaning up all their toxic debt. They were the only company to return to trading status as an OTCQB-listed stock from the SEC COVID trading halts. If the SEC was using the premise of “survival of the fittest” during the COVID halts then BioXyTan might have emerged as a new life form because as you will see their drug not only works but has pandemic-changing potential.

Helping drive the need for new therapeutics is the fall off of vaccine effectiveness, along with COVID-19 becoming an endemic problem. However, it doesn’t seem quite endemic yet as deaths in the United States are still averaging over 2000 weekly. Ongoing infections and hospitalizations as well as antivirals proving effective are going to help validate the long-term stability of a market for antivirals. Thus, this story has become pretty compelling.

BioXyTran’s Value Inflection

Last month, BioXyTran released topline results from its lead asset, ProLectin-M, an orally administered COVID-19 antiviral candidate, in patients with mild-to-moderate COVID-19. The drug exceeded all expectations with:

“-Complete elimination of viral load in 100% of patients at day 7 vs 6% in placebo (p=.001)

-Complete elimination of viral load in 88% of patients at day 3 vs 0% in placebo (p=.001)

-Treated population experienced no viral rebounds within the 14-day observation period”

When looking at these results, investors have to keep in mind that BioXyTran achieved these pristine-looking results despite enrolling patients 1) with high viral load (Ct<25), 2) regardless of vaccination status (unvaccinated and vaccinated), and 3) with any medical conditions—no limits. This is noteworthy because current COVID antivirals aren’t technically indicated for patients who are otherwise considered healthy and vaccinated—Merck (NYSE: MRK) and Pfizer (NYSE: PFE) excluded vaccinated individuals in their phase 3 studies to help them achieve their endpoints. In the case of Paxlovid, there are many contraindications for Paxlovid, which limits its market, which is enormous anyway; Pfizer expects $22 billion in 2022 Paxlovid sales.

It’s a bit of an apples-and-oranges comparison to try to compare these results to Paxlovid because of methods and materials differences and data availability. But by all available measures, it sure looks like ProLectin-M is overthrowing Pfizer’s Paxlovid as the superior COVID-19 antiviral.

The company released data a while ago in a small phase 1 study which suggested that the drug would work fairly well, but issues in gathering data on placebo patients made it really difficult to draw solid conclusions confidently.

However, the new data BioXyTran released arguably puts it in the lead in the COVID-19 antiviral field with respect to viral load data. It seems that no other company could compete to this degree if they wanted to use their antiviral as a prophylactic, which could be especially useful in, for instance, travel or healthcare situations since the viral load can have a great effect on transmissibility.  These two clinical trials denote what looks to be an unstoppable trend that could culminate with regulatory approval.

ProLectin-M Likely Eliminates SARS-CoV-2 More Effectively

This is where the red-apple-to-green-apple comparison sets in. ProLectin is much more effective at quickly bringing the viral load down since it prevents viral entry while helping mop up the existing viral load. However, the only way to really compare the rate of viral elimination (by time-to-Ct≥30) is through two different studies with two different PCR tests, and heterogeneous populations. Despite that, the drastic difference between time-to-undetectable viral burden is so different between the groups that it paints a pretty clear picture of which antiviral likely works better:

A real-world study of Paxlovid and Lagevrio was done in a hospitalized group of patients, where key endpoints measured were time to achieving low viral burden, or Ct≥30. The real-world study showed that the antivirals were highly effective in getting patients’ viral loads down, with cycle threshold values increasing over placebo by ~3 by days 5-7. However, the antivirals failed to cause a large portion of patients to have a low viral burden by days 5-7; if one looks at the excerpted charts below, ~4-5% of patients on those two antivirals had low viral burdens vs ~1-2% in the match controls. Compare this to BioXyTran’s 100% of treated patients reaching Ct≥30 vs 6% of the placebo group reaching Ct≥30.

Adapted from https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00507-2/fulltext

BioXyTran’s treated patient data outperforms the real-world Paxlovid/Lagevrio data to the extent that when it is superimposed on the journal’s graph of the antivirals’ performances, the Prolectin curve doesn’t even fit on the chart, which is cut off at 50%. Note that in BioXyTran’s trial, the placebo arm reached a mere 6% Ct≥30, so the placebo line would basically look flat up until day 7. Does it even matter that the compared populations are heterogenous when Prolectin-M outperforms by such a large margin?

We can do a further comparison with Paxlovid and see that after day 7, Paxlovid mustered a mere ~-1log10 change in viral load over placebo (about 1/10th the viral load). This is good but when compared to Prolectin-M it falls short. Prolectin-M, which is showing about an average Ct value of ~+8 versus placebo on day 7 (which translates to over 1/100th the viral load in my estimation). The picture starts becoming clearer; Prolectin clears the virus really quickly.

https://www.nejm.org/doi/full/10.1056/nejmoa2118542

The last drug to achieve such a high responders rate for viral load was Gilead’s drug Harvoni which is a cure for Hepatitis C.  This drug supplemented Gilead’s HIV business and helped bolster its market capitalization by $80 billion of dollars in the course of 1.5 years.

Tweet

Hepatitis C was indeed an incurable chronic condition that isn’t the same as an acute infectious disease like COVID. But they both have enormous economic burdens. And COVID-19 can lead to Long-COVID.

Long-COVID, however, is also a chronic condition with an immense burden to the person and the overall economy. It is likely that with a lack of viral rebound seen in BioXyTran’s COVID-19 phase 2 and some symptom measurement in the anticipated phase 3 trial, they would be making a great case for Long-COVID. And in terms of economic burden, Long-COVID is estimated to be much greater ($3.7 trillion) than Hepatitis-C, especially when one considers the fact that every time COVID mutates and reinfects patients, it has the chance of causing Long-COVID again. Hepatitis C doesn’t pose the same issue since it’s not airborne.

Two of the leading theories for Long-COVID include viral persistence and the persistence of the spike protein S1 subunit in monocytes. Prolectin-M targets this part of the spike and therefore could theoretically address Long-COVID from either perspective. In fact, when looking at viral rebound after therapy, Prolectin-M exhibited no patients with viral rebound whereas it is documented that “Paxlovid has significant rebound issues: 3.53% and 5.40% for COVID-19 infection, 2.31% and 5.87% for COVID-19 symptoms, and 0.44% and 0.77% for hospitalizations.” So when considering these facts it isn’t a stretch to expect BioXyTran to measure viral rebound in its upcoming phase 3 and potentially even start to pursue Long-COVID.

Financials

BioXyTran has maintained about a $2 million cash burn for the past 2 years, but only has about $0.37 million of cash in the bank. The company will need an estimated $2.7 million outlined in its latest presentation for running its pivotal acute COVID-19 trial. If it wants to pay off its convertible notes, it will need an additional $2.2 million. While this picture, makes it seem like BioXyTran is insolvent and unable to finance a phase 3 trial, its cost structure is extremely lean with officers forfeiting accrued salaries and benefits. The biggest risk with BIXT is their ability to attract capital because the risk of the medicine failing is just not realistic and it may seem too good to be true.  This assumes that the peer review goes off without a hitch and doesn’t turn into a Theranos scandal. While a risk, it is important to characterize it as a very low risk since their journal article included the Mechanisms of Action (MOA) deduced from Nuclear Magnetic Resonance (NMR) imaging. The NMR tests show binding to the spike and arguing against that conclusion is equivalent to saying 1+1 is not equal to 2.

There is also the traditional regulatory risk, but the company is going after approval in the United States and India, so its dual track offers investors a plan B should any barriers present themselves.  The Indian regulatory climate makes it very tough to get a drug into trials because unlike the US FDA all the manufacturing needs to be done beforehand.  However, it’s a dual-edged sword because if the study meets its endpoints in India approval happens swiftly whereas in the United States there is a lot of back and forth on the safety and manufacturing of the drug.

The risk of dilution is very high given that they filed an S-1 on April 12, 2022, but it has not gone effective.  It’s reasonable to assume that BioXyTran got a “no comment” S-1, meaning all they have to do is mark in a price and resubmit it for effectiveness.  The fact that they didn’t complete a raise in light of these phase 2 trial results suggests that the valuation levels might not be high enough or that they might have another plan.

Valuation

The quickest way to figure out what kind of value these homerun phase 2 results brings to BioXyTran is to compare the market potential to existing antivirals on the market and in development. From a sales perspective, Pfizer’s antiviral Paxlovid pulled in sales of $7.5 billion just this last quarter, which met the company’s expectations for $22 billion in the full year. There is a significant market opportunity for new market entrants with differentiated products; a Fierce Pharma article stated that:

“More needs to be done to convince doctors that Paxlovid is a good option for patients, said Angela Hwang, chief commercial officer and president of Pfizer’s global biopharmaceutical business.

‘The one area of education that we need to emphasize is: Who are the eligible people for Paxlovid,” Hwang said. “There are 22 risk factors for who should be eligible and those include those who are over 65—age-related risks—but equal risks like mental health illness, inactive lifestyle, risks you may not be aware of. I think that’s where we want to focus now.’”

BioXyTran probably doesn’t expect to sell its drug with a large sales force. What is more likely is that the company pursues a licensing deal with pharma or sells directly to governments, like when Pfizer sold 10 million courses of Paxlovid to the U.S. government for $5.3 billion.

With respect to stock market value, we can compare to a company that lost billions in market capitalization when its phase 2 results for a COVID-19 antiviral flopped. BioXyTran isn’t the first company to design a phase 2 trial to measure viral load. Well-backed Atea Pharmaceuticals (NASDAQ: AVIR) released topline results from its Phase 2 trial of its own COVID-19 antiviral about a year ago. Atea Pharmaceuticals lost over $2 billion in market capitalization the day it announced that its oral RdRp inhibitor called AT-527, intended to be an improved version of Gilead’s remdesivir, failed to meet its primary endpoint, and the company cited that in a subset of patients, the viral load went down (a little bit): “In high-risk patients with underlying health conditions, a reduction of viral load of approximately 0.5 log10 at Day 7 was observed at 550 mg (prespecified subgroup analysis) and 1,100 mg BID (exploratory subgroup analysis) compared with placebo”.

The drug failed to meet its primary endpoint in patients with mild-to-moderate COVID-19, where BioXyTran passed with flying colors. Compare Atea’s subgroup 0.5log10 reduction in viral load vs placebo at day 7 to my estimate of BioXyTran’s reduction: 2log10 reduction at day 7 for ProLectin vs placebo. Prolectin even compares favorably to Paxlovid’s ~1log10 change vs placebo). So we can speculate that BioXyTran’s results, in the heat of COVID-19, might have been worth $2 billion. While the pandemic fear has subsided, these results are still highly valuable and it’s likely safe to say that an antiviral with robust viral clearance such as Prolectin-M should be worth at least a few hundred million.

In a hypothetical situation where BioXyTran completes its phase 3 trial successfully and secures an order to a government organization in 2024 for 1/5th of what Pfizer did, we can discount that value to the present using a modest P/S multiple of 2.5x and a WACC of 30%, as well as a risk factor of 50%. The resulting value is $784 million. Accounting for some additional dilution, using 150 million shares outstanding, we arrive at $5.23/share. This valuation is well below the $2.2 billion AVIR lost when posting negative phase 2 results, and it is significantly less than the total revenue Pfizer posted for Paxlovid in this latest quarter. From about $0.50 for BIXT shares, this would be a 10-bagger, hypothetically.

Risks

Primary risks at this point include funding; the company needs money to run its phase 3. The company may also have to compete with big pharma to sell their antiviral, though at this point the patient populations do not necessarily overlap much. Lastly, the endpoints currently set in its planned phase 3 trial are primarily seropositivity and secondarily, symptoms, time to discharge, duration of hospitalization, and mortality. Other key antivirals have been approved based on time to resolution of disease/alleviation of symptoms (Tamiflu – Roche (OTCMKTS: RHHBY)) and reduction in hospitalization and death (Paxlovid – Pfizer, and Lagevrio – Merck), all of which are clinical endpoints rather than biomarker endpoints (serum positivity). However, BioXyTran is still measuring clinical endpoints; they’re just listed as secondary endpoints at this time.

As with all clinical-stage biotechnology companies, there are management, funding, and clinical trial outcome risks that in general put biotech companies like this in a very high-risk category, which balances against the high reward. BIXT also trades on the OTC, where volumes are lower and investments can be more speculative.

Conclusion

Bioxtytran is fighting the mindset that COVID is over and that there is no way a small pharma can produce a pandemic-ending therapeutic. The prevailing thought is that the world has entered the endemic phase and that we all must find ways to live with the virus.  The facts tell a different story. Although there are no head-to-head comparisons of ProLectin-M to Paxlovid, BioXyTran’s phase 2 results appear superior in every metric.  There is no known toxicity or drug-to-drug interactions compared to the 40+ known drugs that Paxlovid interferes with. The efficacy results are unprecedented because BIXT had almost a 90% response rate by day 3 and no viral rebounds within 14 days like those that are reported with Paxlovid use. The company also proved their MOA that their drug attaches to the spike protein and galectins to prevent viral entry—these results are not expected to be a fluke. Their journal article BIXT published harps on the idea of reducing infectivity and introduces the idea that by treating the disease early we can potentially prevent Long-COVID.  ProLectin-M is a drug designed for the masses and would likely have broad appeal given its currently-observed tolerability profile.

BIXT has about a $50 million market cap despite its completion of a phase 2, and the price attempted a readjustment on the day of the release but it appears that profit takers had other plans, and the stock isn’t quite well-known yet.  Given the high insider ownership of 75% and the low float of 12 million shares, it takes some time to get the word circulated.  Some may speculate that this could be a cure for COVID because two clinical trials denote a very favorable trend, but what’s arguably more important is counteracting the increased infectivity as the variants have mutated to become more transmissible or evade existing anti-spike antibodies from mass vaccination.  The time spent quarantining and the productivity lost before returning to work or feeling better is all calculus in the future pricing of the drug.  In all likelihood, with governments buying bulky contracts, the governments will set the pricing and consider these factors.  ProLectin-M has the potential to be one of the biggest hits of all time, like Pfizer’s $22 billion Paxlovid, though this claim might seem ridiculous in light of BioXyTran’s market capitalization.  Having a small amount in a portfolio could dramatically improve its performance as word of the clinical breakthrough starts to spread.

Disclosure: MicroCapDaily has not been compensated for this article. This post was written by a guest contributor and posted on our website for free. The owners of MicroCapDaily have no position in any of the securities mentioned.

Continue Reading

BioPharma

Cosmos Holdings Inc (NASDAQ: COSM) Huge Short Position Panicks as COSM Rockets Up the Charts

Published

on

Cosmos Holdings Inc (NASDAQ: COSM) is rocketing up the charts northbound since reversing off $0.0675 lows earlier this month where we first gave the heads up on COSM at around a dime in our article here. Since than COSM has rocketed northbound recently surpassing $0.60 per share with speculators pointing at $1 as the next stop. In our previous article on COSM on November 13 when COSM was $0.10 we stated: “COSM was trading well over $3 at the beginning of this year but has been heavily shorted since than with current estimates of well over 5 million shares sold short and almost the entire public float sold short. 

While COSM has been heavily shorted into oblivion, the Company is actually doing quite well recently reporting revenues for the 3 months ended September 30 were $12 million. The Company is successfully developing their business recently closing a deal with Iberica, a European Airline, for in flight distribution of their products. The CEO has bought millions of shares at current levels and COSM is beginning to go viral on social media trending on the sub reddit Short Squeeze, Number #1 on Stocktwits and multiple videos being made on YouTube about a massive short squeeze taking place in small caps. 

COSM Friday December 2, 4PM Close Update: COSM had a wild trading day on Friday dropping to $0.42 in the morning before rocketing up to $0.61 highs. This was followed by another drop to the $0.47 range before COSM rocketed up in late afternoon trading, closing at $0.53 on 205 million shares traded. COSM was up 33% on the day on around $110 million in dollar volume. COSM is setup for an enormous week ahead, looking to overtake the $0.845 from Monday and embark on a blue-sky breakout with $1 as the first stop. We gave the heads up on COSM when the stock was below $0.10 per share at the beginning of November. We will be updating on COSM as soon as anything new happens so make sure you are subscribed to Microcapdaily by entering your email in the box below.  

Subscribe to Our 100% Free Penny Stock Newsletter. We Have Something Big Coming!

No alternative text description for this imageCosmos Holdings Inc (NASDAQ: COSM) is a global healthcare group that was incorporated in 2009 and is headquartered in Chicago, Illinois. Cosmos Health is engaged in the nutraceuticals sector through its own proprietary lines of products “Sky Premium Life” and “Mediterranation.” Additionally, the Company is operating in the pharmaceutical sector through the provision of a broad line of branded generics and OTC medications and is involved in the healthcare distribution sector through its subsidiaries in Greece and UK serving retail pharmacies and wholesale distributors. Cosmos Health is strategically focused on the R&D of novel patented nutraceuticals (IP) and specialized root extracts as well as on the R&D of proprietary complex generics and innovative OTC products. Cosmos has developed a global distribution platform and is currently expanding throughout Europe, Asia and North America. Cosmos Health has offices and distribution centers in Thessaloniki and Athens, Greece and Harlow, UK. 

The Number #2 post on the subreddit ShortSqueeze currently is titled: COSM about to test resistance. A pump through $0.66 and lift off to over $1.00 is possible now. 

In another post on COSM in the subreddit ShortSqueeze rubio2430 states: “$COSM you cant make this stuff up. this baby is ready for space. the shorts are burying themselves on the daily. constant pr’s, growing fundamentals, no plans on dilutions, dual listing on upstream soon—the list goes on! 

nimble_broccoli replied: Why this is a good play: 

1.) Extremely tiny Marketcap 2.) CEO buying 15’000’000 shares 3.) Good fundamentals, unlike other plays, they actually sell products valued around 10x the valuation. Q1/22 was profitable. 4.) Getting momentum on social media (Reddit Twitter, YT) 

Next catalysts: -Info that they will not be delisted from NASDAQ -Degen and Retail FOMO kicking in -Shorts starting to cover their asses 

In addition, consider this: The stock was somewhere between USD 2 and USD 12 the past ~8 years. Most Hodlers bought back then, do you think they will sell now? Do your own thinking but if one of my stocks dropped 80+ % i d not sell, i d just hope for a miracle or ride it out. Thus, not many regular buy&hold holders of the stock are expected to sell. 

Cosmos operates in the business of full-line pharmaceutical wholesale distribution and serves approximately 1,500 independent retail pharmacies and 40 pharmaceutical wholesalers in Greece region by providing brand-name and generic pharmaceuticals, over-the-counter medicines, vitamins and nutraceuticals. Cosmos invests in technology to enhance safety, distribution and warehousing efficiency and reliability. Specifically, the Company operates a fully automated warehouse system with three robotic systems, two ROWA™ types and one A-frame type, that ensure 0% error selection rate, accelerate order fulfillment, and yield higher cost-efficiency in our distribution center. Cosmos has 3 operating subsidiaries including:

SkyPharm
Sky Pharm SA is headquartered in Thessaloniki, Greece. Sky Pharm trades the excess amounts of about 500 medicines that can be exported within the EU countries. We buy from Greek wholesale pharmaceutical companies and multinational pharmaceutical manufacturers, and export to European markets where demand and prices are substantially higher.
.
DHN
Decahedron Ltd. is a pharmaceutical wholesaler incorporated in the UK in August 2011. It is audited by the MHRA under European GDP (Good Distribution Practices). They are also a full member of the EAEPC and have been audited by TÜV on their behalf.
.
Cosmofarm
Founded in 1994, Cosmofarm is a fully licensed pharmaceutical wholesale company operating in the greater Athens area. The company is approved and authorized by the National Organization for Medicines under Good Distribution Practices to distribute a comprehensive range of pharmaceutical products. Cosmofarm’s core activity is sourcing, procuring, and distributing branded.
.
To Find out the inside Scoop on COSM Subscribe to Microcapdaily.com Right Now by entering your Email in the box below

COSM

Image

COSM business is strong and Q3 highlights include closing a $7.5M capital raise via public offering and signing an exclusive agreement to market and distribute Nickelodeon’s SpongeBob and PAW Patrol kids’ vitamins in Greece and Cyprus, aiming to reach out 11,000 pharmacies and 120 wholesalers in Greece and 780 pharmacies in Cyprus. They also executed a letter of intent for a strategic co-venture agreement with Smart for Life (SMLF) to cross market products and services in their reciprocal markets. COSM also entered into an LOI to acquire ZipDoctor Inc., and entered into an agreement with Virax Biolabs (VRAX), to become the distributor of Monkeypox Virus Real-Time PCR Detection Kits, having the exclusive distribution rights for Greece and Cyprus, with the opportunity to distribute the test kits across Europe on a non-exclusive basis. SkyPharm officially launched its first Sky Premium Life products on Amazon in the United States. Cosmos targets having all 85 SKUs listed on Amazon by year end. COSM entered into an LOI to acquire Pharmaceutical Laboratories CANA S.A., and another LOI to acquire LIFE NLB, Ltd.’s product portfolio, including Bone-Vio® and Bone-X, related to bone health targeting the human gastrointestinal microbiome. 

Last week COSM announced its Sky Premium Life luxury food supplement brand will be sold on Ronda, the official inflight magazine of the airline company Iberia of BRITISH AIRWAYS group. Ronda is available free of charge to the over 10 million passengers who fly Iberian Airlines annually. Iberia Airlines, majority owned by British Airways, has a fleet of 147 aircrafts and engages in over 600 daily flights. 

https://twitter.com/nxtplse/status/1597365583934545920

For More on COSM Subscribe Right Now!

Currently trading at a $36 million market valuation COSM os is 92,008,281 the Company recently reported Q3 Revenues of $12 million down a bit from the same time last year due to a high variation in FX differences between EUR and GBP to USD. COSM was trading over $4 this time last year however OS has increased substantially since then.  COSM is an exciting opportunity in small caps; the stock was shorted into oblivion and currently there are minimum 5.8 million shares short and was way oversold to pennies and it looked as if it would definitely get delisted by the Nasdaq however, led by able CEO Grigorios Siokas, Cosmos is fighting back. Mr. Siokas continues to buy more COSM at current price levels, putting his money where his mouth is as COSM rockets towards $1 which is now just a day and half away if the stock continues up at the same trend.  We will be updating on COSM when more details emerge so make sure you are subscribed to Microcapdaily.

Subscribe to Our 100% Free Penny Stock Newsletter. We Have Something Big Coming!

Disclosure: we hold no position in COSM either long or short and we have not been compensated for this article.

Continue Reading

BioPharma

CytoDyn Inc (OTCMKTS: CYDY) On Watch as Company Hires Ambitious New CEO Who Charts Path Forward (Update on leronlimab)

Published

on

CytoDyn Inc (OTCMKTS: CYDY) has formed a solid base over $0.30 and is beginning to move northbound again. The stock recently made a solid bounce from new 52-week lows of $0.231 to a high of $1.26 per share. CytoDyn was one of the biggest runners of 2020 skyrocketing from pennies to $10 per share before the Citron short attack took the wind out of the stocks sails and the long downward trend began.  CyyoDyn lows earlier this year came as the FDA placed a partial clinical hold on the Company’s HIV program and a full clinical hold on its COVID-19 program in the US. This was followed by the CEO and registered public accounting firm, Warren Averett LLC, both resigning and the Company electing to pause its Brazil COVID-19 trials pending results from its previously scheduled data safety monitoring committee meeting. All of this has culminated in CYDY being offered at a cheap discount to prices from just a few months ago and the opportunity to buy in to Cytodyn for under $0.40 per share.    

CYDY is a highly volatile stock that ran to $10 per share in 2020 with a similar share structure. The underlying science of Leronmilab has not changed; leronlimab has demonstrated significant potential to attack a number of diseases including cancer, and HIV and leronlimab with zero side effects. leronlimab (PRO 140), is an investigational humanized IgG4 mAb that binds to CCR5, a cellular receptor that appears to play multiple roles with implications in HIV infection, tumor metastasis, and immune signaling. leronlimab also has a lot of big believers including many well-respected scientists. Cytodyn recently raised $21.8 million in a stock offering and signed on a new President; Cyrus Arman, Ph.D. who said upon his hiring: “I look forward to uniting our teams and individuals in the pursuit of CytoDyn’s success through a renewed focus on the entrepreneurial spirit. Leronlimab is a unique molecule with the potential to help many individuals, particularly with unmet medical needs. We will focus on enhancing shareholder value through focused execution and refining of the path forward for leronlimab.” 

Subscribe to Our 100% Free Penny Stock Newsletter. We Have Something Big Coming!

CytoDyn Inc (OTCMKTS: CYDY) is a clinical-stage biotechnology company focused on the development and commercialization of Leronlimab, a monoclonal antibody CCR5 receptor antagonist, to be used as a platform drug for a variety of indications. The target of leronlimab (PRO 140) is the important immunologic receptor CCR5. The CCR5 receptor is a protein located on the surface of a variety of cells including white blood cells and cancer cells. On white blood cells, it serves as a receptor for chemical attractants called chemokines. The CCR5 receptor is also the coreceptor needed for HIV to infect healthy T-cells. Recent research has identified the CCR5 receptor as an important target for many disease processes including cancer metastasis and certain immunological conditions. 

Leronlimab is a unique humanized monoclonal antibody. Leronlimab prevents HIV from using the CCR5 receptor as an entry gateway for healthy cells; preclinical research has also shown that leronlimab blocks calcium channel signaling of the CCR5 receptor when present on the cancer cell surface. It is believed that calcium channel signaling of the CCR5 receptor is a crucial component to the spread of metastatic cancer. The CCR5 receptor has been identified as a target in HIV, GvHD, NASH, oncology, transplantation medicine, multiple sclerosis, traumatic brain injury, stroke recovery, and a variety of inflammatory conditions. As we progress in evaluating leronlimab (PRO 140) via a pathways approach, we are encouraged by the opportunity to build a broad pipeline of indications. 

Earlier this year the FDA placed a full clinical hold on CytoDyn’s COVID-19 program and a partial clinical hold on its HIV program in the United States. As the stock price was collapsing Nader Pourhassan resigned and the collapse intensified after the Company’s registered public accounting firm, Warren Averett, LLC resigned. Since than Dr. Cyrus Arman has been appointed as new President of the Company and they are looking at potential strategies including:

  • Strengthening CytoDyn’s pharmacovigilance program enabling it to remove the FDA clinical holds placed on its HIV and COVID-19 programs to allow it to conduct future clinical studies.
  • Advancing CytoDyn’s NASH program to a Phase 2b or Phase 2b/3 trial for steatosis and liver fibrosis associated with NASH.
  • Exploring a study for patients with HIV and NASH as well as review the Company’s strategy for its COVID-19 program.
  • Continuing CytoDyn’s Phase 2 program for metastatic triple-negative breast cancer with current standard of care, explore a Phase 2 colon cancer trial with current standard of care, and explore other solid tumor indications.
  • Continuing CytoDyn’s work to evaluate the feasibility and timelines for the HIV BLA resubmission and explore other cancer and immunologic indications for leronlimab, continue its work on developing a long-acting version of leronlimab, and pursue proof of concept studies for HIV cure using leronlimab and AAV vectors.

To Find out the inside Scoop on CYDY Subscribe to Microcapdaily.com Right Now by entering your Email in the box below

CYDY

Cytodyn has been beefing up its BOD recently appointing Mr. Stephen Simes, a career public company biotech CEO and Mr. Ryan Dunlap, a current CFO with public company biotech experience to its board of directors. They join Tanya Durkee Urbach, Karen J. Brunke, Ph.D. and Lishomwa C. Ndhlovu, M.D., Ph.D. The Company’s corporate website looks more like a big boards. Check out their management team here. As we have reported, on July 9 of this year Dr. Cyrus Arman was appointed President of CytoDyn. 

On October 28 CytoDyn announced it has voluntarily withdrawn its pending BLA for leronlimab as a combination therapy in persons living with HIV with resistance to highly active antiretroviral therapy (HAART) in the HIV multi-drug resistant population (HIV-MDR). The decision to voluntarily withdraw was based on various factors, including systemic issues related to the quality of the data collection and monitoring of the pivotal clinical trials by the clinical research organization (CRO) contracted to manage the trials, resulting in significant concerns with achieving a successful U.S. Food and Drug Administration (FDA) BLA approval. The Company is of the opinion that FDA approval for the HIV-MDR indication is not feasible without significant additional investment to remedy the issues. CytoDyn plans to publish soon the safety and efficacy data in which it met its primary endpoint, in its Phase 2b/3 randomized, double-blinded, placebo-controlled trial for the HIV-MDR population, in a peer-reviewed journal. 

The Company believes the data it currently possesses is sufficient to complete and submit its responses to the FDA to seek the removal of the clinical hold placed on the Company’s HIV program. Further, the Company will continue to leverage the performance of leronlimab in these and other studies to advance leronlimab in other HIV-related, non-alcoholic steatohepatitis (NASH), and oncology indications – where compelling data has been generated – that may benefit a greater number of patients and result in significant shareholder value creation. For example, the Company plans to continue to pursue other underserved HIV-related indications, where it can potentially be first to market. 

Cyrus Arman, Ph.D., President of CytoDyn, stated, “We have decided to voluntarily withdraw our BLA for the HIV-MDR population at this time only after extensive review and deliberation, including audits from three external independent regulatory quality firms. While the Company met its primary endpoints in these pivotal trials, which we think is a clear indication that leronlimab performs well in the clinic, we believe the issues identified in each of the three independent audits related to the quality of the data collection and oversight by the CRO make it difficult to support a successful BLA regulatory submission. Further, we have filed a claim against the CRO seeking damages resulting from its breach of the Master Services Agreement and related agreements and reimbursement of our attorney fees and costs associated with the action. As previously discussed, we are focusing on continued development in other HIV indications, NASH, and oncology, where we have Fast Track designation for metastatic triple-negative breast cancer. We plan to reenter the clinic in those indications and believe these steps will allow us to further build on the strong signals we have seen in these indications. I am very excited and quite optimistic about these opportunities, which are what ultimately attracted me to leronlimab and CytoDyn. I believe we have a unique opportunity to impact a significant number of patient lives while creating long-term value for our shareholders.”

For More on CYDY Subscribe Right Now!

Currently trading at a $310 million market valuation CYDY is fully reporting OTCQB and while they are pre-revenue the Company has close to $100 million in assets and about the same in debt. At current levels CYDY is worth a close look; The stock was one of the biggest runners of 2020 skyrocketing from pennies to $10 per share. Now trading for under $0.40, the underlying science has not changed; leronlimab has demonstrated significant potential to attack a number of diseases including cancer, HIV and coronavirus with zero side effects. leronlimab (PRO 140), is an investigational humanized IgG4 mAb that binds to CCR5, a cellular receptor that appears to play multiple roles with implications in HIV infection, tumor  metastasis, and immune signaling. Now that Cytodyn has completed a stock offering and brough on new CEO Cyrus Arman, Ph.D. things could be on the up and up here. With a recent low of $0.231, a high of $10 CYDY at $0.38 should be at the top of speculators watch lists. We will be updating on CYDY when more details emerge so make sure you are subscribed to Microcapdaily.

Subscribe to Our 100% Free Penny Stock Newsletter. We Have Something Big Coming!

Disclosure: we hold no position in CYDY either long or short and we have not been compensated for this article.

Continue Reading

Trending

© All rights reserved.

Sign up now for our 100% FREE Penny Stock Newsletter

Privacy Policy. we will never share your email with anyone.