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It is not new
it is not fake.
What is it?
Based on the search parameters it mixed information from possible results.
The information it mixed was from a Linkedin post by Chandra:
https://uk.linkedin.com/posts/martinemeeson_fujifilm-diosynth-biotechnologies-on-linkedin-activity-6979092084079112192-HYut?trk=public_profile_like_view
Gaurav Chandra MD,MBA
Chief Operations Officer and Board of Director Enzolytics, VP Research and Development & AI Platform
4mo
Congratulations! Martin Meeson
I don't profess to know anything as my post clearly stated that nobody knows outside the companies involved if there is any relationship.
Still waiting for an answer to what information do you have that there isn't a relationship between the 2 companies?
No need to reply as like as said nobody knows.
Nobody outside of ENZC and REGN knows if there is an agreement (NDA) between the companies.
Nobody is hyping about Regeneron.
Just stating facts of actual events that has occurred.
There are numerous sources that suggest a connection between Regeneron and Enzolytics:
1. The Chandra interview
2. conspicuously similar technology if not identical to Enzolytics
3. NDAs
4. Dr. Suraj Kumar Saggar
What information do you have that there isn't a relationship between the 2 companies?
How monoclonal antibodies lost the fight with new COVID variants
https://www.npr.org/sections/health-shots/2022/11/20/1137892932/monoclonal-antibodies-covid-treatment
Monoclonal antibodies were once the star of COVID-19 outpatient treatments. Since they first became available in 2020 – even before the first vaccines – more than 3.5 million infusions of the factory-grown proteins have been given to patients in the U.S. to help reduce risk of hospitalization.
But one by one, different monoclonal treatments have lost their efficacy against new variants of the coronavirus. The rise of Paxlovid antiviral pills earlier this year, further dented their appeal.
Now, a new wave of omicron subvariants that are the best yet at evading the immune system's current defenses have taken over in the U.S. They're expected to knock out bebtelovimab, the last monoclonal antibody treatment standing against the coronavirus. Soon, it'll join bamlanivimab, casirivimab, sotrovimab and others in the graveyard of monoclonals that once targeted past COVID strains until they were outflanked by variants that evaded their protection.
"Monoclonals had their day, like the Model T or the biplane," says Carl Dieffenbach, director of the Division of AIDS at the National Institutes of Health, and lead of the NIH's Antiviral Program for Pandemics, "Now it's time to move on."
Not everyone entirely agrees. Monoclonals are still useful, some doctors say, for treating a vulnerable population.
"There are severely immunosuppressed patients that are not likely to mount an immune response to the virus, even if you treat them with antiviral drugs," says Dr. Raymund Razonable, an infectious disease specialist in the transplant division at the Mayo Clinic. "This is the group that is going to be the most affected by the absence of antibody-based therapies."
What's more new research is underway to develop new types of monoclonal antibodies that could even hold up against new variants.
How monoclonals work — and what they're up against
Monoclonal antibody treatments have always had a major weakness – they're easily outmaneuvered by new COVID strains. It's a flaw that's baked into how they work.
Monoclonal antibodies are lab-grown proteins that supplement your body's immune system – which, in most people, is naturally producing antibodies to hunt for possible threats all the time.
"You and I and every human being that has a functioning immune system is walking around with probably trillions of totally different antibody molecules just circulating in our blood," says Derek Lowe, a chemist and blogger for the journal Science, "Every one of us has a totally different suite of them. There are more of them than there are stars in the sky."
The tiny, Y-shaped proteins lurk in the blood in low concentrations, "waiting and waiting until they happen to bump into something that they stick to really well, and they find their soulmate, basically," Lowe explains. That "soulmate" is an antigen – a foreign substance that's entered the bloodstream, like a bacterial protein or a virus or a pollen grain.
Once a monoclonal antibody finds its soulmate — in the case of COVID, a specific part at the tip of the SARS-CoV-2 virus – it binds to the surface of the antigen. Then, it sends out signals to the immune system, "like hey, I've got a live one," Lowe says.
The most powerful antibodies can stop the virus in its tracks just by binding to it. For instance, "if you have an antibody that sticks to the tip of the spike protein at the business end of the virus – just the fact that it is stuck tightly to that means the virus cannot infect a cell," says Lowe.
The spike protein has been the target of all the monoclonal antibody treatments that go after the virus thus far. But it's been a fickle soulmate, changing with new variants, leaving the monoclonal antibodies adrift in the bloodstream with nowhere to bind.
Companies have stopped bringing these monoclonals to market. The federal government stopped promising to buy them in quantity, making it a riskier bet for companies.
"There are antibodies out there, but nobody has the $200 million to develop it," Dieffenbach says, citing costs that include producing the antibodies, running trials and getting them authorized by the Food and Drug Administration. Some companies figured it wasn't worth it, for a product that was likely to become obsolete in a matter of months, he says.
To be clear, these are antibody treatments for outpatient treatment. There is a different kind of monoclonal antibody treatment for hospitalized patients that remains viable. Actemra, as it's called, is not susceptible to virus mutation because it targets the body's immune reaction to the virus, rather than the virus itself.
New directions in research, and a potential comeback
There might still be hope for monoclonals. Drugmakers and researchers at government agencies are now retooling the strategy, looking for monoclonal antibodies that could last.
"Initially, the focus was, 'let's just find the most potent antibodies,'" says Joshua Tan, chief of the Antibody Biology Unit at NIH. "Now, there's awareness that we need to find antibodies that are likely to work against not just the [current version of the] coronavirus, but whatever may come."
In his lab in Rockville, Md., Tan and the researchers who work with him are looking for antibodies that target parts of the virus that have stayed the same on several different viruses within the larger coronavirus family. "We're looking at other parts of the spike protein that may be more consistent and may be harder to mutate," Tan says.
To achieve this, researchers in Tan's lab are taking immune cells from the blood of patients that have recovered from COVID, and pelting them with tiny plastic pellets covered with spike proteins from different, older coronaviruses to see which cells respond. "Not the [COVID] variants, but SARS-CoV-1, SARS-CoV-2, MERS [etc.]," post-doctoral researcher Cherrelle Dacon clarifies. "These are seven different coronaviruses, all of which infect humans."
The immune cells that react to several different coronaviruses are making antibodies that bind to a part of the spike protein that's staying the same across them.
It's a painstaking process: Isolating individual immune cells, finding the ones that make antibodies in response to various spike proteins — and then using those to make more antibodies that they can scale up, analyze and test, to figure out what on the virus they're actually binding to. The process takes about three to four months each cycle, Tan says.
Tan says the good news is that they've found some antibodies that stick to multiple different coronaviruses. They published some of the results earlier this summer in Science.
But the problem the researchers have come up against is that the monoclonal antibodies they've found are not so potent. Tan says there seems to be a tradeoff – between how well a monoclonal antibody against COVID-19 works, and how long it lasts before the virus ditches the antibody's target.
An analogy: If the coronavirus had human body parts (which it doesn't) the old, highly effective monoclonals hit the virus's spike protein squarely on the nose. In contrast, the new monoclonals Tan is finding try to grab it by the armpit. "One of the issues appears to be that it's harder to reach those parts," Tan says, "What the broader, less potent [antibodies] need is for the spike protein to shift in shape" in order for them to grab it.
Tan is working to find ways around this tradeoff. He says you can potentially modify the antibody, change out parts of it to increase its potency – a process that's largely theoretical at the moment, and will take some time to work out.
So while Tan and other researchers work on the next generation of monoclonal antibodies – ones that work well against all kinds of coronaviruses, maybe even future pandemic ones – the nation is entering a long lull with no monoclonal antibody treatments that work against dominant strains of SARS-CoV-2.
"The disappointment is there because you're losing a really good drug," says Razonable. "But you focus on the next options. The virus adapts, and we also adapt based on what we have available."
Luckily, as Tan and others pursue the long game with antibodies, there are other treatments, like Paxlovid pills and remdesivir infusions, that still work against COVID.
And the research on and rapid development of antibody treatments has opened up possibilities beyond COVID. "It has improved the production of monoclonals for cancer, for immunologic diseases," says Dieffenbach, "It's going to be easier to produce monoclonals in the future because of the lessons learned from SARS-CoV-2. Nothing was wasted here."
There are numerous sources that suggest a connection between Regeneron and Enzolytics:
1. The Chandra interview
2. conspicuously similar technology if not identical to Enzolytics
3. NDAs
4. Dr. Suraj Kumar Saggar
5. Finally one must recognize that Regeneron are experts when it comes to antibodies however their process for developing antibodies for viruses didn't take in consideration for virus escape so once the virus mutates to a certain degree eventually their antibodies becomes useless.
ENZC has been saying for "years" to defeat a virus:
Big Pharma knew what ENZC was saying however they didn't want to shut down the virus because they were making "boatloads of money", billions and billions of dollars.
Finally the variants outpaced Big Pharma antibodies and the billions stopped flowing.
Well what do you know one of the Big Pharma has technology conspicuously similar to ENZC.
Why? Money
How? NDA?
When? After all Covid Antibodies where shut down by the FDA
Who? Regeneron
Regeneron’s lastest antibody is different as it binds outside the RBD and NTD regions:
Differentiated vs. prior antibody approaches:
• Binding site outside of immunodominant, highly variable RBD and NTD regions, lowering risk of losing activity against future variants
• Targeted epitope highly conserved, with over 99.9% conservation since beginning of the pandemic
• Demonstrated high neutralization potency against all known SARS-CoV-2 variants and lineages to date
https://investor.regeneron.com/static-files/5f682777-4984-400b-bacb-3041044bb4b6
Somehow in a short period of time when the FDA shut down their previous antibody, Regeneron introduces a new and improved antibody that is totally different from their previous antibodies and uses a different procedure from the one they spent decades creating VelocImmune and related VelociSuite technologies.
Regeneron, which early on in the pandemic developed a monoclonal antibody cocktail to address a treatment paradigm for COVID, is pivoting to what CEO Len Schleifer called “the jackpot antibody.”
In the video below (1:50) the CEO also said "our team found a one in million antibody, a very very rare antibody that seems to be able to neutralize in a very potent way in every known variant to date."
https://www.cnbc.com/video/2023/01/10/regeneron-ceo-on-the-prospects-for-its-eye-drug-eylea.html
In response to the original antibodies losing their efficacy, the company has developed a new one. The drug, dubbed REGN-14287, “has demonstrated potency against all known SARS variants and lineages to date,” reported Regeneron chief scientific officer George Yancopoulos, adding that the biotech expects the drug to enter clinical development later this year.
https://www.mmm-online.com/home/channel/jpm23-week-storm-prep-top-of-mind-for-biopharma-ceos/
What changed their focus?
Why the sudden change in direction?
Are other companies involved?
Could Enzolytics be involved?
Monoclonal Antibodies Are Now Being Recognized as a Significant Therapeutic for Treating COVID-19.
A new wave of recognition is now emerging in the healthcare and political arenas regarding the significance of monoclonal antibodies. The U.S. government has spent $2.65 Billion on the Regeneron monoclonal antibodies and on August 20, 2021, the UK approved the Regeneron/Roche antibodies cocktail for COVID-19. There is now widespread recognition of the potential effectiveness and role that monoclonal antibodies can play in current and future pandemics.
The Enzolytics process differs from the process used by Regeneron. Regeneron antibodies are produced by the company's VelocImmune® mice, which have been genetically modified to have a human immune system. Enzolytics’ process does not use mice with a genetically modified human immune system. The Enzolytics’ proprietary methodology for creating hybridomas produces a specific monoclonal antibody secreted by human immune B cells—obtained from convalescent donor patients—followed by isolating a single cell that produces a monoclonal antibody that targets an identified conserved epitope on the virus.
A primary distinction of the Enzolytics process for creating fully human monoclonals is the starting point is from human “immune-B cells” from humans who have survived successfully from a "natural" CoronaVirus infection. These antibodies will retain the original natural antibody affinity and specificity and have a lower risk of immunogenicity when used as a therapeutic. They are expected to provide broad-spectrum coverage against viral variants with increased potency, stability as a single-domain molecule, and, in the recombinant form, will have accessibility to the virus epitopes (binding sites) not accessible with a whole antibody.
https://enzolytics.com/company-news/
There are currently no monoclonal antibody treatments authorized for use in the United States. Because the virus that causes COVID-19 continues to change, previously available monoclonal antibody treatments do not protect against the currently circulating variants and subvariants.
https://www.lung.org/lung-health-diseases/lung-disease-lookup/covid-19/treatment-recovery/monoclonal-antibodies
https://www.cms.gov/monoclonal
Enzolytics Inc. Shares Current BioClonetics Immunotherapeutics, Inc. Update
AccessWire - Fri Nov 13, 2020
PLANO, TX / ACCESSWIRE / November 13, 2020 / Enzolytics Inc. (OTC PINK:ENZC) or the "Company" today shared the following update provided by ENZC's Merger target BioClonetics Immunotherapeutics, Inc. ("BCLS" or "BioClonetics"), resulting from the application of proceeds from the initial funding received on October 26, 2020. The full text of the update is presented below.
November 13, 2020
Dear Investors and Supporters,
We are making great progress on our plans to further develop additional anti-HIV monoclonal antibodies and to now begin the production of fully human monoclonal antibodies targeting the CoronaVirus. On December 1, we are expanding our lab to the campus of Texas A&M University at its Institute for Preclinical Studies. This expansion will allow us to complete production of monoclonal antibodies against both the HIV virus and the CoronaVirus and collaborate with the biopharma experts on the campus. Although we have NIH grant applications pending for the production of anti-HIV and anti-CoronaVirus monoclonal antibodies, we have secured funding that allows us to proceed without delay.
We welcome the recent news from Eli Lilly regarding its production of monoclonal antibodies for treatment of COVID-19 patients. We note that experts agree that for a monoclonal antibody therapy to be effective, a "combination" (or "cocktail") of such antibodies used in combination will likely be needed. Dr. Anthony Fauci, head of NIAID/NIH, has repeatedly clarified (as recently in his keynote address at the AIDS International Conference) that a success in treatment of such viruses can be expected to be found in the use of multiple broadly neutralizing HIV antibodies - meaning several antibodies that neutralize a broad spectrum of a virus in its numerous mutation forms.
Thus, we recognize that while other pharma companies may produce effective antibodies, there will necessarily be a need for additional monoclonal antibodies to be used in tantum with those initially discovered. Also, and unfortunately, the mutation of viruses, both the HIV and the CoronaVirus, will necessitate the production of numerous effective antibodies as the virus mutates around the therapeutics initially discovered.
Here is why we are confident in our technology.
It will be imperative that produced antibodies target a conserved and immutable site on the virus - otherwise the antibody (over time) will be rendered ineffective due to mutation - known as "virus escape". Our anti-HIV monoclonal antibody targets an immutable virus site on the HIV virus - one that is constant within virtually all 6000 now known different HIV isolates (strains) of the virus. The CoronaVirus has structure correlative to that of the HIV virus. Because our primary anti-HIV monoclonal antibody has been proven to neutralize numerous different strains of the HIV virus in tests in 5 international labs, and knowing the binding site on the HIV virus to which our antibody binds resulting in neutralization, this knowledge provides insight necessary to identifying corresponding structure (amino acid sequences) on the CoronaVirus that should be targeted to effectively neutralize the CoronaVirus. Moreover, we have proprietary methodology needed to produce anti-CoronaVirus monoclonal antibodies targeting such known - to us - sites.
Thus, while the Eli Lilly monoclonal antibody will hopefully have lasting effect, if it is targeting a mutable site on the virus, the virus may "escape" around it. And indeed, a close look at the results of the Eli Lilly initial tests of its antibody show that the antibody reduced the effect of the virus in some but not all of the patients receiving the antibody.
Thus, even these initial Eli Lilly trials demonstrate that additional monoclonal antibodies can be expected to be needed to fully treat COVID-19 patients.
The procedure for producing monoclonal antibodies is also significant and our procedure differs from those used by other pharma companies. In some cases, other pharma companies produce "humanized" rat and mouse monoclonal antibodies where the original antibody affinity and specificity are not maintained, and the chances of immunogenicity are increased. Our methodology also differs significantly from other pharma approaches using the transgenic mouse model [a human immune system which has been "grafted" within a mouse model] having been "vaccinated" with specific and selected purified CoronaVirus Proteins.
In contrast, our model starts with human "immune-B cells", obtained from convalescent individuals who have recovered from the CoronaVirus. The primary distinction of our process for creating fully human monoclonals is the starting point - namely from human "immune-B cells" from humans who have survived successfully from a "natural" CoronaVirus infection. From these, we then produce antibodies that target conserved immutable sites on the virus - to avoid "virus escape".
Additionally, our antibodies retain the original natural antibody affinity and specificity and have lower risk of immunogenicity when used as a therapeutic. They will provide broad-spectrum coverage against viral variants with increased potency, stability as a single-domain molecule, and, in the recombinant form, will have accessibility to the virus epitopes (binding sites) not accessible with a whole antibody.
We are actively moving forward in our production and testing of such antibodies.
Sincerely,
Charles S. Cotropia
CEO
BioClonetics Immunotherapeutics, Inc.
The recent appointment of Dr. Ronald Moss to the medical advisory board is another step toward achieving a successful combination of the management and technology teams and business strategies of the two entities. The second tranche of the initial funding is scheduled for receipt early next week and those funds will be used to further our clinical and administrative progress. Final documentation of the combination agreement is currently being reviewed with closing anticipated to be before the end of the month.
About Enzolytics, Inc;
Enzolytics, Inc. is a drug development company committed to the commercialization of its proprietary proteins for the treatment of debilitating infectious diseases. Immunotech is committed to creating drugs for the better health of mankind. Enzolytics is a 49% shareholder of IMMB BG.
Enzolytics' flagship compound ITV-1 (Immune Therapeutic Vaccine-1) is a suspension of Inactivated Pepsin Fraction (IPF), which studies have shown is effective in the treatment of HIV/AIDS. IPF is the active drug substance of ITV-1 and is a purified extract of porcine pepsin. ITV-1 has been shown to modulate the immune system.
About BioClonetics Immunotherapeutics, Inc.
BioClonetics Immunotherapeutics, Inc. is a Dallas Texas biotech company with proprietary technology for producing fully human monoclonal antibodies (mAbs) against infectious diseases including HIV, rabies, influenza A, influenza B, tetanus, and diphtheria. Its proprietary methodology for produce fully human monoclonal antibodies may be used to produce therapeutics treatments for many infectious diseases including the CoronaVirus.
Safe Harbor Statement:
This news release contains forward-looking statements that involve risks and uncertainties associated with financial projections, budgets, milestone timelines, clinical development, regulatory approvals, and other risks described by Enzolytics, Inc. (f/k/a Eco Petroleum Solutions, Inc. / Immunotech Laboratories, Inc.) from time to time in its periodic reports filed with the SEC. IPF is not approved by the US Food and Drug Administration or by any comparable regulatory agencies elsewhere in the world.
While Enzolytics, Inc. believes that the forward-looking statements and underlying assumptions contained therein are reasonable, any of the assumptions could be inaccurate, including, but not limited to, the ability of Enzolytics to establish the efficacy of IPF in the treatment of any disease or health condition, the development of studies and strategies leading to commercialization of IPF in the United States, the obtaining of funding required to carry out the development plan, the completion of studies and tests on time or at all, and the successful outcome of such studies or tests. Therefore, there can be no assurance that the forward-looking statements included in this release will prove to be accurate.
Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of the statements made, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. These forward-looking statements are made as of the date of this press release, and the Company expressly disclaims any intention or obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements.
IR Contact:
Enzolytics, Inc.
2000 North Expressway
Plano, TX 75074
Phone: (972) 292-9414 Fax: (972) 292-9414
SOURCE: Enzolytics, Inc.
https://www.biospace.com/article/releases/enzolytics-inc-shares-current-bioclonetics-immunotherapeutics-inc-update/
Yup and I realize` that some jackpots are small and some JACKPOTS are BIG.
I believe the CEO of Regeneron was most likely referring to a big jackpot as his company created approximately a quarter of all original, FDA-approved fully human monoclonal antibodies currently available.
It depends on what the news is.
Long term ENZC technology/patents can sustain it stock price to a much higher level than where it is today.
There is no reason for it to be higher than it is now.
The company is not producing any income.
The company has been at Texas A&M creating shareholder value that has yet to be realized.
Regeneron next generation Covid antibody is very similar to ENZC process.
Even if Enzolytics and Regeneron are not working together, there is a very likely chance that the targeted conserved site Regeneron intends to use has been patented by ENZC so there is a revenue flow in the making.
Again the Regeneron CEO said it all:
Regeneron, which early on in the pandemic developed a monoclonal antibody cocktail to address a treatment paradigm for COVID, is pivoting to what CEO Len Schleifer called “the jackpot antibody.”
What is extremely important and powerful about ENZC process is that it can be used against different diseases/viruses.
Nope that is the SEC job to stop illegal manipulation.
It is the CEO job is to create sustained value for shareholders.
Big Pharma don't care nothing about what is going on with ENZC stock.
Big Pharma only want ENZC technology.
What did Regeneron CEO say about their next Covid Antibody:
Regeneron, which early on in the pandemic developed a monoclonal antibody cocktail to address a treatment paradigm for COVID, is pivoting to what CEO Len Schleifer called “the jackpot antibody.”
Why did he call it the “the jackpot antibody.”
Binding site outside of immunodominant, highly variable RBD and NTD regions, lowering risk of losing activity against future variants
Targeted epitope highly conserved, with over 99.9% conservation since beginning of the pandemic
How does Regeneron process compares to Enzolytics process?
The Enzolytics’ proprietary methodology for creating hybridomas produces a specific monoclonal antibody secreted by human immune B cells—obtained from convalescent donor patients—followed by isolating a single cell that produces a monoclonal antibody that targets an identified conserved epitope on the virus.
Although we all want to know what the heck is going on with ENZC and why they have been so silent on where they stand on results of on-going operations, we do know progress have been made albeit a bit or should say quite a bit behind schedule.
The biggest mystery is who are ALL the other players.
ENZC has shared over the past couple of years their progress and intentions as evident in press releases.
They have been limited in what they can release on certain information when NDAs were set up.
https://www.theglobeandmail.com/investing/markets/stocks/ENZC/pressreleases/
The NDAs suck do to lack of information however because of them we are likely to make a very profitable return on our investment.
To accelerate and fully execute the successful production of the multiple monoclonal antibodies, the subject of the Company's intellectual property (specifically the numerous monoclonal antibodies (mAbs) targeting both human and animal viruses), the Company continuously engages with numerous entities to accelerate its progress toward production, testing, and delivery of successful therapeutics. Entities with whom the Company is working include other Biotech Companies having:
? Technology and processes for accelerating the production of monoclonal antibodies that target critical virus
sites identified by the Company using its A.I. platform. The Company has identified critical conserved target
sites on 20 viruses, including human and animal viruses, and is engaging with biotech companies having
expertise in accelerating the production of such antibodies.
? Related, synergistic or complimentary therapeutics and business structure for the purpose of potential
combination with other biotech entities.
? Expertise in providing specialized peptides having precise amino acid sequences corresponding to the precise
target sites on both the Coronavirus and HIV viruses which are then used in the Company’s Texas lab against
which mAbs are being produced. This strategy accelerates the production of the mAbs for further development.
? Specialized cell sorting technology that is complementary to the process used in the Company’s lab to
accelerate production of mAbs for advancing production.
? Expertise in hybridoma production techniques for producing mAbs using hybridoma methodologies
complementary to the process used in the Company's lab.
? Animal trials centers, both in the U.S. and abroad, for the preparation of animal trials.
? Promotional entities with specialized expertise in targeting large funding sources for the purpose of raising the
substantial funds needed for the production of the recombinant mAbs necessary for future trials and for
conducting animal trials.
As to each of these entities and those with whom the Company currently works on an ongoing basis, the Company has
entered into NDAs (Nondisclosure Agreements) necessary to preserve and protect the Company plans and intellectual
property being discussed and exchanged between the parties. These contractual restrictions are critical for the Company
and its partners. Maintenance of strict confidentiality is essential to preserving intellectual property rights (patent rights)
which are now being sought and will be sought in the future. Premature disclosure of information can bar the right to
seek patent protection at a later date. The Company is not able to share specific details regarding arrangements
regarding these NDAs.
The term of these NDAs is not time limited. The term extends until the later of five (5) years from the Effective Date or
"until such time as the proprietary information is publicly known and made generally available". This provision is
necessary because under Patent Laws an issued patent may be invalidated where the patent is filed subsequent to
public disclosure of the invention claimed. In view of this limitation, the Company makes no public disclosure of
information subject to NDAs and inventions covered by them.
Additionally, certain technical information shared with companies with whom the Company has entered into an NDA may
not be included in a patent application, but rather the subject technical information is maintained as Company confidential
("secret") indefinitely. Also, in these Agreements, the parties generally agree not to reveal the names of the contracting
parties for a specified period.
The Company is very confident in its Artificial Intelligence empowered Intellectual Property Portfolio. It has allowed the
Company to claim exclusive rights on an international stage covering critical target sites on numerous human and
animal viruses. This places the Company on an equal level with the largest biotech companies in that the Company is
the first to identify and patent critical sites on many human and animal viruses. This same technology and strategy are
being implemented by the Company on new viruses, human or animal. The Company identified the conserved sites on
the Monkeypox Virus even before the World Health Organization declared it a global health emergency last week.
The Company believes that its extensive patent portfolio will provide a return on investment through partnering or
licensing technology covered by multiple international patents.
http://www.otcmarkets.com/otcapi/company/financial-report/346487/content
Crazy Amazing.
ENZC technology fingerprints is all over REGN 14287.
Regeneron:
Targeted epitope highly conserved, with over 99.9% conservation since beginning of the pandemic
Enzolytics:
The Enzolytics’ proprietary methodology for creating hybridomas produces a specific monoclonal antibody secreted by human immune B cells—obtained from convalescent donor patients—followed by isolating a single cell that produces a monoclonal antibody that targets an identified conserved epitope on the virus.
When will the full story of Enzolytics, Regeneron and probably other unnamed suitors come to light.
Regeneron previous antibody had limitations due to the way it attacked the virus:
REGEN-COV (casirivimab and imdevimab) is a cocktail of two monoclonal antibodies that was designed specifically to block infectivity of SARS-CoV-2, the virus that causes COVID-19, using Regeneron's proprietary VelocImmune® and VelociSuite® technologies. The two potent, virus-neutralizing antibodies that form the cocktail bind non-competitively to the critical receptor binding domain of the virus's spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population, as detailed in Cell and Science.
About Regeneron's VelocImmune Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and
Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately a quarter of all original, FDA-approved fully human monoclonal antibodies currently available. This includes REGEN-COV (casirivimab and imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb) and Inmazeb™ (atoltivimab, maftivimab and odesivimab-ebgn).
https://investor.regeneron.com/news-releases/news-release-details/regeneron-announces-new-us-government-agreement-purchase
Regeneron’s lastest antibody is different as it binds outside the RBD and NTD regions:
Differentiated vs. prior antibody approaches:
• Binding site outside of immunodominant, highly variable RBD and NTD regions, lowering risk of losing activity against future variants
• Targeted epitope highly conserved, with over 99.9% conservation since beginning of the pandemic
• Demonstrated high neutralization potency against all known SARS-CoV-2 variants and lineages to date
https://investor.regeneron.com/static-files/5f682777-4984-400b-bacb-3041044bb4b6
Somehow in a short period of time when the FDA shut down their previous antibody, Regeneron introduces a new and improved antibody that is totally different from their previous antibodies and uses a different procedure from the one they spent decades creating VelocImmune and related VelociSuite technologies.
Regeneron, which early on in the pandemic developed a monoclonal antibody cocktail to address a treatment paradigm for COVID, is pivoting to what CEO Len Schleifer called “the jackpot antibody.”
In response to the original antibodies losing their efficacy, the company has developed a new one. The drug, dubbed REGN-14287, “has demonstrated potency against all known SARS variants and lineages to date,” reported Regeneron chief scientific officer George Yancopoulos, adding that the biotech expects the drug to enter clinical development later this year.
https://www.mmm-online.com/home/channel/jpm23-week-storm-prep-top-of-mind-for-biopharma-ceos/
What changed their focus?
Why the sudden change in direction?
Are other companies involved?
Could Enzolytics be involved?
Monoclonal Antibodies Are Now Being Recognized as a Significant Therapeutic for Treating COVID-19.
A new wave of recognition is now emerging in the healthcare and political arenas regarding the significance of monoclonal antibodies. The U.S. government has spent $2.65 Billion on the Regeneron monoclonal antibodies and on August 20, 2021, the UK approved the Regeneron/Roche antibodies cocktail for COVID-19. There is now widespread recognition of the potential effectiveness and role that monoclonal antibodies can play in current and future pandemics.
The Enzolytics process differs from the process used by Regeneron. Regeneron antibodies are produced by the company's VelocImmune® mice, which have been genetically modified to have a human immune system. Enzolytics’ process does not use mice with a genetically modified human immune system. The Enzolytics’ proprietary methodology for creating hybridomas produces a specific monoclonal antibody secreted by human immune B cells—obtained from convalescent donor patients—followed by isolating a single cell that produces a monoclonal antibody that targets an identified conserved epitope on the virus.
A primary distinction of the Enzolytics process for creating fully human monoclonals is the starting point is from human “immune-B cells” from humans who have survived successfully from a "natural" CoronaVirus infection. These antibodies will retain the original natural antibody affinity and specificity and have a lower risk of immunogenicity when used as a therapeutic. They are expected to provide broad-spectrum coverage against viral variants with increased potency, stability as a single-domain molecule, and, in the recombinant form, will have accessibility to the virus epitopes (binding sites) not accessible with a whole antibody.
https://enzolytics.com/company-news/
There are currently no monoclonal antibody treatments authorized for use in the United States. Because the virus that causes COVID-19 continues to change, previously available monoclonal antibody treatments do not protect against the currently circulating variants and subvariants.Dec 7, 2022
https://www.lung.org/lung-health-diseases/lung-disease-lookup/covid-19/treatment-recovery/monoclonal-antibodies
https://www.cms.gov/monoclonal
Nasser Alhaj Ali, Ph.D.
Research Scientist
About
I am a research scientist with Enzolytics Inc, a drug development company that focuses on multiple therapies for infectious diseases. I am leading the development of vaccines in the areas of infectious disease and chronic medical disease to create effective therapeutic monoclonal antibodies. My project focus on designing and developing next-generation monoclonal antibodies (mAbs) that represent one of the fastest-growing classes of protein therapeutics.
I have demonstrated expertise in understanding of immune system, preparing and optimizing protocols, identifying and troubleshooting experimental issues, and determining appropriate solutions.
I am an articulate team player, proficient in evaluating and analyzing validation data, verifying the adequacy of data, organizing and managing documents/reports, organizing and arranging large-scale experiments.
I possess in-depth knowledge and working understanding of immunoassays and molecular assays in BSL1 and BSL2 environments.
I orchestrate strong communication, critical thinking, and exceptional lab skills. Capable of leading research projects within strict time and budget constraints.
While others take pride in meeting all standards set before them, my passion is for delivering service that goes beyond organizational expectations, creating a win-win scenario for everyone involved!" Please feel free to contact me at alhaj2001@aggienetwork.com with any thoughts, comments, or questions about my work. I'm always interested in making new professional acquaintances.
Postdoctoral Researcher
Enzolytics Immunotherapeutics
May 2021 - Present1 year 9 months
College Station, TX, United States
https://www.linkedin.com/in/nasser-alhaj-ali-ph-d-90b07658
Biopharma buyers continue to shift deal-making spending away from M&A
10-Jan-2022 By Jane Byrne
Strategic partnerships rather than M&A will be key for biopharma companies in 2022, finds a report from EY.
HTTPS://WWW.BIOPHARMA-REPORTER.COM/ARTICLE/2022/01/10/BIOPHARMA-BUYERS-CONTINUE-TO-SHIFT-DEAL-MAKING-SPENDING-AWAY-FROM-M-A
Investor Relations Considerations for Biotechs Partnering with Big Pharma
Public and private investors in biotechnology stocks always look for the third-party validation of a biotech’s claims and technology. Multiple parties can provide such endorsements, including marquee investors, the scientific conferences at which biotechs present, the journals in which preclinical and clinical data is published, the caliber of members on your board and, most importantly, Big Pharma.
Big Pharma, the collective term for the world’s largest pharmaceutical companies, includes companies like Johnson & Johnson, Roche, Pfizer, Novartis and GlaxoSmithKline. These are huge companies bristling with scientific expertise, and they are the names behind some of the world’s most successful and efficacious therapeutics.
The logic follows that if Big Pharma invests in a biotech, then it must possess a winning technology – something Big Pharma hasn’t been able to produce itself and is keen on fostering or getting its hands on. Moreover, there is often the assumption that a biotech’s Big Pharma partner will one day be its acquirer.
There are important matters biotechs should consider when partnering with Big Pharma, and this article discusses a few of those issues, in order to help readers avoid some of the common pitfalls.
1. Understand news flow and materiality
The first thing to realize when partnering with Big Pharma is that what might be newsworthy for you will almost certainly not be newsworthy for them. Unless handled thoughtfully, this can leave a small biotech company materially disadvantaged.
Take, for example, the actual terms of a partnership agreement, which typically include a series of milestone payments and possibly a royalty on future sales of an approved product. The milestone payments will be material to the small biotech company, and must be reported in regulatory filings, but Big Pharma typically prefers for the majority of the partnership terms to remain private. They may also push back on a biotech issuing a press release that announces when payments have been made or disclosing them ahead of time.
The best way to avoid the above scenario is to decide on a clear strategy for disclosing future payments and their timing at the time of signing. These payments will need to be communicated to a biotech’s analysts and could even soothe fears about a funding gap if the terms are transparent.
Another example is announcing clinical trial results for a program under partnership. Big Pharma seldom announces the results of early clinical trials, but as points of value inflexion and opportunities to raise capital, they are all-important for biotech companies. A biotech will want to talk about them and should pre-agree on a clinical communications strategy at the time the partnership is signed. They should also be prepared, if need be, to issue standalone press releases rather than joint releases for such early stage trials.
In all cases, key contacts should be identified within each company to deal with the future news flow resulting from a partnership. Formalizing policies and how future results will be announced is important to set in stone when a partnership is formed, since senior management from both firms tend to step back from the process once a deal is signed.
2. Be careful not to cap your upside
An important consideration when forming a partnership with Big Pharma is leaving enough “meat on the bones” for future equity investors. Biotech investments are some of the riskiest that can be made. In return, investors expect a lot of upside. Partnering your best assets with Big Pharma may avoid some short-term dilution, but it may also rob your shareholders of the upside they deserve. It may diversify or mitigate the company’s risk, but investors typically mitigate risk themselves through diversification, so chances are they are looking at you for a pure play on your underlying opportunity.
Be thoughtful about which programs you partner with, and be sure to leave some serious value on the table for those who own your stock. Very few biotech investors want to invest in a “royalty machine.”
Moreover, once you’ve sold off some of the “family silver,” be sure to give those programs second (or third) priority in your investment deck. This will help would-be equity investors focus on what programs remain unencumbered, since that is the primary risk they will be taking by investing in your equity.
3. Don’t create a monopsony
A monopsony is a market condition where there is only one buyer (as compared to a monopoly where there is only one seller). If you sell equity to Big Pharma as part of any partnership deal you strike, be careful that you are not creating a situation where they become the only bidder for your company in the event that your drug candidate is a success. By doing so, you are robbing shareholders of upside to their equity investment.
4. Carefully explain the division of partnership responsibilities to your stakeholders
Partnerships take all forms. Some involve a total outsourcing of responsibilities for clinical trials, regulatory and commercialization, while others involve a different division of labor/specialties and potentially even cost sharing. Your own situation will depend on what you have and how much Big Pharma wants it. Your analysts and investors, however, will need to be able to build a financial model of your company, so these details of your partnership will need to be fully explained and therefore reflected in your valuation and/or equity price targets. These agreements are complicated, so analysts will often make mistakes in published research, which you will need to subtly get rectified.
5. All partnerships are not equal
Lastly, note that all partnerships are not equal. As such, do not overplay the importance of yours if it really doesn’t amount to much. The Street is savvy and will see through a partnership that barely warrants the name. Examples of this include the kinds of drug-supply agreements that exist, particularly in oncology, whereby Big Pharma agrees to partner with you in a combination trial and provides one of its approved drugs by way of its contribution. Yes, this provides some validation, but not much. The trend towards combination therapy means that Big Pharma benefits from having its drugs approved in as many combinations as possible, hence their participation in your trial may show you have promise, but it is not a full-blown endorsement of your approach. Don’t try and paint it as such.
Want To Partner With Big Pharma? Take This Expert Advice
https://www.clinicalleader.com/doc/want-to-partner-with-big-pharma-take-this-expert-advice-0001
For a small pharma company, taking a therapy from a positive Phase 2 study to FDA approval is a daunting task. Standing in the way is generally a large, challenging, and expensive Phase 3 trial. Oftentimes, the best way for small companies to overcome that challenge is with the help of a Big Pharma partner.
But how do you connect with much larger companies? And what are the best practices for working with them? A panel at the 2018 Clinical Leader Forum in Philadelphia attempted to bring some clarity to those questions.
The panel consisted of Art Fratamico, chief business officer at Galera Therapeutics; John Hubbard, a pharma veteran and member of the board of directors at Agile Therapeutics; Howard Johnson, SVP of corporate development, alliance management, and program management at Iovance Biotherapeutics; and Tony Meehan, SVP and chief business officer at VenatoRx Pharmaceuticals. Between them, these four executives have over 110 years of pharma experience.
The Best Time To Partner
One of the first decisions an executive must make is when to partner. Is there a perfect time to find a development partner? Are there conditions that exist within a company that should be a signal to executives that it is the right time to sign a partnering deal?
Johnson believes a good time to consider a partnering deal is when a Big Pharma company or similar potential partner shows an interest in your company. He notes many smaller companies can toil in obscurity until their technology or data comes to the forefront. When that happens, there is suddenly interest from everywhere.
“The advice I like to give companies is that you have to be ready for that interest when it happens,” says Johnson. “I think you have to run your firm as if you’re going to be a standalone company. You have to make decisions to always be ready for the next step in the evolution of what you’re trying to accomplish.”
In other words, you can’t depend on a third-party to create value for you. You must create it yourself and always put yourself and your company in the best possible position to advance. Of course, the best way to make that happen is to always build value in your asset and its clinical data.
“There’s nothing like clinical data,” states Johnson. “You have to position your asset in the most attractive manner possible for potential partners. When there is interest in your company, you can decide on the timing of a partnership. But you must have that interest first, and the best way to achieve interest is to make relentless forward progress with your asset and data.”
Some companies will, of course, announce to the industry that they are for sale. Johnson does not recommend that approach. With the right data, you can generate the interest you need from pharma and the investment community. Seeking potential partners, rather than waiting for them to come to you, is not the best negotiating strategy.
Hubbard agrees, noting it is important for companies to keep all their options open. One of those options must be the ability to move forward on your own. He believes in having a sales plan, a commercial model, a valuation, and the capabilities necessary to move forward. That will put your company in a position of strength.
Is It Too Early Or Too Late?
If you’re looking for a partner, timing is important. Make a deal too early and you could lose millions. Wait too long and you could lose everything. So, how do you know when it’s the right time to strike a deal? Meehan doesn’t think it is ever too early to speak to potential partners.
“I am always very honest with companies,” says Meehan. “Competition is good, and I don’t hesitate to let them know that we have other options. If a company is not ready to put money down, I will tell them that we will finance our development another way. I think it’s healthy to have a competitive tension. I just look at them as two sides of the same coin.”
All panel members agreed that at various times one therapeutic area can be hot or cold when it comes to deals and investment. This is something companies cannot control. If your molecule is not hot, that is when you need to be prepared to move forward on your own.
“This is an interesting conundrum in our industry,” says Hubbard. “We look at innovation as a really valuable thing. We see the value presented by new therapeutic areas and new targets. But at the same time, we are also risk-averse. No one wants to be the first company to enter a new area of research. For example, at one time statins were a niche product. Today, they have completely changed the course of medicine. The same can be said of immunotherapy. If your technology is not currently a hot area of interest, you must find a way to persevere. As you generate positive clinical results, eventually someone will develop an interest.”
Find The Right Partner
Even if the time is right to partner, and you have potential suitors, you still must choose the right company. When you reach that point, how do you go about making that decision?
“I believe the best option is to always cast an extremely wide net,” says Meehan. “You may not know where the market for your product is. We might all prefer a buyout from a Big Pharma company, but the truth is they may not want you.”
Meehan has often been on the other side of the equation. He would find an asset that interested him, but would not have sufficient cash to purchase it. You can instead offer equity and downstream milestones, but don’t be surprised if you get turned down.
“Companies want that large chunk of cash right up front,” he says. “I understand that. So, I told them that when they get turned down by the big companies, that I would be their back-up date. You never know what another company’s needs are. That is why you keep all of your options open and talk to as many people as you can.”
Perform Due Diligence
Fratamico stresses the importance of due diligence. Two years ago, he was with a company that decided to find a partner for a licensing deal. He started the process of filtering through the firms that were interested and narrowed the shortlist to six companies. Each one was asked to present on why they would make the best partner.
“At the end of that process, the decision was obvious,” says Fratamico. “Our goal was to strike a licensing deal, and the top company was very clear to us. We looked at how they did things and knew it closely aligned with how we were thinking. If you can perform that type of diligence, I strongly recommend it.”
“The term ‘strategic fit’ gets thrown around a lot,” adds Johnson. “Still, that is definitely something you need to look at. A company might make a good partner because of its strategic needs, their strategic assets, or their strategic capabilities. It’s always important to do your homework.”
There are certainly potential suitors that you might rule out right from the start. There are companies that seem to be making it difficult for you to work with them. They might be very slow in responding or will always have conflicts that you have to work around.
“There are some companies you will like and some you will love,” says Hubbard. “When the selection process is all over, you never know who will be standing at the altar. Until the final decision is made, do your best to keep each company engaged and never say no to anyone.”
Finally, be sure you understand the future plans of your partner, especially if you strike a deal that includes downstream earnings, royalties, or milestone payments. In those cases, you must be concerned with the other party’s ability to take the asset forward and finance the development. If your new partner ends up just sitting on the asset, you are stuck.
Strike The Right Deal
Once you find the right partner, the final thing you will need to do is strike the right deal. What are some critical considerations you need to keep in mind when negotiating a collaboration or licensing deal?
Fratamico recommends focusing on two things, both of which are introspective. First, know your program, where it stands, where it is going, and your next milestone. You also need to know what activities are required to achieve that milestone.
“That piece really boils down to having a development plan that goes all the way through to approval,” says Fratamico. “It doesn’t matter if that approval is still years away. You must have that roadmap to guide you.”
The other recommendation is to focus on your internal abilities. Fratamico notes you should always know your company’s strengths and weaknesses. In any licensing deal, that will help you know where to focus your partner search efforts.”
“Companies will always have their own internal challenges,” states Hubbard. “When you bring together two different organizations, those challenges are multiplied. Spend as much time as possible really getting to know the person or the company you’re working with. Iron out as many details as possible before starting the work and be clear in your communications. And always have a good governance structure in place, especially if you are working across cultures. Doing that will help you head off any surprises.”
5 REASONS WHY ENZOLYTICS IS A COMPELLING CHOICE!
https://www.aviseanalytics.com/5-reasons-why-enzolytics-inc-is-a-compelling-choice/
!
11 JUN 5 REASONS WHY ENZOLYTICS IS A COMPELLING CHOICE!
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Enzolytics Inc. (OTCPK: ENZC) is leveraging over 40 years of drug development experience to develop proprietary antiviral peptides and monoclonal antibodies for the treatment of Infectious Diseases. The Company is using a combination of patented-HIV therapeutics and an exclusive methodology, for creating fully human IgG1 monoclonal antibodies, which can target and neutralize HIV Virus to treat infectious diseases with non-toxic passive immunotherapy.
Enzolytics is committed to the development of proteins and monoclonal antibodies, which can combat a wide array of infectious diseases such as Hepatitis (A, B, C), rabies, influenza A and B, tetanus and diphtheria, besides Rheumatoid Arthritis and some forms of cancer. The Company is extending its proprietary technology to create anti-SARS-CoV-2 (Coronavirus) monoclonal antibodies, intended for the treatment of COVID-19.
Enzolytics Inc. (OTCPK: ENZC)
Market Cap: $ 676.73M; Current Share Price: 0.278 USDChart
Data by YCharts
An Industry with Large Unmet Needs
Human Immunodeficiency Virus (HIV) compromises the body’s immunity by attacking CD4 cells (a type of T cell), exposing it to a host of infections and diseases and ultimately leading to the development of AIDS. According to data provided by Centres for Disease Control and Prevention, an estimated 1.1 million people in the U.S are afflicted with this disease and 1 in 7 or 15% of those affected are unaware of their condition. In 2017, over 38,739 people were diagnosed with HIV and 6 dependent areas and nearly 15,807 deaths were registered among people diagnosed with HIV.
Advances in treatment and care, such as development of antiretroviral therapy (ART), have increased the life expectancy of people diagnosed with HIV and helped arrest the disease from progressing to AIDS, with an estimated 20.9 million people on ART as of 2017. There is no cure for the disease as yet, with existing therapeutic options seeking to stop the progression of the disease and alleviating symptoms.
Antiretroviral Therapy can be categorised as highly active antiretroviral therapy (HAART) or combination antiretroviral therapy (cART), however they can cause adverse reactions, severe toxicity and exacerbate existing co-morbidities. Scientific advancements have led to the discovery and development of Protease Inhibitors, Integrase Inhibitors, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), Non-nucleoside reverse transcriptase inhibitors (NNRTIs), Chemokine co-receptor antagonists and Entry inhibitors that seek to overcome the limitations of the existing treatment options.
According to a report by GlobalData, the global HIV market will reach $22.5 billion by 2025 growing at a CAGR of 3% from $16.3 billion in 2015.
Image Source: Company
A Key Collaboration with Intel Corporation
In May 2021, the Company published a white paper through a thought leadership collaboration with Intel Corporation (NASDAQ: INTC) titled “Optimizing Empathetic A.I. to Cure Deadly Diseases”. The paper highlights the Company’s use of Artificial Intelligence, which is a novel approach to assessing virus sequences so that the segments essential for a virus survival are promptly identified. Intel’s Empathetic A.I helps outsource healthcare related decisions to machines, thereby enabling healthcare practitioners to spend more time in developing relationships with patients. Furthermore, Intel’s Programmable Integrated Unified Memory Architecture (PIUMA) will speed up drug discoveries and predict virus mutations with great speed and accuracy.
Speaking on the collaboration with Intel, Charles Cotropia, CEO of Enzolytics, stated,
“We are honored and privileged to work with the preeminent international corporation Intel in a collaborative manner focused on the optimum way to advance healthcare using science and technology together. Combining science with technology will guarantee success.”
A Promising Therapeutic Candidate for HIV
The Company’s lead candidate is an anti-HIV therapeutic known as ITV-1, which is a suspension of Inactivated Pepsin Fragment (IPF) that has demonstrated the potential to strengthen the immune system and neutralize the HIV virus, in clinical studies conducted in the European Union. Enzolytics proprietary technology enables the creation of human cell lines that are capable of producing fully human monoclonal antibodies. CLONE 3, one of these antibodies has the potential to completely neutralize 95 percent of HIV-1 strains and viral subtypes.
Enzolytic’s portfolio of therapeutics may not only be used as immunotherapeutic treatment for HIV/AIDS but also serve as a prophylactic and therapeutic vaccine against HIV. The treatment offers significant improvement over existing therapies such as ARV, by demonstrating a better efficacy and non-toxicity, besides being for a shorter duration and cost effective.
Merger with BioClonetics Immunotherapeutics, Inc brings in a Synergistic Platform
In December 2020, the Company announced the completion of the merger with BioClonetics Immunotherapeutics, Inc. The Companies are now pursuing two diverse but complementary therapy platforms, namely antiviral peptide and fully human anti-monoclonal antibodies.
Speaking on the synergy of these two technologies Harry Zhabilov, CSO of Enzolytics, commented,
“The technologies of the combined entities will afford the Company the opportunity to unlock the potential of our HIV-AIDS treatments at a time when the seriousness of the disease is still a major concern given that the current form of treatment for HIV patients is antiretroviral treatment and where such treatment is only accessible to 40% of the 36 million peoples in the world infected by HIV – leaving 60% of the 36 million infected HIV patients with no treatment.”
The Company’s anti-HIV mAb in PBMC neutralization assays are in the final testing phase and will be followed by animal trials at the California National Primate Research Center, UC Davis (Davis, CA). In addition, Enzolytics is developing anti-SARS-Cov-2 (CoronaVirus) monoclonal antibodies, based on its research that there is a significant correlative structure between the HIV virus and the SARS-CoV-2 virus. The antibodies are intended to act as a therapeutic and produce a phage display anti-SARS-CoV-2 (CoronaVirus) vaccine.
Extensive Intellectual Property Rights Portfolio
Enzolytics has built a strong intellectual property rights portfolio with patents covering its technology related to peptide which cover Pepsin Fragment (IPF) identified and characterized by the amino acid sequence GDEPLENYLDTEYF and the Clone 3 cell line, fully human monoclonal antibodies (mAbs) that specifically target and neutralize the HIV-1 virus. The Company also has multiple patents pending covering the recombinant of the Clone 3 antibody and coverage of small molecules (mini-peptides) among others.
Key Takeaways
On June 7, the Company announced a protocol to produce therapeutics for HIV as well as existing and future pandemics, an outcome of its collaboration with Intel Corporation, which seeks to leverage Artificial Intelligence to aid discoveries and development in healthcare. The coloration extends to investigating the relationship and interaction between monoclonal antibodies with viruses in 3-dimensional matrices.
The Company has built multiple strategic research and development collaborations and partnerships and has currently set milestones, which are necessary to land partnerships with other biopharmaceutical companies, which have expressed interest in the Company’s technology and pipeline. Some of these milestones include Testing of anti-HIV Monoclonal Antibodies at University of Montana, Broad-based neutralization testing of existing anti-HIV Monoclonal Antibodies at University of Strasbourg, France, Animal Studies of anti-HIV Monoclonal Antibodies at California National Primate Research Center, University of Southern California, Using Artificial Intelligence, identification of additional conserved immutable target sites (epitopes) on the HIV-1 virus and Production of additional Monoclonal Antibodies targeting identified sites (epitopes) on the HIV virus as per a Company
Clinical Trials are fraught with risk and uncertainty. The Company is looking at developing a diverse pipeline of candidates which will help mitigate the risk in case of adverse results or the failure to meet endpoints in any of its ongoing trials of a particular candidate. The success of its clinical trials will help the Company advance its pipeline but it should also be prepared to face any setbacks, in case its trials fail to meet their endpoints.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
Click here to please visit our detailed disclosure
References
https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics
https://enzolytics.com/
https://www.globaldata.com/hiv-market-will-see-modest-growth-to-22-5-billion-by-2025-says-globaldata/
https://www.biospace.com/article/releases/enzolytics-inc-completes-merger-with-bioclonetics-immunotherapeutics-inc-/
https://finance.yahoo.com/news/enzolytics-inc-intel-corporation-co-110000244.html
https://stockdaymedia.com/enzolytics-reports-progress-on-its-multiple-therapeutics-platforms-and-initiatives-enzc/
Enzolytics, Inc. Announces the Completion of the 2020 and 2021 Audited Financials
COLLEGE STATION, TX / ACCESSWIRE / December 19, 2022 / Enzolytics, Inc. (OTC PINK:ENZC) (https://enzolytics.com/).
Enzolytics, Inc. announces the completion of the 12/31/2020 and 12/31/2021 audited financials. The Company has refiled the 12/31/2021 Disclosure Statement reflecting the completion of the audit covering 2020 and 2021. These filings provide investors with detailed audited information about the Company's operations, business strategies, and financials. The reports will assist the Company's investors in understanding the Company's operations and its focus. In conjunction with the completion of the audits, and as part of the Company's ongoing commitment to transparency and accountability, Enzolytics is planning to become a fully reporting 34 Act Filer with the SEC.
The Company CEO, Charles Cotropia, said, "Enzolytics is focused on accelerating the growth of our clinical products, technology platforms, and multiple applications now in progress. The Company is making substantial advancement in its three synergistic therapeutic platforms generating multiple clinical products for human and veterinary use. Over the last two years, we have focused on advancing our research and development and strengthening our Intellectual Property portfolio covering our technologies. As a result, we have made significant strides and substantive progress on multiple fronts. Our completion of a two-year audit is just one of the many objectives we have set and achieved.
"In the year ahead, Enzolytics will share additional plans regarding our technologies, planned partnerships, and projects, as well as achievements in each of our therapeutics platforms. We have full faith in our long-term vision and mission and are confident in our team's ability to achieve set goals."
The Company's IPF Immune™ therapeutic, a dietary supplement that supports the body's self-defense system, is now available to the public through Onelavi (www.onelavi.com) and through the Company's IPF Immune website (www.enzolyticstherapeutics.com). The product will be widely available through national retailers and their internet platforms and websites. In the coming weeks, the product will be available through Walmart and later through other national outlets. Pre-sales promotions have been aired during the past months, and future promotions and advertising are planned. Product promotion will also be achieved through platforms provided by retailers carrying the product.
To meet demand, additional production of IPF Immune is ongoing. In addition, the Company plans to introduce the product in foreign markets.
The Company COO, Dr. Gaurav Chandra, noted, "At Enzolytics, innovation is driven through our ecosystems with a collective mission to accelerate innovation. Our A.I. platform drives the Company's drug discovery and development and represents an overall strategy to produce therapeutics covered by an all-encompassing Intellectual Property portfolio. We take pride in strengthening our I.P. portfolio covering the anti-virus therapeutics, their method of production, diagnostics and prognostics. Our application of Artificial Intelligent to drug formulation and creation has made possible our move beyond big pharma's monoclonal antibody discovery and development. Enzolytics continues to forge ahead with the immediate strategy to identify novel biomarkers and therapeutic targets, design innovative diagnostic and prognostic tests, and expand the Company's Patent portfolio.
"In addition, Enzolytics' long-term plan is to be a serious contender in the personalized medicine market. The Company acknowledges the importance of an all-encompassing One Health approach recognizing the link between the health of people, animals, and the environment. As part of that approach, we identified conserved sites for Monkey Pox (https://www.nasdaq.com/press-release/enzolytics-announces-the-discovery-of-conserved-target-sites-on-the-monkeypox-virus) 2 weeks before WHO declared it a Global Public Health Emergency. Enzolytics continues to partner and engage with technology, genetics, veterinary centers, diagnostic and regulatory companies applying that strategy in each of these areas."
Safe Harbor Statement: This news release contains forward-looking statements that involve risks and uncertainties associated with financial projections, budgets, milestone timelines, clinical development, regulatory approvals, and other risks described by Enzolytics, Inc. from time to time in its periodic reports filed with the SEC. ITV-1 is not approved by the U.S. Food and Drug Administration or any comparable regulatory agencies elsewhere in the world.
While Enzolytics, Inc. believes that the forward-looking statements and underlying assumptions contained therein are reasonable, any of the assumptions could be inaccurate, including, but not limited to, the ability of Enzolytics to establish the efficacy of its therapeutics in the treatment of any disease or health condition, the development of studies and strategies leading to commercialization of its therapeutics in the United States, the obtaining of funding required to carry out the development plan, the completion of studies and tests on time or at all, and the successful outcome of such studies or tests. Therefore, there can be no assurance that the forward-looking statements included in this release will prove accurate.
Such forward-looking statements are based on current expectations. They involve inherent risks and uncertainties, including factors that could delay, divert or change any of the statements made, and cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. These forward-looking statements are made as of the date of this press release. The Company expressly disclaims any intention or obligation to update the forward-looking statements or update the reasons why actual results could differ from those projected in the forward-looking statements.
Company Contact:
Enzolytics, Inc.
Texas A&M University Institute for Preclinical Studies
College Station, TX 77843-44
www.enzolytics.com
SOURCE: Enzolytics, Inc.
View source version on accesswire.com:
https://www.accesswire.com/732304/Enzolytics-Inc-Announces-the-Completion-of-the-2020-and-2021-Audited-Financials
Also from the Regeneron Pharmaceuticals, Inc. (REGN) 41st Annual J.P. Morgan Healthcare Conference (Transcript)
Question-and-Answer Session
Chris Schott
Great. And just maybe last question for me. You mentioned COVID antibody. That seems to have a pretty unique profile. Just maybe give us a sense of how quickly that could move forward and how much capacity the organization could build with that?
George Yancopoulos
Well, we've shown before that we can move very quickly, and we have capacity to treat millions of patients. And it's going to be less limited by our technologies and our capabilities than our discussions and negotiations with the FDA. And also, at the time that we're doing our clinical studies, what kind of studies will be required by the FDA, part of that negotiation, and also the prevailing amount of disease, which obviously would allow any studies to go more quickly.
Chris Schott
Great. Well, I think we're just out of time. Really appreciate the comments today, and thanks for joining us.
https://seekingalpha.com/article/4568895-regeneron-pharmaceuticals-inc-regn-41st-annual-j-p-morgan-healthcare-conference-transcript
Sooner than later.
I hope the study is started by March, if not sooner and be done by June/July if product is available.
I believe the hold up is lack of product.
It takes time to make monoclonal antibodies.
The only definitive date we have from REGN is from the infamous slide #27:
On slide #27, the Company stated its 'Next-gen COVID antibody binds outside variable RBD and has demonstrated high neutralization activity against all known variants and lineages and disclosed it anticipates initiating the REGN14287 phase 3 clinical trial in 2023, pending regulatory discussions.
I suspect the share price will be going a wild ride and with all the irons ENZC have in the fire it is no telling WHERE the ride will END.
Not a mistake.
It you click on the link it my post, the full article has a link to REGN original monoclonal antibody.
Regeneron Pharmaceuticals, Inc. discretely revealed its intentions to expand its Anti-SARS-CoV-2 Monoclonal Antibody offerings at the J.P. Morgan Healthcare Conference on January 9, 2023.
https://www.precisionvaccinations.com/2023/01/11/regenerons-next-gen-monoclonal-antibody-revealed
ENZC
The Company's targeted approach is to produce fully human monoclonal antibodies against the identified conserved epitopes on the Coronavirus. Using computer analysis (Artificial Intelligence [AI]), the Company has identified 19 conserved sequences identified on the Coronavirus on the basis that they are 98.71% to 99.29% conserved over the entirety of the 50,512 Coronavirus isolates analyzed. Significantly, these conserved sequences have been identified in the UK, Brazil and South African variants.
This discovery is significant in Enzolytics' continued commitment to producing therapeutics for the treatment of COVID-19. Specifically, Enzolytics is creating human heterohybridoma cell lines using convalescent human patients' peripheral "immune" human B cells to create fully human monoclonal antibodies directed individually against the identified conserved sites on the virus and against both S1 protein and S2 (transmembrane) protein on the Coronavirus. These monoclonal antibodies will expectedly have universal effect (on all known variants) and will be durable in that as the virus mutates, the targeted site will still exist in the virus subjecting it to neutralization. Such therapeutics would have universal (world-wide application), be durable (have long term successful benefit) and thereby prevent failure of successful vaccines and/or provide effective treatment, which are both points of failures that have occurred as a result of "mutational virus escape".
The Company's pending patents claim the identified target sites and include patent claims to the CDR sequences of the produced antibodies. Such patent claim structure will expectedly provide the Company the exclusive rights to therapeutics based on these findings for a 20 years period from the date of filing. International patent coverage is also being sought.
https://money.yahoo.com/coronavirus-targeted-epitopes-claimed-enzolytics-140000567.html
REGN
We have one of the most sophisticated and largest screening efforts for COVID antibodies, and we believe we have identified one-in-a-million antibody that works very differently to all prior antibodies by binding outside of the immuno-dominant highly variable RBD and NTD domains. These domains have been the primary site of antibody binding and correspondingly of variant mutations.
We have caused the initial vaccines in previous COVID antibody therapies to lose their activities. We hope that by binding outside of these domains to a unique targeted epitope that is highly conserved, with over 99.9% conservations since the beginning of the pandemic, it will lower the risk of losing activity against future variants. Importantly, this antibody, known as REGEN14287 demonstrates high neutralization potency against all known SARS-CoV-2 variants and lineages to date. Activities enabling clinical manufacturing have commenced, and we expect to enter clinical development later this year.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=170955564
Regeneron Pharmaceuticals, Inc. discretely revealed its intentions to expand its Anti-SARS-CoV-2 Monoclonal Antibody offerings at the J.P. Morgan Healthcare Conference on January 9, 2023.
Regeneron's presentation stated that in the U.S. alone, millions of immuno-compromised people will not adequately respond to vaccination.
And antibodies can be dosed prophylactically to prevent infection and severe COVID-19 disease.
On slide #27, the Company stated its 'Next-gen COVID antibody binds outside variable RBD and has demonstrated high neutralization activity against all known variants and lineages and disclosed it anticipates initiating the REGN14287 phase 3 clinical trial in 2023, pending regulatory discussions.
The NCT04425629 study was last updated on July 29, 2022.
https://www.precisionvaccinations.com/2023/01/11/regenerons-next-gen-monoclonal-antibody-revealed
From Science Immunology:
We compared the binding epitopes of SP1-77 with those of the LY-CoV1404 (bebtelovimab) and S309 neutralizing antibodies. The RBD epitope targeted by SP1-77 overlapped very modestly with that of the LY-CoV1404, which is currently approved for therapeutic use (Fig. 4C) (14). The RBD-binding site of LY-CoV1404 included the 440–445 segment of the RBD that was also bound by SP1-77 (Fig. 4C). Similar to SP1-77, LY-CoV1404 potently neutralizes all currently known VOCs (14). However, the bulk of the LY-CoV1404 footprint overlaps with the RBM, which mechanistically allows LY-CoV1404 to achieve neutralization by blocking ACE2 binding. S309 and its sotrovimab derivative, previously used therapeutically, bind outside of the RBM (23). However, S309 is quite distinct from SP1-77 in that it fails to neutralize Omicron BA.2 in vitro (48), although it does prevent BA.2 infection in vivo through utilization of Fc effector function interactions (49). In this regard, the S309 footprint covered both the 339–346 and 440–451 segments that were also in the SP1-77 footprint, with the long axis of the S309 footprint aligning along the exposed ridge of the RBD in the closed S trimer (Fig. 4C). However, the same axis of the SP1-77 footprint was almost perpendicular to that of S309, which made it possible for SP1-77 to reach the NTD (Fig. 4B).
https://www.science.org/doi/10.1126/sciimmunol.add5446
Enzolytics Patent Portfolio and Strategy
As of August 19, 2022, the Company has three (3) pending Patent Cooperation Treaty (PCT) Patent applications covering its fully human monoclonal antibodies targeting the CoronaVirus and HIV. Additional patent applications are being prepared to cover the numerous viruses against which the Company plans to produce monoclonal antibodies.
In the first PCT Patent Office Official Action on the Company’s International Patent Application covering its discovery and exclusive claim to conserved antigens and epitopes of the HIV virus, the PCT International Search Report concluded that inventions claimed therein are novel and inventive and thus will expectedly be issued in final international patents. The Company’s International Patent application covers (1) the discovered highly conserved antigens and epitopes (sites) on the HIV virus, (2) antibodies that bind to the disclosed antigens and epitopes, (3) vaccines based on the antigens, (4) methods of treating, preventing, or reducing the risks of HIV infection with the antigens or binding proteins, and (5) methods and kits for detecting or diagnosing infection by HIV using the antigens or binding proteins.
The Company discovered the claimed virus sites through computer analysis (Artificial Intelligence (A.I.)), wherein tens of thousands of HIV isolates were curated to identify these critical, conserved, immutable epitopes on the virus. These sites are now claimed as patentable based on their novel specificity and the finding that they are conserved on the HIV virus. This is significant in that by producing antibodies that attack these conserved, immutable sites, the virus can be neutralized rather than unaffected due to virus mutation that avoids the therapeutic.
The Company is producing fully human monoclonal antibodies against these claimed sites. The International Patent Office has now confirmed these discoveries to be novel and inventive, capable of being patented and claimed exclusively for a 20-year term in every member country under the Patent Cooperation Treat in which the Company pursues these claims.
Due to the novel nature of the Company’s discoveries, the Company fully expects the same favorable results in the PCT Patent Office for its pending applications covering epitopes (binding sites) on the CoronaVirus (covering all variants), on the Monkeypox Virus, and on numerous animal viruses, namely Feline Leukemia Virus (FeLV), Feline Immunodeficiency Virus (FIV), Elephant Endotheliotropic Virus, Equine Infectious Anemia, and Koala Retrovirus. The Company fully expects the issuance of multiple international patents covering these discoveries.
The Company's PCT applications also cover the identification of highly conserved antigens and epitopes of these viruses that can be used in the production of antibodies and the production of vaccines for treating, preventing, or reducing the risks of infections caused by these viruses.
The patents also cover the discovery of using these identified antigens and epitopes as targets for detecting and diagnosing viral infection. This is a significant development since these patents cover treatment and prevention and target detecting and diagnosing infections for all viruses pursued by Enzolytics.
In the Company's unique process, computer analysis (A.I.) was used to identify conserved, immutable epitopes on the target virus utilizing Enzolytics' proprietary A.I. platform invented by Dr. Gaurav Chandra, the Company COO. The sequences (structure) of over 87,500 HIV isolates were analyzed in the initial A.I. step for HIV, and for the Coronavirus, over 2 million SARS-CoV-2 virus isolates were curated. In the case of HIV, eight (8) epitopes (target sites) were identified and claimed in the Company's PCT application. As a part of this process, 3 Dimensional models of these conserved targets were generated, and the targets were analyzed for linearity, accessibility by antibodies, and neutralizability by antibodies. From this, Enzolytics' scientists are producing multiple broadly neutralizing antibodies targeting these multiple conserved, immutable epitopes on the targeted virus. As a result, the monoclonal antibodies produced against these targets will be universal, durable, broadly neutralizing, and unaffected by virus mutation. In the case of SARS-CoV-2, nineteen (19) conserved sites were identified and are claimed in the Company's pending PCT applications.
The Company considers the forthcoming patent protection highly significant in view of the following facts:
For a monoclonal antibody to be effective (that is, to be fully capable of neutralizing a virus), it must target an immutable site on the virus. Otherwise, a virus mutation will render the therapeutic ineffective.
The Company has analyzed over 2 million Coronavirus isolates and over 87,000 HIV isolates and has identified 19 conserved sites (98 to 99% conserved) on the Coronavirus and 8 conserved sites on the HIV virus.
The Company's patent claims cover these findings. From the most recent PCT International Patent Office Action, claims have been recognized as novel and Inventive. They thus can be expected to issue in the U.S. and many foreign countries pursued. The Company claims the use of anyone identified epitope or any combination of any of the multiple identified epitopes in any of the following ways:
For producing a therapeutic monoclonal antibody to treat HIV or the CoronaVirus.
For producing a vaccine against HIV or the CoronaVirus.
For producing related prophylactic/therapeutic methods relating to the epitopes/antigens.
For use in any diagnostic test to identify whether a person has HIV or the Coronavirus.
The term of these NDAs is not time limited. The term extends until the later of five (5) years from the Effective Date or "until such time as the proprietary information is publicly known and made generally available". This provision is necessary because under Patent Laws an issued patent may be invalidated where the patent is filed subsequent to public disclosure of the invention claimed. In view of this limitation, the Company makes no public disclosure of information subject to NDAs and inventions covered by them. Additionally, certain technical information shared with companies with whom the Company has entered into an NDA may not be included in a patent application, but rather the subject technical information is maintained as Company confidential ("secret") indefinitely. Also, in these Agreements, the parties generally agree not to reveal the names of the contracting parties for a specified period.
A few questions?
Are the epitopes Boston Children/Duke using patent protected by ENZC?
Are Boston Children/Duke in a relationship with ENZC.
Scientists Discovered an Antibody That Can Take Out All COVID-19 Variants
And they hope to create a new vaccine with it.
COVID-19 vaccines have been effective at keeping people from getting severely ill and dying from the virus, but they’ve required different boosters to try to keep on top of all of the coronavirus variants that have popped up. Now, researchers have discovered an antibody that neutralizes all known COVID-19 variants.
The antibody, called SP1-77, is the result of a collaborative effort from researchers at Boston Children’s Hospital and Duke University. Results from mouse studies they’ve conducted were recently published in the journal Science Immunology, and they look promising.
But what does it mean, exactly, to have an antibody that can neutralize all variants of COVID-19, and what kind of impact will this have on vaccines in the future? Here’s what you need to know.
What is SP1-77?
SP1-77 is an antibody developed by researchers that so far can neutralize all forms of SARS-CoV-2, the virus that causes COVID-19. It was created after researchers modified a mouse model that was originally made to search for broadly neutralizing antibodies to HIV, which also mutates.
The mice used in the study have built-in human immune systems that mimic the way our immune systems develop better antibodies when we’re exposed to a pathogen. The researchers inserted two human gene segments into the mice, which then created a range of antibodies that humans might make. The mice were then exposed to SARS-CoV-2’s spike protein (which is what the virus uses to latch onto your cells) and produced nine different families of antibodies that bound to the spike protein to try to neutralize it.
Those antibodies were then tested and one—SP1-77—was able to neutralize Alpha, Beta, Gamma, Delta, and all Omicron strains (including the current circulating ones) of COVID-19.
The antibody works in a slightly different way than many of the antibodies people make to vaccines. To infect you, SARS-CoV-2 has to first attach to ACE2 receptors in your cells. The current COVID-19 vaccines block this binding from happening by attaching to the spike protein’s receptor-binding domain (RBD) at certain spots, a press release from Boston Children’s Hospital explains.
The SP1-77 antibody also binds to the RBD, but doesn’t prevent the virus from binding to ACE2 receptors. What it does do is block the virus from fusing its outer membrane with the membrane of your cells, which is what needs to happen to make you sick.
“SP1-77 binds the spike protein at a site that so far has not been mutated in any variant, and it neutralizes these variants by a novel mechanism,” study co-author Tomas Kirchhausen, Ph.D., said in a statement. “These properties may contribute to its broad and potent activity.”
What does this mean for the future of COVID-19 vaccines and treatments?
It’s not clear right now. It’s important to note that this research was done in mice—not humans—although studies on the antibody are ongoing.
“This is very early-stage proof-of-concept work to illustrate that broadly neutralizing antibodies can be generated using a mouse model,” says Amesh A. Adalja, M.D., infectious disease expert and senior scholar at the Johns Hopkins Center for Health Security. “Such work, if replicated and expanded, could form the basis of new monoclonal antibody products as well as a vaccine.”
Experts say that a vaccine that could take out all variants of COVID-19 would definitely be welcome. “We’d love to have a vaccine that is active against all circulating variants, including those yet to come,” says Thomas Russo, M.D., professor and chief of infectious disease at the University at Buffalo in New York. “It’s the holy grail of vaccines.”
That could potentially mean that you would only need to get a COVID-19 shot or booster once a year or even less frequently, depending on how long protection from the vaccine lasted, Dr. Russo says.
The researchers have applied for a patent for the SP1-77 antibody and mouse model used to create it, and plan to create something that can be used by the general public if all goes well.
https://www.prevention.com/health/a41092334/antibody-neutralize-covid-variants/
How monoclonal antibodies lost the fight with new COVID variants
Monoclonal antibodies were once the star of COVID-19 outpatient treatments. Since they first became available in 2020 – even before the first vaccines – more than 3.5 million infusions of the factory-grown proteins have been given to patients in the U.S. to help reduce risk of hospitalization.
But one by one, different monoclonal treatments have lost their efficacy against new variants of the coronavirus. The rise of Paxlovid antiviral pills earlier this year, further dented their appeal.
Now, a new wave of omicron subvariants that are the best yet at evading the immune system's current defenses have taken over in the U.S. They're expected to knock out bebtelovimab, the last monoclonal antibody treatment standing against the coronavirus. Soon, it'll join bamlanivimab, casirivimab, sotrovimab and others in the graveyard of monoclonals that once targeted past COVID strains until they were outflanked by variants that evaded their protection.
"Monoclonals had their day, like the Model T or the biplane," says Carl Dieffenbach, director of the Division of AIDS at the National Institutes of Health, and lead of the NIH's Antiviral Program for Pandemics, "Now it's time to move on."
Not everyone entirely agrees. Monoclonals are still useful, some doctors say, for treating a vulnerable population.
"There are severely immunosuppressed patients that are not likely to mount an immune response to the virus, even if you treat them with antiviral drugs," says Dr. Raymund Razonable, an infectious disease specialist in the transplant division at the Mayo Clinic. "This is the group that is going to be the most affected by the absence of antibody-based therapies."
What's more new research is underway to develop new types of monoclonal antibodies that could even hold up against new variants.
How monoclonals work — and what they're up against
Monoclonal antibody treatments have always had a major weakness – they're easily outmaneuvered by new COVID strains. It's a flaw that's baked into how they work.
Monoclonal antibodies are lab-grown proteins that supplement your body's immune system – which, in most people, is naturally producing antibodies to hunt for possible threats all the time.
"You and I and every human being that has a functioning immune system is walking around with probably trillions of totally different antibody molecules just circulating in our blood," says Derek Lowe, a chemist and blogger for the journal Science, "Every one of us has a totally different suite of them. There are more of them than there are stars in the sky."
The tiny, Y-shaped proteins lurk in the blood in low concentrations, "waiting and waiting until they happen to bump into something that they stick to really well, and they find their soulmate, basically," Lowe explains. That "soulmate" is an antigen – a foreign substance that's entered the bloodstream, like a bacterial protein or a virus or a pollen grain.
Once a monoclonal antibody finds its soulmate — in the case of COVID, a specific part at the tip of the SARS-CoV-2 virus – it binds to the surface of the antigen. Then, it sends out signals to the immune system, "like hey, I've got a live one," Lowe says.
The most powerful antibodies can stop the virus in its tracks just by binding to it. For instance, "if you have an antibody that sticks to the tip of the spike protein at the business end of the virus – just the fact that it is stuck tightly to that means the virus cannot infect a cell," says Lowe.
The spike protein has been the target of all the monoclonal antibody treatments that go after the virus thus far. But it's been a fickle soulmate, changing with new variants, leaving the monoclonal antibodies adrift in the bloodstream with nowhere to bind.
Companies have stopped bringing these monoclonals to market. The federal government stopped promising to buy them in quantity, making it a riskier bet for companies.
"There are antibodies out there, but nobody has the $200 million to develop it," Dieffenbach says, citing costs that include producing the antibodies, running trials and getting them authorized by the Food and Drug Administration. Some companies figured it wasn't worth it, for a product that was likely to become obsolete in a matter of months, he says.
To be clear, these are antibody treatments for outpatient treatment. There is a different kind of monoclonal antibody treatment for hospitalized patients that remains viable. Actemra, as it's called, is not susceptible to virus mutation because it targets the body's immune reaction to the virus, rather than the virus itself.
New directions in research, and a potential comeback
There might still be hope for monoclonals. Drugmakers and researchers at government agencies are now retooling the strategy, looking for monoclonal antibodies that could last.
"Initially, the focus was, 'let's just find the most potent antibodies,'" says Joshua Tan, chief of the Antibody Biology Unit at NIH. "Now, there's awareness that we need to find antibodies that are likely to work against not just the [current version of the] coronavirus, but whatever may come."
In his lab in Rockville, Md., Tan and the researchers who work with him are looking for antibodies that target parts of the virus that have stayed the same on several different viruses within the larger coronavirus family. "We're looking at other parts of the spike protein that may be more consistent and may be harder to mutate," Tan says.
To achieve this, researchers in Tan's lab are taking immune cells from the blood of patients that have recovered from COVID, and pelting them with tiny plastic pellets covered with spike proteins from different, older coronaviruses to see which cells respond. "Not the [COVID] variants, but SARS-CoV-1, SARS-CoV-2, MERS [etc.]," post-doctoral researcher Cherrelle Dacon clarifies. "These are seven different coronaviruses, all of which infect humans."
The immune cells that react to several different coronaviruses are making antibodies that bind to a part of the spike protein that's staying the same across them.
It's a painstaking process: Isolating individual immune cells, finding the ones that make antibodies in response to various spike proteins — and then using those to make more antibodies that they can scale up, analyze and test, to figure out what on the virus they're actually binding to. The process takes about three to four months each cycle, Tan says.
Tan says the good news is that they've found some antibodies that stick to multiple different coronaviruses. They published some of the results earlier this summer in Science.
But the problem the researchers have come up against is that the monoclonal antibodies they've found are not so potent. Tan says there seems to be a tradeoff – between how well a monoclonal antibody against COVID-19 works, and how long it lasts before the virus ditches the antibody's target.
An analogy: If the coronavirus had human body parts (which it doesn't) the old, highly effective monoclonals hit the virus's spike protein squarely on the nose. In contrast, the new monoclonals Tan is finding try to grab it by the armpit. "One of the issues appears to be that it's harder to reach those parts," Tan says, "What the broader, less potent [antibodies] need is for the spike protein to shift in shape" in order for them to grab it.
Tan is working to find ways around this tradeoff. He says you can potentially modify the antibody, change out parts of it to increase its potency – a process that's largely theoretical at the moment, and will take some time to work out.
So while Tan and other researchers work on the next generation of monoclonal antibodies – ones that work well against all kinds of coronaviruses, maybe even future pandemic ones – the nation is entering a long lull with no monoclonal antibody treatments that work against dominant strains of SARS-CoV-2.
"The disappointment is there because you're losing a really good drug," says Razonable. "But you focus on the next options. The virus adapts, and we also adapt based on what we have available."
Luckily, as Tan and others pursue the long game with antibodies, there are other treatments, like Paxlovid pills and remdesivir infusions, that still work against COVID.
And the research on and rapid development of antibody treatments has opened up possibilities beyond COVID. "It has improved the production of monoclonals for cancer, for immunologic diseases," says Dieffenbach, "It's going to be easier to produce monoclonals in the future because of the lessons learned from SARS-CoV-2. Nothing was wasted here."
https://www.npr.org/sections/health-shots/2022/11/20/1137892932/monoclonal-antibodies-covid-treatment
Two years after Covid vaccines rolled out, researchers are calling for newer, better options
Despite the success of mRNA vaccines, researchers think a new generation of Covid vaccines could provide broader, longer-term protection in the future.
Two years after the first Covid shots went into arms, a growing chorus of researchers is calling for a new generation of vaccines that provide broader and more long-term protection against the disease.
The U.S. is currently recording around 430 Covid deaths per day, on average, according to NBC News’ tally. That includes many people who received at least two Covid shots: Six in 10 adults who died of Covid in August were vaccinated or boosted, according to a report by KFF, a nonprofit health think tank. And for the most part, vaccinated people don’t avoid infections or reinfections anymore.
“Coming up with a vaccine that’s going to last longer and cover a wider range of the Covid family of viruses is a life and death problem,” said Dr. Tom Frieden, who directed the Centers for Disease Control and Prevention until 2017 and is now president of the public health organization Resolve to Save Lives.
Many people thought the solution to that problem had arrived two years ago, on December 14, 2020, when Sandra Lindsay became the first person in the U.S. to get a Covid vaccine outside of a clinical trial.
“My whole life just changed tremendously in that one moment in time,” said Lindsay, who is now the vice president of public health advocacy at Northwell Health.
“What was going through my mind is, ‘I cannot wait for this needle to pierce my arm,’” she said.
Millions of people shared her impatience, for good reason: Adults who are up to date on their shots are 15 times less likely to die from Covid than those who are unvaccinated. Covid vaccines prevented more than 3.2 million deaths and 18.5 million hospitalizations in the U.S. from December 2020 through November 2022, according to an analysis published Tuesday by the Commonwealth Fund and Yale School of Public Health.
But at first, the shots were perceived to be even more powerful than that — a shield against mild symptoms and a ticket back to pre-pandemic life. The reality proved more complicated and, in certain ways, disappointing.
Many experts maintain that we can — and must — do better.
In particular, researchers think sprays or drops given through the nose or mouth could do a better job of stopping transmission. They also hope that vaccines that target multiple parts of the virus or several variants at once could reduce the need for continuous boosters.
“It’s sometimes easy to forget what a tremendous achievement it was to get a brand new vaccine against a brand new class of viruses. … It was pragmatic, and it was tremendously successful. But it’s certainly not the panacea,” said Matthew Miller, scientific director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University. “We can certainly improve on what we know now.”
The promises and shortcomings of mRNA
Vaccine researchers generally agree that mRNA technology was suited to the needs of this pandemic, since it allowed scientists to develop a vaccine quickly at a time when each day meant more lives lost. Scientists then updated the shots relatively easily to target new variants.
“If it wasn’t mRNA, it wouldn’t have gotten done so fast,” said Dr. Barney Graham, former deputy director of the National Institutes of Health’s Vaccine Research Center, now a senior adviser for global health equity at Morehouse School of Medicine.
To date, he added, the Covid vaccine is “one of our simplest, safest vaccines that we’ve ever made.”
When Lindsay got her vaccine in 2020, she was dealing with severely ill Covid patients every day as director of nursing critical care at Long Island Jewish Medical Center.
“It felt like you were just walking into a burning building, but it’s your job,” she said. “It’s what I love doing: taking care of people. So I was going in there no matter what, and just praying every day that I don’t fall ill.”
Despite the odds, Lindsay still hasn’t gotten Covid, as far as she knows. But the majority of Americans have, according to CDC estimates — a situation most of the public did not anticipate when clinical trial results showed 95% efficacy against symptomatic disease.
“It may be that the vaccines were their own worst enemies in some ways, because they were so good initially that people had an expectation that went beyond reason,” Graham said.
Experts agree now, though, that protection from Covid shots fades too fast. Plus, a lack of access to vaccines in many countries allowed the virus to spread rampantly and mutate over time, which has undermined vaccines and treatments.
“If we had immunized the whole world in six months, we may not be having all the problems with the variants because we would have constrained [the] virus’ spread earlier,” Graham said.
The future of Covid vaccines: No needles
When Lindsay volunteered to get her vaccine on day one, she wasn’t aware that she was the country’s very first recipient — despite the cameras.
Now, she said, she still gets recognized.
“I was in TJ Maxx the other day and this man who I didn’t expect was basically bowing down at my feet, [saying] that through my one action, I saved his life, his family’s lives, and so many more,” Lindsay said. “Those are the stories that just solidify for me that what I did on that day made a big difference.”
But others see Lindsay as the face of a promise that fell short.
“You get this on social media, when you post anything: ‘Well, how do you feel now that this thing was all a lie? People are not supposed to get Covid and you got the shots and it’s a big letdown,’” she said.
Researchers still hope that in the future, nasal spray vaccines could inspire more confidence by offering more protection against illness, reducing side effects and removing needles from the equation.
Because Covid seems to infect most people through the nasal passages first, administering a vaccine in the nose could vanquish the virus before it has a chance to spread, the thinking goes.
“It’s sort of akin to having guards placed outside the door in the mucus layer, versus waiting for the invaders to come in,” said Dr. Akiko Iwasaki, an immunobiology professor at Yale University who is developing an intranasal Covid vaccine.
Globally, 117 intranasal Covid vaccines are in development or have been rolled out, according to an analysis provided to NBC News by Airfinity, a health analytics company. Five have been approved in at least one country — two in China and one each in India, Iran and Russia — and 20 more have entered clinical trials. The majority rely on traditional vaccine platforms, not mRNA.
“There’s probably a number of advantages to the intranasal route that will be realized once that route is fully exploited. People can administer it themselves. You can use it in a developing world setting. You can use lower doses,” said Dr. David Curiel, a professor of radiation oncology at Washington University School of Medicine in St. Louis. “There may even be a safety gain, and you get sterilizing immunity and possibly block transmission.”
Curiel developed the technology for the nasal vaccine approved in India. But the vaccine hasn’t entered trials in the U.S., and trial results from India haven’t been published in a peer-reviewed journal.
Other researchers are betting on inhaled vaccines, which come in the form of aerosolized mists administered through a nebulizer into the lungs, where the virus tends to wreak the most havoc.
In September, China approved an inhaled version of a previously authorized Covid shot, called Convidecia. A small trial showed that the inhaled booster dose produced a stronger antibody response than a booster of the intramuscular shot.
Miller and his McMaster colleagues are testing two inhaled vaccines in phase 1 human trials. The more effective candidate will likely advance to phase 2, he said.
Those vaccines might offer an additional advantage, according to Miller: They target three parts of the coronavirus, whereas the current shots target just the spike protein, which mutates faster than the virus’ other components.
Still, some researchers worry that protection from nasal or inhaled vaccines could also wane quickly.
“If we can give a vaccine at the site where infection typically occurs, we would always love to do it that way. The challenge, of course, is that sometimes it doesn’t generate the same type of bloodstream immunity that we really want,” said Dr. Buddy Creech, director of the Vanderbilt Vaccine Research Program.
Creech said future versions of mRNA shots could potentially be tweaked to target three or more coronavirus strains. (The new bivalent boosters target two.)
“It will not be surprising if at some point we need something like a trivalent vaccine or some other permutation of what we have now,” he said. “It could very well mirror what we do with influenza.”
Then there’s the idea of targeting several different coronaviruses at once. The National Institute of Allergy and Infectious Diseases has allocated more than $62 million for research and development of pan-coronavirus vaccines.
In July, researchers at the California Institute of Technology showed that their candidate protected mice and monkeys from the viruses that cause both Covid and SARS. In October, researchers at Duke University School of Medicine similarly showed that their pan-coronavirus vaccine protected animals from multiple SARS-related viruses.
But unlike in 2020, the federal government’s motivation to fund Covid-related innovations is drying up. Whatever Covid vaccine comes next is likely three to five years off, Miller estimated — or perhaps longer, according to other experts.
“The mRNA technology is remarkably successful — these vaccines work better than we had the right to expect,” Frieden said. “But the virus is adapting. And as the virus adapts, we need to adapt.”
https://www.nbcnews.com/health/health-news/two-years-covid-vaccines-rcna57902
Happy Holidays to All
What a way for ENZC to end the year with such GREAT NEWS. Dot the i and cross the t have been ENZC philosophy.
Are we there yet?
No, however the train has left the station.
It has been over 2 years of blood, sweat and tears. Rumors, speculations and and many close encounters with legit players, ENZC never loss focus of the task at hand.
While HIV has always been the central focus, the work along the way has opened up unlimited potential for ENZC.
There is favorable profit potential for the HIV therapy and definitely entities that don't what ENZC products in the markets as it will cut into their profits. It will be very very interesting how this plays out in the weeks and months ahead.
Technology Potential
Projected Earnings from the BioClonetics’ passive immunotherapy have been calculated by an independent national consulting firm.
This analysis examines the expected potential profits from 2 perspectives: (1) considering sales only to North America and Western Europe and (2) considering sales to the major Markets including North America, Western and Central Europe, Eastern Europe and Central Asia, South and Southeast Asia and Latin America. The potential earnings and underlying assumptions for application of our passive immunotherapy to major Markets are set forth here:
Potential Profit from Technology
A most appropriate market for the Company’s therapy includes the regions referred to as the “Major Markets”, including North American, Western and Central Europe, Eastern Europe and Central Asia, South and Southeast Asia and Latin America wherein there are 10.6 million HIV positive individuals. Assuming a penetration rate of 1% rising to a maximum 15% over a five-year period, profit from making treatment available to these 10.6 million HIV positive individuals in the 7 major world markets would be $105 billion in the first 11 years.
Patient Population:
Major Markets – HIV population[1]
North America, Western and Central Europe - 2.2 million
Eastern Europe and Central Asia – 1.4 million
South and Southeast Asia (including India) – 5.2 million
Latin America – 1.8 million
Total – 10.6 million
Assumes 10.6 million potential patient populations with HIV/AIDS
Assumes 1.5% annual increase in potential population growth over the forecast period
$8,000 treatment total cost per patient (single series of treatments for one year only)
(Without insurance coverage, the average monthly cost of Biktarvy (30, 50-200-25 mg tablets) is $7,797, or a little over $90,000 for one year of treatment. The actual cash price of the drug will depend on the quantity and dosage prescribed by a healthcare provider, as well as the location where the drug is purchased.) https://www.singlecare.com/blog/biktarvy-without insurance/#:~:text=Without%20insurance%20coverage%2C%20the%20average,for%20one%20year%20of%20treatment.
Assumes penetration of from 1% in year one to maximum of 15%
An HIV vaccine.
A vaccine against HIV has a much broader application and will produce significantly larger earnings
https://www.bloomberg.com/press-releases/2022-04-25/enzolytics-inc-reports-progress-and-future-plans
The Importance of Toxicology Research in Preclinical Studies
Before a study reaches Phase I clinical trials, scientists spend years conducting preclinical research. One vital part of this includes performing toxicology research on a particular medication or pharmaceutical product. The U.S. Food and Drug Administration (FDA) put great emphasis on the importance of preclinical safety evaluations.
According to the FDA’s guidance for industry on preclinical safety evaluation, pharmacokinetic research needs to include experimental medicines or biopharmaceutical products that represent drugs meant for toxicity testing. This administration route should be similar to the one which will be used in clinical trials.
During toxicity testing, systemic exposure should be monitored, along with patterns of absorption. Before beginning a clinical trial, it will be necessary to provide information on absorption, clearance, and disposition of each compound in animal models in order to anticipate safety of exposure in human subjects.
Additionally, the methods for evaluating absorption, clearance, and disposition should be equivalent in animal and human models. It is important to determine the metabolism of tested drugs and how they will react within the human body. There are two types of strategies to use in toxicology research. These are:
1. Single Dose Toxicity Study
With single dose studies, useful information may be gathered on local toxicity or the connection between dosage and systemic reaction. Along with single dose testing, information on the dose-response relationships can also be obtained from animal model efficacy studies. When designing this type of study, it is imperative to incorporate safety pharmacology parameters.
2. Repeated Dose Toxicity Study
The dosing regimen in preclinical studies needs to follow the regimen that will be used in clinical trials. Some researchers choose daily repeated dosing while others use intermittent dosing, the choice will depend upon the particular medications that are being developed and tested. Repeated dose studies will need to monitor toxicokinetic effects.
Animal toxicity studies usually take between one to three months for biotechnology-derived pharmaceutical products. For any medications that are intended for short-term use – less than seven days typically – a toxicity study lasting two weeks is generally adequate for federal regulations and marketing authorization.
On the other hand, for medication meant to treat chronic disease, toxicity studies lasting approximately six months are typically required. Various pharmaceutical products may trigger or suppress an immune response, in which case, immunotoxicity studies may be added in preclinical trials.
https://www.pharmamodels.net/blog/importance-toxicology-research-preclinical-studies/
Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies
Regulatory toxicology studies
Regulatory toxicology studies are mandatory in the drug development process and aim to evaluate the toxicity level of a substance using protocols that follow the guidelines recommended to conduct non-clinical studies of pharmaceutical products. In addition, it is important to emphasize that they have to be conducted in compliance with the GLP principles. After the preliminary toxicity studies, the GLP studies should be conducted in two animal species (with the exception of mutagenicity tests). The planning of these studies could be based on the data obtained by the exploratory studies of both efficacy and toxicity. These findings could help to define doses, the duration of study, and any side effects that could require special attention. Some GLP toxicology studies are required before beginning clinical trials, but others could be conducted during different phases of the clinical trials; this will be discussed further in this section.
Although there are no unique and standard plans for drug development, it is recommended to perform genotoxicity studies (in vitro and in vivo) as well as a study of dose selection and repeated-dose toxicity (28 days), before the first exposure of humans to the substance. Usually, with these studies series, together with pharmacokinetic, efficacy, safety pharmacology and substance chemical characterization studies, it is possible to submit a dossier to the regulatory agencies to request permission to start the tests in humans. It is important to emphasize that for toxicology studies following GLP principles, the test article should be in its final formulation, in other words, in the same formulation that will be used to treat individuals during the clinical studies, together with its complete chemical certificate of analysis. In addition, the route of administration should be, preferably, the same as that intended for human treatment. These requirements are clearly described in the guidelines of non-clinical studies of the main regulatory agencies, such as the FDA, European Medicines Agency (EMA) and Agência Nacional de Vigilância Sanitária (ANVISA, Brazil).
In this step, the genotoxicity tests previously described (in vitro Ames No. 471 (4) and in vitro micronucleus No. 487 (36)) should be performed in accordance with the GLP requirements, even when it has already undertaken exploratory studies. Thus, the in vivo micronucleus test No. 474 (37) is also recommended, as it provides relevant genotoxicity data of a substance involved in active processes, such as metabolization, pharmacokinetics and DNA repair, which are not totally detected by an in vitro system. This test evaluates micronucleus formation in erythrocyte samples from the bone marrow or from rodents’ peripheral blood samples, allowing the identification of possible cytogenetic damage, resulting in micronucleus formation and chromosomal alterations. In many cases, the genotoxicity assays, performed according to the GLP principles, are conducted before the repeated dose toxicity tests for decision-making reasons. However, it depends on the strategy programmed for each substance and on the obtained preliminary data. Also, execution of the GLP genotoxicity test concomitant with initial repeated dose toxicity studies is common.
The toxicity data described in the guidelines suggested by the FDA comprise an important basis for the IND application; however, it depends on the intended application of each substance and can vary case-by-case. After the authorization to start clinical studies, other non-clinical toxicity studies should be conducted; for example, sub-chronic and chronic studies. The toxicity evaluation is normally classified in accordance with a chronological scale, such as the acute studies that are performed to verify the substance effect using single or repeated dose administration for 24 h. Indeed, sub-acute studies are those that comprise the toxic effects for 30 days, whereas sub-chronic studies are defined by the toxic effect of a substance between 30 and 90 days. Studies that are superior to 90 days are normally classified as chronic. However, this classification can be specific for some species; for example, chronic studies can be performed for six months in rodents and 9 months in non-rodents (41).
The sub-chronic study (90 days) can be conducted in parallel with phase I clinical studies. This study is very similar to the toxicity study of 28 days, and the guidelines for both require a daily treatment with at least three doses of the substance and the vehicle, together with clinical, biochemical, hematological, anatomical and histological analysis that are detailed in each guideline. Despite standard measurements, some additional analyses could be included for the observation of a particular effect of the substance, mainly when several toxic effects are described. These tests should be conducted in accordance with the GLP principles; together with the clinical data obtained from phase I, these can help to decide whether the study should continue or not to phase II.
As previously described in this section, the toxicology tests are very important and require high responsibility from the non-clinical and clinical teams. The available amount of substances could require specific protocols and requirements from the regulatory point of view. For example, the development of vaccines frequently does not require reproductive toxicity, mutagenicity or carcinogenicity tests. On the other hand, each substance has particular characteristics and is developed for the treatment of a specific and complex disease; for this reason, the development program should be analyzed case-by-case. Although the regulatory agencies suggest a basic battery of tests to be performed, it is fundamental that the developmental team anticipates possible additional side effects to elaborate a complete clinic plan with important information and avoiding unnecessary studies. Thus, the previous and direct contact between the pharmaceutical industry and the regulatory agencies is highly recommended, aiming to establish the most appropriate tests for each drug candidate.
Conclusion and perspectives
In this review, we highlighted the most recent and relevant aspects necessary to conduct non-clinical studies to attend the guidelines to develop new drugs recommended by major regulatory agencies. Although great efforts in recent years have been occurring to reduce, and perhaps in the future, ban the use of animals in the process of new drug development, several alternative methods are being adopted and recommended by the main international regulatory agencies. However, the use of animals in the new drug development process is still required.
Based on this review, it is possible to conclude that there is no single recommended sequence for the achievement of non-clinical studies during the process of new drug development (Figure 1). Many of the studies may be performed in parallel, and the sequence may vary widely depending on the disease. The use of GLP standards is absolutely necessary, especially for the evaluation of safety studies, and is a decisive factor for the acceptance of non-clinical studies in other countries where GLP has been recommended since 1970. Although Brazil adopts practically the same procedures (guidelines) recommended by the FDA and EMA, few laboratories or national institutions can conduct non-clinical studies in accordance with GLP requirements necessary for new drug registration purposes. The lack of reproducibility and reliability of non-clinical studies has been a limiting factor in the process of new drugs development for some national pharmaceutical companies.
Therefore, the need for high quality standard animals, associated with well-designed protocols, qualified human resources, use of positive and negative controls, blind experiment execution, proper use of statistical analyses, among other aspects, are mandatory factors to obtain reliable and reproducible non-clinical results. Non-clinical studies should be strictly performed in accordance with good institutional scientific practices and also employing GLP requirements (indispensable for the request and approval of a IND) in order to ensure the quality, reproducibility and reliability of non-clinical data, which will support the early clinical studies contributing to the successful development of a new drug.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5188860/
Why does someone think/believe ENZC drugs will fail?
Why are monoclonal antibodies so hard to produce?
Antibodies are expensive to produce because of the difficult process of isolating and quality testing thousands and thousands of candidates. This process can take up to a year and requires a lot of technical expertise.
"You've got to go through validation: Does it block the disease?" said John Kenney, president and co-founder of Antibody Solutions, a contract research company specializing in monoclonal antibody development. "You might come up with many potential candidates."
This process can involve checking donated human immune cells to see if they make good antibodies. It can also involve infecting mice that have been genetically modified to have a human immune system.
Regeneron confirmed to Knox News that they used both a humanized mouse process and patient samples to rapidly identify candidates.
"One of the antibodies came from human survivor blood," wrote Regeneron spokesperson Tammy Allen an email to Knox News. "The other came from one of our special mice."
Each candidate cell and antibody is stress-tested until the field is narrowed down. The cells need to produce a lot of antibody. The antibodies need to attach to the target of interest.
"It takes about 3 to 6 months to discover the cell that's making a high number of the antibody you really want," Sullivan said. "Once you have it, you have to put it into a large bioreactor to feed the cells to have it make the protein (antibody)."
As the coronavirus mutates new antibodies need to be identified and scaled up. Larger companies maintain pools of candidates in the event this occurs. Regeneron confirmed to Knox News that they maintained a bank of candidates in case their current cocktail loses efficacy.
Why monoclonal antibodies so expensive?
Scaling up production is not simple. Antibody production is typically measured by grams, not tons.
On average, it costs between $95 and $200 to manufacture a single gram of antibody. That cost does not include research, development or the cost of infusion into a patient.
The manufacturing cost is high because antibodies need to be built inside of mammalian cells to be kept alive. This means the cells need a body-temperature home, fluids, nutrients and cell-signaling molecules that say, “Yes, keep making antibodies.”
Each cell only makes so much each day. A single gram of antibody requires about a liter or more of expensive, nutrient-laced culture to produce. Although some processes can generate higher yields.
On the small scale, laboratories can spend thousands of dollars on grams of custom-built antibodies.
At the start of the pandemic, Regeneron had about 40,000 liters of bioreactor capacity per year. After a partnership with Roche, the company gained about 100,000 liters of new capacity. Unlike a smaller manufacturer, their process is able to deliver higher yields per liter.
Regeneron said that they had delivered nearly 2.65 million doses to the federal government this year meaning that this is enough to make roughly 9,700 doses a day, each containing slightly more than a gram of antibody.
Scaling that up means building tank-sized reactors that are capable of circulating thousands of gallons of nutrient-balanced fluids to billions of cell clones every day. The tanks aren’t empty, either. The interiors are often multi-chambered and full of fibrous surfaces on which cells can grow.
"You are talking about an apparatus the size of a tanker truck," Sullivan said. "And it's not just an empty bag. It has a lot of complex engineering."
Kenney told Knox News that bioreactors are difficult to clean and are often designed to be used once and discarded. That means a part of the cost is constantly replacing bioreactors.
And don't forget antibodies must be purified and quality tested to ensure they're safe to give to patients.
https://www.knoxnews.com/story/news/2021/10/04/monoclonal-antibodies-expensive-hard-manufacture-covid-coronavirus/5887418001/
Why monoclonal antibodies are expensive and hard to make in the fight against COVID-19.
What is monoclonal antibody therapy?
When a patient undergoes monoclonal antibody therapy, they are infused with high concentrations of antibodies engineered to fight the coronavirus.
Regeneron and Ely Lily are pharmaceutical companies that have been given an FDA emergency use authorization for their cocktail of monoclonal antibodies. A third company, GlaxoSmithKline, has an FDA emergency use authorization for a single antibody infusion.
These therapies cost about $2,000 a dose, which includes only about a gram of each antibody. They're expensive, in part, because they aren't traditional chemical drugs.
Each antibody takes months to identify, isolate and scale and thousands of gallons of nutrients to produce.
The therapy can be injected with a needle or administered intravenously.
What are antibodies?
Your body makes its own antibodies in response to infections. The main difference between a monoclonal antibody and your body’s antibodies is diversity.
Each antibody is like a unique key in search of a lock. Keys find their compatible locks, they bind to it, tagging it for the immune system to attack. Antibodies also “neutralize” viruses, preventing them from attaching to cells to infect them.
Dr. David Sullivan, an infectious disease physician at Johns Hopkins Hospital explained that antibody was about the third the size of the spike protein that the coronavirus uses to attach to human cells. "So you just have to have three or four (per spike protein) to prevent it from interacting with a cell. But if you have one antibody on one virus that virus is still going to be able to infect."
During a COVID-19 infection, your body makes hundreds — if not thousands — of different antibodies each tuned to a different part of the virus. Each is made by a single, unique immune cell. No other immune cell, not even those that are closely related, can produce that exact antibody.
Over time, the most successful antibody-making cells edit their antibodies to be better fits while cloning themselves to increase their manufacturing power. This is like your body figuring by trial and error out which key fits a lock.
Fundamentally, your body always makes more than one version of antibody against the same infectious agent.
OK, so what are monoclonal antibodies?
Unlike your body's natural spectrum response, monoclonal antibodies are grown in a lab from a single clone. That’s where the name “mono” comes from. The antibodies are all the same from clones of the same cell.
The second difference is between monoclonal antibody and your own home-grown antibody is speed. You need several days to mount a natural antibody response, or fewer if you are vaccinated. But administered monoclonal antibodies start working immediately.
"The first part of the disease is nothing more than the replication of SARS-COV2 in your nose," said Myron Cohen MD, director of the Institute for Global Health and Infectious Diseases at the University of North Carolina-Chapel Hill. "We are trying to check the disease in your nose before severe disease and death, and monoclonal can clearly do that."
How effective are monoclonal antibodies against COVID-19?
When a patient undergoes monoclonal antibody therapy, he or she is effectively getting a very small slice of someone else’s COVID-19 immune response. For that to work on a disease, you need lots more of that one artificial antibody than your body would normally make for itself.
Sullivan likened it to using water to put out a fire.
"Vaccines are like a little bit of water on the matches beforehand. It doesn't take much to prevent a fire," he explained.
Monoclonal antibodies are like using a small amount of water to put out a lit match. Those drops will work on a match, but not on a big fire.
As the infection gets worse, monoclonal antibodies are less and less effective.
"If I put a cup of water on an actual fire, it doesn't do as much," he said.
I didn't say the price rise wasn't REAL.
I said the price rise was unrealistic for ENZC and many other OTC in February 2021.
As my post stated for no apparent reason other than a lot of money was poured into the OTC with very high trading volume and then it all came crashing down.
ENZC trading to 95 cents may have been based on hype, potential, pump or whatever however it wasn't based on results from the company.
This is the OTC stocks fly high and fall low.
Nothing new here.
Just like most of the other OTC stocks that rose to unrealistic highs in February 2021.
The whole OTC market skyrocketed in February 2021. Many stocks with no potential, some potential and a lot of potential blew upward. The OTC market traded nearly 2 trillion February 2021.
https://www.nytimes.com/2021/03/18/business/penny-stocks-trading.html
https://www.bloomberg.com/news/articles/2021-03-19/way-off-exchange-stock-volume-hit-a-trillion-then-it-doubled#xj4y7vzkg
https://lastfuturist.com/why-are-penny-stocks-down-in-2021/
https://markets.businessinsider.com/news/stocks/penny-stock-trading-volume-soars-2000-amid-retail-trading-boom-2021-3-1030224239
When did EZNC explode up to 95 cents?
ENZC value will be determine by the results or lack there of moving forward.
Nobody knows what is going to come from the company and when it is going to come.
We all have our opinions of what can or may happen however at the end of the day it is all up to the company.
Results or lack there of is all the matters.
Biotech companies take years to get products to the marketplace.
This is a biotech company and what they have done in 2 years is amazing.
It take many many years for a biotech company to bring a product to market.
What did you expect this to happen over a short period of time.
The company has been very informative and forthcoming about what they are doing, how they are doing and how long it will take.
Also with NDAs in place there is information they cannot share.
2 years of progress with many patents applied for to ensure a bright and fruitful future.
The stock price will appreciate as clinical trials succeed, products come to the market or partnerships/licensing deals revealed.
ENZC is a high RISK high REWARD investment.
Will ENZC succeed?
Probably, however it take years for ANY biotech company to bring drugs to the marketplace.
ENZC has laid the foundation, created an A.I .platform , started producing product and is now going through the protocols to commercialization.
ENZC is assisted by multiple scientists with significant experience in the technology relating to production of monoclonal antibodies.
It hasn't been 2 years since Charles & company restarted what was created many years ago.
Will the stock price ever rise again significantly?
Probably
What we don't know is when and how.
Based on what we do know, once ITV-1 anti-HIV therapeutic is used in Africa and results start to filter out then ENZC will have the catalyst needed to move the stock price.
Why?
First off from a historical view point ITV-1 is already known to work better than anything on the market and less costly.
The original EPIC rise of ENZC was a normal occurrence seen in OTC stocks with possible potential. Also the Covid-19 pandemic and the fact at the time the WHOLE OTC market was on fire, Stocks across the board was making EPIC rises.
This is different now.
ENZC stock appreciation will be based on what is under the hood and does it work.
Africa first then Europe and the rest is history.
How will it flows nobody knows.
Big Bucks will be needed for ENZC to continue to GREATNESS:
Technology and processes for accelerating the production of monoclonal antibodies that target critical virus sites identified by the Company using its A.I. platform. The Company has identified critical conserved target sites on 20 viruses, including human and animal viruses, and is engaging with biotech companies having expertise in accelerating the production of such antibodies.
Related, synergistic or complimentary therapeutics and business structure for the purpose of potential combination with other biotech entities.
Expertise in providing specialized peptides having precise amino acid sequences corresponding to the precise target sites on both the Coronavirus and HIV viruses which are then used in the Company’s Texas lab against which mAbs are being produced. This strategy accelerates the production of the mAbs for further development.
Specialized cell sorting technology that is complementary to the process used in the Company’s lab to accelerate production of mAbs for advancing production.
Expertise in hybridoma production techniques for producing mAbs using hybridoma methodologies complementary to the process used in the Company's lab.
Animal trials centers, both in the U.S. and abroad, for the preparation of animal trials.
Promotional entities with specialized expertise in targeting large funding sources for the purpose of raising the substantial funds needed for the production of the recombinant mAbs necessary for future trials and for conducting animal trials.
As to each of these entities and those with whom the Company currently works on an ongoing basis, the Company has entered into NDAs (Nondisclosure Agreements) necessary to preserve and protect the Company plans and intellectual property being discussed and exchanged between the parties. These contractual restrictions are critical for the Company and its partners. Maintenance of strict confidentiality is essential to preserving intellectual property rights (patent rights) which are now being sought and will be sought in the future. Premature disclosure of information can bar the right to seek patent protection at a later date. The Company is not able to share specific details regarding arrangements regarding these NDAs.
The term of these NDAs is not time limited. The term extends until the later of five (5) years from the Effective Date or "until such time as the proprietary information is publicly known and made generally available". This provision is necessary because under Patent Laws an issued patent may be invalidated where the patent is filed subsequent to public disclosure of the invention claimed. In view of this limitation, the Company makes no public disclosure of information subject to NDAs and inventions covered by them. Additionally, certain technical information shared with companies with whom the Company has entered into an NDA may not be included in a patent application, but rather the subject technical information is maintained as Company confidential ("secret") indefinitely. Also, in these Agreements, the parties generally agree not to reveal the names of the contracting parties for a specified period.
The Company is very confident in its Artificial Intelligence empowered Intellectual Property Portfolio. It has allowed the Company to claim exclusive rights on an international stage covering critical target sites on numerous human and animal viruses. This places the Company on an equal level with the largest biotech companies in that the Company is the first to identify and patent critical sites on many human and animal viruses. This same technology and strategy are being implemented by the Company on new viruses, human or animal.
The Company identified the conserved sites on the Monkeypox Virus even before the World Health Organization declared it a global health emergency last week.
Funding and audit being addressed:
Company Programs Funding
Given the large number of therapeutics being advanced by Enzolytics, the Company is focused on raising the necessary funds for the production and sale in the U.S. and abroad of IPF Immune™, final development of its anti-HIV ITV-1 therapeutic, accelerating the development of multiple monoclonal antibodies for human therapy, and production of animal monoclonal antibodies. The Company’s audit is being finalized, and the Company fully expects to be able to acquire the funding necessary to complete its multiple programs.