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It is not SPAM.
It is FACTS about ENZC!!!
Do you even know what SPAM mean?
irrelevant or inappropriate messages sent on the internet to a large number of recipients.
unsolicited usually commercial messages (such as emails, text messages, or Internet postings) sent to a large number of recipients or posted in a large number of places
Here are some more FACTS about ENZC:
Toxicity and ENZC:
Toxicity or should I say "lack there of" is part of ENZC secret sauce.
The Company has also pioneered a proprietary method for creating human cell lines that produce fully human monoclonal antibodies directed against many infectious diseases. One antibody (designated as CLONE 3) has been demonstrated in tests in 5 international labs to fully neutralize over 95% of all strains and viral subtypes of HIV-1 against which it has been tested.
These HIV therapeutics may be used as an immunotherapeutic treatment for individuals with HIV/AIDS. They may also be developed for use as a prophylactic and therapeutic vaccine to prevent uninfected populations from contracting the HIV virus. Treatment using the fully human anti-HIV antibody will be far superior to current ARV therapy for several significant reasons: (1) the therapy will be effective and non-toxic, (2) will not require lifetime treatment and (3) will be far less expensive.
http://enzolytics.com/our-technology/
Inactivated Pepsin Fragment (IPF) Technology
One Company technology, invented by Harry Zhabilov the CSO of the Company, includes a patented antiviral peptide that has been tested in clinical studies at the National Center of Infectious and Parasitic Diseases in Bulgaria. This therapeutic, known as ITV-1, is a suspension of Inactivated Pepsin Fragment (IPF), a purified extract of porcine pepsin. ITV-1 has been shown to strengthen the immune system and may be used to facilitate a broad range of applications. ITV-1 has been tested in HIV patients in a clinical trial conducted under the strict guidelines of the European Union. HIV patients tested in these trials showed the following beneficial outcomes:
Improvement in the immune indices in the absolute number of Ly, CD3 T, CD4 T, CD8 T, B Ly, NK and in the percentage of CD3 T, CD4 T, CD8 T, B Ly, NK, and of the index CD4/CD8.
Decrease in the viral load.
Demonstrated beneficial effect on opportunistic infections.
Demonstrated very good compatibility with all of the other modern antiretroviral drugs.
Demonstrated very good tolerance in all patients and complete absence of side effects.
This Enzolytics anti-HIV treatment is now being advanced through the certification stage, after which it will be available for patient therapy. ITV-1 also has also demonstrated a positive effect on different kinds of cancer due to its ability to stimulates the immune system.
http://enzolytics.com/our-science/
ITV, produced by Enzolytics, Inc. is a brand-new specific protein for the treatment of HIV and other viral infections. For the
first time a naturally occurring strong binding with gp41 HIV-1 envelop protein “in vitro” was demonstrated.
Current market sales indicate that the majority of products show annual sales of 100 plus million, with a significant number
ranging from 300 million up to 1 billion dollars in annual sales. Many of the major drug companies, have entered into
partnership agreements with newcomers, or with companies in different stages of development in the research pipeline,
combining current ARVs with new drug families that impact the HIV/AIDS virus through different mechanisms of action.
Partnerships of this nature are a direct result of the major seven Pharmas who control a market with a potential of reaching
over $ 15 billion in year 2018, prevent their control and stake in the market share from sliding, due to numerous issues,
among which it is important to note, compliance to the drug regimen, adverse reactions to their chemotherapeutic agents
impacting the human organs, cost, and eventual viral resistance.
In summation our product’s differentiation is based on:
1- Minimal and minor side effects
2- Zero toxicity issues
3- Tremendous cost savings
4- Short and limited treatment cycle
5- Easier Compliance adherence
6- Zero risk of viral resistance and mutation
https://backend.otcmarkets.com/otcapi/company/financial-report/270351/content
How important is TOXICITY?
What is toxicology?
Toxicology is a field of science that helps us understand the harmful effects that chemicals, substances, or situations, can have on people, animals, and the environment. Some refer to toxicology as the “Science of Safety” because as a field it has evolved from a science focused on studying poisons and adverse effects of chemical exposures, to a science devoted to studying safety.
Toxicology uses the power of science to predict what, and how chemicals may cause harm and then shares that information to protect public health. When talking about toxicology it is important to keep a few things in mind.
Not everyone will respond to substances in exactly the same way. Many factors, including the amount and duration of exposure, an individual’s susceptibility to a substance, and a person’s age, all impact whether a person will develop a disease or not. There are times in a person’s life when he or she may be more susceptible to chemicals. These times may include periods of active cell differentiation and growth in the womb and in early childhood, as well as during adolescence, when the brain is continuing to develop. Just because someone is exposed to a harmful substance, does not always mean they will get sick from it.
The dose of the chemical or substance a person is exposed to is another important factor in toxicology. All substances have the potential to be toxic if given to humans and other living organisms in certain conditions and at certain doses or levels. For example, one or two aspirins may be good for you, but taking a bottle of aspirin may be harmful. The field of toxicology tries to understand and identify at what dose and through what exposure a substance poses a hazard.
Toxicologists also realize that even low-dose exposures that may seem insignificant may have biological meaning or lead to an adverse health effect if the exposure is continuous or happens during a critical window of development.
What is a toxicologist?
A toxicologist is a scientist who has a strong understanding of many scientific disciplines, such as biology and chemistry, and typically works with chemicals and other substances to determine if they are toxic or harmful to humans and other living organisms or the environment.
Just like there are different types of doctors, there are different types of toxicology specialists.
A toxicologist working in the pharmaceutical industry, for example, might work to make sure that potential new drugs are safe for testing in clinical trials for humans.
A toxicologist working at the National Toxicology Program (NTP) might be involved in designing and overseeing studies that create a controlled environment that replicates exposures that humans may encounter. NTP toxicologists work to identify hazards from the chemicals or substances they are studying.
https://www.niehs.nih.gov/health/topics/science/toxicology/index.cfm
How does the science of toxicology improve people’s lives?
Toxicology provides critical information and knowledge that can be used by regulatory agencies, decision makers, and others to put programs and policies in place to limit our exposures to these substances, thereby preventing or reducing the likelihood that a disease or other negative health outcome would occur. For example, the state of California used NTP findings to establish the first in the nation drinking water standard for Hexavalent Chromium. This standard will help reduce people’s exposure to this metallic element. Other benefits of toxicology include:
Government agencies have a sound scientific basis for establishing regulations and policies aimed at protecting and preserving human health and the environment.
Companies, such as pharmaceutical and chemical, are able to develop safer products, drugs, and workplaces.
Consumers have access to information that helps them make decisions about their own health and prevent diseases.
The PROBLEM with your BULLSHIT is that the company NEVER said anything about the STOCK PRICE!
Recently, we have become aware of commentators on our technology who, rather than fairly and validly analyzing our technology and our findings, instead propound, for what we perceive as some self-serving reasons, erroneous and irrelevant assertions to mislead those interested in knowing the fundamental truth about our discoveries. For example, one "red flag" raised by one commentator has been to criticize our AI team - not on the basis of the technology and substance of its findings - but by focusing on the date of incorporation of the partner. Obviously, the date an entity is incorporated is irrelevant when those on the research team have decades of experience with the knowledge, skill and capability to analyze the amino acid sequences (containing thousands in number) of each of over 50,000 different Coronavirus isolates. It is from this sophisticated analysis and resulting findings that the Achilles' heels of the Coronavirus are revealed, namely those epitopes that must be and that can be targeted by monoclonal antibodies to effectively treat the virus not only today but into the future. We question the motive behind these grossly misdirected comments, made for what we perceived as self-serving reasons and not to provide an honest, fair and truthful dialogue about a most serious medical crisis. While we perceive such irrelevant and misleading comments as intending to divert attention from the problem at hand and the solutions that are possible, we stand resolved to focus on the science and applying our capabilities to achieve success for all who will confront this virus - a virus that has and will do societal damage around the world, not only today but in the future".
And the BEAT goes ON:
For example, one "red flag" raised by one commentator has been to criticize our AI team - not on the basis of the technology and substance of its findings - but by focusing on the date of incorporation of the partner. Obviously, the date an entity is incorporated is irrelevant when those on the research team have decades of experience with the knowledge, skill and capability to analyze the amino acid sequences (containing thousands in number) of each of over 50,000 different Coronavirus isolates. It is from this sophisticated analysis and resulting findings that the Achilles' heels of the Coronavirus are revealed, namely those epitopes that must be and that can be targeted by monoclonal antibodies to effectively treat the virus not only today but into the future. We question the motive behind these grossly misdirected comments, made for what we perceived as self-serving reasons and not to provide an honest, fair and truthful dialogue about a most serious medical crisis. While we perceive such irrelevant and misleading comments as intending to divert attention from the problem at hand and the solutions that are possible, we stand resolved to focus on the science and applying our capabilities to achieve success for all who will confront this virus - a virus that has and will do societal damage around the world, not only today but in the future".
ITV-1 aka "SNAKE OIL BULLSHIT"
Patent US-7479538
Enzolytics has a License Agreement for US Patent 7479538. The claim is Irreversibly-inactivated Pepsinogen Fragments for Modulating Immune Function.
Enzolytics, Inc.'s flagship compound ITV-1 is a suspension of Inactivated Pepsin Fragment (IPF), which studies have shown is effective in the treatment of HIV. 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. IPF is a platform technology that can be used to facilitate a broad range of applications. It is free from major neurological, gastrointestinal and hematological side effects seen in the anti-retrovirals in use today. IPF has not shown to be subject to viral resistance and is cost effective.
This bio-product has shown low toxicity and is well accepted by the body system. Clinical trials in Bulgaria show improvements in immunity.
ITV-1 has been through Phase I, II and III clinical Trials however due to ENZC being informed that the inclusion of the BDA in the EMA restricted the permitting of our Treatment by the BDA and the permitting will now be done by the EMA for all the European Union. As a result, some, if not all of the Phase III clinical trials may need to be completed under the EMA standards.Additionally, the Company has created a proprietary cell line that produces fully human monoclonal antibodies that target and neutralize the HIV virus.
Cell line is a general term that applies to a defined population of cells that can be maintained in culture for an extended period of time, retaining stability of certain phenotypes and functions. Cell lines are usually clonal, meaning that the entire population originated from a single common ancestor cell.
Clone 3
The Company has clarified the lack of significance of the prior expired Company patents covering the Company's "parent" Clone 3 anti-HIV antibody. The expired Company patents were issued on the "parent" Clone 3 antibody. As is the case with virtually all parent antibodies, the parent antibody is a "slow producer" - which means it could not produce sufficient antibody therapeutics to treat the 36 million individuals infected with HIV. Thus, a recombinant form of the antibody had to be created employing a fast-producing CHO cell line. This has been accomplished by the Company and patent applications are pending claiming the recombinant form of the antibody, the form that will be used in patient therapy. The term of issued patents will be 20 years from filings, such filings having been made in 2020.
We have seen real RESULTS.
Biotechs can take years to get a product to the market however with the PANDEMIC hitting if our technology is to be used and as we already know is needed it will be in the marketplace in months.
Developing therapeutic monoclonal antibodies at pandemic pace
The time from discovery to proof-of-concept trials could be reduced to 5–6 months from a traditional timeline of 10–12 months.
Outbreaks of emerging infectious diseases have become increasingly common in recent decades. Epidemics have spread across the globe, including AIDS, H1N1 influenza and most recently coronavirus disease (COVID-19). In the face of a pandemic infectious disease outbreak, new approaches should be explored to enable the most rapid evaluation of antibodies for passive immunization or treatment. The fastest timeline from discovery to clinical evaluation of novel recombinant antibodies for medical use has been a focus of the biopharmaceutical industry for decades. For potentially life-saving therapies, the benefits of the earliest clinic testing should translate to accelerated pivotal trial testing and maximal patient benefit. Process and product development groups at major biopharmaceutical companies have reduced phase 1 timelines for recombinant antibody production through a universal convergence on similar technologies and strategies. Yet there may be opportunities for substantially faster timelines arising from a combination of the latest technological advances with acceptance of higher business risk or costs without an increased risk profile to patients in the first clinical trials.
A faster path
During a pandemic, there is no time to waste in the development and clinical testing of therapeutic modalities, including vaccines, nucleic acids, small molecules, convalescent serum, intravenous immunoglobulin G (IgG) and monoclonal antibodies (mAbs).
Until recently, the evaluation of mAb therapies for this scenario has been slow and the production capacity was limited. What has changed to enable rapid evaluation of mAb therapies in this case?
The product development timeline from lead mAb identification to phase 1 investigational new drug application (IND) is 10–12 months at many companies today — a dramatic reduction from the 18 months that was standard in the industry 5 or more years ago. A combination of recent technical advances and the acceptance of business (but not product quality or patient safety) risks offers a further acceleration for clinical trials. Rapid clinical production capacity has benefited from development of highly productive cell lines and larger bioreactors using single-use technology, enabling the production of thousands of doses from a single batch of over 5 kilograms.
Today, we can accelerate these activities and enable production capacity for clinical studies for therapeutic mAbs. What could be the fastest path to provide mAbs for clinical evaluation during a pandemic outbreak? I propose that the answer could be 5–6 months, rather than 10–12 months.
Lead mAb identification and characteristics
In a conventional discovery program, mAb identification usually takes several months to identify an attractive candidate. But one way of increasing the speed of identifying leads is to screen prospectively isolated panels against new pathogens and many viral strains1,2,3. This enables rapid identification of the best mAb for development and puts process development and manufacturing on the critical path to clinical evaluation. There are several other mAb discovery approaches (reviewed in ref. 4) that may also be capable of rapid lead identification that would subsequently benefit from this development strategy.
I present here an assessment of accelerated mAb discovery and development based on the use of the clinically proven IgG1 isotype. Over 50 IgG1 therapeutic mAbs have been commercialized5 and hundreds more have been clinically tested. The IgG1 mAb safety and quality risk profiles are low and enable a shift in risk tolerance. Substantial platform knowledge, product development history, current good manufacturing practice (cGMP) production experience and facilities are also broadly established for IgG1 mAbs. In response to a pandemic disease outbreak, IgG1 mAbs therefore have a distinct advantage as prophylactic or therapeutic biological agents.
Speed to phase 1 cell line
To accelerate clinical development, the production host should be a Chinese hamster ovary (CHO) cell line. Although alternative hosts, such as yeast, Escherichia coli and plants, have been proposed to have benefits of rapid genetic engineering and production, major deficiencies preclude them from enabling a rapid response to a pandemic outbreak. The established cGMP production infrastructure cannot support large clinical trials and post-licensure demand. For such hosts, the lack of clinical experience presents a substantive patient safety risk arising from the potential impacts of rare mAb post-translational modifications or variants, including unusual glycans, host cell proteins, and so forth. In contrast, the low risk profile of mAbs produced by CHO cell lines has been established and supports a rapid development model based on platform development, manufacturing technology and infrastructure.
Several companies have developed cell lines using targeted integration of mAb expression vectors6,7. These cell lines provide more consistent expression through integration of low copy numbers in highly active transcriptional hotspots. This consistency can reduce the time for screening cell pools or clones leading to a phase 1 cell line. By not assessing multiple pools of transfectants, generating interim cell banks, and assessing productivity of pools as part of the routine cell line development used for decades with random integration, savings of several months could be gained between transfection and cloning. (Although targeted integration is a critical advance, it is possible that an optimized random integration technology may also produce a high percentage of transfectants with suitable productivity.)
Moving directly from the stable transfectant pool to cloning is becoming a standard practice today. Until recently, an intermediate stage of expansion — generation of several pools of transfectants and subsequent screening — was used to increase the probability of finding a high-producing line, but this takes many weeks, including the typical 2-week production culture screen followed by analysis of product quality. If instead one moves directly to cloning from a pool of transfectants with consistent productivity, the final clone screening step could be conducted much earlier. Another few weeks may also be saved by conducting a single round of cloning using fluorescence-activated cell sorting (FACS) or limiting dilution, with supporting imaging to establish the clonal derivation of the resulting cell line, rather than performing two rounds of limiting dilution8,9. Finally, multiple candidate clones can be screened with very small bioreactors using small-volume tubes or ambr15 bioreactors of 15?mL volume10, which could save roughly 5 days instead of screening using 5-liter bioreactors.
In aggregate, these new technologies and approaches could save 2 months in the timeline from lead identification to establishment of a clonally derived cell line suitable for phase 1 production (Fig. 1). If toxicology studies are shortened, chemistry, manufacturing and control (CMC) activities may comprise the critical path to the IND filing.
Process and formulation development
In parallel with cell line development, transient expression cultures produce material to support downstream process, formulation and analytical development. Large-scale transient cultures (≥100 liters) generate many grams of product in a single batch11. The availability of this feedstock weeks earlier than material from clonal cell lines accelerates the timeline to cGMP production, informing the final process definition and drug product formulation.
By selecting an IgG1 mAb, one can leverage experience with platform processes and production facilities. High-throughput screening of platform polishing chromatographic steps uses very little material and is highly predictive of process performance12. These studies can be conducted before the final clone selection, with little risk of an impact on the downstream process.
What PROOF does ENZC have on their FINDINGS?
Scientific research is the neutral, systematic, planned, and multiple-step process that uses previously discovered facts to advance knowledge that does not exist in the literature. It can be classified as observational or experimental with respect to data collection techniques, descriptive or analytical with respect to causality, and prospective, retrospective, or cross-sectional with respect to time.
All scientific investigations start with a specific research question and the formulation of a hypothesis to answer this question. Hypothesis should be clear, specific, and directly aim to answer the research question. A strong and testable hypothesis is the fundamental part of the scientific research. The next step is testing the hypothesis using scientific method to approve or disapprove it.
Scientific method should be neutral, objective, rational, and as a result, should be able to approve or disapprove the hypothesis. The research plan should include the procedure to obtain data and evaluate the variables. It should ensure that analyzable data are obtained. It should also include plans on the statistical analysis to be performed. The number of subjects and controls needed to get valid statistical results should be calculated, and data should be obtained in appropriate numbers and methods. The researcher should be continuously observing and recording all data obtained.
Data should be analyzed with the most appropriate statistical methods and be rearranged to make more sense if needed. Unfortunately, results obtained via analyses are not always sufficiently clear. Multiple reevaluations of data, review of the literature, and interpretation of results in light of previous research are required. Only after the completion of these stages can a research be written and presented to the scientific society. A well-conducted and precisely written research should always be open to scientific criticism. It should also be kept in mind that research should be in line with ethical rules all through its stages.
In medical research, all clinical investigations are obliged to comply with some ethical principles. These principles could be summarized as respect to humans, respect to the society, benefit, harmlessness, autonomy, and justice. Respect to humans indicates that all humans have the right to refuse to participate in an investigation or to withdraw their consent any time without any repercussions. Respect to society indicates that clinical research should seek answers to scientific questions using scientific methods and should benefit the society. Benefit indicates that research outcomes are supposed to provide solutions to a health problem. Harmlessness describes all necessary precautions that are taken to protect volunteers from potential harm. Autonomy indicates that participating in research is voluntary and with freewill. Justice indicates that subject selection is based on justice and special care is taken for special groups that could be easily traumatized.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491675/#:~:text=Scientific%20research%20is%20the%20neutral,not%20exist%20in%20the%20literature.
Many Many things are going on with ENZC.
Many projections have been made and haven't yet come to fruition.
A projection deferred is not a projection denied.
Some may expect certain things this week however they may not happen to next week or the week after.
ALL is GOOD!!!!
What we expect that is imminent in the next 15-45 days:
1. NSF and NIH applications Forthcoming
2. Additional Funding Anytime
3. Texas A&M University Institute for Preclinical Studies. Anytime
4. 2020 Annual Report (completed)/PCAOB Audit April 2021 Anytime
5. Toxicity Study Anytime
6. Progress on ENZC plans to further develop additional anti-HIV monoclonal antibodies and to now begin the production of fully human monoclonal antibodies targeting the CoronaVirus Anytime
7. Status on the completion of production of monoclonal antibodies against both the HIV virus and the CoronaVirus Anytime
8. Status of testing in combination the Enzolytics ITV-1 peptide in conjunction with our anti-HIV monoclonal antibodies. There is reason to believe that there will be synergistic effect achieved with this combination therapy. Anytime
9. Status on the process of identifying a clinical research organization for the preparation of pre-IND protocols for submission to the FDA. Completed
10. GMP manufacturer Completed
11. Status of finalizing the necessary steps for completing the permitting process for our ITV-1 HIV/AIDS therapeutic in Bulgaria. Anytime
12. Status of received proposals from FDA approved manufacturers to produce the quantities necessary for such certification. Under Review
13. Results of testing of the newly produced monoclonal antibodies. This includes testing of our now being produced recombinant anti-HIV monoclonal antibodies created from the parent antibody. Such testing is now scheduled for early 2021 at the University of Strasbourg in Strasbourg, France. Additional testing of the Company's antibodies is also being planned at San Raffaele Scientific Institute, Milan, Italy.Anytime
14. Acquisition Anytime
15. Status of collaborative opportunities with other drug development companies to expand our product reach. Forthcoming
16. Gilead Relationship to ENZC
17. Eli Lily Relationship to ENZC
18. Immunome Relationship to ENZC
BOOM time COMING!!!
Why ENZC is the FUTURE?
BECAUSE mAbS are the FUTURE.
The Future of Monoclonal Antibodies
Over the last decade monoclonal antibodies (mAbs) have been one of the fastest-growing classes of pharmaceutical drugs. As more potential targets are identified through a greater understanding of molecular mechanisms underlying disease, it offers opportunities for the development of new mAb-based drugs.
Key areas over the last decade have included cancer immunotherapy, inflammatory diseases, and certain autoimmune diseases. There have also been developments in the structure of mAbs, including antibody fragments, bispecific antibodies, and polyclonal antibodies.
Other areas include diagnostic and analytical uses for mAbs as an important tool in biochemistry. However, this article will focus on the new disease areas undergoing development for the clinical use of mAbs.
Autoimmune disease
Immunotherapy is a key area of treatment against autoimmune diseases. They can help to block autoantibodies from binding to their target, causing the immune system to act against the host’s cells.
Many treatments for Alzheimer’s disease target the amyloid-ß (Aß) peptide. Passive immunization with mAbs has been a key area of research within anti-Aß therapy options, but trials have gained conflicting results.
For example, in phase II/III trial of Gantenerumab, including 799 participants, no significant improvements were measured in either brain activity or Aß levels. However, patients with the fastest progression of the disease may have benefited.
A common explanation for these conflicting results has been the use of participants who are in the latter stages of the disease. The problem with addressing this is the difficulty of obtaining the same size of the study group, as it is harder to find people diagnosed in the early stages of disease progression.
Overall though, a more complete understanding of Alzheimer’s disease may be required before immunotherapy can see significant results.
The specific role of Aß is still poorly understood, particularly whether its role is closer to being a symptom or cause of disease. Different targets for mAbs may be an area for research as the molecular mechanisms of Alzheimer’s are better understood.
Coronavirus
Recent advancements in the development of mAbs against coronavirus, specifically SARS-CoV and MERS-CoV, could represent a potential avenue for prophylaxis or treatment of the novel coronavirus, SARS-CoV-2.
Passive immunization of patients with mAbs would unlikely to result in an outright cure but may help to reduce the severity of disease and limit the virus from replicating.
This could be especially useful in patients suffering from moderate to severe disease and help to increase survival rates in these individuals.
Both SARS-CoV and SARS-CoV-2 enter the host cell via the receptor, angiotensin-converting enzyme 2 (ACE-2). This represents a potential target for immunotherapy, preventing the virus from binding with the host cell. A variety of mAbs have been proposed against ACE-2, but none have been approved.
An alternative target would be the spike protein on the virus that binds with the receptor. While the structure of SARS-CoV is known, further understanding of the structure and mechanism of SARS-CoV-2 pathogenesis would be required.
The pandemic nature of SARS-CoV-2 would likely mean that using a mAb as prophylaxis would not be feasible except in the most vulnerable patients, as it would not be possible to produce a high enough quantity for global use.
Whether mAb research could result in the development of a therapeutic for SARS-CoV-2 is up for debate. However, this area should be an area for research in the future regardless, as recent history shows us that there is a strong likelihood of future coronavirus outbreaks.
Fungal infections
As the incidence of systemic fungal infections increases there is a greater need for vaccines or therapy. Changes in climate, worldwide travel, and more immunocompromised individuals have contributed to this increase.
Infection with Cryptococcus neoformans is often associated with HIV infection. As people are living longer with anti-retro virals, more people are susceptible to this species. A major component of C. neoformans pathogenesis is its ability to downregulate the immune response.
Capsular polysaccharides are important in doing this and are therefore a good target for mAbs. A study generated a mAb targeting a capsular polysaccharide, resulting in the clearance of the antigen from the serum of mice and increased overall survival of cryptococcosis.
Another mAb that acted against C. neoformans polysaccharide, 18B7, was shown to be both effective and safe. But it had funding issues and clinical trials had to be stopped prematurely.
Other mAbs have also shown promising results in clinical trials. Mycograb, which acts against a chaperone protein in Candida albicans, was shown to be clinically effective, but there were problems in production.
The use of mAbs in the treatment of systemic mycoses represents a promising area of research. However, issues in the cost-effectiveness and efficiency of production need to be improved to make it a viable option.
The problems with funding indicate a lack of economic or political will by pharmaceutical companies and governments to commit to fungal immunotherapy.
https://www.azolifesciences.com/article/The-Future-of-Monoclonal-Antibodies.aspx
The EVOLUTION of ENZC is not BULLSHIT!
It is all in BLACK and WHITE in the PRESS RELEASES.
What ENZC is trying to accomplish didnot happen overnight, it was well planned out and there have been setbacks and will be more setbachs however ENZC continues to press on.
The company was a mess FINANCIALLY.
They were behind in the reporting.
The had 100 of millions of shares in toxic financing.
Their Phase III trial for ITV-1 although successful has to be done again to get proper regulatory approval.
So what did they do?
It all started more than a year ago.
Here is where ENZC publicly stated THIS IS NOT FROM OUR COMPANY!!!
Enzolytics Comments on Recent Market Activity and Shareholder Update
DALLAS, TX / ACCESSWIRE / February 6, 2020 / Enzolytics- (OTC Pink Sheet-ENZC) was notified by FINRA that an unauthorized press release titled, "Enzolytics Inc., Launches Coronavirus Prevention Kit" was distributed to the public. Enzolytics and its management had no knowledge of this press release in any manner, and disavows any information contained in this press release. The company does not have a "Coronavirus Prevention Kit" and finds the claim reckless and fraudulent.
Enzolytics, Inc., Inc. is diligently working to bring its filings current and continue with its initiatives for the commercialization of its proprietary proteins for the treatment of HIV.
PLANO, TX / ACCESSWIRE / April 16, 2020 / Enzolytics- (OTC PINK:ENZC) is pleased to update shareholders on the current corporate initiatives. The company has retained SEC counsel for the purpose of updating all corporate information, financials and to bring the company current from a public company perspective and allow the achievement of the company objectives.
The immediate goals include:
- Regain Current Status with OTC Markets
- Open operation in the Dallas, Tx area where the company has relocated
- Identify a CMO, Contract Manufacturing Organization, to produce the validation batch for Immunotech Laboratories BG-Europe.
- Assist Immunotech Laboratories BG-Europe in the registration of ImmunH as an Immunomodulator for HIV treatment.
- Further our development in North America of our Flagship HIV immune treatment compound IPF
PLANO, TX / ACCESSWIRE / September 16, 2020 / Enzolytics, Inc. (OTC PINK:ENZC or the "Company") today announced the execution of a non-binding letter of intent (the "LOI") to merge with BioClonetics Immunotherapeutics, Inc. ("BCLS" or "BioClonetics") a biotech company located in Dallas Texas.
The link below has all ENZC Press Releases:
https://marketwirenews.com/stock/enzc/news/
This is an Analysis of what may become of ENZC.
Analysis:
ENZC is a penny stock and as with penny stock there is a high risk that one could lose most if not all of their investment. The possibility exist that all we have witness up-to date is one of the most intricate frauds in the history of the stock market.
Benjamin Graham
ENZC is a drug development company committed to the commercialization of its proprietary proteins for the treatment of debilitating infectious diseases.
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.
BioClonetics Immunotherapeutics, Inc., a wholly owned subsidiary of Enzolytics, is a Dallas and College Station, 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 producing fully human monoclonal antibodies may be used to produce therapeutics treatments for many infectious diseases including the SARS-CoV-2 Coronavirus.
ENZC is in a great position to disrupt the drug market for HIV, Coronavirus, Multiple Sclerosis and other diseases. They have been making great strides to accomplish this and much more progress is necessary to enable them to get their technology to the marketplace. They have been very forthcoming and keep shareholders abreast of certain developments as they move through the necessary processes to reach their intended results.
The beauty of ENZC is the 2 prong punch of the ITV-1 1 (Immune Therapeutic Vaccine-1), and Cl3hmAb (human monoclonal antibody) and the man in Charge, Chares S. Cotropia.
Mr. Cotropia appears to have a well-defined game plan that he has shared with shareholders through press releases and is evident as seen in the share price. The game plan seems to be working beautifully as he pointed out in the Press Release dated October 19, 2020:
All of our steps are taken with two objectives in mind.
First our focus is on creating successful therapeutics against infectious diseases, including HIV and now our focus on the Coronavirus.
Secondly, our efforts are also intended to increase the value of our technology and the value of our company - which directly translates into value for our investors. Please know that these are our two guiding objectives with every effort we make.
Now with the way the stock price is performing, objective one from the above paragraph is more likely to happen than not and objective two is already happening.
Well Said!
Criticism certainly is expected however outright dismissal of actions that ENZC has performed is manipulative and a whole lot of gibberish to what extent.
Nothing we or anyone on this board or any board is going to affect the progress of ENZC.
The EVOLUTION of ENZC is not BULLSHIT!
It is all in BLACK and WHITE in the PRESS RELEASES.
What ENZC is trying to accomplish didnot happen overnight, it was well planned out and there have been setbacks and will be more setbachs however ENZC continues to press on.
The company was a mess FINANCIALLY.
They were behind in the reporting.
The had 100 of millions of shares in toxic financing.
Their Phase III trial for ITV-1 although successful has to be done again to get proper regulatory approval.
So what did they do?
It all started more than a year ago.
Here is where ENZC publicly stated THIS IS NOT FROM OUR COMPANY!!!
Enzolytics Comments on Recent Market Activity and Shareholder Update
DALLAS, TX / ACCESSWIRE / February 6, 2020 / Enzolytics- (OTC Pink Sheet-ENZC) was notified by FINRA that an unauthorized press release titled, "Enzolytics Inc., Launches Coronavirus Prevention Kit" was distributed to the public. Enzolytics and its management had no knowledge of this press release in any manner, and disavows any information contained in this press release. The company does not have a "Coronavirus Prevention Kit" and finds the claim reckless and fraudulent.
Enzolytics, Inc., Inc. is diligently working to bring its filings current and continue with its initiatives for the commercialization of its proprietary proteins for the treatment of HIV.
PLANO, TX / ACCESSWIRE / April 16, 2020 / Enzolytics- (OTC PINK:ENZC) is pleased to update shareholders on the current corporate initiatives. The company has retained SEC counsel for the purpose of updating all corporate information, financials and to bring the company current from a public company perspective and allow the achievement of the company objectives.
The immediate goals include:
- Regain Current Status with OTC Markets
- Open operation in the Dallas, Tx area where the company has relocated
- Identify a CMO, Contract Manufacturing Organization, to produce the validation batch for Immunotech Laboratories BG-Europe.
- Assist Immunotech Laboratories BG-Europe in the registration of ImmunH as an Immunomodulator for HIV treatment.
- Further our development in North America of our Flagship HIV immune treatment compound IPF
PLANO, TX / ACCESSWIRE / September 16, 2020 / Enzolytics, Inc. (OTC PINK:ENZC or the "Company") today announced the execution of a non-binding letter of intent (the "LOI") to merge with BioClonetics Immunotherapeutics, Inc. ("BCLS" or "BioClonetics") a biotech company located in Dallas Texas.
The link below has all ENZC Press Releases:
https://marketwirenews.com/stock/enzc/news/
This is an Analysis of what may become of ENZC.
ENZC is a penny stock and as with penny stock there is a high risk that one could lose most if not all of their investment. The possibility exist that all we have witness up-to date is one of the most intricate frauds in the history of the stock market.
Analysis:
ENZC is a penny stock and as with penny stock there is a high risk that one could lose most if not all of their investment. The possibility exist that all we have witness up-to date is one of the most intricate frauds in the history of the stock market.
ENZC came out of trips because of the company's potential.
It ran because people believe in that potential and the continuous results from the company.
There has been a downward pressure on the stock for weeks.
It is not because of the company.
People that have an understanding of what ENZC is all about and where it is headed are very patient.
What really is a tale tale sign is all the attention ENZC has been getting lately.
We hope it continues after the pending reversal.
ENZC
Enzolytics, Inc. is committed to the development and commercialization of its proprietary therapeutics for the treatment of debilitating infectious diseases. The Company’s technology is broad, including technology for treating HIV-1, Hepatitis (A, B, C), Rheumatoid Arthritis, certain forms of cancer, rabies, influenza A and B, tetanus, and diphtheria. The Company’s therapies are also being developed to treat chronic infection and certain forms of cancer.
Fully Human Monoclonal Antibody Technology
With the recent acquisition of the technology created by BioClonetics Immunotherapeutics, Inc., the Company has additional and complementary technology for producing fully human monoclonal antibodies (mAbs) that neutralize the HIV virus. The Company is in the final development of the recombinant of the parent antibody (identified as “Clone 3”), which has been shown in in vitro tests conduction in 5 international laboratories to fully neutralized over 95% of all strains and viral subtypes of HIV-1 against which it was tested. The basis for its broad-spectrum efficacy is the fact that Clone 3 mAb targets an immutable epitope on the HIV virus. The targeted epitope has remained present in 98% (either directly or by way of conserved substitutions) of all now known 87,336 HIV isolates analyzed by the Company’s use of artificial intelligence. The failure of other mAbs, such as the Vaccine Research Group VRC01 [Bar KJ, et al. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016;375(21):2037-50. PMCID|5292134] resulted from the targeting of mutable epitopes of the HIV virus.
http://enzolytics.com/proprietary-therapeutics/
Development of therapeutic antibodies for the treatment of diseases
It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.
Background
Monoclonal antibodies (mAbs) are produced by B cells and specifically target antigens. The hybridoma technique introduced by Köhler and Milstein in 1975 [1] has made it possible to obtain pure mAbs in large amounts, greatly enhancing the basic research and potential for their clinical use. Other scientific and technological advances have also enabled the successful translation of mAbs to the clinic. Around the world, at least 570 therapeutic mAbs have been studied in clinical trials by commercial companies [2], and 79 therapeutic mAbs have been approved by the United States Food and Drug Administration (US FDA) and are currently on the market [3], including 30 mAbs for the treatment of cancer (Table 1).
The increasing importance of therapeutic mAbs is apparent (Fig. 1), as mAbs have become the predominant treatment modality for various diseases over the past 25?years. During this time, major technological advances have made the discovery and development of mAb therapies quicker and more efficient. Since 2008, 48 new mAbs have been approved, contributing to a total global market of 61 mAbs in clinical use at the end of 2017, according to the US FDA. Strikingly, a total of 18 new antibodies were granted approval by the US FDA from 2018 to 2019 – this number was tallied from information contained on various websites, including the antibody society [3], the database of therapeutic antibodies [4], and company pipelines and press releases. A list of antibody-based drugs approved by the US FDA is shown in Table 1.
The first therapeutic mAb, muromonab-CD3 (Orthoclone OKT3), was approved by the US FDA in 1986 [5] and comprises a murine mAb against T cell-expressed CD3 that functions as an immunosuppressant for the treatment of acute transplant rejection. The marketing end date of muromonab-CD3 is on July 30th, 2011 (Table 1). To overcome problems of decreased immunogenic potential and efficacy, while making possible the therapeutic use of antibodies for an extended duration, researchers developed techniques to transform rodent antibodies into structures more similar to human antibodies, without loss of binding properties. The first chimeric antibody, anti-GPIIb/IIIa antigen-binding fragment (Fab) (abciximab), was approved in 1994 by the US FDA for inhibition of platelet aggregation in cardiovascular diseases (Fig. 1). The drug was developed by combining sequences of the murine variable domain with human constant region domain (Fig. 2b) [6, 7]. Then the first mAb with an oncologic indication, rituximab, a chimeric anti-CD20 IgG1 approved for non-Hodgkin’s lymphoma in 1997 by US FDA (Fig. 1) [8, 9].
One exceptional advance that accelerated the approval of therapeutic mAbs was the generation of humanized antibodies by the complementary-determining region (CDR) grafting technique [10]. In CDR grafting, non-human antibody CDR sequences are transplanted into a human framework sequence in order to maintain target specificity [10] (Fig. 2c). The first humanized mAb approved by the US FDA in 1997 was the anti-IL-2 receptor, daclizumab, for the prevention of transplant rejection (Fig. 1) [11]. [color=red]The humanization of antibodies made it possible to clinically apply a new class of biologics directed against diseases that require long-term treatment, such as cancer and autoimmune diseases [12].[/color]
Based on the success of humanized mAbs in the clinic, a key discovery technology to obtain fully human mAbs (Fig. 2d) was developed in 1990 by Sir Gregory P. Winter . This technique was based on phage display, wherein diverse exogenous genes are incorporated into filamentous bacteriophages to compose a library. The library proteins are then presented on the phage surface as fusions with a phage coat protein, allowing the selection of specific binders and affinity characteristics. The phage display technique was first introduced by George P. Smith and comprises a powerful method for the rapid identification of peptides or antibody fragments, such as single chain fragment variable (scFv) or Fab, that bind a variety of target molecules (proteins, cell-surface glycans and receptors) (Fig. 3b). The Nobel Prize in Chemistry 2018 was awarded to George P. Smith and Sir Gregory P. Winter. George Smith developed phage-displayed peptides, which can be used to evolve new proteins . Gregory P. Winter was able to apply the phage-displayed antibody library to the discovery and isolation of antibodies . Phage display technology has also been used for antibody maturation by site-directed mutagenesis of CDR and affinity selection. Based on these techniques, the first fully human therapeutic antibody, adalimumab (Humira), an anti-tumor necrosis factor a (TNFa) human antibody, was approved in 2002 by the US FDA for rheumatoid arthritis (Fig. 1). Until now, nine human antibody drugs generated by phage display have been approved by the US FDA (Table 5).
Transgenic animals represent another technology for obtaining fully human mAbs (Fig. 3c). This technology was introduced in 1994 by the publication of two transgenic mouse lines, the HuMabMouse [35] and the XenoMouse [36]. The lines were genetically modified such that human immunoglobulin (Ig) genes were inserted into the genome, replacing the endogenous Ig genes and making these animals capable of synthesizing fully human antibodies upon immunization [35, 37]. The first human antibody generated in a transgenic mouse to anti-epidermal growth factor receptor (EGFR), panitumumab, was approved by the US FDA in 2006 (Fig. 1) [38, 39]. The number of fully human antibodies made from transgenic mice has increased rapidly, with the number of approved drugs currently at 19 (Table 5). Depending on the immunization protocol, high-affinity human antibodies can be obtained through further selection of hybridoma clones generated from immunized transgenic mice. Using a theoretically similar approach, the generation of neutralizing human antibodies from human B cells has also yielded promising results for infectious disease therapeutics.
The recent development of bispecific antibodies offers attractive new opportunities for the design of novel protein therapeutics. A bispecific antibody can be generated by utilizing protein engineering techniques to link two antigen binding domains (such as Fabs or scFvs), allowing a single antibody to simultaneously bind different antigens. Thus, bispecific antibodies may be engineered to exhibit novel functions, which do not exist in mixtures of the two parental antibodies. Most bispecific antibodies are designed to recruit cytotoxic effector cells of the immune system to target pathogenic cells [40]. The first approved bispecific antibody was catumaxomab in Europe in 2009 [41]. Catumaxomab targets CD3 and EpCAM to treat solid tumors in patients with malignant ascites. However, this drug was withdrawn from the market in 2017 for commercial reasons. Currently, two bispecific antibodies have obtained US FDA approval and are on the market. First, blinatumomab is a bispecific T-cell engager (BiTE) that targets CD3 and CD19 for treatment of B-cell precursor acute lymphoblastic leukemia (ALL) [42]. Second, emicizumab is a full-size bispecific IgG with natural architecture, which binds to activated coagulation factors IX and X for the treatment of haemophilia A [43]. To date, there are more than 85 bispecific antibodies in clinical trials, about 86% of which are under evaluation as cancer therapies [40]. The concepts and platforms driving the development of bispecific antibodies continue to advance rapidly, creating many new opportunities to make major therapeutic breakthroughs.
While mAbs are routinely used in biochemistry, molecular and cellular biology, and medical research, perhaps the most beneficial application is their use as therapeutic drugs for the treatment of human diseases, such as cancer, asthma, arthritis, psoriasis, Crohn’s disease, transplant rejection, migraine headaches and infectious diseases (Table 1). Important advances in antibody engineering made over the past decade have enhanced the safety and efficacy of the therapeutic antibodies. These developments, along with a greater understanding of the immunomodulatory properties of antibodies, have paved the way for the next generation of new and improved antibody-based drugs for the treatment of human diseases.
Clinical applications and market for therapeutic antibodies
Therapeutic antibodies currently approved as disease treatments
The mAb market enjoys a healthy pipeline and is expected to grow at an increasing pace, with a current valuation of $115.2 billion in 2018 [44]. Despite this high growth potential, new companies are unlikely to take over large shares of the market, which is currently dominated by seven companies: Genentech (30.8%), Abbvie (20.0%), Johnson & Johnson (13.6%), Bristol-Myers Squibb (6.5%), Merck Sharp & Dohme (5.6%), Novartis (5.5%), Amgen (4.9%), with other companies comprising the remaining 13% [44].
Many mAbs products achieved annual sales of over US$3 billion in 2018 (Fig. 1), while six (adalimumab, nivolumab, pembrolizumab, trastuzumab, bevacizumab, rituximab) had sales of more than $6 billion (Table 2). Adalimumab (Humira) had the highest sales figure ever recorded for a biopharmaceutical product, nearly $19.9 billion. The top ten selling mAb products in 2018 are listed in Table 2. Top-selling mAb drugs were ranked based on sales or revenue reported by biological or pharmacological companies in press announcements, conference calls, annual reports or investor materials throughout 2018. For each drug, the name, sponsors, disease indications, and 2018 sales are shown.
mAbs are increasingly used for a broad range of targets; oncology, immunology, and hematology remain the most prevalent medical applications [45]. Most mAbs have multiple disease indications and at least one that is cancer-related (lymphoma, myeloma, melanoma, glioblastoma, neuroblastoma, sarcoma, colorectal, lung, breast, ovarian, head and neck cancers). As such, oncological diseases are the medical specialty most accessible to mAb treatments [45]. Moreover, the number of target proteins known to function as either stimulatory or inhibitory checkpoints of the immune system has dramatically expanded, and numerous antibody therapeutics targeting programmed cell death protein 1 (PD-1, cemiplimab, nivolumab, pembrolizumab), its ligand programmed death-ligand 1 (PD-L1, durvalumab, avelumab, atezolizumab) or cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4, ipilimumab) have been granted marketing approvals [46].
Adalimumab (Humira) was the world’s best-selling drug in 2018. Adalimumab is a subcutaneously administered biological disease modifier used for the treatment of rheumatoid arthritis and other TNFa-mediated chronic debilitating diseases. It was originally launched by Abbvie in the United States after gaining approval from the US FDA in 2002. It has been shown that Adalimumab reduces the signs and symptoms of moderate to severe rheumatoid arthritis in adults, and it is also used to treat psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis, hidradenitis suppurativa, uveitis, and juvenile idiopathic arthritis [47, 48]. It may be used alone or in combination with disease-modifying anti-rheumatic drugs [49].
Immune checkpoints are important for maintaining self-tolerance and tempering physiologic immune responses in peripheral tissues. Therefore, the molecules underlying checkpoints have recently drawn considerable interest in cancer immunotherapy [50]. Both nivolumab (Opdivo) and pembrolizumab (Keytruda) are anti-PD-1 mAbs and were the second and third best-selling mAb drugs in 2018 (Table 2). Nivolumab is a human antibody, which blocks a signal that normally prevents activated T cells from attacking cancer cells. The target for nivolumab is the PD-1 receptor, and the antibody blocks the interaction of PD-1 with its ligands, PD-L1 and PD-L2, releasing PD-1 pathway-mediated immune inhibition [51, 52]. Pembrolizumab is a humanized antibody used in cancer immunotherapy to treat melanoma, lung cancer, head and neck cancer, Hodgkin’s lymphoma, and stomach cancer [53,54,55]. Pembrolizumab is a first-line treatment for NSCLC if cancer cells overexpresse PD-L1 and have no mutations in EGFR or in anaplastic lymphoma kinase [56, 57]. Large randomized clinical trials indicated that NSCLC patients treated with nivolumab and pembrolizumab (both approved by the US FDA in 2014) showed increased overall survival compared with docetaxel, the standard second-line treatment [58].
A total of 12 new mAbs were approved in the US during 2018. The majority of these products were approved for non-cancer indications, perhaps reflecting the higher approval success rate for antibodies as treatments for other diseases. Three antibodies (erenumab, galcanezumab, and fremaezumab) were approved for migraine prevention, and one (Ibalizumab) is used for human immunodeficiency virus (HIV) infection. The three migraine-preventing drugs, Erenumab (Aimovig), galcanezumab (Emgality), and fremaezumab (Ajovy), are mAbs that block the activity of calcitonin gene-related peptide (CGRP) receptor in migraine etiology [59]. CGRP acts through a heteromeric receptor, which is composed of a G protein-coupled receptor(calcitonin receptor-like receptor: CALCRL) and receptor activity-modifying protein 1 (RAMP1) [60, 61]. Both galcanezumab and fremaezumab bind to CGRP and block its binding to the receptor. However, erenumab is the only one of the three antibodies to target the extracellular domains of human G protein-coupled receptors CALCRL and RAMP1,interfering with the CGRP binding pocket [62].
Many mAbs are under development for treatment of infectious diseases, currently only four have been approved by the US FDA: raxibacumab and obiltoxaximab for treatment of inhalational anthrax [63], palivizumab for prevention of respiratory syncytial virus in high-risk infants [64], and ibalizumab for treatment of HIV infection patients [65]. Ibalizumab (Trogarzo) is a humanized IgG4 mAb that is used as a CD4 domain 2-directed post-attachment HIV-1 inhibitor. The US FDA approved ibalizumab for adult patients infected with HIV who were previously treated and are resistant to currently available therapies.
Therapeutic antibodies currently in clinical trials
Companies are currently sponsoring clinical studies for more than 570 mAbs. Of these, approximately 90% are early-stage studies designed to assess safety (Phase I) or safety and preliminary efficacy (Phase I/II or Phase II) in patient populations. Most of the mAbs in Phase I (~?70%) are for cancer treatment, and the proportions of mAbs intended to treat cancer are similar for those currently in Phase II and late-stage clinical studies (pivotal Phase II, Phase II/III or Phase III) [2].
Twenty-nine novel antibody therapeutics were in late-stage clinical studies for non-cancer indications in 2018. Among the trials for these mAbs, no single therapeutic area predominated, but 40% were for immune-mediated disorders, which comprised the largest group. From this group of potential treatments, leronlimab and brolucizumab entered regulatory review by the end of 2018, and five mAbs (eptinezumab, teprotumumab, crizanlizumab, satralizumab, and tanezumab) may enter regulatory review in 2019. In comparison, there were 33 novel antibody therapeutics in late-stage clinical studies for cancer indications in 2018. Antibody therapeutics for solid tumors clearly predominated, with less than 20% of the candidates intended solely for hematological malignancies. Five mAbs (isatuximab, spartalizumab, tafasitamab, dostarlimab, and ublituximab) license applications were submitted to the US FDA in 2019 [2].
Isatuximab is an anti-CD38 IgG1 chimeric mAb under evaluation as a treatment for patients with multiple myeloma (MM). Combinations of isatuximab and different chemotherapies are being tested in three Phase III studies (ICARIA, IKEMA, and IMROZ) on MM patients. The ICARIA study (NCT02990338) is evaluating the effects of isatuximab in combination with pomalidomide and dexamethasone compared to chemotherapy only in patients with refractory or relapsed MM. Pivotal Phase III ICARIA-MM trial results demonstrated that isatuximab combination therapy showed statistically significant improvements compared to pomalidomide and dexamethasone alone in patients with relapsed or refractory MM in 2019. The US FDA has accepted for review the biologics license application for isatuximab for the treatment relapsed or refractory MM patients. The target action date for the FDA decision is April 2020 [66]. The IKEMA (NCT03275285) and IMROZ (NCT03319667) studies are evaluating the isatuximab with other chemotherapeautic combinations in MM patients [67].
Spartalizumab is a humanized IgG4 mAb that binds PD-1 with sub-nanomolar affinity and blocks its interaction with PD-L1/PD-L2, preventing PD-1-mediated inhibitory signaling and leading to T-cell activation. Clinical study of Spartalizumab is underway with a randomized, double-blind, placebo-controlled Phase III COMBI-i study (NCT02967692), which is evaluating the safety and efficacy of dabrafenib and trametinib in combination with spartalizumab compared to matching placebo in previously untreated patients with BRAF V600-mutant unresectable or metastatic melanoma. The primary endpoints of the study are an assessment of dose-limiting toxicities, changes in PD-L1 levels and CD8+ cells in the tumor microenvironment, and progression-free survival. Key secondary endpoints are overall survival, overall response rate and duration of response. The estimated primary completion date of the study is September 2019 [68].
Dostarlimab is an anti-PD-1 mAb that may be useful as a treatment for several types of cancers. GlaxoSmithKline announced results from a Phase I dose escalation and cohort expansion study (GARNET; NCT02715284) in 2018, which is expected to support a biologics license application submission to the US FDA in 2019. Dostarlimab is being assessed in patients with advanced solid tumors who have limited available treatment options in the GARNET study. The drug is administered at a dose of 500?mg every 3?weeks for the first 4?cycles, and 1000?mg every 6?weeks thereafter in four patient cohorts: microsatellite instability high (MSI-H) endometrial cancer, MSI-H non-endometrial cancer, microsatellite-stable endometrial cancer, and non-small cell lung cancer. Dostarlimab is also being evaluated in another Phase III study (NCT03602859), which is comparing platinum-based therapy with dostarlimab and niraparib versus standard of care platinum-based therapy as first-line treatment of Stage III or IV non-mucinous epithelial ovarian cancer [69].
Ublituximab is a glyco-engineered anti-CD20 antibody currently under clinical investigation in five late-stage clinical studies for different cancers (chronic lymphocytic leukemia, CLL, non-Hodgkin’s lymphoma) and non-cancer (multiple sclerosis) indications. Three Phase III studies are exploring the efficacy of ublituximab in combination with other anti-cancer agents. Among these studies, the UNITY-CLL Phase III study (NCT02612311) is evaluating the combination of ublituximab and TGR-1202, a PI3K delta inhibitor, compared to anti-CD20 obinutuzumab plus chlorambucil in untreated and previously treated CLL patients. Two other Phase III studies (ULTIMATE 1, NCT03277261 and ULTIMATE 2, NCT03277248) are evaluating the efficacy and safety of ublituximab compared to teriflunomide in 440 patients with relapsing multiple sclerosis [70].
Methodologies for developing therapeutic antibodies
Human, humanized, chimeric, and murine antibodies respectively account for 51, 34.7, 12.5, and 2.8% of all mAbs in clinical use, making human and humanized mAbs the dominant modalities in the field of therapeutic antibodies. In the next section, we first introduce techniques for antibody humanization. Then, we describe three technical platforms related to the generation of fully human antibodies, including phage display, transgenic mice and single B cell antibody isolation (Fig. 3). Last, we describe the use of an affinity maturation method to optimize antibody binding activity.
Humanization of mAbs
Due to the availability, low cost and quick production time for mouse mAbs, humanization of mouse mAbs has been implemented on a large scale. Non-humanized murine mAbs have many disadvantages as treatments. For example, patients treated with mouse mAbs will produce a rapid human anti-mouse antibody (HAMA) response. HAMAs will not only hasten the clearance of mouse mAbs but may also produce undesirable allergic reactions and tumor penetration. Moreover, the ability of patients to initiate antibody-dependent cellular cytotoxicity (ADCC) in response to murine fragment crystallizable region (Fc) is limited. On the other hand, humanized mAbs are able to effectively exert effector functions while decreasing the immunogenicity of murine antibodies.
Generation of human antibodies by phage display
Overview of antibody phage libraries
Phage display is the first and still the most widely used technology for in vitro antibody selection. The strategy was developed based on the excellent work of George P. Smith in 1985, who used recombinant DNA techniques to fuse foreign peptides with a coat protein (pIII) of bacteriophage M13 in order to display peptides on the bacteriophage surface. He then created “antibody-selectable phage vectors” and described an in vitro method that enabled affinity selection of antigen-specific phage-displayed antibodies from 108-fold excess phage pools. It was later discovered that scFv, small antibody formats, can be expressed on phage filaments. At the time, there were three different research institutions independently establishing phage-displayed scFv or Fab antibody libraries: the MRC Laboratory of Molecular Biology in the UK, the German Cancer Research Center in Germany, and Scripps Research Institute in the USA. Since then, these phage-displayed antibody libraries have proven to be a reliable discovery platform for the identification of potent, fully human mAbs.
The process of identifying mAbs from a phage-displayed library begins with antibody-library construction (Fig. 4a). The variable heavy (VH) and variable light (VL) polymerase chain reaction (PCR) products, representing the Ig gene-encoding repertoire, are ligated into a phage display vector (phagemid). High quality mRNA from human peripheral blood mononuclear cells (PBMCs) is reverse-transcribed into cDNA. The different VH and VL chain-region gene families are then amplified using specific primers to amplify all transcribed variable regions within the Ig repertoire [98, 99]. The format of antibodies in a phage-displayed library can be either scFv or Fab fragments (Fig. 4b); scFvs are composed of the VH and VL domain connected by a short flexible linker. Antibody Fab fragments displayed on the phage coat protein have comparably higher structural stability and can be readily converted to intact IgG antibodies, usually without impairing binding activity [100, 101]. The elegance of phage-displayed libraries is apparent in the linkage between antibody phenotype (specificity and sensitivity) and genotype (genetic information) via the phage particle. Due to the small size and high solubility (1013 particles/ml) of phage particles, repertoire sizes up to 1011 independent clones can be efficiently produced and displayed in a single library [102,103,104].
Gene repertoires for phage display libraries can be obtained from naïve or immunized animals, or the libraries may be synthetically constructed using randomized CDR sequences within fixed frameworks. Phage display naïve antibody libraries are constructed from rearranged V genes of IgM repertoires. Because the gene sequences are derived from B cells of human donors, the naïve libraries are relatively close to the human antibody germ line and have a low risk of immunogenicity. The main advantage of an immunized library over a naïve library is that antibody genes in the immunized library have undergone natural affinity maturation in vivo, allowing the development of high-affinity antibodies against the target. However, this approach requires that immunogenic response can be successfully induced by the antigen of interest, and new libraries must be prepared for each new target. Single large naïve [94, 104, 105] and synthetic [102, 106, 107] libraries have yielded high affinity antibodies (sub-nanomolar range) against a wide spectrum of targets. Therefore, such non-immunized libraries have the distinct advantages of avoiding issues with immunological tolerance in immunized mice, and they do not require new immunized libraries for each new target.
Currently, almost all widely accessible commercial libraries are based on highly diverse non-immunized gene repertoires, which allow selection of antibodies against a virtually unlimited number of targets [108]. It is worth noting that most antibody drugs that have undergone evaluation in clinical trials originated from a few company-owned libraries. These libraries include: Cambridge Antibody Technology’s (now MedImmune, a subsidiary of AstraZeneca) scFv-fragment library, Dyax Corp’s (now Shire) human Fab-fragment libraries, scFv and Fab libraries from XOMA, and the fully synthetic human combinatorial antibody scFv (HuCAL) and Fab (HuCALGold) libraries developed by MorphoSys [97].
https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0592-z
Why ENZC is the FUTURE?
BECAUSE mAbS are the FUTURE.
The Future of Monoclonal Antibodies
Over the last decade monoclonal antibodies (mAbs) have been one of the fastest-growing classes of pharmaceutical drugs. As more potential targets are identified through a greater understanding of molecular mechanisms underlying disease, it offers opportunities for the development of new mAb-based drugs.
Key areas over the last decade have included cancer immunotherapy, inflammatory diseases, and certain autoimmune diseases. There have also been developments in the structure of mAbs, including antibody fragments, bispecific antibodies, and polyclonal antibodies.
Other areas include diagnostic and analytical uses for mAbs as an important tool in biochemistry. However, this article will focus on the new disease areas undergoing development for the clinical use of mAbs.
Autoimmune disease
Immunotherapy is a key area of treatment against autoimmune diseases. They can help to block autoantibodies from binding to their target, causing the immune system to act against the host’s cells.
Many treatments for Alzheimer’s disease target the amyloid-ß (Aß) peptide. Passive immunization with mAbs has been a key area of research within anti-Aß therapy options, but trials have gained conflicting results.
For example, in phase II/III trial of Gantenerumab, including 799 participants, no significant improvements were measured in either brain activity or Aß levels. However, patients with the fastest progression of the disease may have benefited.
A common explanation for these conflicting results has been the use of participants who are in the latter stages of the disease. The problem with addressing this is the difficulty of obtaining the same size of the study group, as it is harder to find people diagnosed in the early stages of disease progression.
Overall though, a more complete understanding of Alzheimer’s disease may be required before immunotherapy can see significant results.
The specific role of Aß is still poorly understood, particularly whether its role is closer to being a symptom or cause of disease. Different targets for mAbs may be an area for research as the molecular mechanisms of Alzheimer’s are better understood.
Coronavirus
Recent advancements in the development of mAbs against coronavirus, specifically SARS-CoV and MERS-CoV, could represent a potential avenue for prophylaxis or treatment of the novel coronavirus, SARS-CoV-2.
Passive immunization of patients with mAbs would unlikely to result in an outright cure but may help to reduce the severity of disease and limit the virus from replicating.
This could be especially useful in patients suffering from moderate to severe disease and help to increase survival rates in these individuals.
Both SARS-CoV and SARS-CoV-2 enter the host cell via the receptor, angiotensin-converting enzyme 2 (ACE-2). This represents a potential target for immunotherapy, preventing the virus from binding with the host cell. A variety of mAbs have been proposed against ACE-2, but none have been approved.
An alternative target would be the spike protein on the virus that binds with the receptor. While the structure of SARS-CoV is known, further understanding of the structure and mechanism of SARS-CoV-2 pathogenesis would be required.
The pandemic nature of SARS-CoV-2 would likely mean that using a mAb as prophylaxis would not be feasible except in the most vulnerable patients, as it would not be possible to produce a high enough quantity for global use.
Whether mAb research could result in the development of a therapeutic for SARS-CoV-2 is up for debate. However, this area should be an area for research in the future regardless, as recent history shows us that there is a strong likelihood of future coronavirus outbreaks.
Fungal infections
As the incidence of systemic fungal infections increases there is a greater need for vaccines or therapy. Changes in climate, worldwide travel, and more immunocompromised individuals have contributed to this increase.
Infection with Cryptococcus neoformans is often associated with HIV infection. As people are living longer with anti-retro virals, more people are susceptible to this species. A major component of C. neoformans pathogenesis is its ability to downregulate the immune response.
Capsular polysaccharides are important in doing this and are therefore a good target for mAbs. A study generated a mAb targeting a capsular polysaccharide, resulting in the clearance of the antigen from the serum of mice and increased overall survival of cryptococcosis.
Another mAb that acted against C. neoformans polysaccharide, 18B7, was shown to be both effective and safe. But it had funding issues and clinical trials had to be stopped prematurely.
Other mAbs have also shown promising results in clinical trials. Mycograb, which acts against a chaperone protein in Candida albicans, was shown to be clinically effective, but there were problems in production.
The use of mAbs in the treatment of systemic mycoses represents a promising area of research. However, issues in the cost-effectiveness and efficiency of production need to be improved to make it a viable option.
The problems with funding indicate a lack of economic or political will by pharmaceutical companies and governments to commit to fungal immunotherapy.
https://www.azolifesciences.com/article/The-Future-of-Monoclonal-Antibodies.aspx
darron427
No I don't work for ENZC.
The majority of my POSTS have links to the CURREN INFORMATION I provide.
CURRENT meaning having occured in the past YEAR!
I OWN SHARES therefore I OWN PART of the COMPANY.
Yes We at ENZC FOLLOW the SCIENCE.
Speaking of MISLEADING people.
you said:
ENZC have already been through CLINICAL TRIALS!!!
We follow the SCIENCE!!!
CLINICAL TRIALS already PROVED ITV-1 is EFFECTIVE against HIV!!!
ENZC CLAIMS is based on SCIENTIFIC DATA
One Company technology, invented by Harry Zhabilov, the CSO of the Company, includes a patented antiviral peptide that has been tested in clinical studies at the National Center of Infectious and Parasitic Diseases in Bulgaria. This therapeutic, known as ITV-1, is a suspension of Inactivated Pepsin Fragment (IPF), a purified extract of porcine pepsin. ITV-1 has been shown to strengthen the immune system and may be used to facilitate a broad range of applications. ITV-1 has been tested in HIV patients in a clinical trial conducted under the strict guidelines of the European Union. HIV patients tested in these trials showed the following beneficial outcomes:
1. Improvement in the immune indices in the absolute number of Ly, CD3 T, CD4 T, CD8 T, B Ly, NK and in the percentage of CD3 T, CD4 T, CD8 T, B Ly, NK, and of the index CD4/CD8.
2. Decrease in the viral load.
3. Demonstrated beneficial effect on opportunistic infections.
4. Demonstrated very good compatibility with all of the other modern antiretroviral drugs.
5. Demonstrated very good tolerance in all patients and complete absence of side effects.
You Said:
FINAL REPORT
https://www.researchgate.net/publication/320011459_ITV-1_Irreversible_Pepsin_Fraction_Clinical_Data_from_Bulgarian_Phase_III_Clinical_Trial
SINGLE-CENTER PARALLEL-GROUP TRIAL WITH AN OPEN-LABEL AND TWO TREATMENT ARMS, TO EVALUATE THE EFFICACY AND SAFETY OF 16-WEEKS OF INJECTION ADMINISTRATION OF ITV-1-IMMUNH IN COMBINATION WITH AN ANTIRETROVIRAL THERAPY IN HIV-POSITIVE PATIENTS WITH ADVANCED AIDS”
Dated: 07 August, 2014
Summarizing the results from the present clinical trial, we can draw the following conclusions:
1. The application of the product ITV-1-lmmunH shows good efficacy in patients with HIV-1 infection in its various stages - in 21 of them (68%) from the main group we note an increase in CD4 + T- lymphocytes; in 16 of them the increase is accompanied by an increase in the index CD4/CD8 and CD4%, which corresponds to a reduction in the immune activation. The increase in these parameters is statistically significant compared to the control group. The
absolute number and the relative share of C08 + T lymphocytes is decreasing, too.
2. We observe a very good virological effect – the viral load in 80.5% of the patients is below the threshold of detection (however, we have no comparison to the control group).
3. The application of the product ITV-1-lmmunH is well tolerated - only one patient manifested allergic dermal response. With regard to none of them we found variations in the hematological and biochemical parameters, neither did we establish clinically significant abnormal vital signs.
Many Many things are going on with ENZC.
Many projections have been made and haven't yet come to fruition.
A projection deferred is not a projection denied.
Some may expect certain things this week however they may not happen to next week or the week after.
ALL is GOOD!!!!
What we expect that is imminent in the next 15-45 days:
1. NSF and NIH applications Forthcoming
2. Additional Funding Anytime
3. Texas A&M University Institute for Preclinical Studies. Anytime
4. 2020 Annual Report (completed)/PCAOB Audit April 2021 Anytime
5. Toxicity Study Anytime
6. Progress on ENZC plans to further develop additional anti-HIV monoclonal antibodies and to now begin the production of fully human monoclonal antibodies targeting the CoronaVirus Anytime
7. Status on the completion of production of monoclonal antibodies against both the HIV virus and the CoronaVirus Anytime
8. Status of testing in combination the Enzolytics ITV-1 peptide in conjunction with our anti-HIV monoclonal antibodies. There is reason to believe that there will be synergistic effect achieved with this combination therapy. Anytime
9. Status on the process of identifying a clinical research organization for the preparation of pre-IND protocols for submission to the FDA. Completed
10. GMP manufacturer Completed
11. Status of finalizing the necessary steps for completing the permitting process for our ITV-1 HIV/AIDS therapeutic in Bulgaria. Anytime
12. Status of received proposals from FDA approved manufacturers to produce the quantities necessary for such certification. Under Review
13. Results of testing of the newly produced monoclonal antibodies. This includes testing of our now being produced recombinant anti-HIV monoclonal antibodies created from the parent antibody. Such testing is now scheduled for early 2021 at the University of Strasbourg in Strasbourg, France. Additional testing of the Company's antibodies is also being planned at San Raffaele Scientific Institute, Milan, Italy.Anytime
14. Acquisition Anytime
15. Status of collaborative opportunities with other drug development companies to expand our product reach. Forthcoming
16. Gilead Relationship to ENZC
17. Eli Lily Relationship to ENZC
18. Immunome Relationship to ENZC
BOOM time COMING!!!
We at ENZC follow the SCIENCE and SCIENCE leads to results!!!
ENZC does not have a CURE_ALL drug!!!
ENZC:
Enzolytics, Inc. is a drug development company committed to the commercialization of its proprietary proteins for the treatment of debilitating infectious diseases. Enzolytics is committed to creating drugs for the better health of mankind.
Enzolytics is a Texas based biotechnology company with both patented anti-HIV therapeutics and a proprietary methodology for producing fully human IgG1 monoclonal antibodies for treating infectious diseases with non-toxic passive immunotherapy. The Company has clinically tested its anti-HIV therapeutics known as ITV-1. ITV-1 is a suspension of Inactivated Pepsin Fragment (IPF), a purified extract of porcine pepsin. ITV-1 has been shown to strengthen the immune system and may be used to facilitate a broad range of applications. ITV-1 has been tested in HIV patients in a clinical trial conducted under the strict guidelines of the European Union where it demonstrated beneficial outcomes. Additionally, the Company has created a proprietary cell line that produces fully human monoclonal antibodies that target and neutralize the HIV virus.
The Company’s scientific team, Harry Zhabilov, Joseph Cotropia MD and Gaurav Chandra MD, pioneered the Company’s proprietary therapeutics for treating infectious diseases, including HIV-1, Hepatitis (A, B, C), rabies, influenza A and B, tetanus and diphtheria. The Company’s therapeutics may also be used to treat Rheumatoid Arthritis and certain forms of cancer.
The Company has also pioneered a proprietary method for creating human cell lines that produce fully human monoclonal antibodies directed against many infectious diseases. One antibody (designated as CLONE 3) has been demonstrated in tests in 5 international labs to fully neutralize over 95% of all strains and viral subtypes of HIV-1 against which it has been tested.
These HIV therapeutics may be used as an immunotherapeutic treatment for individuals with HIV/AIDS. They may also be developed for use as a prophylactic and therapeutic vaccine to prevent uninfected populations from contracting the HIV virus. Treatment using the fully human anti-HIV antibody will be far superior to current ARV therapy for several significant reasons: (1) the therapy will be effective and non-toxic, (2) will not require lifetime treatment and (3) will be far less expensive.
Thus, for the patient, immunotherapy will be remarkably different — it will be safer, provide a much-needed immunotherapeutic cure rather than requiring lifelong treatment and costs substantially less than current antiretroviral therapy.
The Company also has created human cell lines that produce human antibodies against other infectious diseases, including rabies, influenza, tetanus and diphtheria. As a part of its mission, the Company is testing these antibodies to prepare them for use as therapies against these diseases.
As a result of the recent acquisition of the biotech company BioClonetics Immunotherapeutics, Inc., Enzolytics is now advancing additional complementary therapeutic platforms for treating infectious diseases, including a focus on production of anti-SARS-CoV-2 (CoronaVirus) monoclonal antibodies to treat COVID-19.
What PROOF does ENZC have on their FINDINGS?
Scientific research is the neutral, systematic, planned, and multiple-step process that uses previously discovered facts to advance knowledge that does not exist in the literature. It can be classified as observational or experimental with respect to data collection techniques, descriptive or analytical with respect to causality, and prospective, retrospective, or cross-sectional with respect to time.
All scientific investigations start with a specific research question and the formulation of a hypothesis to answer this question. Hypothesis should be clear, specific, and directly aim to answer the research question. A strong and testable hypothesis is the fundamental part of the scientific research. The next step is testing the hypothesis using scientific method to approve or disapprove it.
Scientific method should be neutral, objective, rational, and as a result, should be able to approve or disapprove the hypothesis. The research plan should include the procedure to obtain data and evaluate the variables. It should ensure that analyzable data are obtained. It should also include plans on the statistical analysis to be performed. The number of subjects and controls needed to get valid statistical results should be calculated, and data should be obtained in appropriate numbers and methods. The researcher should be continuously observing and recording all data obtained.
Data should be analyzed with the most appropriate statistical methods and be rearranged to make more sense if needed. Unfortunately, results obtained via analyses are not always sufficiently clear. Multiple reevaluations of data, review of the literature, and interpretation of results in light of previous research are required. Only after the completion of these stages can a research be written and presented to the scientific society. A well-conducted and precisely written research should always be open to scientific criticism. It should also be kept in mind that research should be in line with ethical rules all through its stages.
In medical research, all clinical investigations are obliged to comply with some ethical principles. These principles could be summarized as respect to humans, respect to the society, benefit, harmlessness, autonomy, and justice. Respect to humans indicates that all humans have the right to refuse to participate in an investigation or to withdraw their consent any time without any repercussions. Respect to society indicates that clinical research should seek answers to scientific questions using scientific methods and should benefit the society. Benefit indicates that research outcomes are supposed to provide solutions to a health problem. Harmlessness describes all necessary precautions that are taken to protect volunteers from potential harm. Autonomy indicates that participating in research is voluntary and with freewill. Justice indicates that subject selection is based on justice and special care is taken for special groups that could be easily traumatized.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491675/#:~:text=Scientific%20research%20is%20the%20neutral,not%20exist%20in%20the%20literature.
Who HOLDS the SHARES!
FLOAT
1,670,830,512
There only so many HELD by POSTERS on this BOARD.
What are MAJORITY SHAREHOLDERS doing with their SHARES?
Don't Know
The daily trade volume has not been that SIGNIFICANT.
SOMETHING has to GIVE!!!
Are we there YET?
We have seen real RESULTS.
Biotechs can take years to get a product to the market however with the PANDEMIC hitting if our technology is to be used and as we already know is needed it will be in the marketplace in months.
Developing therapeutic monoclonal antibodies at pandemic pace
The time from discovery to proof-of-concept trials could be reduced to 5–6 months from a traditional timeline of 10–12 months.
Outbreaks of emerging infectious diseases have become increasingly common in recent decades. Epidemics have spread across the globe, including AIDS, H1N1 influenza and most recently coronavirus disease (COVID-19). In the face of a pandemic infectious disease outbreak, new approaches should be explored to enable the most rapid evaluation of antibodies for passive immunization or treatment. The fastest timeline from discovery to clinical evaluation of novel recombinant antibodies for medical use has been a focus of the biopharmaceutical industry for decades. For potentially life-saving therapies, the benefits of the earliest clinic testing should translate to accelerated pivotal trial testing and maximal patient benefit. Process and product development groups at major biopharmaceutical companies have reduced phase 1 timelines for recombinant antibody production through a universal convergence on similar technologies and strategies. Yet there may be opportunities for substantially faster timelines arising from a combination of the latest technological advances with acceptance of higher business risk or costs without an increased risk profile to patients in the first clinical trials.
A faster path
During a pandemic, there is no time to waste in the development and clinical testing of therapeutic modalities, including vaccines, nucleic acids, small molecules, convalescent serum, intravenous immunoglobulin G (IgG) and monoclonal antibodies (mAbs).
Until recently, the evaluation of mAb therapies for this scenario has been slow and the production capacity was limited. What has changed to enable rapid evaluation of mAb therapies in this case?
The product development timeline from lead mAb identification to phase 1 investigational new drug application (IND) is 10–12 months at many companies today — a dramatic reduction from the 18 months that was standard in the industry 5 or more years ago. A combination of recent technical advances and the acceptance of business (but not product quality or patient safety) risks offers a further acceleration for clinical trials. Rapid clinical production capacity has benefited from development of highly productive cell lines and larger bioreactors using single-use technology, enabling the production of thousands of doses from a single batch of over 5 kilograms.
Today, we can accelerate these activities and enable production capacity for clinical studies for therapeutic mAbs. What could be the fastest path to provide mAbs for clinical evaluation during a pandemic outbreak? I propose that the answer could be 5–6 months, rather than 10–12 months.
Lead mAb identification and characteristics
In a conventional discovery program, mAb identification usually takes several months to identify an attractive candidate. But one way of increasing the speed of identifying leads is to screen prospectively isolated panels against new pathogens and many viral strains1,2,3. This enables rapid identification of the best mAb for development and puts process development and manufacturing on the critical path to clinical evaluation. There are several other mAb discovery approaches (reviewed in ref. 4) that may also be capable of rapid lead identification that would subsequently benefit from this development strategy.
I present here an assessment of accelerated mAb discovery and development based on the use of the clinically proven IgG1 isotype. Over 50 IgG1 therapeutic mAbs have been commercialized5 and hundreds more have been clinically tested. The IgG1 mAb safety and quality risk profiles are low and enable a shift in risk tolerance. Substantial platform knowledge, product development history, current good manufacturing practice (cGMP) production experience and facilities are also broadly established for IgG1 mAbs. In response to a pandemic disease outbreak, IgG1 mAbs therefore have a distinct advantage as prophylactic or therapeutic biological agents.
Speed to phase 1 cell line
To accelerate clinical development, the production host should be a Chinese hamster ovary (CHO) cell line. Although alternative hosts, such as yeast, Escherichia coli and plants, have been proposed to have benefits of rapid genetic engineering and production, major deficiencies preclude them from enabling a rapid response to a pandemic outbreak. The established cGMP production infrastructure cannot support large clinical trials and post-licensure demand. For such hosts, the lack of clinical experience presents a substantive patient safety risk arising from the potential impacts of rare mAb post-translational modifications or variants, including unusual glycans, host cell proteins, and so forth. In contrast, the low risk profile of mAbs produced by CHO cell lines has been established and supports a rapid development model based on platform development, manufacturing technology and infrastructure.
Several companies have developed cell lines using targeted integration of mAb expression vectors6,7. These cell lines provide more consistent expression through integration of low copy numbers in highly active transcriptional hotspots. This consistency can reduce the time for screening cell pools or clones leading to a phase 1 cell line. By not assessing multiple pools of transfectants, generating interim cell banks, and assessing productivity of pools as part of the routine cell line development used for decades with random integration, savings of several months could be gained between transfection and cloning. (Although targeted integration is a critical advance, it is possible that an optimized random integration technology may also produce a high percentage of transfectants with suitable productivity.)
Moving directly from the stable transfectant pool to cloning is becoming a standard practice today. Until recently, an intermediate stage of expansion — generation of several pools of transfectants and subsequent screening — was used to increase the probability of finding a high-producing line, but this takes many weeks, including the typical 2-week production culture screen followed by analysis of product quality. If instead one moves directly to cloning from a pool of transfectants with consistent productivity, the final clone screening step could be conducted much earlier. Another few weeks may also be saved by conducting a single round of cloning using fluorescence-activated cell sorting (FACS) or limiting dilution, with supporting imaging to establish the clonal derivation of the resulting cell line, rather than performing two rounds of limiting dilution8,9. Finally, multiple candidate clones can be screened with very small bioreactors using small-volume tubes or ambr15 bioreactors of 15?mL volume10, which could save roughly 5 days instead of screening using 5-liter bioreactors.
In aggregate, these new technologies and approaches could save 2 months in the timeline from lead identification to establishment of a clonally derived cell line suitable for phase 1 production (Fig. 1). If toxicology studies are shortened, chemistry, manufacturing and control (CMC) activities may comprise the critical path to the IND filing.
Process and formulation development
In parallel with cell line development, transient expression cultures produce material to support downstream process, formulation and analytical development. Large-scale transient cultures (≥100 liters) generate many grams of product in a single batch11. The availability of this feedstock weeks earlier than material from clonal cell lines accelerates the timeline to cGMP production, informing the final process definition and drug product formulation.
By selecting an IgG1 mAb, one can leverage experience with platform processes and production facilities. High-throughput screening of platform polishing chromatographic steps uses very little material and is highly predictive of process performance12. These studies can be conducted before the final clone selection, with little risk of an impact on the downstream process.
The stock price will move according to the the results of the company.
NOT BY WHAT IS POSTED ON A MESSAGE BOARD
Besides the company unlimited potential, the minor results (getting current, new patent, hired PCAOB auditor, toxicity study etc..) management and board of directors has put ENZC on a trajectory of preeminence.
Will ENZC fill the shoes of such an important distinction?
Time will tell.
The company is just in the development stage with some powerful tools in their closet. The have some processes that the MUST go through to get to the final goals of getting products to the marketplace.
ENZC is very fortunate to be at Texas A&M Institute for Preclinical Studies(TIPS)
TIPS provides translational researchers with unique access to expertise in all major medical and scientific disciplines including surgery, biomedical engineering, advanced imaging, pathology, radiography, interventional cardiology, neurology, animal behavior, chemistry, and engineering.
ENZC have shared their plans, goals mission and commitments as well as updates along the way. What they have shared thus far is just a sliver of what is coming down the road.
We are not even 6 months into this journey and the attention the company is getting is unprecedented. They posses some unique technology that may be the answer to help shutting Covid-19 down or at least keeping it in check.
You said:
It may be pretty TYPICAL of HARRY however HARRY is not running the ENZC, CHARLES is in CHARGE!
Does ENZC fit the definition of A Pump and Dump?
First one would eed to idenitfy what a Pump and Dump is:
Pump-and-dump is a scheme that attempts to boost the price of a stock through recommendations based on false, misleading or greatly exaggerated statements. ... Then, once the price of the stock has been increased sufficiently by unsuspecting marks, the promoters then sell the stock at high prices.
So now the we know what a pump and dump is, ENZC clearly does not qualify.
So what is ENZC?
I'm glad you asked.
It is not a dotcom BOMB.
It is a RECENTLY organized combination of two (2) companies into one.
PLANO, TX / ACCESSWIRE / December 1, 2020 / Enzolytics, Inc. (OTC Markets "ENZC" or the "Company") announced the execution of the definitive business combination agreement successfully merging the biotech companies Enzolytics, Inc. and BioClonetics Immunotherapeutics, Inc. on World AIDS Day.
Through a merger of biotech companies, Enzolytics now advances two separate but complementary therapy platforms for treating infectious diseases, targeting HIV and the CoronaVirus. One technology, invented by Harry Zhabilov, the CSO of the Company, is a patented antiviral peptide that has been tested in clinical studies at the National Center of Infectious and Parasitic Diseases in Bulgaria. In these trials, the therapeutic, known as ITV-1, demonstrated effectiveness in the treatment of HIV patients in various stages of the disease. In trials conducted in 31 patients, the therapeutic showed efficacy, with 68% of those individuals tested experiencing an increase in CD4 + T lymphocytes. This increase was accompanied by an increase in the CD4/CD8 index and CD4% in over 50% of those tested. The increase in these parameters demonstrated statistical significance compared to the control group. The absolute number and the relative percent of CD8 + T lymphocytes were also decreased. And the viral load in 80.5% of those tested was below the threshold of detection. This Enzolytics anti-HIV treatment is now being advanced through the certification stage to thereafter be made available for patient therapy.
Enzolytics, Inc. is a drug development company committed to the commercialization of its proprietary proteins for the treatment of debilitating infectious diseases. Enzolytics is committed to creating drugs for the better health of mankind.
Our mission is clear – to create therapeutics that are effective and affordable for treating infectious diseases that plague the world. This goal includes the development of therapeutics and monoclonal antibodies targeting infectious diseases, including the CoronaVirus. Our ultimate objective is to provide such therapeutics to improve health around the world.
Enzolytics, Inc. is a Texas-based biotech company committed to the development and commercialization of its proprietary proteins and monoclonal antibodies for the treatment of infectious diseases, including HIV-1, Hepatitis (A, B, C), rabies, influenza A and B, tetanus and diphtheria. The Company’s multiple therapeutics also are being developed to treat Rheumatoid Arthritis and certain forms of cancer. Our technology for producing fully human monoclonal antibodies is now being employed to produce anti-SARS-CoV-2 (CoronaVirus) monoclonal antibodies for treating COVID-19.
OUR TECHNOLOGY
Enzolytics is a Texas-based biotechnology company with both patented anti-HIV therapeutics and a proprietary methodology for producing fully human IgG1 monoclonal antibodies for treating infectious diseases with non-toxic passive immunotherapy. The Company has clinically tested its anti-HIV therapeutics known as ITV-1. ITV-1 is a suspension of Inactivated Pepsin Fragment (IPF), a purified extract of porcine pepsin. ITV-1 has been shown to strengthen the immune system and may be used to facilitate a broad range of applications. ITV-1 has been tested in HIV patients in a clinical trial conducted under the strict guidelines of the European Union, where it demonstrated beneficial outcomes. Additionally, the Company has created a proprietary cell line that produces fully human monoclonal antibodies that target and neutralize the HIV virus.
The Company’s scientific team, Harry Zhabilov, Joseph Cotropia MD, and Gaurav Chandra MD, pioneered the Company’s proprietary therapeutics for treating infectious diseases, including HIV-1, Hepatitis (A, B, C), rabies, influenza A and B, tetanus, and diphtheria. The Company’s therapeutics may also be used to treat Rheumatoid Arthritis and certain forms of cancer.
The Company has also pioneered a proprietary method for creating human cell lines that produce fully human monoclonal antibodies directed against many infectious diseases. One antibody (designated as CLONE 3) has been demonstrated in tests in 5 international labs to fully neutralize over 95% of all strains and viral subtypes of HIV-1 against which it has been tested.
These HIV therapeutics may be used as an immunotherapeutic treatment for individuals with HIV/AIDS. They may also be developed for use as a prophylactic and therapeutic vaccine to prevent uninfected populations from contracting the HIV virus. Treatment using the fully human anti-HIV antibody will be far superior to current ARV therapy for several significant reasons: (1) the therapy will be effective and non-toxic, (2) will not require lifetime treatment, and (3) will be far less expensive.
Thus, for the patient, immunotherapy will be remarkably different — it will be safer, provide a much-needed immunotherapeutic cure rather than requiring lifelong treatment, and costs substantially less than current antiretroviral therapy.
The Company also has created human cell lines that produce human antibodies against other infectious diseases, including rabies, influenza, tetanus, and diphtheria. As a part of its mission, the Company is testing these antibodies to prepare them for use as therapies against these diseases.
OUR SCIENCE
??
Enzolytics, Inc. is committed to the development and commercialization of its proprietary therapeutics for the treatment of debilitating infectious diseases. The Company’s technology is broad, including technology for treating HIV-1, Hepatitis (A, B, C), Rheumatoid Arthritis, certain forms of cancer, rabies, influenza A and B, tetanus, and diphtheria. The Company’s therapies are also being developed to treat chronic infection and certain forms of cancer.
As a result of the recent acquisition of the biotech company BioClonetics Immunotherapeutics, Inc., Enzolytics is now advancing additional complementary therapeutic platforms for treating infectious diseases, including a focus on the production of anti-SARS-CoV-2 (CoronaVirus) monoclonal antibodies to treat COVID-19.
Inactivated Pepsin Fragment (IPF) Technology
One Company technology, invented by Harry Zhabilov, the CSO of the Company, includes a patented antiviral peptide that has been tested in clinical studies at the National Center of Infectious and Parasitic Diseases in Bulgaria. This therapeutic, known as ITV-1, is a suspension of Inactivated Pepsin Fragment (IPF), a purified extract of porcine pepsin. ITV-1 has been shown to strengthen the immune system and may be used to facilitate a broad range of applications. ITV-1 has been tested in HIV patients in a clinical trial conducted under the strict guidelines of the European Union. HIV patients tested in these trials showed the following beneficial outcomes:
Improvement in the immune indices in the absolute number of Ly, CD3 T, CD4 T, CD8 T, B Ly, NK and in the percentage of CD3 T, CD4 T, CD8 T, B Ly, NK, and of the index CD4/CD8.
Decrease in the viral load.
Demonstrated beneficial effect on opportunistic infections.
Demonstrated very good compatibility with all of the other modern antiretroviral drugs.
Demonstrated very good tolerance in all patients and complete absence of side effects.
This Enzolytics anti-HIV treatment is now being advanced through the certification stage, after which it will be available for patient therapy. ITV-1 also has also demonstrated a positive effect on different kinds of cancer due to its ability to stimulatesstimulate the immune system.
Fully Human Monoclonal Antibody Technology
With the recent acquisition of the technology created by BioClonetics Immunotherapeutics, Inc., the Company has additional and complementary technology for producing fully human monoclonal antibodies (mAbs) that neutralize the HIV virus. The Company is in the final development of the recombinant of the parent antibody (identified as “Clone 3”), which has been shown in in vitro tests conduction in 5 international laboratories to fully neutralized over 95% of all strains and viral subtypes of HIV-1 against which it was tested. The basis for its broad-spectrum efficacy is the fact that Clone 3 mAb targets an immutable epitope on the HIV virus. The targeted epitope has remained present in 98% (either directly or by way of conserved substitutions) of all now known 87,336 HIV isolates analyzed by the Company’s use of artificial intelligence. The failure of other mAbs, such as the Vaccine Research Group VRC01 [Bar KJ, et al. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016;375(21):2037-50. PMCID|5292134] resulted from the targeting of mutable epitopes of the HIV virus.
Final testing of the Company’s anti-HIV mAb in PBMC neutralization assays is currently being completed, to be followed by animal trials at the California National Primate Research Center, UC Davis (Davis, CA).
The anti-HIV therapies of Enzolytics’ two technologies, that produced by Enzolytics and created at BioClonetics, are expected to be synergistic in treating HIV. Tests to establish such synergy are scheduled.
Anti-CoronaVirus Monoclonal Antibodies
The Company’s proprietary methodology may also be applied to produce monoclonal antibodies against other infectious diseases. This includes the production of monoclonal antibodies against the SARS-CoV-2 virus (CoronaVirus), as well as other infectious diseases, including HIV-2, anthrax, smallpox, H1N1 influenza, herpes zoster, varicella zoster, Rh (+) auto-immune disease, and the Ebolavirus. A Company program is underway to produce monoclonal antibodies against the SARS-CoV-2 virus (CoronaVirus). Such production will be achieved using the proprietary methodology used to previously produce monoclonal antibodies (mAbs) against HIV, rabies, influenza A, influenza B, tetanus, and diphtheria.
Having produced neutralizing antibodies against the HIV-1 virus and recognizing a significant correlative structure between the HIV virus and the SARS-CoV-2 virus, the Company is developing anti-SARS-Cov-2 (CoronaVirus) monoclonal antibodies using its proprietary technology. These antibodies are expected to provide a therapeutic for patients infected with COVID-19. Identification of these neutralizable epitopes also will permit the production of a phage display anti-SARS-CoV-2 (CoronaVirus) vaccine.
Production of these monoclonal antibodies is being conducted in the Company’s lab at the Texas A&M University Institute for Preclinical Studies in College Station, Texas.
INTELLECTUAL PROPERTY
The Company protects its technology through an aggressive strategy to cover its intellectual property. The Company’s intellectual property includes:
Issued Patents
Enzolytics is the owner of the following issued U.S. Patents covering its technology relating to a peptide that has been demonstrated in clinical trials to provide anti-HIV-1 retroviral benefit in vivo.
U.S. Patent No. 7,479,538, issued January 20, 2009, entitled Irreversibly-Inactivated Pepsinogen Fragment and Pharmaceutical Compositions Comprising the Same for Detecting, Preventing and Treating HIV
U.S. Patent No. 8,066,982, issued November 29, 2011, entitled Irreversibly-Inactivated Pepsinogen Fragment and Pharmaceutical Compositions Comprising the Same for Detecting, Preventing, and Treating HIV.
These patents cover an Inactivated Pepsin Fragment (IPF) identified and characterized by the amino acid sequence GDEPLENYLDTEYF. This peptide has demonstrated a significant in vitro binding affinity for HIV-1 gp 120 and gp 41 and human CD4 cells. The peptide exhibits antiretroviral activity in vivo, particularly anti-HIV-1 activity. IPF appears to modulate helper T1 cells’ expression of elaborate cytokines INFy, IL-2, which selectively promote cell-mediated immune response and subsequently stimulate cytotoxic lymphocytes. These lymphocytes have a prominent role in the host’s immunologic response to HIV infection. Proteins encoded by these pathogens enter the endogenous pathway for antigen presentation and are expressed on the surface of the infected cell as a complex with class I MHC – proteins. IPF appears to present a novel mechanism to reduce the viral burden and stimulate innate immune responses to the virus for patients with significant antiretroviral resistance.
Proprietary Cell Line Producing Clone 3 anti-HIV monoclonal antibody
The Company’s Clone 3 cell line, which produces fully human monoclonal antibodies (mAbs) that specifically target and neutralize the HIV-1 virus, is proprietary to the Company.
Pending Patent Applications
The Company has the following pending patents covering its anti-HIV monoclonal antibody technology:
Pending Patent covering the recombinant of the Clone 3 antibody. This form of the Clone 3 antibody is prepared using the known amino acid sequence of the antibody in conjunction with a high producing CHO cell line for generating recombinant form of the monoclonal antibodies that will ultimately be used in patient application.
Pending Patent coverage of small molecules (mini-peptides) for commercial use derived from the structure of the Clone 3 antibody for interrupting and preventing binding between the HIV virus and the human CD4+ cell.
Coverage is directed to blocking peptides that bind to and neutralize the HIV virus, and
Competitive peptides that bind to the target CD4+ cells at the point of virus access into the human cell to prevent infection.
Pending Patent covering the proprietary methodology for producing fully human neutralizing monoclonal antibodies against infectious diseases, including Rabies, influenza A, influenza B, Tetanus, Diphtheria, HIV-2, Anthrax, Smallpox, H1N1 influenza, Herpes Zoster, Varicella Zoster and Ebola.
Pending Patent covering the proprietary methodology for produced anti-antigen monoclonal antibodies to produce vaccines to achieve a broad and durable humoral protective antibody response against the corresponding infectious agent.
Proprietary Methodology for Producing Fully Human Monoclonal Antibodies
The Company proprietary mAb methodologies & immunotherapeutic technologies platform will be used to create therapeutics for treatments of viral infectious diseases against:
HIV-2
Anthrax
Smallpox
H1N1 Influenza
Herpes Zoster
Varicella Zoster
Ebola
The Company antibody-based immunotherapeutic platform can be utilized for both human and all animal infectious-disease applications.
In addition to the anti-HIV monoclonal antibodies produced by the Company, the Company currently has also produced fully human monoclonal antibodies against:
Rabies
Influenza A
Influenza B
Tetanus
Diphtheria
The Significance of the Methodology for Producing Fully Human Therapeutic Monoclonal Antibodies
Biologics, specifically fully human neutralizing monoclonal antibodies directed against infectious disease, is considered the new frontier in biotechnology. In the past, the initial starting products were “humanized” rat and mouse mAbs being created for therapeutic use. “Humanized” immunoglobulins are the major immunotherapeutic that is prevalent today. What sets the Company’s antibody technology apart from that employed by other pharma? The Company’s technology permits the cloning of human or animal immune system cells. With the Company’s proprietary methodologies, stable parent hybridomas cell lines can be created that produce fully human antibodies.
Enzolytics specializes in the creation of human neutralizing monoclonal antibodies, not “humanized” mouse or rat counterparts, as are many mAb therapeutics in pharmaceutical use today. The Company’s technological methodologies have developed an effective, strong, and robust portfolio of biologics that have a pharmaceutical application with significant benefits to patients or animals in the global marketplace. From an identified and created parent hybridoma cell line, four distinct and effective products can be produced: (1) fully human neutralizing monoclonal antibody—directed against any pathogen based disease entity—through use in passive immunotherapy; (2) an effective humoral active vaccine that is safe and effective; (3) an oral mini-antibody peptide-based medication with an efficacy that is equivalent to the immunologic capacity of the monoclonal antibody produced by parent hybridoma cell; and (4) an entry-fusion inhibitor that is immunologic in character and scope. The applications are broad, effective, and beneficial for immunotherapeutic use.
The methodologies and processes for creating immortalized cells that stably produce human monoclonal antibodies are Company proprietary trade secrets.
Anti-HIV Technology and Products
Using its proprietary technology, The Company has created a proprietary cell line that produces a fully human monoclonal antibody (known as Clone 3) that specifically targets and neutralizes the HIV virus (i.e., renders the virus incapable of reproduction). This capability to neutralize the virus means that Clone 3 may be used successfully to treat those infected with HIV and provide an ideal immunogen in the development of an active anti-HIV/AIDS vaccine that is both prophylactic and therapeutic.
Additional supplemental products may be produced as well, for example, vaginal creams for prevention of transmission of the virus. Additionally, Clone 3 has the potential to enormously reduce the incidence of mother-to-child transmission (MTCT) of the virus. Not only might it prevent in-utero viral transmission but, postnatally, effective treatment can be administered without fear of antiretroviral (ARV) toxicity or resistance.
Each of these distinct products flows from the Company’s technology. The first is the use of the antibody itself or a recombinant of the antibody. The second is the Clone 3 vaccine, the third is a mini-antibody or paratope of the Clone 3 antibody, and the fourth is a competitive binding entry-fusion inhibitor that prevents infectivity.
In addition to the Clone 3 monoclonal antibody against HIV, the Company has also created human monoclonal antibodies against other infectious diseases, including rabies, influenza A, influenza B, tetanus, and diphtheria. This immunotherapeutic technology platform can be readily applied to creating monoclonal antibodies against other pathogenic diseases, including the SARAS-CoV-2 (CoronaVirus), HIV-2, anthrax, smallpox, H1N1 influenza, herpes zoster, varicella zoster, Rh (+) auto=immune disease, and the Ebolavirus. The Company’s antibody-based Immunotherapeutics platform can be utilized across both human and animal infectious-disease applications. For example, the technology can be used to produce treatment for elephant and equine diseases that threaten these species.
The LOWER ENZC GOES
The BIGGER she BLOWS
Watch out ABOVE
ENZC is in a quagmire devised by some unidentified schemers.
What these SCHEMERS don't know and what we don't know is when is the SHIT going to HIT the FAN.
It is going to HAPPEN!!
It will be our UNFORGETTABLE Emeril MOMENT!
Bam
BAm BAm
BAM BAM BAM
rockie101,
It is all good.
Read what MAGA_Patriot wrote and then read it again.
There are 1,670,830,512 on the float.
Between February 2, 2021 and March 30, 2021 1,757,000 ENZC shares have been traded within the range of 0.2121 to 0.958 with the MAJORITY (971 MILLION) of the shares traded for OVER 40 cents a share. That is not the average as I suspect the average should be much higher.
What one would have to put in perspective is WHO traded these shares:
1. Long-term Holders?
2. Traders?
3. Flippers?
4. Debt Conversion holders?
5. ???
What is the driving force of ANY stock is the RESULTS from the company and not the activity of day-to-day stock price movement.
No CEO can speak up and stop a downturn.
RESULTS RESULTS RESULTS
This is a OTC stock.
You may make money or you may lose money.
ENZC has potential.
The question is will that potential be realized.
Thus far ENZC have been PRODUCING RESULTS.
Any number of CATALYSTS may send ENZC stock price on an upward trajectory.
It can happen anytime and here lies the problem, nobody knows when.
How LOW will the STOCK price GO
The more they drop it the more we can buy at cheaper prices.
It hung around the 30 cent range for weeks.
It has now drifted to the 20 cents range and will probably hang hear until something DRAMATIC happens or drift lower and lower.
Now is the TIME to take a STAND aand follow some sound advice:
Be GREEDY Very Very GREEDY
Spring is in the AIR and I smell the SCENT of a PRESS RELEASE in the not so distant future.
What will it be?
ENZC news will be released when CHARLES who is Charge has something to report to the shareholders. He has done so in the past and will continue to do so in the future. There is a variety of activities presently going on with ENZC that we know about and many that we don’t.
There have been 21 Press Releases since September 2020 which is about 2 per month. Don’t expect 2 press releases per month but do expect press releases to come when Charles has something to report.
Activities awaiting updates of what we know about:
1. NSF and NIH applications Forthcoming
2. Additional Funding Anytime
3. Texas A&M University Institute for Preclinical Studies. Anytime
4. PCAOB Audit April 2021
5. Toxicity Study Anytime
6. Progress on ENZC plans to further develop additional anti-HIV monoclonal antibodies and to now begin the production of fully human monoclonal antibodies targeting the CoronaVirus Anytime
7. Status on the completion of production of monoclonal antibodies against both the HIV virus and the CoronaVirus Anytime
8. Status of testing in combination the Enzolytics ITV-1 peptide in conjunction with our anti-HIV monoclonal antibodies. There is reason to believe that there will be synergistic effect achieved with this combination therapy. Anytime
9. Status on the process of identifying a clinical research organization for the preparation of pre-IND protocols for submission to the FDA. Anytime
10. GMP manufacturer Anytime
11. Status of finalizing the necessary steps for completing the permitting process for our ITV-1 HIV/AIDS therapeutic in Bulgaria.
Anytime
12. Status of received proposals from FDA approved manufacturers to produce the quantities necessary for such certification. Under Review
13. Results of testing of the newly produced monoclonal antibodies. This includes testing of our now being produced recombinant anti-HIV monoclonal antibodies created from the parent antibody. Such testing is now scheduled for early 2021 at the University of Strasbourg in Strasbourg, France. Additional testing of the Company's antibodies is also being planned at San Raffaele Scientific Institute, Milan, Italy.
Early 2021
14. Acquisition Anytime
15. Status of collaborative opportunities with other drug development companies to expand our product reach. Forthcoming
16. Gilead Relationship to ENZC
17. Eli Lily Relationship toENZC
18. Immunome Relationship to ENZC
There will be other updates of activities we don’t know about however based on the processes of Biotechnologies companies one can surmise what these could possibly be. Anytime
Remember two things.
First and foremost CHARLES is in Charge
Second and very important from the Press Release dated October 19, 2020:
All of our steps are taken with two objectives in mind. First our focus is on creating successful therapeutics against infectious diseases, including HIV and now our focus on the Coronavirus. Secondly, our efforts are also intended to increase the value of our technology and the value of our company - which directly translates into value for our investors. Please know that these are our two guiding objectives with every effort we make.
The link below has all ENZC Press Releases:
https://marketwirenews.com/stock/enzc/news/
ITV-1
Patent US-7479538
Enzolytics has a License Agreement for US Patent 7479538. The claim is Irreversibly-inactivated Pepsinogen Fragments for Modulating Immune Function.
Enzolytics, Inc.'s flagship compound ITV-1 is a suspension of Inactivated Pepsin Fragment (IPF), which studies have shown is effective in the treatment of HIV. 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. IPF is a platform technology that can be used to facilitate a broad range of applications. It is free from major neurological, gastrointestinal and hematological side effects seen in the anti-retrovirals in use today. IPF has not shown to be subject to viral resistance and is cost effective.
This bio-product has shown low toxicity and is well accepted by the body system. Clinical trials in Bulgaria show improvements in immunity.
ITV-1 has been through Phase I, II and III clinical Trials however due to ENZC being informed that the inclusion of the BDA in the EMA restricted the permitting of our Treatment by the BDA and the permitting will now be done by the EMA for all the European Union. As a result, some, if not all of the Phase III clinical trials may need to be completed under the EMA standards.Additionally, the Company has created a proprietary cell line that produces fully human monoclonal antibodies that target and neutralize the HIV virus.
Cell line is a general term that applies to a defined population of cells that can be maintained in culture for an extended period of time, retaining stability of certain phenotypes and functions. Cell lines are usually clonal, meaning that the entire population originated from a single common ancestor cell.
Clone 3
The Company has clarified the lack of significance of the prior expired Company patents covering the Company's "parent" Clone 3 anti-HIV antibody. The expired Company patents were issued on the "parent" Clone 3 antibody. As is the case with virtually all parent antibodies, the parent antibody is a "slow producer" - which means it could not produce sufficient antibody therapeutics to treat the 36 million individuals infected with HIV. Thus, a recombinant form of the antibody had to be created employing a fast-producing CHO cell line. This has been accomplished by the Company and patent applications are pending claiming the recombinant form of the antibody, the form that will be used in patient therapy. The term of issued patents will be 20 years from filings, such filings having been made in 2020.
These revised applications incorporate the focus on the capability to produce multiple (a "cocktail" of) monoclonal antibodies for therapeutic treatment. While the Company sees value in pursuing NIH grant funding, the progress of the Company is not in any way affected or delayed by awaiting the review of such applications. Preparing such applications allows the Company to marshal its technology in a detailed confidential technical presentation that can be used in discussing our technology with potential biotech partners.
Additionally, the Company has entered negotiations with Pro Wave Ad Product ("PWA"), a Bulgarian Company, to supply the raw material for PWA's Contract in India for the production of a spray modulating the immune system under U.S. Patent No. 8,309,072 owned by Zhabilov Trust. This contract is valued at more than $50 million to PWA. This is the only approved use of this technology as a nutraceutical. The FDA issued a nutraceutical number to Harry Zhabilov on October 12, 2018. The first delivery under this agreement with PWA is expected to be in late spring 2021. The value to the Company is yet to be determined.
SOME NOT SO KNOW IT ALL KEEPS LOOKING IN THE WRONG DIRECTION AND WHEN THEY LOOK IN THE RIGHT DIRECTION IT WILL SLAP THEM IN THE FACE SO HARD THE GONNA THINK IT WAS MIKE TYSON IN HIS PRIME.
Filling the pipeline: licensing and M&A trends in life sciences
It's a challenging time for pharmaceutical companies, with several blockbuster products soon to come off patent, increased competition from generic manufacturers and gaps in product pipelines. This has prompted a flurry of licensing and M&A activity, as large pharmaceutical companies compete to secure new products externally. These trends are illustrated in recent research produced by Simmons & Simmons, based on interviews with senior executives from leading global pharmaceutical companies and investment bankers in the sector. "We found a broad consensus in the industry that competition for new products in the market is prompting changes in the commercial terms on which these deals are being done," says Charles Mayo, head of Simmons & Simmons' Life Sciences Group.
2020 Trends In Pharma Asset Licensing And Deal Terms: A Survey Of Key Decision-Makers
Across biopharma, asset licensing has increasingly been leveraged as a means to build on existing disease area leadership and/or diversify portfolios, be that in new disease areas, mechanisms of action (MoAs), modalities or geographies. Alignment of buy- and sell-side expectations is vital for deal execution. Parties broadly agree on the importance to asset value of development stage, revenue potential, target proof-of-concept (POC), competitive landscape and other factors. However, defining appropriate expectations of total asset value and component deal terms can be challenging, given the lack of transparency and detail in publicly available deal term data.
L.E.K. Consulting conducted a survey of 80+ biopharma business development (BD) professionals experienced in deal-making to gain insight into deal terms, provide more visibility into key factors driving deal value and structure, and identify forward-looking trends. In this article, we describe some key drivers of asset value, as well as areas of alignment and divergence between parties on deal expectations. We extract insights to level-set deal expectations and inform a more strategic approach to deal term negotiations for both buyers and sellers. Survey respondents represent a cross section of senior business development (BD) professionals with varied deal-making experience and company characteristics (see Figure 1).
Key factors driving asset value for licensing
As expected, therapeutic areas with high unmet need, market exclusivity and differentiated efficacy over the standard of care (SOC) are among the most important attributes for BD teams considering asset in-licensing. In a sign of the synergy licensing brings, companies that are out-licensing assets rate commercialization capabilities and disease area expertise as key determinants of suitable acquirers. Encouragingly, these complementary expertise areas converge to increase the probability of bringing treatments to patients in need. Factors of greatest importance to buyers during asset evaluation and deal negotiation ? differentiation, high unmet need and exclusive rights outweigh other considerations (see Figure 2).
The Therapeutic Monoclonal Antibody Product Market
Commercial development of therapeutic monoclonal antibodies (MAbs) began in the early 1980s, and by 1986 the first MAb product had been approved in the United States: muromonab-CD3 (trade name Orthoclone OKT3, marketed by Janssen-Cilag) for prevention of kidney-transplant rejection. Since its approval, therapeutic MAbs and antibody-related products such as Fc-fusion proteins, antibody fragments, and antibody–drug conjugates (collectively referred to herein as “MAb products”) have grown to become the dominant product class within the biopharmaceutical market. They have been approved for treating a broad range of of diseases, from those with patient populations of a few thousand or less (e.g., orphan indications such as hemophagocytic lymphohistiocytosis) to those afflicting hundreds of thousands (e.g., some cancers and multiple sclerosis) or even millions of patients (diseases such as asthma and rheumatoid arthritis). With recent approvals of MAb products for infectious diseases such as those associated with Clostridium difficile, anthrax, and human immunodeficiency virus (HIV) infections, the potential for MAb products to combat coronavirus diseases certainly exists. However, some debate remains over just how significant a role any antibody treatment could play in treating COVID-19. (Editor’s Note: See the article by Nick Hutchinson on page 14 for more of that discussion.)
Market Growth
Sales growth and approval of additional MAb drugs was slow until the late 1990s, when the first chimeric antibodies were approved. With the approval of such products, followed over time by that of humanized and then fully human antibodies, the rate of product approvals and sales of MAb products increased dramatically. In 2019, global sales revenue for all MAb drugs was nearly US$163 billion (1), representing about 70% of the total sales for all biopharmaceutical products (about $230 billion). That is a significant (~50%) increase in both sales and proportion since 2013, when it was $75 billion (2). Continued growth in sales of currently approved MAb products, along with more than 1,200 MAb product candidates currently in development — many for multiple indications (1) — will increase sales of MAb products further in the coming years and continue to drive the overall sales of all biopharmaceutical products.
As Figure 1 shows, the number of MAb products approved for commercial sale in the United States and Europe has grown significantly, with three to five new products approved each year between 2010 and 2014, then 10–19 new products approved each year between 2015 and 2019.
Although a total of 139 MAb products have been approved in Europe and/or the United States since 1985, 14 of these products have been withdrawn for different reasons, leaving 125 approved MAb products currently on the market (Table 1). As of 27 August 2020 (1, 3, 4), only six of those products are expressed by microbial systems whereas the remaining 119 are produced by mammalian cells. Five of the six microbial products are antibody fragments, including one fragment conjugate; also, for the first time, a full-length MAb expressed in a microbial system (Pichia pastoris yeast) was approved this year. Vyepti (eptinezumab-jjmr) from Lundbeck Seattle BioPharmaceuticals has been approved for prevention of migraines (5).
Given the large number of candidates currently in development, we expect that the number of MAb products approved each year for the coming years will be similar to the numbers approved over the past several years. In fact, nine MAb products have been granted first approvals this year as of 27 August 2020, including the first developed and manufactured MAb biosimilar from China: Zercepac trastuzumab from Shanghai Henlius Biotech and Accord Healthcare (6).
Currently 21 MAb products are under regulatory review, with approval decisions expected for at least two of those by the end of this year. Based on a conservative approval rate of 10 products per year, we anticipate that 180 or more MAb drugs on the global market in 2025. Additionally, we predict that within the next year, some COVID-19 MAb products, will be included within these forecasted numbers. But none of them yet has reached the biological license application (BLA) or marketing authorization application (MAA) regulatory review phase. Based on the number of novel MAb products in development for COVID-19 (1, 7), an accelerated timeline for those high-priority drugs (8), and the prospective use of MAb products as a stop-gap preventative until a successful vaccine is launched (9), we forecast that two to four novel MAb products will be approved specifically related to COVID-19.
As Figure 2 shows, most of the 119 MAb products expressed in mammalian systems are full-length naked MAbs (60%), followed by biosimilar full-length naked MAbs (19%). Six other types of antibody products represent the remaining 21% of mammalian-expressed MAb products.
Global sales of MAb products have grown faster than all other biopharmaceutical product classes over the past five years. Figure 3 shows the breakdown of sales based on product type (e.g., full-length antibodies, antibody conjugates, fragments, and so on) and production system (mammalian cell culture or microbial fermentation). As the data show, sales of all MAb products (regardless of the production system or type) have grown from ~$84 billion in 2014 to nearly $163 billion in 2019, a 93% increase. By comparison, sales of other recombinant-protein therapeutics have remained virtually unchanged in the same time period (~$68 billion).
Corresponding to the increasing sales of MAb products, the total quantity of these products produced annually has increased to meet the market demand. Nearly 25 metric tons of MAb products were produced around the world in 2019 — compared with about 11 metric tons of all other recombinant-protein products, regardless of expression system. The demand for mammalian-expressed MAb products has resulted in a significant amount of global manufacturing capacity devoted to their production and to significant investments in improved methods and approaches to MAb manufacturing process design and optimization (10, 11).
In 2019, 36 of the MAb products listed in Table 1 achieved annual sales of over $1 billion, with five products reaching sales of >$7 billion: AbbVie’s Humira (adalimumab), Merck’s Keytruda (pembrolizumab), Regeneron’s Eylea (aflibercept), Bristol-Myers Squibb’s Opdivo (nivolumab), and Genentech/Roche’s Avastin (bevacizumab). AbbVie recorded Humira sales of about $19 billion for two consecutive years, making that the highest selling (bio)pharmaceutical product.
Based on a review of historical sales data, company annual reports, and sales-projection data collected in our group’s proprietary bioTRAK database, we determined a five-year compound annual growth rate (CAGR) of 14.1% for the MAb product market and forecast that the market feasibly could continue to grow at a CAGR of 10% or more over the next several years. With that 10% growth rate, sales of currently approved MAb products combined with those of new products approved in the coming years should drive global sales of MAb products to about $240 billion by 2023 and nearly $315 billion by 2025.
Factors Contributing to Market Growth
With MAb drug approvals rising over time (Figure 1) along with the demand for and revenue generated by such products (Figure 3), interest in developing them remains strong. No single specific reason can be cited for the increase in approvals or growth of this class of products, but several contributing factors have combined to create an environment that is conducive to rapidly expanding the number of approved MAb drugs.
Significant funding availability, ongoing advancements in MAb technologies, expansion of MAb products into new markets, and the emergence of biosimilars all have contributed to nearly all pipeline MAb products (1), thus driving regulatory approvals, widening market reach, and increasing revenues for this class of products.
Between 2015 and 2018, fundraising though venture capital, initial public offerings (IPOs), and follow-ons has exceeded such funding in 2010–2014 (12) and provided financial support for advancing our understanding of disease at a molecular level. Although failing to meet some observers’ initially high expectations, genomics, proteomics, and other systems-biology tools do continue to provide important new targets for modulating disease (13). MAb products often provide the most direct route to a clinical proof-of-concept for activating, inhibiting, or blocking those new targets. Timelines for developing a lead product to investigational new drug application (IND) have shortened while production timelines for clinical products have lengthened (8).
MAb products and industry technologies also have expanded product types from basic “naked” MAbs to more complex structures such as conjugates that deliver targeted cytotoxic or radiologic materials and bispecific antibodies that can bind multiple targets. Because production of most MAb products is easily amenable to efficient platform-based approaches for both discovery and manufacture, and because antibodies are generally well-tolerated and highly specific, the risk of unexpected safety issues is lower in human clinical trials of MAb products than with many other types of therapeutic products. Thus, for many novel targets, MAb products often are the first product candidates advancing into clinical studies. If the initial proof-of-concept results are successful, these products can make rapid progress toward commercialization, providing a “first-to-market” advantage.
Also fueling the growth in MAb product sales is the global market expansion of the pharmaceutical market overall, which results from an increasing and aging worldwide population along with improved standards of living in emerging markets. In addition, continued evaluation of MAb products for new and expanded clinical indications contributes to demand for clinical study materials and subsequent sales in newly approved indications. As the biopharmaceutical industry continues to mature, the number and types of diseases that will be treated economically with MAb products will increase. Driven in part by the need for cost-effective supply of large quantities of products for such cost-sensitive indications as rheumatology and asthma, recent improvements in MAb production technologies have improved process yields and reduced actual manufacturing costs substantially. As a result, these products have an ever-increasing opportunity to penetrate relatively cost-sensitive indications and markets.
As patents providing exclusive rights to many of high-profile and blockbuster MAb products expire, interest in biosimilar development has grown (Figure 2). In September 2013, the first biosimilar monoclonal antibodies — sold under the brand names Remsima (marketed by Celltrion) and Inflectra (marketed by Pfizer) — were approved for commercial sale in Europe. These biosimilar versions of Janssen’s blockbuster MAb product Remicade (infliximab) were the first of 32 MAb product biosimilars currently approved, and in the coming years, many more biosimilar MAb products certainly will be approved for commercial sale in both the United States and Europe.
Biosimilars have received significant attention in the press and are discussed often as an aid to lowering healthcare costs and a vehicle by which larger patient populations could receive needed treatments. However, these products actually represent a small portion of the development pipeline. But we do anticipate modest acceleration of sales growth for all MAb products as biosimilars gain market acceptance. Interest in them continues surge in the markets of Latin America, China, Southeast Asia, India, and Russia. Several such products already have been approved in these regions.
Introduction of biosimilars in those markets is likely to have a large impact on the global sales of MAb products as biosimilar MAbs are approved in regions that currently have no access to expensive innovator products.
A Bright Future Ahead
MAb products will continue to be a dominant therapeutic modality for treatment of a broad range of diseases in the foreseeable future. The potential impact of MAb therapeutics in the race to build up COVID-19 vaccine treatments is uncertain. But in spite of the ongoing pandemic, global MAb approvals and sales will continue to increase over the next five years. As approvals of biosimilar products initially bite into MAb innovator sales, adoption of biosimilars is expected to increase overall access to antibody product types for a net increase in the overall number of patients (and hence, sales) for this biopharmaceutical industry segment. Manufacturing capacity to make such products continues to expand to meet the continually growing demand as well.
https://bioprocessintl.com/business/economics/the-market-for-therapeutic-mab-products/
Developing therapeutic monoclonal antibodies at pandemic pace
The time from discovery to proof-of-concept trials could be reduced to 5–6 months from a traditional timeline of 10–12 months.
Outbreaks of emerging infectious diseases have become increasingly common in recent decades. Epidemics have spread across the globe, including AIDS, H1N1 influenza and most recently coronavirus disease (COVID-19). In the face of a pandemic infectious disease outbreak, new approaches should be explored to enable the most rapid evaluation of antibodies for passive immunization or treatment. The fastest timeline from discovery to clinical evaluation of novel recombinant antibodies for medical use has been a focus of the biopharmaceutical industry for decades. For potentially life-saving therapies, the benefits of the earliest clinic testing should translate to accelerated pivotal trial testing and maximal patient benefit. Process and product development groups at major biopharmaceutical companies have reduced phase 1 timelines for recombinant antibody production through a universal convergence on similar technologies and strategies. Yet there may be opportunities for substantially faster timelines arising from a combination of the latest technological advances with acceptance of higher business risk or costs without an increased risk profile to patients in the first clinical trials.
A faster path
During a pandemic, there is no time to waste in the development and clinical testing of therapeutic modalities, including vaccines, nucleic acids, small molecules, convalescent serum, intravenous immunoglobulin G (IgG) and monoclonal antibodies (mAbs).
Until recently, the evaluation of mAb therapies for this scenario has been slow and the production capacity was limited. What has changed to enable rapid evaluation of mAb therapies in this case?
The product development timeline from lead mAb identification to phase 1 investigational new drug application (IND) is 10–12 months at many companies today — a dramatic reduction from the 18 months that was standard in the industry 5 or more years ago. A combination of recent technical advances and the acceptance of business (but not product quality or patient safety) risks offers a further acceleration for clinical trials. Rapid clinical production capacity has benefited from development of highly productive cell lines and larger bioreactors using single-use technology, enabling the production of thousands of doses from a single batch of over 5 kilograms.
Today, we can accelerate these activities and enable production capacity for clinical studies for therapeutic mAbs. What could be the fastest path to provide mAbs for clinical evaluation during a pandemic outbreak? I propose that the answer could be 5–6 months, rather than 10–12 months.
Lead mAb identification and characteristics
In a conventional discovery program, mAb identification usually takes several months to identify an attractive candidate. But one way of increasing the speed of identifying leads is to screen prospectively isolated panels against new pathogens and many viral strains1,2,3. This enables rapid identification of the best mAb for development and puts process development and manufacturing on the critical path to clinical evaluation. There are several other mAb discovery approaches (reviewed in ref. 4) that may also be capable of rapid lead identification that would subsequently benefit from this development strategy.
I present here an assessment of accelerated mAb discovery and development based on the use of the clinically proven IgG1 isotype. Over 50 IgG1 therapeutic mAbs have been commercialized5 and hundreds more have been clinically tested. The IgG1 mAb safety and quality risk profiles are low and enable a shift in risk tolerance. Substantial platform knowledge, product development history, current good manufacturing practice (cGMP) production experience and facilities are also broadly established for IgG1 mAbs. In response to a pandemic disease outbreak, IgG1 mAbs therefore have a distinct advantage as prophylactic or therapeutic biological agents.
Speed to phase 1 cell line
To accelerate clinical development, the production host should be a Chinese hamster ovary (CHO) cell line. Although alternative hosts, such as yeast, Escherichia coli and plants, have been proposed to have benefits of rapid genetic engineering and production, major deficiencies preclude them from enabling a rapid response to a pandemic outbreak. The established cGMP production infrastructure cannot support large clinical trials and post-licensure demand. For such hosts, the lack of clinical experience presents a substantive patient safety risk arising from the potential impacts of rare mAb post-translational modifications or variants, including unusual glycans, host cell proteins, and so forth. In contrast, the low risk profile of mAbs produced by CHO cell lines has been established and supports a rapid development model based on platform development, manufacturing technology and infrastructure.
Several companies have developed cell lines using targeted integration of mAb expression vectors6,7. These cell lines provide more consistent expression through integration of low copy numbers in highly active transcriptional hotspots. This consistency can reduce the time for screening cell pools or clones leading to a phase 1 cell line. By not assessing multiple pools of transfectants, generating interim cell banks, and assessing productivity of pools as part of the routine cell line development used for decades with random integration, savings of several months could be gained between transfection and cloning. (Although targeted integration is a critical advance, it is possible that an optimized random integration technology may also produce a high percentage of transfectants with suitable productivity.)
Moving directly from the stable transfectant pool to cloning is becoming a standard practice today. Until recently, an intermediate stage of expansion — generation of several pools of transfectants and subsequent screening — was used to increase the probability of finding a high-producing line, but this takes many weeks, including the typical 2-week production culture screen followed by analysis of product quality. If instead one moves directly to cloning from a pool of transfectants with consistent productivity, the final clone screening step could be conducted much earlier. Another few weeks may also be saved by conducting a single round of cloning using fluorescence-activated cell sorting (FACS) or limiting dilution, with supporting imaging to establish the clonal derivation of the resulting cell line, rather than performing two rounds of limiting dilution8,9. Finally, multiple candidate clones can be screened with very small bioreactors using small-volume tubes or ambr15 bioreactors of 15?mL volume10, which could save roughly 5 days instead of screening using 5-liter bioreactors.
In aggregate, these new technologies and approaches could save 2 months in the timeline from lead identification to establishment of a clonally derived cell line suitable for phase 1 production (Fig. 1). If toxicology studies are shortened, chemistry, manufacturing and control (CMC) activities may comprise the critical path to the IND filing.
Process and formulation development
In parallel with cell line development, transient expression cultures produce material to support downstream process, formulation and analytical development. Large-scale transient cultures (≥100 liters) generate many grams of product in a single batch11. The availability of this feedstock weeks earlier than material from clonal cell lines accelerates the timeline to cGMP production, informing the final process definition and drug product formulation.
By selecting an IgG1 mAb, one can leverage experience with platform processes and production facilities. High-throughput screening of platform polishing chromatographic steps uses very little material and is highly predictive of process performance12. These studies can be conducted before the final clone selection, with little risk of an impact on the downstream process.
ENZC is a Biotech company with a lot of potential.
Biotech companies are risky investments.
Why?
Because they are trying to create something that usually takes quite a long time to do. Usually years.
While ENZC is just as RISKY as any other Biotech there are some GREEN FLAGS that make them less RISKY.
1. Low Toxicity
2. NO Virus Escape
3. Laboratory at Texas A&M Institute for Preclinical Studies
4. Numerous Patents
While we all would love the stock price to be somewhere else, it is not because there is a separation of what the company is doing and what the stock price is doing.
ENZC is full of potential and that is why it continue to hold in the 20s
as we await for the next leg up.
As with any Biotech company, ENZC can crash and burn and be forgotton or SHE could explode and FLY and be REMEMBERED as the GREATEST rise of a BIOTECH stock.....
We will just have to wait and see how it all plays out.