Despite claiming the lives of over 320 children and almost 3000 adults every 24 hours, HIV has not received the public attention or private investment that it deserves. Many people think the HIV outbreak is over, but for millions of people worldwide it is still a terrifying reality.
Today, 57% of those infected with HIV have no treatment, while the 43% who are treated are treated using antiretroviral drugs (ARVs) which are both toxic and expensive. BioClonetics is committed to finding an accessible and affordable HIV cure.
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What is a Convertible Note?
A convertible note offers you the right to receive shares of Common Stock in BioClonetics. The number of shares you will receive in the future will be determined at the next equity round in which BioClonetics raises at least $1,500,000 in qualified equity financing. The highest conversion price per share is set based on a $15M company valuation cap or if less, then you will receive a 30% discount on the price the new investors are purchasing. You also receive 2% interest per year added to your investment. When the maturity date is reached, if the note has not converted then you are entitled to either receive your investment and interest back from the company or convert into stock.
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Frequent updates on our technology progress
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Twice yearly update through call from the COO - Your place on the Official Founders Page of the website - Access to the investors only BioClonetics Founder Group on Facebook
*All perks occur after the offering is completed.
Most people know of the U.S. HIV epidemic of 1980s, and although the alarming death rates due to HIV/AIDS has slowed, it is still a prominent and fatal disease. HIV is still one of the top causes of death worldwide. Moreover, the number of newly infected patients greatly outnumbers (by 1 Million per year) those who perish and thus the number of infected is ever increasing.
In the U.S., the FDA has approved the use of ARVs (antiretroviral chemotherapy) as the main treatment for HIV patients. And though ARVs can improve a patient's health for decades, they are highly toxic. ARVs can cause severe damage to organs including the heart and kidneys, decrease bone-mineral density, and result in Vitamin D deficiency. ARVs treatment is also necessary for life and cost of treatment is high and non existent for many patients.
At BioClonetics Immunotherapeutics, we’re one step closer to ending the search for the HIV cure. We have discovered and developed a proprietary cell line that produces a fully-human antibody proven to specifically target and effectively neutralize HIV-1. These validating tests were conducted at Harvard Medical School, Duke University, Univ. of Calif. San Francisco, Univ. of South Florida and Polymun Scientific.
Monoclonal antibodies mimic the ones your body naturally produces as part of your immune system's response to germs, viruses and other invaders. Because monoclonal antibodies come from a single cell source, they’re engineered to target a specific part of a virus. The Clone 3 monoclonal antibodies that we’re developing target a specific site on HIV and as a result neutralizes the virus.
BioClonetics has created a cell line that produces a fully human monoclonal antibody, the Clone 3 antibody, that binds to and neutralizes the HIV virus.
Clone 3 Antibody targets 98% of all HIV viral strains worldwide, via epitope KLIC.
Tests in 5 international research institutes have shown that Clone 3 Antibody neutralizes 41 out of 43 (over 95%) of primary HIV isolates tested. By comparison, clinical use of approved Fuzeon (used as an HIV inhibitor) shows the viral burden to be less than 50 copies of HIV in only an average of 33% of patients.
Isolating and cloning of the B cells of HIV patients to create monoclonal antibodies. Screening of the resulting antibodies and the identification of Clone 3. In-vitro testing of Clone 3 against HIV strains to confirm neutralizing capability. Identification of the binding site of Clone 3 on the HIV virus. Full identification of the complete heavy chain amino acid structure of Clone 3.
A major pharmaceutical company has indicated that it will promote our technology upon our successful completion of the next step of producing and testing what is known as the “recombinant” form of Clone 3.
We have several world-class laboratories with whom we are working who are assisting us in conducting the next steps of our plan.
Producing the recombinant of the Clone 3 antibody for testing and later patient therapy.
Testing of the recombinant against HIV strains to validate effectiveness.
Pre-clinical primate macaque trials to validate effectiveness in primates.
Dear potential investors,
We hope you have had an opportunity to review our technology and its potential for providing a meaningful and revolutionary therapy for HIV patients. We have laid out information showing the potential of our technology - and even more information may be found on our website.
All of that information is about the therapeutic potential of our technology. However, let me share information about another side of our effort – namely the underlying motivation.
As Pollyannaish as it may sound, the primary motivation of each member of our team is the desire to save lives. Each year, HIV takes the lives of over 1 million individuals. And in 2015, 115,000 children died of AIDS-related illnesses (over 300 each day).
Approximately 2 million people are newly infected each year with HIV. And over 36 million individuals today have the virus.
The time for a cure for HIV has long since passed. However, the efforts of Big Pharma have been misdirected, either through their failure to properly apply new and more effective technology or a desire to focus on the financial bottom line rather than the needs of patients – with a focus on profit from providing a treatment and not a cure.
With regard to HIV, all one needs to know is that over 300 children die each day from this disease. This is far more more than the number who perish from cancer. However, this present day tragedy is allowed to continue day to day, week to week and year to year without proper focus or financial support from either governments or the private or big Pharma establishments.
We recognize however that sometimes good intentions are not enough to raise capital needed to properly address a pandemic that has existed for decades. Indeed, you are probably reading this letter with the rightful focus on the potential for a probable successful financial investment. While we have as a primary focus the good that can come from our technology, it is a fact, and in this day sometimes a rare situation, that our case presents both a potential for humanitarian good and financial reward.
We believe that our technology provides the rare opportunity to invest in something that is meaningful for mankind and particularly in areas of the world where medical therapies are not as readily available as in the US, and at the same time provide the potential for financial success. As to this potential, we point to the fact that $16 Billion is now spent every year on antiretroviral drugs that treat but do not cure HIV patients. As an investor, I am sure your interest is focused initially on the financial potential, but in this case, you can participate both in that potential as well as the potential humanitarian benefit that arises for a cure for HIV. Your contribution would be a step toward both.
We hope you will join us in this endeavor.
Sincerely,
Charles S. Cotropia
CEO
BioClonetics Immunotherapeutics, Inc.
To put it simply, Dr. Cotropia created a human cell line producing a specific human antibody that targets a genetic sequence on the surface of HIV’s outer envelope. When tested in 5 separate lab, this antibody demonstrated that it neutralized over 95% of those HIV stains against which it was tested.
Although there have been many advancements in treatments that help slow the virus's growth and allow patients to remain relatively healthy for several years, the world continues its relentless pursuit of the cure to HIV. At BioClonetics Immunotherapeutics, we're one step closer to ending that search
INVESTMENT OPPORTUNITY
Convertible Note
Note converts to Common Stock when the company raises $1,500,000 in qualified equity financing
Maturity Date: 11/30/2020
$15M valuation cap
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*Annual Interest Rate subject to adjustment 10% bonus for StartEngine shareholders. See 10% Bonus below
30% Discount
Maximum ($683,234) of Convertible Notes
Minimum ($10,000) of Convertible Notes
| Company | BioClonetics Immunotherapeutics, Inc. |
| | |
| Corporate Address | 1756 Bison Meadow Lane, Heath, Texas 75032 |
| | |
| Description of Business | BioClonetics is developing a cure for HIV using fully human monoclonal antibodies. |
| | |
| Type of Security Offered | Convertible Note |
| | |
| Minimum Investment Amount (per investor) | $400 |
What is a Convertible Note?
A convertible note offers you the right to receive shares of Common Stock in BioClonetics. The number of shares you will receive in the future will be determined at the next equity round in which BioClonetics raises at least $1,500,000 in qualified equity financing. The highest conversion price per share is set based on a $15,000,000 company valuation cap or if less, then you will receive a 30% discount on the price the new investors are purchasing. You also receive 2% interest per year added to your investment. When the maturity date is reached, if the note has not converted then you are entitled to either receive your investment and interest back from the company or convert into stock.
Perks
All investors - Frequent updates on our technology progress
$1,000+ Your place on the Official Founders Page of the website - Exclusive content and frequent company updates - Access to the investors only BioClonetics Founder Group on Facebook
$5,000+ Twice yearly update through call from the COO - Your place on the Official Founders Page of the website - Access to the investors only BioClonetics Founder Group on Facebook
*All perks occur after the offering is completed.
The 10% Bonus for StartEngine Shareholders (This bonus period is concluded as of 5:30PM PT on January 5, 2018)
BioClonetics Immunotherapeutics, Inc. will offer a 10% bonus on the annual interest rate for all investments that are committed by StartEngine Crowdfunding Inc. shareholders (with ≥ $1,000 invested in the StartEngine Reg A+ campaign) within 24 hours of this offering going live.
StartEngine shareholders who have invested $1,000+ in the StartEngine Reg A+ campaign will receive a 10% increase in the annual interest rate on Convertible Promissory Notes in this Offering if they invest within a 24-hour window of their campaign launch date. For example, if invest in the first 24 hours, your annual interest rate will be 2.2% instead of 2%.
This 10% Bonus is only valid for one year from the time StartEngine Crowdfunding Inc. investors receive their countersigned StartEngine Crowdfunding Inc. subscription agreement.
A crowdfunding investment involves risk. You should not invest any funds in this offering unless you can afford to lose your entire investment. In making an investment decision, investors must rely on their own examination of the issuer and the terms of the offering, including the merits and risks involved. These securities have not been recommended or approved by any federal or state securities commission or regulatory authority. Furthermore, these authorities have not passed upon the accuracy or adequacy of this document. The U.S. Securities and Exchange Commission does not pass upon the merits of any securities offered or the terms of the offering, nor does it pass upon the accuracy or completeness of any offering document or literature. These securities are offered under an exemption from registration; however, the U.S. Securities and Exchange Commission has not made an independent determination that these securities are exempt from registration.
Dear Investors and Supporters,
We have had a very productive second quarter in 2019 and I can summarize the current progress as follows:
We have completed the production of additional recombinants of our anti-HIV monoclonal antibodies and are conducting additional testing prior to embarking on animal trials.
Testing these promising recombinant anti-HIV monoclonal antibodies are ongoing at Responsive BioServices in Smyrna, Georgia and we are working together with Scripps Research Institute in California where our antibodies have been accepted for efficacy testing.
These tests are preparatory to animal trials. We are current making plans and have proposals from two renown animal trial institutions in California and Texas.
We have also engaged a grant writing consulting group to assist us in the submission of NIH and SBIR grant applications for additional funding to support our progress. With our new data, we are encouraged by the prospect of successful grant funding. Grant funding is naturally optimum as it is funding that does not have to be repaid and thus does not dilute (but only increases) your value in our company.
We hope to have progress on all of these fronts this quarter and will keep you apprised of developments. We again thank you for your support - which has made our progress possible.
Best regards,
Charles
Charles Cotropia
BioClonetics
To Our Investors and Supporters,
We are pleased to provide this end of first quarter report for 2019. We are reminded how fortunate we have been to have investors and supporters such as you. Your support has made possible the great progress we have made and we thank you for your support and partnership.
Because this report may seem overly lengthy and technical, let me give you the bottom-line latest results first.
In testing completed on our recombinant form of our parent anti-HIV monoclonal antibody, the recombinant antibody performed significantly better than the parent antibody. Specifically, our newly produced recombinant form of the antibody reached a 93.2% neutralization (as compared to an 80% neutralization achieved by the parent antibody) while requiring only 1/16th of the concentration required by the parent. The recombinant required only 0.05 µg/ml of antibody to reach 93.2% neutralization as compared to the parent antibody requiring 0.8 µg/ml (16 times more) to achieve an 80% neutralization rate.
These tests were conducted on a single HIV virus isolate (SF162) – a laboratory HIV isolate (strain of virus) known to be very difficult to neutralize. Additional testing is planned and will now be conducted on a greater number of HIV isolates.
Let me recap our developments that have led to this latest data.
Our parent Clone 3 anti-HIV antibody has been successfully tested in five international laboratories where it conclusively neutralized 95% of the HIV isolate strains against which it was tested. http://www.bioclonetics.com/validation.html.
Our Clone 3 antibody is very unique in broad-spectrum coverage – it neutralizes all HIV clades across the world and the targeted epitope – the “Achilles heel” to which our antibody binds resulting in neutralization – is highly conserved and has remained present in the over 6000 HIV isolates that have become known over the past 15 years. The epitope of the Clone 3 antibody has remained present (has not mutated) and is 98% conserved – over the past 15 years (2003 through 2019), as recorded in the Los Alamos National Laboratory HIV Database for amino acid sequencing for primary HIV clinical isolates gp41 amino acid sequence 601-KLIC-604. From this data, it can be seen that 78% of the over 6000 isolates contain the absolute amino acid core epitope for Clone 3 Antibody [= KLIC] and 20% contain conservative substitutions of amino acids within the epitope range 601 through 604. This fact is shown here https://www.hiv.lanl.gov/cgi-bin/QUICK_ALIGNv2/convent.cgi?seq_input=epitope%09KLIC&nucpro=pro
A successful antibody must be “broadly neutralizing” – meaning it must neutralize HIV virus strains by binding to a site on the viruses that does not mutate. If an antibody initially neutralizes the virus by binding only to a site that mutates, the virus simply “escapes” around the antibody and the antibody will ultimately not be successful in controlling the HIV virus. This “virus escape” has rendered other monoclonal antibodies unsuccessful.
As an example, a most recent candidate was the antibody VRC01 produced and tested by Vaccine Research Center in conjunction with the National Institute of Health (NIH). In studies of use of the anti-HIV antibody VRC01, it was found that patients treated experienced viral rebound (virus escape) shortly after suspension of the administration. https://www.nejm.org/doi/full/10.1056/NEJMoa1608243. Also see, K.J. Bar, New England Journal of Medicine, 9 November 2016 (“Viral rebound after 4 weeks and 5.6 weeks).
Another example is the broadly neutralizing antibodies (bNAbs) 3BNC117 and 10-1074 currently in NIH clinical trials. These antibodies fail to bind to an immutable site on the virus – and thus used by themselves or in their combination, will not provide a successful treatment of HIV. Specifically, for mAb 3BNC117, virus escape is documented in the reference Viraemia Suppressed in HIV-1-infected Humans by Broadly Neutralizing Antibody 3BNC117, Marina Caskey, et al., Nature, Vol 522, pp 487 (June 25, 2015); https://www.ncbi.nlm.nih.gov/pubmed/25855300.
As to the monoclonal antibody 10-1074, the reference in Nature Medicine (volume 23, no. 2 February 2017 page 185) entitled “Antibody 10-1074 suppresses viremia in HIV-1-infected individuals” reveals the virus escape that is experienced when used in tests. Careful analysis of the binding site of this mAb reveals that there will be from 19% to 39% virus escape in use of this antibody.
These antibodies will have to be combined with a broadly neutralizing antibody such as our Clone 3 – which binds to an immutable, linear epitope site on the virus – for them to be successful in the real world.
Because – as is usual – the parent antibody producing cell line does not produce a sufficient quantity of antibody to treat the millions of individuals infected with HIV, a “recombinant form” of the antibody (using a fast-producing cell line) had to be produced and then tested. With your support, we successfully produced several recombinants of the parent – each with a slightly difference amino acid sequence composition.
We have now completed the first tests of these recombinants and more testing is under way.
What did this initial testing reveal?
First let me note that the tests were conducted against a lab HIV isolate – a strain identified as SF231 – an HIV strain known to be very resistant to neutralization.
In prior testing of the parent Clone 3 antibody against this isolate SF231, to achieve 80% neutralization required a concentration of 0.8 µg/ml of the parent antibody.
In the tests just completed of the recombinant form of our antibody, to achieve a 93.2% neutralization, only a concentration of 0.05 µg/ml of the antibody was required – a 16-fold improvement over the parent antibody.
More tests are being conducted and will be conducted on many more HIV viral isolates. As noted above, the parent antibody was tested in 5 international labs against 43 isolates, where it fully neutralized over 95% of those tested. We expect a similar or better result from the recombinant form of our antibody. We hope to accumulate more data to solidify interest by an appropriate pharma partner to conduct animal trials and then clinical trials.
We expect that in animal and then clinical trials, our antibody will perform better than the results in these in vitro (test tube) tests and expectedly will perform better those antibodies being studied by others – again because our antibody binds to the virus at an immutable site that exists of 98% of all strains of the HIV virus. This is a characteristic of our antibody that we believe sets it apart from others.
We will keep you informed of our progress. And we thank you again for your support.
Best regards,
Charles
Charles Cotropia
CEO BioClonetics Immunotherapeutics, Inc.
Dear Investors and Supporters,
As we approach the end of 2018, we are reminded how fortunate we have been to have investors and supporters such as you. Your support has allowed us to made great strides as we move into 2019. Thank you for your support and partnership. And we wish you peace, joy and prosperity throughout the coming year!
Our recombinant anti-HIV monoclonal antibodies were successfully produced in 2018 at Genscript Biotech and are in testing against a full panel of HIV isolates at two labs – the University of Antwerp, Institute of Tropical Medicine (https://www.itg.be/), Antwerp, Belgium and at the Texas BioMedical Research Institute (https://www.txbiomed.org/) in San Antonio, Texas.
We have obtained a proposal and protocol for animal trials and plan to later test the recombinants in macaques at the Keeling Center for Comparative Medicine at M.D. Anderson in Bastrop, Texas. Such tests do require a substantial investment and we are conferencing with several potential supporters to obtain the necessary funding.
Our recombinant antibody is also being scheduled for testing in combination with other HIV therapies in the lab of the Italian National Center for Aids Research (CNAIDS) at Istituto Superiore Di Sanità, Rome, Italy. The expectation in such tests is to combine our antibody with other non-antibody therapies to attach to and thereby neutralize the virus in combination. These tests are now being scheduled.
We are continuing our dialogue with potential pharma partners. In addition to using our anti-HIV monoclonal antibodies to address HIV, potential pharma partners are interested in how our technology can address infectious disease other than HIV.
Specifically, our technology can be applied to address diseases like HTLV-1 and HTLV-2 – diseases which effect 20 million people around the world? HTLV-1 and HTLV-2 viral agents cause an increase in white blood T-cell lymphocyte counts leading to leukemia cancer. Here is how our technology can be used to address this cause of cancer.
To achieve the same result that we have achieved with HIV through the creation of an anti-HIV antibodies, one must know how to successfully target the HTLV-1 and HTLV-2 viral agents that cause human T-cell leukemias. Specific structures within the HTLV-1 and HTLV-2 molecular sequence must be targeted to achieve effective control of these viral agents.
The significant point here is that we have the knowledge and methodology necessary to successfully target HTLV-1 and HTLV-2. And we hope to work with a pharma partner to address this cancer.
We will keep you updated. And we thank you for your continued support.
Best regards,
Charles
Charles Cotropia
BioClonetics
Dear Investors and Supporters,
Before I share a final summarizing update, I want to first extend a most sincere thanks to all of our investors and followers. You have truly made our progress possible and we will continue to work tirelessly to assure that we are worthy of your support and that our technology fulfills the promise that it offers.
Our campaign ends in 1 day - November 2, 2018. We will not be extending our campaign and thus we ask that those that have considered reinvesting, please do so on or before November 2nd – and pass the word onto your friends.
There are so many things happening, it is hard to give a final report. I have been accused (by those helping me with these reports) of saying too much in these updates. But there is a lot to say and a lot to convey – after all, our progress has been great and gives hope in light of the devastation caused by the HIV pandemic – a disease that takes the lives of 400 children every day - and 4000 adults each day. With that level of loss, it is hard for me to simply capsulize what we are doing because the goal of an effective therapeutic cure (which can reach those who currently have no treatment) cannot be adequately conveyed in a short summary.
Our strength lies in the fact that we have two distinct areas of technology. First, we have a fully human, and effective, anti-HIV monoclonal antibody - called Clone 3 - and second, we have a proprietary methodology for producing fully human monoclonal antibodies against numerous infectious diseases. Our methodology is superior because it can be used to identify – not just antibodies - but highly effective, neutralizing antibodies.
As we have reported, the parent antibody has demonstrated its effectiveness in 5 separate labs where it neutralized 95% of the HIV isolates against which it was tested. We have now produced recombinant forms of the parent antibody and they are being tested in two labs - University of Antwerp, Institute of Tropical Medicine, Antwerp, Belgium and Texas BioMedical Research Institute, San Antonio, Texas. We have this past week, starting plans for macaque trials at the Michale E. Keeling Center for Comparative Medicine and Research at M.D. Anderson, Bastrop, Texas.
Regarding the methodology, in addition to producing our anti-HIV monoclonal antibody, we have proof of concept in use of the method to generate monoclonal antibodies against Rabies, Influenza A, Influenza B, Tetanus and Diphtheria. The methodology can be used for so many more diseases, both those that effect humans and those that kill animals.
The recombinant forms of the parent antibody were generated for us (with your investment!) by Genscript (www.genscript.com) and we have worked with this superior lab for years. We are now in discussions with Genscript about a partnering or licensing arrangement. As these discussions continue, we are not limiting our search for a biopharma partner to one company. We have had interest by big pharma and have had discussions with Johnson & Johnson and Gilead. To identify the correct partner, we have this week engaged with several highly experienced consultants in the field of identifying and negotiating technology licenses and acquisitions.
As we proceed with negotiations, a partner, licensee or an acquiring company may be interested in some or all of our technology. Each piece has significant value. Our primary interest is in partnering with a pharma company to assure that the full scope of our technology is implemented.
We will keep you up to date on our progress. And we sincerely thank you for all your support.
Kind regards,
Charles
Charles Cotropia
CEO BioClonetics Immunotherapeutics, Inc.
www.bioclonetics.com
For all of our supporters who have come on board since August 1, your investment will be processed when our campaign closes on November 2, if it was not previously processed. Be on the lookout for an email that will give you the details as to when your investment will be actually processed for funding to our company.
We again express our appreciation for your confidence and support.
Best regards,
Charles
CEO BioClonetics
Our Campaign Ends in 1 Week
Dear Investors and Supporters,
Our discussions to partner with a large international biotech are progressing. Genscript (https://www.genscript.com/), an internationally recognized pharma, has expressed an interest in more than one of our technologies. There is remarkable potential that could flow from a partnership with this entity. Combining our technology with their expertise, scientists and lab facilities can only lead to remarkable successes.
Before I share more about that progress, let me first extend my sincere appreciation to all of our new and existing investors and our supporters. Your support has made the difference. However, our StartEngine campaign will end in 1 week on November 2, 2018. We will not be extending our campaign and so ask that those that have considered reinvesting, please do so before November 2nd – and pass the word onto your friends.
For those who have indicated an intent to invest but have thus far not completed the process, we ask that you do that now – before our campaign closes.
We have worked with Genscript for years and their expertise is unmatched by any with whom we have been associated. Our most recent developments have been made in conjunction with them. We have multiple separate major areas of technology to offer them and the synergy between our technology and their scientists and facilities would result is success on many fronts. Our technologies in which they are interested include:
1) Our existing anti-HIV monoclonal antibody Clone 3.
2) The methodology for creating fully human monoclonal antibodies against numerous other infectious diseases.
3) The methodology for creating fully human monoclonal antibodies against animal infectious diseases.
Let me also list the ongoing testing we are completing as we negotiate with this potential pharma partner.
Additionally,
Both of these labs requested our antibody to be combined with their distinctively different HIV therapies. The expectation is that a combined therapy will offer a greater probability of success in completely defeating the HIV virus – a virus that big pharma has failed to adequately address and failed to conquer over many decades.
We will keep you informed.
If you have considered investing but have not yet done so, please do so now.
Best regards,
Charles Cotropia
CEO
BioClonetics Immunotherapeutics, Inc.
Dear Investors and Supporters,
We have very promising news regarding our plans to partner with a large Biopharma company to license our proprietary methodology for producing fully human monoclonal antibodies against other infectious diseases. In this update, I want to share this news.
Let me first extend my sincere appreciation to all of our investors and supporters. Your support has made our progress possible. However, our campaign on www.startengine.com/bioclonetics will end in 2 weeks on November 2, 2018. We will not be extending our campaign and thus ask that those who have considered investing, please do so before this deadline – and pass the word to your friends. For those who have begun the investment process, we ask that you conclude that process on www.startengine.com.
OUR EFFORTS TO PARTNER WITH A MAJOR BIOPHARMA COMPANY ARE PROGRESSING
As we have reported, tests of our fully human monoclonal antibody in 5 separate international laboratories have demonstrated that our anti-HIV monoclonal antibody fully neutralizes over 95% of the multiple HIV isolates (strains) against which it was tested.
The recombinant forms of the parent antibody (necessary for animal and clinical trials) have been produced and are currently being tested for efficacy in 2 world class laboratories, at Texas BioMedical Research Institute, San Antonio, Texas and the University of Antwerp, Institute of Tropical Medicine, Antwerp, Belgium.
To produce these recombinant forms of our antibodies, we have worked closely with a large Biopharma entity that is a leader in multiple areas of pharmaceutical development. In a conference with this entity yesterday, they have expressed an interest and we are discussing partnering to share the method for producing fully human monoclonal antibodies – a method that can be used (and has been successfully used by us) to produce fully human monoclonal antibodies against numerous infectious diseases. This prospective partner’s interest is due to the fact that our methodology for producing fully human (not mouse-based) monoclonal antibodies can be used not only to produce neutralizing antibodies against HIV but can similarly be used to product fully human monoclonal antibodies against many other infectious diseases. We have already proven proof of concept in producing fully human monoclonal antibodies against:
- Rabies
- Influenza A
- Influenza B
- Tetanus
- Diphtheria
The process can likewise be used to produced fully human monoclonal antibodies against other infectious diseases, such as:
- IV-2
- Anthrax
- Smallpox
- H1N1 Influenza
- h (+) auto-immune disease
- HTLV1 & HTLV2 Leukemia
- Herpes Simplex I & II
- onic Fatigue Syndrome
The method can similarly be used to produce animal-specific monoclonal antibodies for animal viruses such as:
- Asian and African Elephant Herpes
- Primate Herpes
- American Bison Brucellosis
- Australian Koala HIV and Chlamydia
- Feline Immunodeficiency Virus
- African Lion Drug-Resistant Tuberculosis
Given the breath of scope and reach of our proprietary methodology, this large Biopharma company is interested in and we intend to move forward aggressively with a program of development with this company using our methodology.
Look for great progress on this front in the near future.
Best regards,
Charles
Charles Cotropia
CEO BioClonetics Immunotherapeutics, Inc.
PROGRESS BEING MADE
Dear Investors and Followers,
Let me first extend my sincere appreciation to all of our new investors as well as all of our existing investors.
Testing of our recombinant antibodies are now underway at 2 world class laboratories, (1) Texas BioMedical Research Institute, Dan Antonio, Texas and (2) University of Antwerp, Institute of Tropical Medicine, Antwerp, Belgium. These tests are being conducted on our recently produced recombinant antibodies.
To recap our current status, the parent Clone 3 anti-HIV antibody has been successfully tested in five international laboratories where it conclusively neutralized 95% of the HIV isolate strains against which it was tested.
The recombinant form of the antibody has been produced from the parent antibody, a form of the antibody necessary for proceeding to animal and then clinical trials.
As mentioned, the testing of the recombinant antibodies is now underway at two laboratories. The testing system being used is one where the recombinants are tested against multiple, live HIV viruses, called a PBMC based assay test system. Most, if not all, big Pharma companies do not use this more sophisticated PBMC based assay test which tests antibodies against live viruses. This system is not used due to its complexity, higher costs and time required by the method. Unfortunately, for those researchers using the substituted, less expensive, rapid fluoresce test, the results are not, in our view, a valid indication of whether a tested antibody will succeed in the real world. In other words, the test system used by big Pharma is not against actual HIV virus strains but rather against man-made targets that supposedly “are equivalent” to the real-world virus. We are not willing to use such shortcut procedures as we find them to produce erroneous results.
Our testing in the two labs we be in the more accurate and costlier PBMC based assay test system – a test system that takes several months to complete. But the tests are against live HIV virus strains which produce a valid indication of efficacy.
Thereafter, the antibodies will be ready for animal trials.
In a conversation this week with Johnson & Johnson, a company focused on HIV therapy, our technology was well received and recognized as being significant and the data persuasive. However, Johnson and Johnson indicated that it would need to see results in animal trials before it would be in a position to buy-in to the technology.
We are actively, very actively pursuing a pharma partner who does not require the completion of animal trails before partnering in our technological development. As we attempt to identify such partner, we are proceeding to make plans for animal trials at one of several macaque trial centers including Southwest National Primate Research Center, in San Antonio, Texas (http://snprc.org/primates/macaques/) and Keeling Center for Comparative Medicine, MD Anderson Cancer Center. (http://www.kccmr.org/).
As we have reported, there are several efforts by others to develop anti-HIV monoclonal antibodies and we welcome their research advancements. As we have reported before, a combination of neutralizing antibodies may well be necessary to completely defeat HIV. A combined therapy is the norm in many if not most cases, including treating cancer and many many other diseases. As to these other attempts to identify a successful anti-HIV antibody, for an antibody to effective in the real world, it must have at least these qualities:
It must be capable of being produced in quality (have stability once produced) and quantity sufficient amounts for patient application.
It must bind to an immutable site on the virus (otherwise the virus will escape around it).
It must interrupt an essential step in the infectious process as a result of its binding to the virus (it must be neutralizing).
Those antibodies produced thus far have not succeed in each of these requirements. Ours does.
As to those monoclonal antibodies now being or recently considered, a most recent candidate was the antibody VRC01 produced and tested by Vaccine Research Center in conjunction with the National Institute of Health (NIH). In studies of use of the anti-HIV antibody VRC01, it was found that patients treated experienced viral rebound (virus escape) shortly after suspension of the administration. https://www.nejm.org/doi/full/10.1056/NEJMoa1608243. Also see, K.J. Bar, New England Journal of Medicine, 9 November 2016 (“Viral rebound after 4 weeks and 5.6 weeks).
Another example is the broadly neutralizing antibodies (bNAbs) 3BNC117 and 10-1074 currently in NIH clinical trials. These antibodies fail to bind to an immutable site on the virus – and thus used by themselves or in their combination, will not provide a successful treatment of HIV. Specifically, for mAb 3BNC117, virus escape is documented in the reference Viraemia Suppressed in HIV-1-infected Humans by Broadly Neutralizing Antibody 3BNC117, Marina Caskey, et al., Nature, Vol 522, pp 487 (June 25, 2015); https://www.ncbi.nlm.nih.gov/pubmed/25855300.
As to the monoclonal antibody (mAb) 10-1074, the reference in Nature Medicine (volume 23, no. 2 February 2017 page 185) entitled “Antibody 10-1074 suppresses viremia in HIV-1-infected individuals” reveals the virus escape that is experienced when used in tests. Careful analysis of the binding site of this mAb reveals that there will be from 19% to 39% virus escape in use of this antibody.
These antibodies will have to be combined with a broadly neutralizing antibody such as our Clone 3 that binds to an immutable, linear epitope site on the virus for them to be successful in the real world. We are facing a real-world attack by HIV. We must recognize that an antibody that the virus can defeat is not sufficient.
We firmly believe that our recombinant testing and then animal trials of our antibodies will produce the necessary evidence for a pharma partner to fully embrace them.
Best regards,
Charles
CEO
Charles Cotropia
CEO BioClonetics
How Does Our Monoclonal Antibodies Compare to Those of Big Pharma Now Being Tested?
A good question – which each investor and each party to this search for a cure for HIV should ask.
Here is the answer.
Our technology is significant because it is a critical component to other unsuccessful monoclonal anti-HIV antibodies now being tested and developed. Specifically, those monoclonal antibodies being tested by the industry, referenced below, have been shown to face “virus escape” and thus will fail by themselves in providing a therapeutics cure for HIV. The investments made will be lost without combining those antibodies with one – like ours – that binds to an immutable site on the virus.
Please consider these points and share them with others that you know.
A most current example is the NIH clinical trial of what it calls “two highly potent, HIV-specific, broadly neutralizing antibodies (bNAbs) — 3BNC117 and 10-1074.” https://www.nih.gov/news-events/news-releases/nih-launches-study-test-combination-antibody-treatment-hiv-infection.
Thus, to be successful, it will be critical to combine additional broadly neutralizing antibodies that bind to an immutable site – otherwise, the combinations now being examined will fail.
In view of these facts, we ask that you share this information with others who want to see a successful therapy for HIV.
Charles
Charles Cotropia
CEO/President
BioClonetics Immunotherapeutics, Inc.
OUR PROGRESS CONTINUES
To all of our new and current investors, we thank you for your continued support.
Our funding campaign is set to end in 60 days and we plan to conclude our fundraising effort at that time. We ask that you share our technology and story with friends and acquaintances as I am sure they will have the same interest in our program as you. Everything described here is made possible by the support of investors like you and the support of those you know.
Let me update you on the several programs we have ongoing:
Our monoclonal anti-HIV antibody development.
As we have reported, our parent anti-HIV monoclonal antibody has been tested against multiple HIV viral isolates (strains of the virus) and has been shown to neutralize these virus strains. These results can be viewed on our website at - http://www.bioclonetics.com/validation.html.
We have produced recombinants of this parent antibody (necessary for animal and clinical trials) and are in the process of testing these recombinants against multiple isolates (strains) of the virus. These recombinants are being scheduled for testing at the Texas BioMedical Research Institute (https://www.txbiomed.org/) in San Antonio, Texas. Thereafter, the antibodies will be tested in macaques at the Southwest National Primate Research Center, also in San Antonio, Texas (http://snprc.org/primates/macaques/). Our recombinants are also scheduled to be tested for efficacy at the University of Antwerp, Institute of Tropical Medicine (https://www.itg.be/), Antwerp, Belgium.
Why haven’t these tests been completed?
The required test method for confirming the efficacy of these recombinant forms of our antibody (to assure that they are as effective against HIV as the parent antibody) requires a very specialized test method (called the PBMC based assay test) conducted using live multiple HIV isolates (strains of the virus). As you can appreciate, this requires a very specialized lab and protocol using a process that takes several months to complete. For this reason, we have engaged 2 labs to independently complete these necessary tests, one in Texas (https://www.txbiomed.org/) and one in Antwerp, Belgium (https://www.itg.be/). We have also requested another lab in Milan, Italy (also known for its expertise in conducting these tests) to provide a proposal for testing. These test results will be completed before the end of this year. We wish this could be completed sooner but this is the necessary timetable required.
A more rapid (and cheaper) test is used by some researchers – called the rapid fluorescent assay method [TZM-bl cells]. However, this procedure performs the test using pseudo viruses, not actual HIV viruses and is known to fail to provide a true reading as to efficacy. This fact of non-concordance between the TZM-bl rapid throughput test method and the test method we are using, called the PBMC-based in vitro neutralization test, is well documented dating back to 2008 (Polonis, et al., Virology 375, pp. 315–320 (2008)).
Why many researchers would use a test known to not produce a valid result is hard to believe as there is no rational reason for using such a test if it produces an erroneous result. Could this be part of the reason why further meaningful progress has not been made over these many years?
Patenting our technology.
We have just filed a comprehensive additional patent on the technology for using our recombinant monoclonal antibodies to treat HIV. This application covers the precise multiple recombinant antibody configurations that have been created (and their equivalents). This additional application is being filed in the U.S. with foreign country applications to follow.
Complimentary therapy to our monoclonal antibody.
As a second and complimentary therapy, we have now created another functional antibody category called "IgA antibody” that can be used against HIV. IgA antibodies protect against HIV infections that occur at mucosal surfaces, specifically, for example, vaginal, anal and oral mucosal surfaces of the human body. HIV exposure at the mucosal surfaces accounts for the majority of HIV infections which occur upon initial contact with the HIV virus.
This therapy will expectedly provide a protective immunological defense against initial exposure to HIV virus at mucosal surfaces, such as occurs in the passage of the virus from mother to child through maternal breast feeding or other body to body contact.
Just this week, our lab completed production of this IgA antibody form and initial tests of its ability to bind to the gp 41 structure of the HIV virus have been positive. Our development of this additional technology is continuing.
An additional strategy is now also being pursued.
Recall that combination therapy always offers a potential for a superior and more complete control of any infectious disease and few if any diseases are more difficult to control than the HIV virus. As an additional approach to controlling and eliminating the HIV virus from the human body, we are cooperating with a University research lab to use our antibody to deliver cell-killing drugs or radionuclides or toxins to the virus to eliminate persistent reservoirs of HIV infection.
Let me explain this approach.
Our Clone 3 antibody, has been shown to neutralize (render incapable of replicating) the virus by itself. But, an additional strategy is to deliver further controlling drugs or radionuclides or toxins to the virus to provide additional effective control. In non-medical terms, the approach is to deliver a “hand grenade” to the virus to destroy it. To be effective, a delivery system must effectively deliver the “grenade” to the HIV virus – and deliver it to a site on the virus that is always present in all of the 5000+ various strains of the virus now known to exist.
This is what we know our antibody is capable of doing and why it is valuable. In this therapy, the control drug or radionuclides or toxins are attached to our antibody – which we know binds to the virus and which we know binds to the virus at a site that exists in virtually all of 5000+ strains of the virus now known.
In such an approach, it is critical to use an antibody that binds to the HIV virus at a site that will always be present – even as the HIV virus “mutates” (changes its amino acid structure). It is well known that the virus readily mutates but we also know that all the mutation variants of the virus continue to contain the “binding site” to which our antibody binds. You can see the invariant site to which our antibody binds as shown on our website at http://www.bioclonetics.com/effectiveness.html. Our antibody’s binding site exists in 98% of all 5000+ HIV virus strains now know.
This is just a further use of our technology for developing an effective control and neutralization of the virus. We are encouraged by this current effort.
We greatly appreciate your being a part of all of these efforts. Stay tuned for further updates and results. Share our technology with those you know.
Best regards,
Charles Cotropia
BioClonetics
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