Good afternoon. This is Yvonne Briggs with LHA. Thank you all for joining us today for OPKO Health's R&D Day, highlighting ModeX Therapeutics' multi-specific technology platforms. Following management's prepared remarks, we will host a question and answer session. You may submit online questions at any time today using the window on the webcast. Please note this event is being recorded and a replay will be available on OPKO Health's website. I'd like to remind you that any statements made during this call by management, other than statements of historical fact, will be considered forward-looking and, as such, will be subject to risks and uncertainties that could materially affect the company's expected results. Those forward-looking statements include, without limitation, the various risks described in the company's SEC filings, including the annual report on Form 10-K for the year ended December 31, 2022, and in subsequently filed SEC reports.
The contents from the webcast contain time-sensitive information that is accurate only as of the date of the live broadcast today, March 20, 2023. Except as required by law, OPKO undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this call. Now I'd like to turn the call over to Dr. Gary Nabel, Chief Innovation Officer.
Thank you, Yvonne. Hi, I'm Gary Nabel, President and CEO of ModeX Therapeutics and Chief Innovation Officer at OPKO. I'm delighted to welcome you to the first research and development day for ModeX Therapeutics. Elias Zerhouni and I co-founded ModeX in November of 2020, and we've been working since then to bring innovative medicines to benefit patients facing serious medical challenges in cancer and viral infection. In May 2022, we merged with OPKO Health, where we now operate as an independent subsidiary of OPKO. Together, the efforts of OPKO and ModeX have been synergistic, building on the experience and infrastructure of OPKO to accelerate our therapeutics program and to provide a new story of growth for OPKO outlined in this slide.
Now, I would like to introduce you to the President, CEO, and Board Chair of OPKO, Dr. Phillip Frost, who will provide his perspectives in his opening remarks. After his comments and Elias's overview, I'll be back to guide you through the program that describes the assets and capabilities of our team. Phil?
Hi, everyone, thanks for joining us for our first R&D Day. It's a real pleasure to tell you about the innovative work of the ModeX team and the opportunities we see for the ModeX pipeline portfolio and platform technologies to treat infectious diseases and cancer. Since OPKO's acquisition of ModeX mid-last year, the ModeX team has made really great progress. Two weeks ago, we announced ModeX's first collaboration with Merck for an Epstein-Barr virus vaccine program using ModeX's Ferritin Nanoparticle platform. This was an extraordinary public debut for the team's scientific programs, and we'll be talking more about that deal later. We've seen with OPKO's collaboration with Pfizer for NGENLA, we have a track record of working with great global partners to realize the potential of our technologies. We expect ModeX pipeline will provide even more opportunities to continue the pattern.
In evaluating ModeX as an addition to OPKO's portfolio of companies, we saw a truly differentiated therapeutic developer with next generation technologies focused on major global health needs. As you'll see today, the leadership is exceptional and the integration has been a great success. I want to take a moment to welcome ModeX CEO, Gary Nabel, and Chief Scientific Officer, John Mascola. Dr. Nabel was Founding Director of the Vaccine Research Center at the National Institutes of Health and was a leader at NIH for many years before becoming Chief Scientific Officer at Sanofi, where he led the Breakthrough Laboratory. Dr. Mascola was also Director of the NIH's Vaccine Research Center, overseeing a wide range of research in vaccines and antibody therapeutics for major diseases. Between them, they've advanced some of the world's most important medical research and are now focused on driving a uniquely promising story at ModeX.
Today, Gary and John are joined by Vijay Chhajlani, ModeX Chief Technology Officer, and Ronnie Wei, Head of Biologics Discovery and Development, both scientific leaders who will drive the development of ModeX platform technologies. As we think about the broader OPKO business, we built a diversified base that's allowed us to meet an important challenge for patients in society during the COVID-19 pandemic. Looking ahead to the next phase for OPKO, we see ModeX as an important engine for innovation that will increasingly place therapeutics at the center of our value creation. The people, technologies, culture, and focus at ModeX are a rare combination that places it in an incredibly strong position to build a larger and more diversified pipeline for OPKO into the future. The work you'll hear about today reflects industry-leading expertise in the development of next-generation antibodies and vaccines.
These bring the power of multiple medicines to bear in a single molecule. Many of the most significant infectious diseases and most cancers are notable for their complexity, which presents major challenges for drug design. The core of the ModeX strategy is realizing the potential of truly multi-specific drugs that go far beyond current efforts in the market. We're incredibly enthusiastic about the opportunities we're creating together and the way ModeX is complementing OPKO's legacy of healthcare innovation. I invite you to take part in the Q&A at the end of today's session to learn more about our work and our vision for the future. I'd like to pass over to Elias Zerhouni, our President and Co-founder of ModeX, to give us a brief overview of the company's focus and what to listen for today.
Well, thank you, Dr. Frost, and thank you everybody for attending our R&D Day. What I'd like to do is really give you a perspective about the history of ModeX, how did we come together, and why did we come together. The first thing I would like to tell you is that ModeX is not a completely new company. Actually, Dr. Nabel and myself worked together at the NIH, and then when I went to Sanofi, Dr. Nabel joined me, and we decided to create a Breakthrough Lab, which was led by Dr. Nabel at Sanofi. The idea was to generate transformational technologies based on multispecific antibodies and multivalent nanoparticle vaccine platforms. We decided to focus on immuno-oncology, on viral diseases, and vaccines. Our track record, actually, since 2012, when we created the Breakthrough Lab, is pretty good.
We have three multi-specific antibodies in ongoing phase I trials and proving, in fact, that the strategy can work in the clinic. We established a very strong IP foundation. As of today, we have 28 patent applications filed. Really what brought us together was the vision of Dr. Frost at OPKO to bring top-notch leading-edge R&D to OPKO. For us at ModeX, it also brought us a very experienced organization with all of the things that we would have had to recreate to be an independent company. By merging the two, we really combined our forces to create novel biotherapeutics, and the portfolio that we have is eliciting strong interest from strategic partners, as you will hear from Gary Nabel about our first major partnership with Merck.
The question that I always get is this one: What is the fundamental scientific driver of ModeX Therapeutics? Let me share with you the fundamental scientific concept that is really driving us, and that is the fact that we have learned over the past decades that no disease depends on a single target. That's why you have many, many therapies that are a combination of therapies to achieve success. In fact, if you look at this network of molecules that I drew here on the slide, you can imagine that a certain disease can have multiple pathways leading to the disease. The molecules that are in pathway one or pathway two, pathway three, sometimes correct each other. If you only act on one, the other two may actually persist in creating the disease symptoms.
Our idea was, can we come up with what we call dream molecules, one drug that can attack multiple targets, affect multiple biological functions, and in diverse diseases? This is based on a deep understanding of validated molecular networks and pathways. The thing that is really interesting to appreciate here is that many, many of the targets have been validated in single target, single therapy, drug that have one target. The scientific evidence indicates that many diseases now require a combination to achieve success. We can see it. You can see it in humans with chemotherapy, with antibiotics, even in immunotherapy. We developed a drug called Dupixent, which attacks two targets, IL-4 and IL-13, for a disease pathway called a Th2 pathway, which is responsible for atopic dermatitis, asthma, esophagitis, and other diseases.
What we realized is that by combining the two, the advantage is, number one, you're affecting two targets. Number two, more importantly, because you're affecting two targets, you don't have to really have high doses, and therefore you can decrease side effects. The same is true in vaccines, you will hear about our platform, which can really combine multiple antigens to create stronger vaccines. That is the central concept really. We are aiming to have synergistic targeting of what we know biologically are disease drivers in unique combinations that will actually bring the ability to develop a single drug over a single time period of development that will attack multiple targets, and it will be multifunctional.
This is really what we're based on, and I'll now turn it over to Dr. Nabel to go over the first illustration and then the rest of the portfolio on the of ModeX Therapeutics. Thank you very much. Gary, back to you.
Thank you, Elias. It's a pleasure to introduce you today to ModeX Therapeutics. We're excited to tell you about the pillars of ModeX, the four Ps, our people, platforms, products, and the promise of our growing company. I'll provide a high-level view of the people, platforms, and products of the company in this presentation. After which, I'll describe our EBV vaccine program, the basis of the work in IP that was recently licensed and partnered with Merck. You'll hear about the platforms from Dr. Ronnie Wei, the Head of Biologics, our pipeline portfolio from our CSO, John Mascola, and the CMC manufacturing programs from our Chief Technical Officer, Vijay Chhajlani. The first P of our pillars are people. We value medical experience, scientific excellence, creativity, pragmatism, and collaboration. Our leadership team exemplifies those values. You've heard from Elias already.
He and I are joined in the leadership of ModeX by Elizabeth Nabel, my wife, who's the Executive VP for Strategy. Ji Zhang, who is the Chief Operating Officer, formerly at Sanofi and Flagship Pioneering. Our consultant in oncology, Edward Garmey. Our outstanding Chief Scientific Officer, John Mascola. Our extremely proficient Chief Technology Officer, Vijay Chhajlani. Our Head of Biologics Discovery and Development, Ronnie Wei, that you'll be hearing from later as well. Other heads of our department are CJ Wei and Ziyong Yang, who are heading our basic research programs. All have extensive experience in academia and government and industry, and it's really quite an impressive team and really an exciting work environment where we can all come together.
The promise of next-generation antibody technology is really what we're trying to deliver at ModeX Therapeutics. We're trying to deliver that by creating multispecific antibody technology that allows for synergistic targeting in terms of disease targets, streamlined manufacturing, rapid translation into the clinic, and efficient delivery, either by protein or gene-based vectors, all in a single product. ModeX also builds on known pathways to generate its effective new medicines. We use information about known immune mechanism, T cell signaling, B cell signaling, and K signaling, and validated targets that have worked in the clinic based on established biology, particularly clinical biologies, to develop our new medicines. By using molecular engineering, structure-based design, and digital design and machine learning, our candidates can stimulate biologic responses with novel combinations of antibodies and immune activators all in one molecule to generate first-class candidates with best-in-class potential.
That's what you'll be hearing more details about in the upcoming presentations. The multi-specific technology is newer in terms of antibody modalities. The initial antibody modality that we're all very familiar with were monoclonal antibodies. You'll also see some of the data on bispecifics that represents the next generation. There has been an increasing interest and movement from a number of companies to take advantage of even greater flexibility in attacking targets through tri-specific antibodies and now even beyond tri-specific antibodies to test in clinical trials. The good news is that multiple clinical trials have now been performed, and they help to validate the promise of this platform. When we were at Sanofi, we developed an HIV tri-specific antibody for both the treatment and prevention of HIV. That's now been in phase I studies.
You'll hear more about that from John Mascola. There were two cancer products that have gone to the clinic using trispecific antibodies with arms directed to CD3 and CD28 in addition to the tumor. In these trials, they have shown the ability to manufacture at scale to bring these products to patients. No major adverse events have been observed, and there have been minimal degrees of anti-drug antibodies, providing a good starting point for de-risking the new technology. We'll say a little bit more about that later in Ronnie Wei's talk. The important new technology that we've developed at ModeX is called the MSTAR platform. This is the ModeX platform that allows synergistic targeting of antigens and receptors.
The way this is done is essentially by increasing the valency of our antibodies. A standard antibody is composed of a single variable region, it allows us to basically target our antigens by using the single variable regions to interact with them. In the MSTAR platform, we're able to put these variable regions together in different combinations so that they can give rise to new molecules that can interact with different targets all at once. These new modules are complementary and self-assembling. In addition to the ability to create new combinations, it also has benefits with regard to manufacturing because it eliminates mispairing that reduces the yield of product that we can make during CMC.
We've also been able to engineer them so that they have simplified configurations, single chains for each arm that enable gene delivery that could accelerate clinical development. This is all supported by intellectual property applications. We have 28 patent applications that have been filed to date. In this animation, you can see the rationale for how we create multispecific antibodies. The blocks on the top of the slide represent the variable regions of heavy and light chains that we've made as single molecules, and they can be assembled in different combinations. On top of the constant regions, we can put four copies of one type of variable region, we can put four different types of variable regions, or we can, for example, make up to six different variable regions.
By putting them together in different degrees and in different orientations, it allows us to select the molecules that are best suited for the treatments that we're trying to develop. I should mention also that at the bottom of the slide, you notice the constant region of the immunoglobulin is preserved. The constant region itself carries many important immune functions. It regulates the half-life of proteins. It also interacts with other cells of the immune system. By having the capability of recognizing different targets, for example, on tumor cells or viruses, or bringing together immune cells, based on what we know about their activation pathways, whether it be T cells, B cells, natural killer cells, we now have the ability to selectively both activate and sustain those cells at the sites of disease.
The second technology that has been part of our efforts relates to Ferritin Nanoparticle to vaccines. In this particular case, we're showing an example of the Epstein-Barr virus vaccine, where we can take components derived from Epstein-Barr, we can take different molecules from the surface of the virus. We can extract them out and make genetic forms that we can fuse to specific sites on the ferritin molecule. Ferritin is a molecule found in a wide variety of species. They carry iron. We actually use a bacterial form of ferritin so that there's no cross-reactivity with any human ferritin proteins. It is a multi-unit particle with 24 subunits that self-assembles.
By putting it at the right position on the outer surface of ferritin, we can get a self-assembling nanoparticle, in this case, that has been attached to the GP350, which is a viral entry protein for B cell entry. Or alternatively, we can take other viral proteins like the gH/gL/gp42 trimer that mediates entry of the virus into Epithelial cells, and we can again expose up to 24 copies to the immune system in an effort to stimulate antibodies that will neutralize the virus. Now I'd like to switch and tell you a little bit about the EBV vaccine program. We have partnered this program with Merck.
There was an announcement on March 8th, just a week and a half ago, where OPKO Health entered into an exclusive worldwide license and collaboration agreement to develop this vaccine. It was widely reported in the biotech and biopharma world. This is an important milestone for our infectious disease program. It is an exclusive worldwide licensing agreement and a collaboration agreement for MDX-2201. These are the, this is the program at ModeX that delivers these two vaccine components. We will be working jointly with Merck to advance these candidates to the stage of IND.
After reaching IND, Merck will assume responsibility for all further clinical development. The terms of the agreement included a $50 million upfront payment with the potential for additional payments of up to $872.5 million in milestones, and there will be additional tiered royalties. Importantly, this is a validation of our platform capacity. I think most importantly, what we're most excited about with this collaboration and this license agreement is that we really feel that the, there's a very important unmet medical need globally. Both Merck and ModeX are quite closely aligned and share a very similar vision for how to bring this vaccine forward so that it can really make a profound effect on human health.
My experience in the field of EBV vaccines actually dates back to my time at the NIH, where I was the director of the Vaccine Research Center. We published an article together with Jeff Cohen, Tony Fauci, Harold Varmus, on the need for an EBV vaccine. After working on this project, largely with Jeff and at Sanofi with others, we've now, at 12 years later, created some very encouraging vaccine candidates that we think are ready for further clinical assessment. As you know, Epstein-Barr virus causes infectious mononucleosis in adolescents and young adults, probably more significantly to human health. EBV was the first human cancer virus to be identified. That was over 150 years ago. I'm sorry, over 50 years ago.
It's been linked to more than 200,000 cases and 150,000 deaths each year. It's been implicated in Hodgkin's disease, Burkitt's lymphoma, gastric nasopharyngeal cancers, and also with post-transplant lymphomas. It's also been associated with autoimmune diseases, including multiple sclerosis. Importantly, there are no licensed vaccines or treatments for this disease. There is substantial cost to the medical system in dealing with EBV infection. It's thought that infectious mononucleosis alone accounts for about $2 billion in healthcare costs yearly. You can also see the rising incidence of EBV-associated malignancies with age. You can see here the rise of the lymphomas that occur starting in the 20s and peak in the 50s. Importantly, gastric cancer is also a very frequent malignancy associated with EBV infection.
In terms of the clinical and commercial potential of such a product, there have been analyses done for infectious mononucleosis. Infectious mononucleosis would carry a projected peak sales of about $400 million. Our great interest goes beyond infectious mononucleosis, though, to cancer prevention. We think that there is potential for an EBV vaccine to do for these malignancies, the EBV-related malignancies, what GARDASIL did for HPV. As you know, Merck led the way with GARDASIL, and that's another reason why we're so excited to be working with Merck because they carry that expertise with them to these studies. It's a very nice collaboration where we build on the scientific and the medical understanding that ModeX carries to this disease with the development and the real-world experience in developing a cancer vaccine for Merck.
Obviously for GARDASIL, the commercial impact is well known. Last year, $5.7 billion in sales. After addressing the cancer prevention indication, there are others that we'll be exploring, including multiple sclerosis and perhaps other immune disorders. The reason that we pursued the approach that we did for EBV, a bivalent vaccine, is that there have been previous studies where investigators have looked at GP350, which prevents the entry of virus into B cells. B cells are the cells that make immunoglobulins. In those studies, particularly a study that was published by GSK in 2008, the vaccine did reduce the incidence of infectious mono, which was very encouraging, but it didn't prevent viremia or didn't create a sterilizing virus environment in the body.
The reason for that gets back to the fundamental biology, which is that B cells are not the only cells that the virus infects. They also infect Epithelial cells. The entry of virus into the Epithelial cells comes through the gH/gL/gp42 heterotrimer that I described earlier in the presentation. Our rationale was, if we could make a bivalent vaccine that both targeted the GP350 pathway and the gH/gL/gp42 pathway. That would give us a chance to create the kind of protective immunity that would prevent replication of the virus. Our vaccine is a two-component vaccine, both the GP350, it's a truncated form of GP350 that gets fused to the Ferritin Nanoparticle, as well as a single chain form. We've re-engineered gH/gL/gp42 so that it's made as a single molecule.
This allows for greater consistency and homogeneity and scalability of the product. We now have this two-component vaccine. We think that it's scalable, it should be cost-effective, and there's actually been a phase I human trial of just the GP350 component, providing some de-risking of the technology in humans as well. This work done by Jeff Cohen at NIH. The rationale for the vaccine has been published, and I would direct you to the paper that's been published last year in Science Translational Medicine from our team and from Jeff Cohen at the NIH. In it, you can see that there's very high titers of antibodies, neutralizing antibodies generated by our vaccines that will neutralize infection to both B cells and Epithelial cells.
Most importantly, in our best in vivo models, if we vaccinate in humanized mice, and if we take a serum from immune animals and transfer those to humanized mice and then challenge with infection, you can see that the control animals give rise to over 10 logs of viremia by nine weeks after the infection, whereas the immune animals have a literally undetectable replication. That's been published, so if you have questions, you may wanna look further at those papers. That's where the project stands. It is in terms of our pipeline and our products, which will be the next subject of this presentation, it is the MDX-2201 program. As I mentioned, we will be working with Merck to advance this to IND and for them to then take it beyond that step.
What you're gonna hear about now in the remainder of the presentations today, first you'll hear about the platform from Dr. Ronnie Wei. She will describe some of our tetraspecific technologies. She'll describe what we call a LASER approach, which is the approach where we can simultaneously activate multiple pathways and lymphocytes and prolong their survival. Then you'll hear about our solid tumor and leukemia programs, as well as some of our multispecific immune modulation programs from John Mascola. He also will tell you about our antiviral programs. I look forward to sharing more of our technology. You've heard about the people. You'll next hear in depth about the platforms, followed by the pipeline and manufacturing.
I'll come back at the very end with a few brief closing remarks before we turn to the question and answer session. I thank you for your time, and now what I would like to do is introduce you to Dr. Ronnie Wei, our Head of Biologics Discovery and Development, and she'll tell you more about the details of the ModeX platform technologies. Thank you. Ronnie.
Thanks, Gary, for introducing the MSTAR platform. Next, I will give you an in-depth look of ModeX Technologies, their advantages and potential applications. MSTAR is an agile, multi-specific, multivalent platform built upon lessons learned from nature. Variable domains containing the VHVL pair from monoclonal antibodies, like the one on the left, become building blocks for MSTAR. They are mounted on the constant regions like LEGO pieces in a variety of configurations. MSTAR technology can incorporate up to six specificities in a single molecule, such as monospecific tetravalent, bispecific tetravalent, or tetraspecific to name a few. We are building a true plug-and-play system where we can fine-tune the specificity, valency, and geometry to optimize biological functions. Using the bispecific tetravalent MSTAR as an example, we can build these different permutations to find the most desirable configurations for the targets and applications.
The modular design enables us to rapidly test numerous combinations of antigen-binding building blocks and identify these in about six months. Assessment of many combinations allows us to augment specificity and avidity, minimize off-target effects, and improve therapeutic efficacy. We leverage in silico rational design and are building up deep learning digital biology capabilities to interrogate structure activity relationships and further accelerate the candidate selection process. With a quality by design mindset, we build the MSTAR technology emphasizing both functionality and developability. By optimizing the MSTAR architecture, we overcome long-standing challenges in multispecific antibody design, such as light chain mispairing and interference among binding modules, so we can ensure full functionality. The FC region it contains can be tuned to modulate immune functions and half-life, giving it similar pharmacodynamic behaviors as monoclonal antibodies. It has favorable biophysical attributes and can be manufactured using standard cell lines and processes.
Our Chief Technology Officer, Vijay Chhajlani, will further delve into the manufacturability of MSTAR molecules later in the presentation. When we engineer a novel antibody platform, we are very much mindful of potential immunogenicity risks. We took learnings and insights gained from multispecific molecules that have been exposed to hundreds of human subjects in previous and ongoing clinical trials. We designed MSTAR binding domains to be structurally superposable to human antibodies and linkers to be non-immunogenic to minimize such concerns. We also developed a MSTAR compatible stealth technology that has the potential to improve therapeutic index for cancer treatments. In this embodiment, a tetraspecific stealth molecule can target tumors through two tumor antigens, while the anti-CD3 is masked. Monovalent anti-CD28 can bind and recruit T cells without activating them. Once the stealth molecule reaches tumor, anti-CD3 is uncloaked by proteases enriched in the tumor microenvironment.
Consequently, recruited T cells are activated by anti-CD3 and anti-CD28. This localized activation of T cells mediate potent tumor killing with minimal systemic toxicity that improve the therapeutic window. This next slide shows a proof of concept anti-CD3 unmasking experiment. The masked stealth molecule has minimal CD3 activity, shown in the black binding curve. This activity is restored, shown in the blue curve, upon protease treatment. The MSTAR platform is also well-suited for other immunomodulatory applications. For the next few minutes, I will give you two examples on such approaches. Multitargeting payload delivery and chimeric antigen receptor design. MSTAR can be easily modified to enable multitarget delivery of payloads such as cytotoxic drugs, radionuclides, or immune stimulators. They have the potential to bind two or three targets to maximize specificity and minimize mutational escape. This is exemplified in this slide.
Prostate tumor cells are targeted by conjugated bispecific MSTAR molecules, shown in this cell surface binding experiment. When one binding site is knocked out, or in another word, if one tumor antigen is downregulated, there is still effective binding, demonstrating that this approach can potentially mitigate tumor resistance through antigen escape. The next slide shows an example of a trispecific or Tri-MSTAR antibody with all three active binding sites for their respective targets. The MSTAR cassettes can be readily built into an all-in-one multispecific CAR construct for adoptive cell therapies, where a single gene encodes up to 3 specificities and delivers stimulatory signals simultaneously. In this proof of concept experiment, while using luminescent signals as T cell activation results, CAR- T cells carrying correct receptors for the tumor cells can be activated by matching targets, as shown in the middle red box.
While receptor mismatched CAR- T cells in purple dotted box do not respond to tumor binding. In summary, I hope through these examples, I gave you a flavor of MSTAR as a multivalent and multispecific platform with flexibility, adaptability, and diverse potential applications. We have filed 28 patent applications in the past two years surrounding ModeX Technologies. Next, John Mascola, our CSO, will show you specific programs utilizing MSTAR platform. Thank you.
Thank you, Ronnie, for introducing our platform, Multispecific Antibody Technology. Next, I will give an overview of several of our product development programs, starting with multispecific antibodies for immuno-oncology. As you can see on our pipeline slide, I'll be talking about a multispecific antibody for the treatment of solid tumors and a multispecific antibody for the treatment of leukemia and lymphoma. Here I'm highlighting the growing value proposition and success of multispecific antibodies, specifically bispecific T cell engager antibodies called BiTEs, show clinical efficacy for B cell malignancies. BiTEs are also being developed for solid tumors with encouraging clinical data. However, BiTEs are limited to two targets total, one tumor antigen and one T cell antigen. Tetraspecific antibodies can engage two T cell antigens and two tumor antigens, providing the potential for expanded mechanisms of action and clinical indications.
Here I'm showing that we're going beyond bispecifics with ModeX tetraspecific antibodies. I'll say more about the details of this antibody in a moment. Existing bispecific T cell engager antibodies harness the immune system by directing T cells to kill cancer cells. ModeX is developing the next generation of multispecific antibodies with greater power to recognize tumor antigens and enhance T cell killing. Here I'm showing you a diagram of a tetraspecific antibody molecule. I'll start with the diagram. You can see the antibody on top of the cancer cell, that the antibody engages CD3 to activate the T cell, then CD28 in orange to enhance T cell survival, while also being able to engage a tumor antigen in purple and a second tumor antigen in blue, directing killing of the cancer cell. We call these antibodies lymphocyte activation and survival enhancement receptor antibodies or LASERs.
These are next generation multispecific antibodies activating T cells using signal one CD3, enhancing survival by CD8, signal two CD28 to optimize sustained tumor killing. The dual tumor targeting increases the specificity of tumor recognition and mitigates escape resistance that can occur through the loss of a single tumor antigen. These are some data making the point that I was just explaining. These data were published by the ModeX team in Nature earlier this year. The middle graph highlights the upregulation of a CD4 cell survival signal called Bcl-xL. What the graph shows is that we only see upregulation of that survival signal when the cells see both CD3 as, and CD28, as highlighted in red. Likewise, on the right panel, we see the optimal level of T cell proliferation when the T cells are stimulated by both CD3 or CD28.
In summary here, CD3/CD28 co-signaling activates Bcl-xL, a protein that promotes T cell survival, providing the potential for long-lasting activity against cancer cells. Here I'm highlighting the medical need and clinical potential of solid tumor multi-specific antibodies. There are limitations of standard of care treatments. For many solid tumors, existing treatments do not induce complete and sustained remission. For example, long-term survival rate for lung cancer is less than 30% even with immune modulator therapy. Immunotherapy with antibodies has shown promise for some solid tumors, but relapse and development of resistance remains common, often due to the loss and of expression of tumor antigens. ModeX tetraspecific antibodies have activity against the most common and deadly solid tumors, with potential to be active against relapsed disease after chemotherapy and immunotherapy, including CAR- T cell treatment. Here I'm showing you a tetraspecific LASER antibody for solid tumors, MDX2001.
Our lead candidate has been selected and is in the IND-enabling phase. As I just explained, this antibody signal activates through CD3, enhances survival through CD28, optimizing potent and sustained T cell killing. It binds to two tumor antigens that are undisclosed, but that are highly expressed on diverse solid tumors, and it minimizes the potential for resistance through loss of a single antigen. MDX2001 targets tumor antigens that are found on the four most colons, most common solid tumors, which are listed on the table below, breast, prostate, lung, and colon cancers, which in the U.S. are estimated to account for over 900,000 new cases of cancer per year and over 250,000 deaths.
The antigens targeted by this antibody are able to bind to tumor antigens on those four commonly on those four tumor cells. Here again, we're highlighting the four most common solid tumors worldwide with regard to medical value. The global oncology drug market forecast for 2026 is $328 billion, and the total proportion of cancers accounted for by the top four are generally high in the 40%-50% range, indicating a total addressable global market for the top top four solid tumors, as shown there in red on the right. We use several functional criteria for the lead selection of our antibody. I'm gonna show you an example of two types of data, antitumor efficacy in vivo and antitumor efficacy in vitro.
This is a example of our antibody that mediating antitumor efficacy in vivo, where we can see tumor regression in a xenograft breast cancer mouse model by MDX2001 in black and not by the control antibody in red. Importantly, using in vitro cell killing assays, we can show the advantage of the tetraspecific antibody targeting 2 tumor antigens. Here we use cell lines expressing prostate cancer antigens, gastric cancer, or breast cancer antigens. What one can see is that the MDX2001 tetraspecific antibody is able to kill those three cells and others that we have tested. This is the predicted timeline and pathway to the clinic for the MDX2001 antibody program.
We start talks studies in Q3 this year. We are projecting GMP drug product release early in 2024, IND submission in Q2 or the end of Q1 2024, and first dose, first patient in the middle of 2024. Importantly, we have met with key opinion leaders. We are evaluating optimal clinical study designs based on major unmet medical needs and market potential. I'll talk about our tetraspecific antibody for the treatment of leukemia and lymphoma. A little bit about B cell cancer multispecifics and the medical need. B cell leukemias and non-Hodgkin's lymphomas account for greater than 140,000 new cases and 43,000 deaths per year in the U.S. alone. The overall five-year survival rate for B cell malignancies varies widely by disease type.
Unfortunately, relapse is common for more aggressive types and complete remission rates for relapsed disease is often less than 50%. Antibody immunotherapies, including bispecific T cell engagers, can be effective but are often limited by incomplete responses and loss of expression of key tumor antigens. The total global addressable market for leukemias and non-Hodgkin's lymphomas is estimated at over $22 billion. This is our tetraspecific LASER antibody for B cell malignancies, MDX2003. The lead candidate is in IND-enabling phase currently. I won't review the attributes shown in the slide, which are similar to our other antibody for solid tumors with regard to the ability to stimulate T cells and bind two tumor antigens. Here's an example of in vivo data showing antitumor efficacy in a mouse model.
The histogram here, the bar graphs, show tumor regression in a disseminated B cell lymphoma mouse model, again, showing that three different doses of the MDX2003 antibody are able to mediate tumor regression compared to a control. This is an important slide showing the advantage of dual targeting of tumor antigens and the ability of such an antibody to overcome antigen loss that confers tumor resistance. On the left is a schematic of a cancer cell. It expresses two tumor antigens, purple and green, tumor antigen one and two. The green line shows cell killing by the antibody. If a tumor cell only expresses one of those antigens, it's still killed. If it expresses only the second antigen, it is still killed. Of course, it is not killed if it is null and doesn't express either antigen.
This is an advantage of being able to target two tumor antigens with one antibody. This is the projected timeline and pathway to the clinic. We project starting toxicity studies in 2024, GMP drug release at the end of 2024, submitting an IND and aiming for first dose, first patient either at the very end of 2024 or the beginning of 2025. In summary, for this program, for leukemias and lymphomas, ModeX tetraspecific antibodies are potential therapies against B cell leukemias and non-Hodgkin's lymphomas, including relapsed disease after bispecific T cell engager and CAR- T cell treatments. Multispecifics address immune escape from downregulation of single target antigens. For example, the downregulation of CD19 causing resistance after CAR- T cell treatment.
These antibodies offer a potential off-the-shelf alternative to individualized CAR- T cell treatment, and our IND is planned for late 2024. In the next section, I will review our programs for multispecific antibodies for infectious diseases. Here I'm going to present two programs in our antiviral program at an antibody for our HIV and a multispecific antibody for COVID. I'm going to highlight first the medical need and global impact of HIV infection, both worldwide and the United States. Globally, there are an estimated 38 million HIV-infected people, 1.5 million new infections per year, and 650 deaths per year. Global HIV drug sales are estimated to be greater than $28 billion annually.
In the U.S., there are an estimated 1.2 million people who are HIV-infected and who would require lifelong antiretroviral therapy and 37,800 new estimated HIV infections per year. There are some limitations to current HIV therapy, despite the fact that current therapy is highly effective. These include drug toxicity due to lifelong treatment, for example, renal, metabolic, neurologic, and other toxicities. Drug resistance that can impact efficacy of viral suppression, the need for daily drug therapy, the need for lifelong therapy, and the fact that there are no vaccine or antibodies that can provide long-acting protection to prevent infection. Here I'm showing a schematic of the potential of multispecific antibodies for both HIV treatment and prevention. For example, in an HIV-infected individual who does.
Who has suboptimal antiretroviral drug therapy, for example, due to resistant strains, one could add on an HIV multispecific antibody to their therapy. In the middle, a person who is on successful maintenance therapy who may need better long-term therapy options and wants to shift from daily antiretroviral drugs to long-acting options, which include antiretroviral drugs or adding on an HIV multispecific antibody that can also be given at a, in a several-month regimen for long-acting maintenance therapy. Lastly, at the bottom, for those who are uninfected but at high risk for acquiring HIV, they can take advantage of the HIV multispecific antibody to provide long-acting protection. With regard to HIV multispecific drug development, we are guided by detailed structural knowledge of the virus.
I won't explain the left schematic in detail except to say that we understand the vulnerable regions on the virus where antibodies can attack. Our goal then is to develop a potent HIV multispecific antibody that can attack and neutralize diverse strains of HIV worldwide by targeting independent cells sites, more than one site on the virus, be dosed simply and effectively as a single antibody, and be used for both treatment and prevention of HIV infection. Here are some in vitro data by our team that were published some years ago. In this case, using a trispecific antibody on a platform called CODV. The schematic graph on the right shows is that for HIV, the concept of the % of virus strains neutralized is very important because of the diversity of the virus worldwide.
We aim to get a neutralization level that's close to 100% of viruses. One can see the curves for the individual antibodies, and we can see that one can attain close to 100% neutralization with the curve shifted to the left for the tri-specific antibody. When one builds all three antibodies into one, the tri-specific antibody has greater potency and coverage of HIV diversity than any single parental antibody. This antibody is now in a phase I first in human study, by this antibody at the time made by Sanofi, and it is being conducted by investigators at the AIDS Clinical Trials Group, which is an NIH-funded clinical trials organization.
The antibody has been dose escalated in three cohorts up to a dose of 30 milligrams per kilogram, which we think is a therapeutic dose, and has also been given as multiple doses. So far in this phase I study, the antibody is safe and well-tolerated at both single and multiple doses, and additional data are expected in the middle of 2023. I'll also mention that we are working on even a next generation of multispecific antibodies for HIV. We already have in the laboratory antibodies with tenfold improved potency and breadth than the product that's in the clinic. This is a collaboration between ModeX scientists at the Vaccine Research Center, NIH, at Scripps Research, and at the International AIDS Vaccine Initiative, taking advantage of some of the best scientists in the world studying HIV antibodies.
We have several preclinical pre-IND candidates under development, including a second generation COVID trispecific and a third generation multispecific using our new MSTAR format. Lastly, I'll review our COVID multispecific antibody program. I highlight here the ongoing medical need even in a post-pandemic era of COVID. The left graphic shows the weekly number of COVID deaths in the U.S. reported to the CDC. One can see a persistent high level of deaths in excess of 2,000 deaths per week, even ongoing now in March with about 15,000 deaths per week highlighted in the red text, equaling about 78,000 live loss per year to COVID-19, as we speak, greater than 100,000 cases per week and five million cases annually.
The medically vulnerable, including those with immune suppression, pre-existing conditions, cancer or transplantation, remain at risk for severe disease and death from COVID-19. With COVID-19, we have the problem of viral diversity with the global emergence of resistant strains. On the left, we show the strains that people have heard about, Alpha, Beta, Delta, and now Omicron. Important to note that antibodies have proven effective for the treatment of acute COVID with greater than 80% efficacy in preventing progression to severe disease. Antibodies are also highly effective for passive immunization to protect medically vulnerable patients from acquiring COVID. New Omicron variants have rendered prior antibodies ineffective, highlighting the need for new antibodies that are broadly active against all circulating variants.
Annual 2002 sales of COVID antibodies were in excess of $7 billion. No antibody treatments are currently effective against Omicron, highlighting the need for new therapeutics. Here I'm indicating the clinical indications for a multispecific antibody for COVID, which include treatment of acute COVID in high-risk patients, passive immunization with a long-acting antibody to prevent infection, and potentially as a treatment for long COVID, although that would require clinical studies. The MSTAR advantage for addressing SARS-CoV-2 diversity is again our knowledge of the SARS spike protein shown on the left and the regions of the virus that the antibody can attack to neutralize it, which are shown schematically with the colored overlays. Our MSTAR multispecific antibodies are modular, which allows rational selection of antibodies to optimize potency against current and future strains.
The antibodies allow the potential for synergistic neutralization, leading to improved potency and lower therapeutic dose. They provide simultaneous immune pressure to prevent viral escape. A multispecific antibody potently neutralizes all current variants of concern, including the predominant XBB strain currently dominant in the world. I'm going to show you one example of synergistic neutralization by the multispecific antibody. This is a graph showing the % neutralization. We want the curve to be shifted to the left, indicating we can see high neutralization % at low antibody concentration.
What we're showing here in the red curve of two regular antibodies that can neutralize well, but when we build those two into a single tetravalent bispecific antibody, either as the blue line or the green line, we can see a greater than 20-fold more potent neutralization shift than a combination of the two parental antibodies at the same concentration. This indicates synergistic neutralization. This is a graph which I again won't describe in great detail, but I'll explain the key point, which is that multi-specific antibodies can preempt viral escape, and this is something that's not seen with a single antibody. In the purplish graph, purplish line on the graph, which we can see that that line is flat. The tri-specific antibody, but not the single antibodies, prevent viral escape during serial passage.
If one looks at the red or the blue lines, the virus has grown and escaped after selective rounds of replication because new mutations have arisen that allow it to escape from one antibody, but not from three antibodies at the same time in one molecule. Here I'm showing data with a tetravalent trispecific antibody for COVID, MDX2202, which shows potent neutralization of all circulating variants. In the schematic we show the various variants listed, including the XBB strains now prevalent. These very low IC50 numbers show potent neutralization against all these strains at the nanomotor level. We have selected a lead candidate, and developability assessments have successfully concluded that a lead candidate meets manufacturing criteria. I want to just highlight one or two other points.
An important point is what is the circulating half-life of our MSTAR antibodies? Here we use the humanized mouse model. We have also done non-human primate models. We can show in the red or burgundy line an MSTAR tetravalent bispecific antibody, we're showing right underneath that a human HIV antibody that has been in the clinic and has a serum half-life of greater than 70 days. You can see that our MSTAR tetraspecific antibody is somewhat above that in this mouse model, which is often predictive relatively of the circulating half-life in humans. We expect good pharmacokinetics. Finally, I'll mention that the MSTAR platform is amenable to attacking other viral diseases and pandemic diseases. In this case, I'll mention that we have an early discovery program in influenza, targeting both seasonal influenza and pandemic influenza strains.
We again take advantage of our knowledge of the proteins on influenza here showing hemagglutinin neuraminidase. We can devise antibody, multivalent antibodies and multispecific antibodies that build the right combination of antibodies to mediate broad and potent neutralization of influenza for the potential to protect and passively transfer protection in those who need protection against influenza. Finally, let me highlight some of the advantages of the MSTAR or multispecific antibodies over standard antibodies for viral infections. On the left in green are the MSTAR multispecific antibodies, and on the right would be a standard antibody targeting one epitope on the virus.
Multispecific antibodies target different sites on a viral protein, have the potential for synergistic neutralization, can cross cover antigenic variants, have the potential to minimize viral escape, and are likely to remain active despite viral evolution, in contrast to an antibody that targets one site. Similarly to regular antibodies, we can mediate Fc effector functions to optimize cell killing. We can use mutations to extend serum half-life, and we use standard manufacturing technology like our regular antibodies. Next, I'm going to turn over the next sections to our Chief Technology Officer, Vijay Chhajlani. Thank you.
Thank you, John and Ronnie, for presenting on our programs and on the MSTAR technology platform. I'm happy to present on the manufacturability of these MSTAR molecules. Based on the information we have gathered so far on multiple MSTAR molecules for virology and immuno-oncology indications, we can say that MSTAR multispecific antibodies possess developability and manufacturability attributes similar to that of monoclonal IgGs. In a tetraspecific MSTAR molecule, four distinct binders can coexist and maintain their potency. These molecules can be produced just as monoclonals can be, and are stable both biochemically as well as in serum, and display half-life comparable to monoclonal IgGs.
As a visual example of developability data, you see that multispecifics, a tetravalent bispecific and two tetravalent trispecifics shown on this slide, when subjected to thermal and pH stresses and analyzed by capillary electrophoresis, remain stable over a length of time, confirming the developability of these MSTAR molecules. ModeX lead IO candidates, both MDX2001 and MDX2003, demonstrate manufacturability across a range of assessments. When expressed for production, they assemble predominantly in correct format as heterodimers. These molecules also pass the criteria for stresses such as freeze-thaw, exposure to heat, light, and extreme pH conditions. In addition, they demonstrate excellent stability in human serum and do not bind to predominant blood cells such as neutrophils, platelets, and RBCs.
Based on all these developability and manufacturability data, commonly applied to monoclonal IgGs assessments, we can say that both lead IO candidates pass the manufacturability criteria. As an example of data shown here are the binding potency curves for four binders upon incubation in serum. All four specific binders in the IO lead candidate MDX2001 maintain their potency for binding to targets. Two tumor ton antigens on the top as well as CD3 and CD28. This binding potency maintains over a period of 14 days in human serum, confirming the stability of MDX2001 in natural metrics. We are on the cusp of GMP manufacturing for the lead IO candidates. Cell line development is nearing completion, we have clones with productivity with one gram per liter for MDX2001.
More importantly, these clones produce high percentage of correctly assembled heterodimer, eliminating the need for extensive process development. The process for the purification itself resembles that of a monoclonal IgG, and we have already completed a 50-liter bioreactor of manufacturing run successfully. Our GMP manufacturing for MDX2001 is scheduled for July of this year, and we have high confidence of success as MSTAR molecule MDX2001 demonstrate compatibility with platform monoclonal antibody manufacturing process. With this, I would like to hand over to Gary Nabel, our CEO.
Thank you, Vijay, for this great summary of our productive CMC efforts. Thanks also to Ronnie and John for your excellent explanations of our platform and pipeline. To summarize what you've heard today, I'd like to leave you with both an understanding of the expected timeline on the delivery of our products and key takeaways about ModeX as an evolving biotechnology company. As you've heard today, we have an exciting pipeline that addresses substantial unmet needs in cancer and infection, diseases that inflict untold human suffering and impose significant costs to our medical system and economy. Regarding the delivery of the ModeX pipeline, we expect to deliver our two lead oncology products for solid tumors and lymphoma leukemia in 2024. The first probably earlier in 2024 and the latter in the latter part of the year.
We also have plans to deliver additional products in the infection and infectious disease arena, either in late 2024, 2025 for the COVID antibodies, or 2025 for the HIV multispecifics. And we will be working hard together with Merck to advance the EBV nanoparticle as rapidly as possible, and you'll hear more about that as we make progress in that collaboration. Finally, I'd like to give you the key takeaways about our presentation today related to the promise of people, platforms, and pipeline of ModeX. We have a world-class scientific team that's developed at least three novel platforms and multiple products that are advancing to the clinic with a proven track record of manufacturing. Those products have been de-risked in part by previous trials of analogous products.
More importantly, the company has really developed a mastery of the multispecific and the nanoparticle platforms by building on structure-based design, by building on our learnings through the digital world, and in particular through machine learning and artificial intelligence, that is really only beginning. We're able to deliver products either as protein or by gene delivery, mRNA or DNA, and that will considerably accelerate our path to the clinic. We have a strong foundational intellectual property base with 28 patents that have been filed. The important item to remember after this presentation is that our platforms really allow the company to generate its own products and bring them to the clinic and bring them to patients.
At the same time, to also pursue partnerships, by that are independent of our own product pipeline that will, in sum, maximize the value of the ModeX technologies. We've already begun this process of partnering with external organizations. Some are in the public domain like NIH and DARPA, others in the academic world like Duke, then in the biopharma sector as demonstrated by the license and collaboration agreement that was recently completed with Merck. To summarize, our people, platforms, and products have driven a promising ModeX pipeline of innovative medicine for diseases with significant unmet need and substantial commercial potential. I'd like now to turn over the proceedings to my colleague, Elias Zerhouni, who will moderate the question-and-answer session. Elias?
Everybody for a terrific presentation. I know it's very dense. There are lots of information. The sessions will be available on our website, if anybody wants to review. It's clear that we've had a lot of interest as I see the questions that I'm going to moderate now and aside. The first question is from Maury Raycroft at Jefferies. The question is as follows: With MDX2001 and MDX2003, the CD3 and CD28 combo activation can be very potent. What's the threshold for background or low expression, obviously not null, on non-tumor cells for the two separate tumor antigens you will be targeting? How do you think about that? In other words, the target to background ratio, what is your expectation?
What target are you going to go after that do not present a safety risk because it will, you know, have off-target effects, if you will, because of the CD3/CD28 combo? Gary, I think you're the most experienced in that domain, and perhaps you can begin to answer and anyone else who wants to participate.
Yeah. Great, Elias. Thank you for that really thoughtful question. As you can imagine, you know, this is a topic that we've been looking at and considering from the very beginnings of our programs. In fact, I would refer you to our paper in Nature Cancer that was published in 2020 that actually gives some background information on toxicities in non-human primates, actually, related to that combination. The first thing to recognize is that the toxicities of this combination, we would expect to be probably less than what you see with typical T cell engagers, in part because rather than having two copies of CD3 or two arms engaging CD3 or two arms engaging CD28, we have only one arm.
What we're doing is looking at the cross-linking between the two components to engage the T cell. In our development assays, we are able to actually measure and compare the kinds of signals that we're inducing in the with the CD3/CD28 combination compared to previous molecules that have gone into the clinic. We feel that the side effects, the immune side effects can be fine-tuned. We haven't seen any that are ones that are beyond what has been observed previously. Some of those molecules have already been started in the clinic, and at least thus far, we're not seeing any adverse events that are creating concern. At the same time, you know, your question's a really important one.
It's all about achieving, you know, therapeutic index. What we're trying to do and what we have done by fine-tuning the ability of these to work on these targets in various combinations, we're really trying to minimize any type of adverse response and maximize the signaling that we can see from them. The only other point I would make, and maybe Ronnie wants to comment on this, is that with the new MSTAR platform, there's another screening assay that we've incorporated into our product development research. What we now do is anytime we develop a molecule, we look at the ability of that molecule to activate T cells in the presence or the absence of tumors.
What we now can do is to look at, and select molecules that have minimal activity in the absence of tumor and maximal activity in the presence of tumor. Maybe Ronnie or John, please feel free to amplify on that because those are part of the screening that we've done to advance those products.
Thanks, Gary.
No, you go ahead. Yeah.
Maybe two points to add. The CD3 is a relatively low affinity CD3 to mediate the toxicity concerns. The second point, like Gary mentioned, when we screen, one of the standard assay, we iterate the activity differential between that's against tumor cells versus normal tissue cells.
Can I, Gary, maybe a point of detail? The fact that you choose two targets, two separate targets rather than one, also plays in your favor because it is unlikely that normal cells would have these two targets on the same cell. That's chosen in that way, in many ways. Is that a factor also that plays in your favor or in our favor?
Yeah, absolutely, Elias, especially on the tumor targeting side, right? you know, for example, let's pretend that we're looking at a tumor that expresses two antigens, we'll call them A and B, and we can have the antibody to A and B on our therapeutic. On normal tissues, you'll only see A alone or B alone. by having them both together on the therapeutic and on the tumor target, it allows us to get better honing to the tumor specifically. absolutely that plays in our favor there.
We have a lot of questions, so I'm going to go to the next one from Yale Jen at Laidlaw & Company. One is for the EBV vaccine, what adjuvants might be used? Number two, if you have more than four to five molecular targets, would specificity be impacted versus fewer targets? Three, given current treatment of HIV are mainly oral, how can an IV drug best compete? I'll start with the first one with you, Gary. What adjuvants might be used for the EBV vaccine that we licensed to Merck? Do we know, or are we going to explore that?
That will be an important part of the phase I, and I should say non-human primate preclinical development plan. As you might imagine, we will start and look at some adjuvants that have been well known and well used in medical practice. Adjuvants like alum, for example. MF59 is another one that's had relatively wide usage in clinical trials. We will also be looking at proprietary adjuvants that are available to Merck. We will be doing comparisons and asking questions about the potency and longevity of the immune response, and then we will down select among those different candidates, and pick one, possibly two in the early stages to move forward.
Question two, a reminder, and this is probably a question for you, John. If more than four or five molecular targets, if there are more than that, wouldn't the specificity be impacted versus fewer targets?
Elias, if I understand the question correctly, we're talking about targets, whether they could be viral targets or cancer targets.
It's not specified, I guess. Yale did not say one way or the other. Essentially, he's trying to talk about constructive or destructive interference. As you have more targets, do you have a risk of destructive interference and multiple, you know, collisions, and maybe Ronnie also can comment on that. That's my understanding of the question.
Yeah. I think Gary got at this particular question in part when he gave his answer with regard to the ability to have more selective binding when one targets two antigens of interest that are present on a cell, and therefore maximizes the potential for that antibody to bind the cells of interest rather than off-target interactions. I think that's the, you know, the intent there.
Ronnie, any comment on the issue of design at four, five , six and interference or non-interference relative to specificity versus fewer targets?
Yeah. That's an excellent question because the interference oftentimes is caused both potentially by the geometry of the molecule as well as the epitope on antigen. This is how we actually build up this high throughput screening platform, as well as taking advantage of machine learning knowledge to quickly screen out the potential binders that could interfere with each other.
The third question, John, probably you can answer that. Given current treatment of HIV, are mainly oral drugs, how can an IV drug best compete? What is its place?
Yes. I'm glad this question came up. There's quite a bit of experience in administering antibodies either intramuscularly or subcutaneously, and we would certainly aim to go in that direction. I think even recent experience with licensed antibodies that are self-administered. The advantages here are that one can administer an antibody with a long serum circulating time, long half-life, that potentially could have a therapeutic activity over several months. There is a strong interest in HIV therapeutics of moving towards something that might offer a better quality of life. Certainly, the daily pills work, there's no doubt about that, but there could be an option to do just as well with something that could be self-administered on a several-month basis. I think there is a strong potential for such therapeutics.
What is your estimate of the proportion of patients that would benefit from the three field of applications of antibodies to HIV?
Therapeutically, I think potentially anybody who is benefiting from antiretroviral drug therapy could benefit from an improved regimen. It's essentially all individuals, at least potentially. For those people who might be failing a drug regimen, which is less common now but still occurs, it gives an option there for treatment. The patient population who are at risk is very large, and really there it's more about the opportunity for access. You know.
Depending where in developing world, in less developed regions, many tens of thousands of individuals remain at risk.
Right. Thank you, John. Another question came from Michael Zuk, a shareholder. Have any patents been granted to date out of the 28 patents we mentioned? Maybe Ronnie and Gary, you can pair on this one, because I know some have been because there are earlier and some have been filed and some are provisional. Maybe you can give an indication of that, although it is a evolving situation given the fact that we've applied not only in the U.S. but internationally. Any comments? Ronnie, Gary.
There are two parts. The ModeX proprietary IPs, they have been filed in the past two years. We have non-provisional IPs filed in both in the U.S. and in foreign countries. Their current status is pending, but we also in-license exclusive license from Sanofi that are granted.
That's right. Gary, any addition to that question?
No. I think Ronnie answered it well, and I think that at least two of those have been issued. Yes, it's early days for the ModeX ones, but we're working hard on those and stay tuned.
Thank you. A question from Yi Chen from Wainwright. Does the company plan to produce the initial proof of concept pre-clinical data and then find a strategic partner for each of these programs? I think that goes to you, Gary.
Yeah. Well, again, another great question. We really don't have anything that's fixed in stone. I think we're very flexible, and that we're there are some that would be natural for us to bring at least to a human proof of concept and then partner them. And there are others that we would be perfectly open to partnering at an earlier stage. I think it's not a one-size-fits-all. We're very adaptable, depending on the development costs, depending on the complexity and the cost to get to a human proof of concept. I would say in all cases, our strategy would be to get to a human proof of concept study, whether it be with a partner or on our own, as quickly and efficiently and as cost-effectively as possible.
Now, a question directly from a shareholder about maybe a shorter term outlook. How will you go about creating shareholder value in Q2? That's quite a direct question. The timeframe is a little. Maybe I'll give it a try since I oversee the entire, you know, units. Then maybe Dr. Frost, you can complete. I think that's a very good question. We've been working very hard actually over this year to transition to a posture where we can create value. First example is in Q2, we will receive the $50 million from Merck, which are a license, which would basically fund our ModeX for quite a bit of time.
In addition to that, maybe something that Gary did not mention, is that any work we do, which we will, it will be reimbursed fully by Merck. This is, I think, a contribution to shareholder value. The second is we've worked diligently to provide information and data reanalysis for somatrogon, which is ongoing FDA review, and we're hoping that something will come in the second quarter, maybe. Can't promise, but because it's in the hands of the FDA, we did work to create value that way. The third one is BioReference Laboratories. I'm spending quite a bit of my time to really transition BRL from a COVID to a post-COVID world and bring it into balance financially within Q2, maybe Q3, but bringing us closer to that goal.
Those are the three things I see. In addition, we're working for our other products, Rayaldee and scyllo-inositol and others, to look at different options to create value, if you will, in those programs, or greater value because they're already there. Those are the ways I see creating shareholder value from the R&D and development point of view. I'll turn it over to Dr. Phillip Frost for a more general, perhaps vision and view on how to create shareholder value. We can't hear you, Phillip Frost. Phillip Frost, you're on mute. You're on mute. Sorry. We can't hear you.
Oh, yes. I think you handled the question rather well and completely, but I will add that there are small parts and small assets that have been in OPKO for some time now that we have kept on the back burner. Now that we have more talent in the company and the ability to address some of these, there are projects that have potentially great value, and I hope you'll be hearing about them in the near future. Stay tuned. Otherwise, I think Elias covered the major projects that are gonna contribute to the value of each of the assets and the value of the company as a whole.
Thank you, Phil. Another question from Neil Pennies, a stockholder. Are there competing technologies in development? What competing technologies are in development that compete with us? I don't know who would want to take that question. Ronnie, you might know technologies in the tri-specific, quadri-specific world, or John in the ferritin-based platforms. Could you comment maybe?
Ronnie, why don't you start?
What competing technologies do we know about, Ronnie, that may be competing with us at this time?
Yeah. Because this is really a area with active a lot of active research activities. Different companies are developing different type of technologies to also going into multi-targeting approaches. One of our advantage or what we want to highlight is our approach, even though they are multi-specific, but they are really as regular IgG or regular monoclonal antibody, like, as possible so that we can ensure higher safety profiles and less.
Hello?
Elias, I don't know what happened with Ronnie part to her answer there, and Gary may wanna comment, which is that if t he area of bispecific antibodies has been very active, and there are many under development. You see this kind of pyramid effect where one gets to trispecific, there are very many fewer. When one gets to tetraspecific, we really are in a territory where there is much less competition. I think we really are on the cutting edge of multi-specificity with our platform.
I would definitely add that there is a huge amount of interest in going that way. It's been hampered by manufacturing issues, mispairing issues, quality issues, but it's progressing to the point where, as an example, there was a company that was going into the multi-specific field, TeneoBio, which has been acquired by Amgen, giving you the validation that even the large companies are really exploring this as the next wave of revolutionary therapeutics. I think you can see that also at Xencor, for example, if you want to look at a comparable. I think there is an interest in competing technologies. However, there's no one out there that I know of that has a tri-specific in the clinic and a quadrispecific in the preclinical IND pre-IND stage. That's what we think about our competing field.
The technologies, I think, maybe I'll ask Vijay to address the question that I think relates to that in terms of how competitive are we in this technology. A question from Maury Raycroft, again from Jefferies. Can you talk more about how you minimize light chain mispairing and binding site interference? I think Dr. Wei mentioned capabilities and focus on making the linkers and multi-specifics less immunogenic. Can you talk about the technology here too? Vijay, maybe you can talk about the manufacturing, the mispairing. Maybe I'll have Ronnie talk about the binding site interference because it's a structural designer issue. Vijay, how do you find the quality of the product, I mean, in terms of mispairing of light chains?
First let me say, as Ronnie was describing, she just to remind everyone that the way our molecules, the multispecifics are designed, that we don't have a separate light chain hanging out there which can mispair from one site to the other site. Our molecules are designed in such a way that they are. If there are trispecific, there are two chain molecules, and they're designed in such a way that the heavy and the light components fall within the chain. We don't have that problem of light chain mispairing.
Now let's talk, if I may, Vijay, this is actually the secret sauce, if you will. We don't have any pairs to mispair in the design that was designed by ModeX over the past 18 months, and with Ronnie's help and Gary and Dr. Yang. I think the question is, we minimize it by not having a pair that can mispair. Please, I'm sorry to have interrupted you.
That is one point, if there is a half antibody and things like that can be very effectively removed during the downstream purification of the molecule. As I was saying before as well when I was presenting that the cell clones, when we select the clones, we also select the clones which kind of produce most of it as an heterodimer or as a correctly folded antibody. We put in the methods in place. First of all, the molecules are designed in such a way that we avoid those mispairings, or we don't have those mispairings. Second, we select the clones which produce a correct molecule or correctly folded molecule. Third, our downstream purification is such that those half antibodies can be very easily removed.
That's why I would say that our downstream purification for our MDX2001 looks like a classical monoclonal antibody. You know, protein capture and followed by a couple of ion exchange or mixed mode residence column to do the purification.
Thank you.
Ronnie can add more to it in terms of the binding hindrance and so on.
Right. Ronnie, the question, I know you were not connected when that happened, but let me read it to you. Can you talk more about how you minimize light chain pairing, which Vijay just addressed. Also binding site interference, and there was a mention of what you said, Ronnie, the capability and focus on making the linkers and the multispecifics less immunogenic. Tell us how you do control binding interference and immunogenicity, if you may.
The binding interference part is really to construct the configuration of the different FVs, the binding domains to be spatially relatively opposite from each other, so they are not, for example, on top of each other or facing the same direction. Obviously we are not disclosing the exact details yet, but hopefully we can tell you more in future scientific conferences and publications. In terms of immunogenicity, we understand some of the risk from immunogenicity is MHC binding. Though there are structure and sequence features that can promote MHC recognition and binding, which will lead to potential immunogenicity. When we design the linker, we are very careful about not introducing that type of structure and sequence features.
Yeah. Elias, I might add one thing as well to the part about recognition to really expand on the point that Ronnie just made. I would refer any interested person to our science paper from 2017, because we have in that paper the structure of the trispecific antibody. You can actually see in that structure what Ronnie just was talking about, that the two variable regions are actually almost cocked at angles, you know, almost at right angles to one another. They're not put in a way that they can interfere. It's in the way in which you assemble those V regions so that they avoid that clash with their target antigen, and that's really one of the important ways that we can maximize multi-contact binding.
Can you? Next question from Ed Tenthoff from Piper Sandler. Can you provide examples where multi-valency can be used to increase avidity against specific targets? John, I think you provided some. Maybe you can just highlight that they were illustrated and, perhaps on the cancer side, you can do that as well.
I can start and if Gary wants Gary may wanna also comment. You know, for our antiviral multispecific antibodies, we've actually shown that a specific point. We can show that the increased avidity from the multi-valency leads to the synergistic neutralization. We showed that, for example, in the setting of the spike protein for COVID-19, and that's actually in a preprint that's publicly available that I cited on the website. We carefully choose the configuration of our molecules through our preclinical screening process. Not every single binding arm that we put on there in every configuration gives us the optimal avidity, but one of the beauty of the process and the platform is its modularity. We can look at hundreds of options and screen through those that give us that avidity and synergy.
Thank you. Another question from Yale Jen, again, from Laidlaw. Other than T cells, would you consider targeting other immune cells such as NK cells or others? Gary?
Sure. I can answer that. Of Elias, yes, of course, that's the whole point of the technology. This is a modular, you know, plug-and-play technology. If we want, we can swap out the CD3/CD28 for an NK cell binder or an NK cell activator. It doesn't have to stop there. We can look at, you know, macrophage activators. Yes, those are on the table. We don't currently have candidates in our pipeline with those features, but we certainly are investigating the possibility of including them in the future.
I mean, from Maury Raycroft at Jefferies. Can you talk more about partnership strategy, and what are the key criteria that drive your decision to partner or keep in-house? I'll have you, Gary, answer that, and maybe I'll supplement as well, as well as Dr. Frost. Why don't you start?
You know, Elias, my general approach to collaboration, whether it be with partners on a product or even a scientific collaboration, is always you wanna pick partners where you both have something to gain by working together and where you couldn't do it by yourself alone. I think that with a product development pipeline, that very much applies. I think the best example is really the one we did with Merck. I think with the example where there are capabilities and experience that Merck has on the downstream development side, that simply just are not available at ModeX. At the same time, there was scientific expertise and knowledge, and even early manufacturing expertise at ModeX that Merck didn't have. There were resources that Merck could bring to the table that ModeX didn't have.
Most important to me at the end of the day is that there be alignment on the vision of what you wanna do and how you wanna get there. I think there's nothing that is more important than that. Structuring, you know, the details of the collaboration agreement so that you incentivize both parties to create that alignment and that, you know, mutual benefit and sharing, I think that's really key to any collaboration agreement. That's, that's where I would leave it.
Yeah. Definitely this is a great question, we've thought a lot about it. Really the decision is multifactorial. The scope of the development costs, the time of the development costs. If you wanna to think about timing is important. Do you partner prior to IND, at IND, at phase I? You need to think about the inflection points that are likely to be achieved by the molecule that you're developing. As we've done, you know, many developments and been in charge of 31 developments, there are points where you have to consider partnering or going alone. Now, you can imagine that when we talk about a vaccine that requires several thousand patients before the end of phase II, this is something that you obviously would not be able to do alone.
When you consider a cancer asset, we know that we can get to a proof of concept to a basket trial relatively quickly with reasonable funding. We would tend to, you know, rank our portfolio as to its partnership needs or ability. In addition to what Gary is saying, sometimes you have to be opportunistic. You know, there's a partner that comes and that has exactly the culture that we want, and that has the resources to carry this program much faster than we would be able to. It's a multifactorial, but what drives it is opportunity costs of not doing the partnership, and the second is the ability to create inflection points of value within the timeframe that's affordable and doable within OPKO by ModeX. I hope this is clear.
Can I just maybe, I mean, I don't know, Dr. Frost, do you wanna add about? You have a lot of experience in partnering and keeping assets. I mean, what is your thought here?
I think you and Gary, again, covered the waterfront pretty well. I would add that it also depends on the type of product and the target. For example, if we're dealing with a rare disease, which will be prescribed by a relatively small number of physicians, even a small company might consider taking it all the way, and particularly with a rare disease, since it's more likely to get a shorter development and approval time, versus a drug to treat, say, hypertension or even one of the more common cancers. A lot depends on the product. Traditionally, of course, it's always been a small company licensing it to a bigger company, primarily for economic reasons. All the other reasons that you cited are valid too.
Speed of development to market. Of course, having a great fit. In our case, I'm really happy that our team there that you've seen today have the capability to add technical know-how above and beyond the discovery as a product is developed. I think that will lead to bigger and better partnerships.
Well, we have exhausted questions that I have here on the screen. There were a couple others that showed up and then disappeared, which related to other issues that don't have to do with ModeX Therapeutics and its role within OPKO. Let me say as a moderator, it's been a pleasure to really emcee these great questions from the attendance, the attendees. Finally, I just want to thank you all. I mean, this was an outstanding R&D presentation. Very thorough, very thoughtful, very detailed. I think that anyone versed in the art of biotech would really appreciate what you've done. As a, you know, as a colleague, as a President of OPKO, as co-founder with Gary, as, you know, working with Dr. Frost, it's been a privilege to emcee this Q&A session. I want to essentially turn it over to Gary and Dr. Frost for closing comments.
Gary?
Sure. Well, Elias, I think you said it well, and I think we've had a long exposure to a fairly complicated topic. I'll really just end by thanking everybody. I think what we're really most excited about here at ModeX is really advancing, you know, new technology, innovative therapies that can really make a difference to patients. That's what it's all about. We think the EBV vaccine as one example, is one that could change the way that medicine is practiced in the future. We'd like our cancer drugs to do the same thing. We appreciate the support from OPKO. We appreciate the support from our investors. We appreciate the hard work of our team at ModeX, and we hope to have more sessions like this in the future to share our progress.
I'll just thank you and hand it over to you, Phil, for the last.
Well, again, I wanna thank everybody. I particularly enjoyed listening to the presentations and the answers to the questions. I think this would represent sort of a coming out party for not only ModeX, but for what I consider to be the new OPKO, with a strong emphasis on technology and new products that will be considered breakthrough and significant around the world. Again, thank you, and we look forward to this being the first of many others to follow as the developments come along. Bye-bye now.
Thank you, Dr. Frost. This ends our R&D Day. If you have any other questions, you can send them to the website. If you wanna review some of the presentation, it will be available on the website. Good evening, everybody. Take care.