W elcome to the Imunon 2023 Virtual R&D Day. Today, all participants will be in a listen-only mode. After today's presentation, there will be an opportunity to answer some of your questions. You may submit online questions at any time today by typing in the Ask a Question field at the bottom of the webcast window and then clicking on the Submit button. Please note that today's event is being recorded. I would now like to turn the conference over to your hosts. Please go ahead.
Good afternoon. I'm Corinne Le Goff. I'm President and CEO of Imunon, a clinical-stage biotech company that is focused on harnessing the power of the immune system, as you can see on my slide. I'm here today from Imunon with Dr. Khursheed Anwer, who is our Chief Scientific Officer. Please take a few seconds to look at our safe harbor statement. So I'm very pleased to welcome you to our first R&D Day.
I will start this meeting with a short introduction of our company, our technology, our strategy, and our pipeline, but then we are going to talk about exciting science. Imunon is developing a proprietary non-viral DNA technology platform in immuno-oncology and in infectious diseases. We are going to focus our conversation today on the future of prophylactic vaccines and on the remaining unmet needs in immuno-oncology.
So I'm thrilled to welcome as our speakers today, two eminent physicians and scientists and leaders in their fields. Dr. Sallie Permar is the Nancy C. Paduano Professor and Chair of Pediatrics at Weill Cornell Medicine, and is pediatrician in chief at NewYork-Presbyterian/Weill Cornell Medical Center and NewYork-Presbyterian Komansky Children's Hospital. Dr. Permar has done a lot of work and with her team in the prevention and treatment of neonatal viral infections.
And Dr. Patrick Ott is also with us today, and will talk about the remaining unmet needs in immuno-oncology. He's the Clinical Director of the Melanoma Disease Center and the Director of Clinical Sciences of the Center for Immuno-Oncology at the Dana-Farber Cancer Institute. He's also an Attending Physician in the Department of Medicine at Brigham and Women's Hospital and is an Associate Professor at Harvard Medical School. And Dr. Ott and his team have worked and published on the development of cancer vaccines since really the beginning of this vaccinal approach 10 years ago.
So we believe at Imunon that our technology is transformative and certainly will be a key driver of the future of global medicines. Now, you should look at our non-viral DNA technology as a toolkit, right? That has the potential to be developed across many therapeutic areas and many modalities. Now, we have chosen to develop our technology across four modalities.
We have a modality called TheraPlas, which is for the expression of cytokines, with 1 clinical program right now in phase II. PlaCCine is our modality in, for the next generation of prophylactic vaccines. And then we are now developing 2 new modalities, one called FixPlas, which is for the development of off-the-shelf, cancer vaccines, so tumor-associated antigen vaccines. And the next step will be the development of IndiPlas, so going towards the development of personalized cancer vaccines with a neo-epitope, cancer vaccines.
Our strategy is built to, become a fully integrated biotech company. We are a very focused organization, so our focus immuno-oncology with the cytokines coding and, and cancer vaccines, is an opportunity for us to, develop assets. We have the capabilities to do so.
Our focus on infectious diseases, you know, we—it's, it is about coding for pathogen antigens and develop vaccines, not dissimilar to what mRNA has done with, with COVID-19. This modality is for us an opportunity for partnerships and, and out-licensing opportunities. Now, an essential element of our strategy is the vertical integration of our, of the core elements of our business, like production of our plasmids or production of our facilitating agents. And we've just, in fact, unveiled our cGMP manufacturing in Huntsville, Alabama.
So we are now. We have the capability for in-house early development for our vaccine programs. We also focus on establishing value accretive collaborations, and this is really the bedrock of our business model. You might have seen, if you have followed us, that over the last year or so, we've placed a number of partnerships to expand our R&D capabilities.
Finally, I want to mention here that we are always on the lookout for potential asset acquisitions in areas that are adjacent to what we know and what we do, to our domain of expertise. That's a way for us, of course, to balance the risk profile of our portfolio. Now, I will show you a slide that that's going to be my last slide as part of this introduction to show you that we have a strong balance sheet that supports the strategy into 2025, you know, until the end of 2024.
So we believe that our technology has advantages. I'm gonna start with our focus on prophylactic vaccines, as we want to develop and be positioned in for the next generation of vaccines. And we believe that our technology can address a number of shortcomings of the current technologies that are commercially available. One is durability of protection. It is absolutely essential to ensure, you know, that you don't have to get a booster shot every six months. And here, maybe the DNA has an opportunity.
What we see with DNA is durable antigen expression that potentially can induce robust immunological response, and we have a preclinical data to show that. Another important criteria for the next generation of vaccines is speed, and we've definitely learned this with the pandemic.
Like, similar to mRNA, you know, DNA is a platform, and we have the ability to go from the sequence of the antigen to the clinic, to an approved product, potentially, in record time. So that's extremely important. And finally, I want to mention the flexibility of the manufacturing here. You know, and DNA, again, is very interesting because it is stable. It is stable and has a long shelf life at workable temperature.
So obviously, it simplifies all the handling and distribution of vaccines. And the flexibility of manufacturing means also greater capital efficiency for us. Now, when it comes to cancer vaccines, you know, you, you can apply the advantages I talked about to cancer vaccines. The durability of expression, of the antigen expression, potentially calls for potent, T cell response, and the fact that our technology doesn't require a virus, it's a non-viral DNA technology, means that you have the potential for repeat administration, which is obviously important in the treatment of cancer patients.
Now, DNA, again, is a code, so with FixPlas, we code for shared antigens, and with IndiPlas, code for individualized antigens or individualized and personalized, neoepitopes. Here is the state of our pipeline today. As I mentioned earlier, we have a clinical program in ovarian cancer. It's for the expression of an IL-12. It's an intraperitoneal. This is a phase II program that will read out next year in third quarter.
We also just started a new phase 1/2 program with the same asset, IMNN-001, and this time in combination with bevacizumab in the same population of patients. This is a partnership with the Break Through Cancer Foundation. Now, for our PlaCCine modality, we are getting ready to file an IND early next year for a COVID-19 seasonal vaccine. And we just announced a partnership with the NIH and NIAID, National Institute of Allergy and Infectious Diseases, for the development of a Lassa virus vaccine.
And for FixPlas modality, we are developing TRP2/NY-ESO-1 tumor-associated antigen in melanoma. It's IMNN-201, so of course, we are at the preclinical stage right now. Based on the proof of concepts here that we are going to establish before the end of the year, we'll go forward and work on developing our next modality that will be Indi Plas.
Now, as I said, you know, we have enough cash on the balance sheet to support our strategy and to lead to key milestones over the next 12 months. What you can expect is for IMNN-001, so the IL-12 in ovarian cancer, you can expect interim data in the next few weeks, and the final top-line results in the third quarter next year. And we will also certainly be in a position to produce interim results for the combination trial with bevacizumab.
For the vaccine programs, as I mentioned, we'll file our IND early next year and start a phase 1/2 program. And then this year, for IMNN-102, so the Lassa virus, you know, we are starting in pre-IND phase, with working together with the NIH. And for IMNN-201, so the TRP2/NY-ESO-1 asset, we should be able to generate our proof of concept data this year.
So, you know, stay tuned for more information on very important milestone and value-creating activities. With this short introduction, I had promised it would be short, but I really want to make sure that we have the time to talk about the science. I'm very pleased to turn the call to Dr. Sallie Permar. Sally?
Thank you, Dr. Le Goff, for having me. And yes, we definitely need to prepare for what are certainly gonna be new pandemics, and this platform is an exciting one. So, I'll start. The first slide can move on. And I just have some disclosures that I do consult for a number of companies, mainly focused on the development of a cytomegalovirus vaccine.
So next slide. So, we all lived through the SARS-CoV-2 pandemic, and really it started a new era for vaccine development in that relying on nucleic acid-based vaccines, where the cells produce the antigens for us had a major advantage over either viral-based or recombinant subunit vaccines. Next slide.
However, that is very much in contrast to a disease that I have spent a lot of my career working on, which has been in need of a vaccine for since as long as we know that congenital CMV has been going on, which is millions of years at this point. It's a very common congenital infection, with 1 out of every 200 live babies born with this infection. It, there are 40,000 cases in the US annually, but it is throughout the entire globe, and it costs $4 billion of US healthcare dollars. It is the leading infectious cause of neurologic deficits, including a quarter of all infant hearing loss.
For all these reasons, it's been a top-tier priority vaccine from the National Academy of Medicine for over 20 years. On the next slide, you can see all of the different vaccine platforms that have been applied to this virus. So far, only partial effectiveness has been achieved by either a subunit vaccine or an impaired virus vector.
This is an example of an endemic pathogen that we have needed a vaccine for many years, but now we have new, exciting opportunities with DNA and RNA technologies to it be applied to it, that can be rapidly, iteratively, and iteratively, modified in order to really achieve the efficacy that's needed. Next slide.
We know that the rate of pandemics is increasing, that there's no doubt about that, because of globalization and global travel, et cetera. I was just seeing today there's a Nipah outbreak in India being reported. So, these are gonna be upon us, and the NIH and WHO have both made a list of their viral pathogens in particular, that are gonna be likely to create pandemics, and therefore, we should be developing vaccines not after they hit, but ahead of when they do.
And on the next slide, though, really that's alongside the need to develop a number of vaccines for pathogens that we already live with, that have been pandemics for hundreds and thousands of years and we need novel technologies to address these as well. So on the next slide, you'll see that we also have a change of demographics going on in our population, where those individuals who are more vulnerable to infections is increasing in not only US population, but other developed nations, where the number of elderly patients has increased dramatically over the last 50 years.
And then also, the number of patients that are on immunomodulatory therapies is also increasing, and this again is a vulnerable population for any new infection, but prior ones as well. Another vulnerable patient population on the next slide is pregnant women and children. This is an area where I focus. Pregnant women and lactating women are often left out of vaccines in the early phase developments of vaccines, and this really limits the innovation when so many of the newer viruses or even viruses we have lived with can be more severe or cause issues in the fetus.
Developing vaccines for children is very specific as well, as we saw in the SARS-CoV-2 pandemic, needed specific dose ranging. But it was a health disparity that children didn't have access to the SARS-CoV-2 vaccine for many months and year, even after the rest of us did.
So, on the next slide, what I think of as the ideal immunity for novel vaccine platforms should be seeking is to be able to vaccinate in early life, when pediatricians are very good at getting their patients into their care and, and vaccinated, especially with multi-dose vaccines. And then that elicits immunity that is gonna be protective for the whole lifelong.
The best example of this is the hepatitis B vaccine, which is given on the birth visit in the hospital with the first dose. There are two subsequent doses that come within the first year and a half of life. And this is a neonatal transmitted infection, as well as one that can be acquired later in life.
So there is even a combination of a passive antibody approach that is a type of vaccine, and then active vaccination as well. So this is a lifelong protection that's provided by an early-stage vaccine. But on the next slide, I kind of laid out two advancing areas that I see in the field of vaccinology because of these nucleic acid-based platforms that are really transformative. And I think Imunon has an opportunity to put their platform into the mix of what an mRNA-LNP vaccine was able to do. So two areas that I see developing in vaccinology is the increased use of reverse vaccinology.
Reverse vaccinology is when you isolate a specific type of antibody or a or immune response to a pathogen from a previously infected patient. You pre-screen that patient to see that they developed the right type of response that would be potentially protective. Then you design antigens that can bind to those antibodies, that then becomes the immunogen of the future. Those types of strategies were used for the RSV F and for SARS-CoV-2 antigen vaccines.
The other area that's increasing, and we saw this with SARS-CoV-2 as well, is passive immunization. Passive immunization is providing individuals with a preformed antibody, and this we're seeing with the new infant RSV vaccine becoming into the clinic.
And, and here we have a much greater ability to design monoclonal antibodies that are both potent as well as long-lasting. And even better than having to IV infuse them, which was the bottleneck for using monoclonal antibody technology in the SARS-CoV-2 pandemic, if they can be vectored by RNA or DNA technology, then you don't have to rely on IV infusion capabilities. Next slide. The way that now we see vaccine science developing is that often an antigen is identified from a prior virus that's known to have high pandemic potential.
As well as, there are a lot of individuals who spend time trying to find those few infected patients when it wasn't quite a pandemic virus yet, but one that was shown to have local spread and could be concerning for a future pandemic.
To then isolate those antibodies and do the antigen design, that then goes into structural biology development, which is much easier to do in the setting of having a nucleic acid-based vaccine platform that can be rapidly mutated and changed based on the structure design, and then development of assays and animal models where the new antigens can go into to see if you're eliciting that type of best response that does bind to those important antigens, and then also whether it's protective in challenge trials prior to going into human studies.
So next slide is the one next level of this reverse engineering that I've also seen, that's being applied and having some success in terms of challenging vaccines. Challenging vaccines such as those of HIV, malaria, TB, those where natural immunity is not protective. I think one thing vaccinologists think about is that SARS-CoV-2 was actually fairly easy to elicit neutralizing antibody response against. That's not the case for some of these other pandemic pathogens that have been without a vaccine for many years.
Is that the reverse vaccinology strategy, which is not only do you look for the protective antibodies in patients, but you also look at how those antibodies were developed over time, what mutations went into developing a B cell that then became a potent antibody, and designing vaccines that engage with the early precursors of those B cells in order to drive that type of lineage. This is an approach that's being taken in HIV and now being applied in other pathogens. This also requires iterative vaccine approaches, of which the nucleic acid-based vaccines are going to be most suited for.
So next slide. This is an example of identifying a... here's the lineage of a monoclonal antibody that's potently neutralizing against cytomegalovirus. We identified key mutations that needed to happen in the early phase B cell, mutation there at the beginning of that phylogenetic tree, and then structurally developed where that antibody bound to the antigen, that here we were neutralizing the glycoprotein B fusion of cytomegalovirus, and identified that the vaccine antigen here would have to engage the early stage B cell receptor that had a specific mutation.
So this then is the type of iterative design that again can be most well produced by a nucleic acid-based vaccine technology. Next slide. The other exciting science that I see developing is this protective transfer or providing designer antibodies for delivery to especially specific sites of virus acquisition. In the maternal-fetal interface that I'm often thinking about, we're thinking about antibodies that go beyond just IgG, which has been the typical therapeutic up to now.
When we think about all of the places that antibodies traffic to between the maternal-fetal interface, an IgM-based antibody would stay in circulation. It does not cross the placenta. It has very little transfer into mucosal surfaces.
So that would be one in which you might want to protect the mother against a virus acquisition, such as for Zika infection. Whereas an IgG may be designed because you want to get the antibody over across the placenta to the fetus to be there when the baby is born. That's the example of the RSV F vaccine is utilizing that IgG transfer pathway.
And then another antibody that has come into play is dimeric IgA, which is designed to cross onto mucosal surfaces, and we can think about during breastfeeding, this is a way that antibodies can be transferred directly to the infant gut, to then protect against the diarrheal diseases that are frequently killers in the first few years of life.
Antibodies have the advantage of being very safe and are utilized in pregnancy already. On the next slide, you can see another infection that I have thought about that a lot and worked to develop vaccines for, which is Zika. This is one that we are not prepared for what is gonna be a new outbreak of Zika when the immunity from the last outbreak wanes. It's one in which we need to prevent the new acquisition of the virus in the mom in order to prevent the congenital transmission. There is no licensed vaccine, and certainly no vaccine has been tried in pregnant subjects.
So, on the next slide, looks at some exciting, novel antibody that we isolated from a pregnant patient that had prolonged virus replication in their blood, that did not pass the virus on to the baby. And we wondered, maybe, these types of patients could give us clues about what is a protective immune response against Zika. This was a potent IgM antibody that was isolated, that was more potent than any of the IgG antibodies from this woman. You can see the electron micrograph with the, five or six arms that an IgM has.
And then we later found through structural biology that all five of those arms of the antibody could bind to the virion at the same time, and therefore, why it was so potent, and has the advantage of not having any cross-reactivity to dengue viruses, which can lead to antibody enhancement.
On the next slide, shows how antibody like this may be able to be utilized. It could be provided pre-exposure when maybe a pregnant person is traveling abroad or to an area of transmission, or potentially as a post-exposure prophylaxis to reduce viremia soon after infection. A nd this would be much easier to use, not as an infusion of a antibody, but as a vectored vaccine. Next slide, shows another example of a dimeric IgA approach.
The trafficking pattern of dimeric IgA is that it binds to a poly Ig receptor, which is on the basolateral surface of mucosal epithelial cells, passes through that cell layer, and comes out on the other side as a secretory IgA that then is protected from degradation on mucosal surfaces.
On the next slide is some data where our team developed a dimeric IgA designer antibody that utilized a potently neutralizing rotavirus antibody for the design. The dimeric IgA, they're shown in the electron micrographs. On the next slide, we were able to show some protection of that dimeric IgA provided to postpartum mice who had just given birth.
Gave them this antibody here in protein form, which then trafficked into the breast milk and was able to protect against diarrheal disease in the pups and had a reduced intestinal virus load. And this, again, is an example how potentially after delivery, a mom could be immunized with a DNA that could express long-term an antibody that is specific to be trafficking into breast milk, that then could provide this protective antibody directly to the infant gut.
So the last slide here, just summing up again where I see some novel approaches in vaccinology that I think a DNA-based vaccine would have a lot of advantages for. Again, the reverse vaccinology of identifying what are potent responses and then recreating those through utilizing structure-based design that our antigens can bind to those protective antibodies and that they can be elicited through a vaccine technology is gonna be best done with rapidly developed and iteratively tested vaccines.
And the protective transfer, I think, is another great opportunity for a platform like this that can be durable, can deliver a full protein that could reach into the systemic circulation, that then allows for that protection to be delivered, either stay in the circulation or to mucosal surfaces or even across the placenta. So thank you very much, and I'm happy to take questions.
Thank you very much, Dr. Permar. It's a fascinating presentation. Maybe we'll take the question at the end of our presentation. But I'm gonna ask Khursheed to share where we are with IMNN-001 and our development plan.
Sure. Thank you. Good afternoon. My name is Khursheed Anwer, and I'm Chief Science Officer at Imunon. What a great presentation by Dr. Permar. Clearly, she underscores the need for new types of approaches for vaccine, especially there are pathogens where there's no vaccine, despite conventional vaccines have been used for other pathogens.
T here's also increase in rising pandemics, as she alluded to, and clearly speed is very important. I know she mentioned new types of approaches are needed, such as nucleic acid vaccines. So, to continue with that theme, I would like to share our approach to developing novel vaccines. Especially, here, I'll talk about IMNN-101. That's the lead product of our PlaCCine platform. Dr. Le Goff mentioned about PlaCCine platform in her presentation.
So IMNN-101 is a next-generation COVID-19 vaccine that addresses the limitations of current vaccines. The key distinguishing attributes of 101 and this class of platform or technology is that the antigen expression is durable compared to, say, mRNA or protein vaccines.
The vaccines are stable at working temperature, and there's a plug-and-play design for rapid response, as Dr. Permar pointed out, that has been lacking. So, these distinguishing attributes are intrinsic to the type of molecule you use for vaccination, which is DNA. Now, DNA has these properties that really brings new opportunities or novel approaches in vaccines, but the delivery of DNA has been challenging. Either viruses has been used, where safety is a concern, some adverse events have been seen.
Then, on the other hand, we have devices, which is a compliance issue if you have mass vaccination with a device. So, our approach is an antigen DNA that's put into a plasmid and then delivered with a synthetic delivery system.
So no device, no viruses, a delivery system that is safe and highly efficient. The IMNN-101 has the antigen DNA for Omicron XBB.1.5 spike antigen. That's in the current vaccine that was just recently approved by FDA this week, and it's delivered with a synthetic delivery system, as I mentioned earlier to you. So really, we feel that using a simple system, really, IMNN-101 could be potentially the first vaccine capitalizing on DNA advantages.
We have a plethora of preclinical data to demonstrate the proof of concept. This slide shows the evidence of robust immunogenicity in a mouse model in a prime and boost format. On the left side, the graph shows IgG responses. Light bars are prime, and then darker bars are boost.
You can see that at two different doses, immune responses that's boosted. Then on the right panel is the neutralizing antibody. So these antibodies are neutralizing, as well, and same relationship you see with respect to prime and boost. The bottom graph shows the robust T cell responses with IMNN-101. As I mentioned earlier, that we do have more persistent responses with the DNA-based vaccine.
This slide shows T cell response durable for greater than 12 months in mice, and you can see the responses are higher than a commercial mRNA vaccine that was tested side by side. Then also we saw IgG neutralizing antibody and T cell responses, but the vaccines these vaccines are also protective in a challenge model.
So this is a, an IMNN-101 prototype, which was, against an earlier version of, SP- SARS-CoV-2, that's D614G and Delta, where vaccinated mice cleared the virus were 90%, same case of D614G. The left bar, set of bars were complete, a clearance of the virus, Delta, variant, a challenge of the vaccinated mice.
And we've monovalent vaccines such as pVax-15 and 16, or bivalent, which is pVax-17, expresses two variants in a single plasmid. We then took, our, technology or some of the lead vaccines into non-human primates. Of course, demonstrated the, IgG responses, and now this slide especially shows the, protection or the clearance. Monkeys were vaccinated with, our monovalent vaccines, again, the earlier variants of SARS-CoV-2, and also with a commercial mRNA vaccine side by side.
You can see that interestingly, within a couple of days, there's a complete clearance of the virus from lung that is a bronchoalveolar lavage, and also from nasal passages, that is the bottom set of these slides. The key point is not only that Placine vaccine clears the virus effectively, but also the activity is very comparable to a commercial vaccine. Think about if a vaccine approach that does not require device and virus, that has durable immune responses. It's stable at, you know, workable temperatures, and also has a comparable efficacy to a commercial mRNA vaccine. Clearly, this approach has potential.
This is stability data at 4 degrees, more than 12 months, where you have pairs of bars, which means a freshly made formulation and the one that's been stored for several months, you know, starting from one month up to 12 months, and every time a pair is a freshly made and the one that was stored. So you can see the very rightmost pair is 4 degrees centigrade, kept at 12 months, and very comparable to a freshly made. This is looking at the ITG responses in mice.
So this is especially very important in developing countries where mRNA vaccine has certainly requires minus 80 degrees, you know, freezers. And so it'll be very handy to be able to maintain at workable temperatures. At room temperature, it's stable for one month. So clearly, this is a more feasible in terms of mass dissemination of vaccine in different economic areas of the world. So based on a comprehensive set of preclinical data, we decided to move 101 into an IND path.
So IMNN- 101 expressing XBB.1.5 and delivered with a synthetic delivery system. IND-enabling studies are ongoing. We plan to complete safety tox and biodistribution studies in mice by the end of this quarter. Clinical lot is due for production first quarter next year. I would like to mention that we have our own capability to produce plasmid, a GMP plasmid for clinical grade, the delivery system, clinical grade.
That gives us more flexibility in terms of time to be able to produce a lot, and of course, cost is also a factor. So this is a huge benefit to be able to rapidly produce ourselves and in a timely manner that we can control. The IND filing is planned for end of first quarter 2024. First patient will be in April 2024, and phase II study rapidly within a couple of months in 2024. This is a synopsis of the clinical trial, phase 1/2 in healthy subjects. Three doses of IMNN-101 plus placebo control. We inject a single dose on day one, and for seven days, look for reactogenicity.
By day 28, we'll have safety and immunogenicity data to make a decision at the dose going forward into phase II, with up to 100 subjects, starting in June. The phase I subjects continue for one year for us to collect data on immunogenicity and safety, especially the immunogenicity over a long period of time, stability beyond six months. That has been a benchmark with current vaccines. So, lastly, the plug and play, as we said, speed is very important. Dr. Permar also mentioned that in case of pandemics or endemic.
Here, at the very left side, the top row is the clinical backbone that we have developed with the plasmid, and you can excise the antigen of a current vaccine and replace with an emerging variant very quickly, and being able to manufacture and formulate. Currently, we can do that in a 90-day, which is similar to what's the commercial mRNA vaccine can deliver. So, rapidly mutating virus can be addressed with this plug-and-play approach.
Now, not only just the variant of a one pathogen, but this is also adaptable to any pathogen, and we have shown proof of concept with other viruses, pathogens such as flu, Lassa, Marburg, and monkeypox. Clearly, through some collaborations, the Lassa project is with the NIAID, NIH, and flu and Marburg with Wistar Institute.
So, we're pretty excited about taking this DNA-based approach that does not have virus or device in the clinic, and hopefully very hopeful to make a difference in the current vaccine landscape, where a DNA-based approach with a lot of inherent advantages over other approaches, such as protein and mRNA, could become a valuable tool to fight against pathogens.
Now, with this, I do appreciate your patience in listening. I would like to now introduce Dr. Patrick Ott, who is Associate Professor of Medicine at Harvard Medical School, and also Clinical Director, Melanoma Center at Dana-Farber Cancer Institute. So with this, I will hand it over to Dr. Ott. His talk's title is Personalized Immunotherapy.
Thank you, Dr. Anwer, for the introduction. It's my pleasure to present today at this virtual R&D Day. The title of my talk is gonna be Personalized Immunotherapy, and I'm gonna talk mainly about neoantigen personalized cancer vaccine, a little bit about adoptive cell therapy and then some thoughts on the idea of personalized immunotherapy and what that means. Here are my disclosures. So what is personalized immunotherapy, really? You know, in one sense, one could think of this as biomarker-driven tailoring of immunotherapies in patients.
The example in high-risk myeloma patients in a neoadjuvant setting here would be to really tailor the extent of immunotherapy, for example, combination immunotherapy versus monotherapy, based on richest biomarkers on toxicity or response.
Also using the pathology sample from the surgery, potentially to tailor adjuvant therapy after the surgery, maybe even the duration of adjuvant therapy or the surveillance. And then, of course, even the extent of the surgery could also be tailored based on what the pathology sees in terms of a pathologic response under the microscope. So, another way to think of this is, you know, this could be called personalized, but in some sense, it's also a stratified therapy.
Another example for that would be targeted therapy that we're using in melanoma and other cancers, for example, BRAF/MEK-directed therapies, EGFR, ALK, MET targeted agents, or a new drug in melanoma that has a bispecific antibody that's really only effective in patients that have an HLA-A2 background.
Another way to think about personalized therapy would be that it's actually truly custom-made therapy based on each individual patient. So rather than selecting patients for given treatments, it would be actually making a unique treatment for each patient. And that's where, personalized vaccines and, in some sense, also adoptive T cell therapy comes in. The target of these therapies are really neoantigens, which are attractive antigens because they are really uniquely expressed in the tumor, and we now have the ability, obviously, to identify them.
But as I sort of this personalized approach where you have to custom-made each vaccine, the reason why do we have to do this? Well, because the overwhelming majority of mutations are really unique to an individual tumor.
So while there are driver mutations, those are only present in a subset of patients, and then there's also HLA restriction, and so targeting those would really only be effective in relatively small subsets of patients. And then, so customization sounds great, but of course, we have to acknowledge that this is a relatively challenging approach because it takes time, it costs money, because every individual patient needs whole exome sequencing. We need to do RNA sequencing for each tumor.
Also, we have to do whole exome sequencing on normal tissue in order to reliably call the mutations. And then once we are confident with like the right mutations, we then actually use prediction algorithms in silico that help us to identify the most immunogenic neoantigens.
That's, as I mentioned, a complicated process that typically takes weeks, sometimes even months, although timelines are shrinking as we are scaling these processes up. How can neoantigens be targeted therapeutically? In principle, there are two general strategies. One is vaccines, the other one is adoptive cell therapy.
Neoantigens prime, activate, and clonally expand endogenous neoantigen-specific T cell responses and work primarily in the lymph nodes during priming of an immune response, while adoptive transfer, adoptively transferring TILs that are enriched for neoantigen-specific T cells, or even endogenous T cells that are transduced with neoantigen-specific T cell receptors, those can vastly increase numbers of cells that are effective and therefore, really are primarily exerting their function at the effector phase of the immune response.
Initial studies using such approaches, certainly, adoptive T cell therapy with tumor-infiltrating lymphocytes, using tumor-infiltrating lymphocytes, but also increasingly using transgenic TCRs, have been reported, and, in the case of the TIL therapy, have shown quite remarkable efficacy with response rates about 30% to 40% in heavily pretreated patients with melanoma, leading to the wide expectation of lifileucel as potentially FDA-approved drug in the fairly near future. When you think about transgenic TCR, sort of in general, there are two different approaches.
One would be to enrich tumor-infiltrating lymphocytes. So essentially as the collective... t he collection specimen using the lymphocytes that are already present in the tumor, and so arguably, tumor specific, many of them will be neoantigen specific and then enrich them, potentially even, and then isolate the TCRs, clone the TCRs, and then use those TCR specific in a sense, a highly purified population. This could be up to, you know, probably 100 or so different antigens. That would be one approach where one essentially has as a source the TILs and then enriches and uses the TCRs from those lymphocytes.
The other approach would be to actually first identify the neoantigen and then pull the T cell receptor out from the peripheral blood and then clone them into T cells and then expand and reinfuse in a patient. That has also already been done by a company called PACT, but it is like a really labor-intensive approach.
And so, essentially, just to summarize these approaches, one is basically just using the TILs, so like unselected tumor-infiltrating lymphocyte, versus pulling TCRs out from TILs and then using selected TCRs that are to probably a large extent, neoantigen-specific, versus really identifying neoantigen TCRs, peripheral T cells, cloning them, and then transduce them into T cell populations.
And so by order, by this order, there, there's more—the most clinical evidence is with the TILs, and then there's some clinical reports, mainly case reports, a lot of them from the Rosenberg groups, that have shown remarkable efficacy using those neoantigen selected populations, and then sort of a feasibility approach of the peripheral technology.
So, with regards to vaccines, as I mentioned, those were primarily in the lymph nodes, so they really have the ability to generate new antigen-specific T cell responses against tumor cells. They can also amplify existing tumor-specific T cell responses and increase the breadth and diversity of the tumor-specific T cell repertoire. As we have all witnessed with the development of COVID-19 vaccines, uh, SARS-CoV-2 vaccines, there are many choices of vaccine delivery platforms, including, of course, RNA, but also DNA, protein, peptides, as well as microbial and cellular vectors such as adenovirus and dendritic cells.
The vaccine platform and many other variables can have substantial impact on the vaccine manufacturing time, which in and of itself influences the clinical setting that these vaccines then can be used.
There are also many choices as to how to dose vaccines, including dosing intervals, as well as prime boost approaches, in addition to different routes of administration. And then, vaccines can and arguably should be combined with drugs aimed at dendritic cell stimulation or costimulatory agonists to improve priming, as well as agents directed at the reversal of immune suppression in the tumor microenvironment.
To test the concept of vaccinating against neoantigens in cancer, about 10 years ago now, we started a first-in-man clinical trial in patients with high-risk melanoma utilizing long personalized peptide vaccine. And so these peptides encoding neoantigens were formulated as 4 distinct pools and mixed with the TLR 3 agonist poly-ICLC, and the vaccines were then administered subcutaneously into 4 different anatomical sites and given in a prime boost schedule, which is shown here.
In this study, we saw a robust de novo ex vivo reactivity against peptide pools in a really small study. In all six, in all of the six vaccinated patients, we saw these ex vivo responses, really suggesting induction, the induction of response against multiple epitopes. This was really quite attractive and rewarding because in the past, these types of ex vivo responses with these types of consistency, where we saw the responses against multiple immunizing targets, as well as really consistently in all of the patients, that was quite novel at the time.
We saw a predominance of CD4 responses, as shown on the right side. Deconvoluting those immune responses further, we also established that they were really specific against the mutant epitopes versus wild type.
We saw responses of these, so these vaccine directed T cell responses were also reactive against the tumor, so autologous tumor in a subset of patients. We saw broadening of PD- of the vaccine responses after 2 out of the 6 patients actually had subsequently received PD-1 inhibition, and potentially and arguably, most excitingly, those 2 patients who had received PD-1 inhibition after the vaccines, then actually went on and had complete responses that are ongoing to this day, like more than six to seven years later.
In a follow-up study, we evaluated the functional states of circulating vaccine-induced neoantigens across the course of vaccination using single cell transcriptomics of T cells that we identified by tetramer staining.
So we generated class II tetramers, and initially, as shown here on the right side, demonstrated that tetramer-specific CD4 T cells could be detected ex vivo in PBMCs at serial time points, and so they were persistent over the course of treatment. And this was in three out of the four patients, we then were able to assess transcriptomes at single-cell resolution, and we observed four different clusters that were each composed of cells from three patients. And then looking at the gene composition of the cluster, we found that they represented distinct T cell states and had specific gene signatures.
Neoantigen-specific T cells isolated right after priming and at early time points after boosting had mostly cytotoxicity and an activation-induced cell death phenotype, while neoantigen-specific T cells towards the end of the vaccination course mostly had a memory-like phenotype.
We then assessed single cell clonotypes, TCR clonotypes, and saw a diversification of TCR over time, as shown here on the left side by additional colors from left to right, illustrating novel TCR clones as the vaccine-induced immune responses evolved over time. In the same follow-up analysis, we were also able to test for persistence of vaccine immune, of vaccine-induced immune responses up to four and a half years after vaccination. By the way, all of these, of the now eight patients, we had vaccinated an additional two patients.
So in this analysis, we were able to look at immune responses from eight patients. They were all alive, but there were recurrences in three out of the eight, which were surgically resected. We're also rewardingly, we were able to detect both CD4 and CD8 T cell responses against large proportions of immunizing neoantigens.
So essentially, as you can see in the filled blue bars here on the left side, the CD4 response, on the right side, CD8 responses, is essentially the proportion of vaccine responses that were still persistent years after vaccination. And an example is shown here on the right side. So the week 16s are pretty immediately after the vaccination and then 47 months, so four years after vaccination. You can hopefully appreciate that those are ex vivo responses, and they're all really quite robust.
In a separate study, to test personalized neoantigen vaccines in metastatic cancers and in combination with the checkpoint inhibition, we conducted a Phase 1b study, which was, sponsored by... so it's not a Dana-Farber effort, as well as, like, the vaccine that was, like, developed at Dana-Farber. The company was founded by folks from Dana-Farber, but the study was conducted, by Neon Therapeutics, and I was the national PI there. Neon Therapeutics has since, been bought by BioNTech.
It's now called BioNTech US. But the way the study was designed is that, as I mentioned, actually, I did not mention, but, the title says it's melanoma—it was advanced melanoma, non-small cell lung cancer, and urothelial cancer. These patients received PD-1 inhibition while the vaccines were made for the first 12 weeks.
They were then vaccinated over a course of 12 weeks, and then continued with nivolumab, when, as long as this didn't have toxicity and were responding. We made a pretty good effort on this study to really learn, by really collecting very consistently immune samples, including leukapheresis samples, prior to the nivolumab, prior to the vaccine and post-vaccine, and also core tumor biopsies, which really allowed us to assess the immune activity of these vaccines.
Very similar to the initial Dana-Farber study, we saw ex vivo responses. The proportion of immunizing peptide that induced vaccine-specific responses was about 50% to 60%, again, with a predominance of CD4 responses.
In terms of clinical activity, here shown melanoma, the largest patient population, around 30, around 40 patients that were vaccinated is melanoma, non-small cell lung cancer in the middle, bladder cancer on the right. And you can see that there was, you know, a number, a good number of responses. In melanoma, the response rate was 60%, non-small cell lung cancer, you know, 40%, bladder cancer, about 30%. Not enough to really tell us that these vaccines were effective.
There were a couple of signs I'd argue in the clinic that were suggestive of responses, particularly the deepening of response that we saw after vaccination. And they're certainly in line, the responses were better than what one would expect from historical controls. We saw two specific immunological and pathological features that also indicated potential antitumor activity efficacy.
One was epitope spreading, where we tested for the presence of immune responses against neoantigens that were present in the tumor from the whole exome and RNA sequencing, but they were actually not contained in the vaccines, giving us an opportunity to test for these targets and see whether the vaccine-induced responses had actually expanded to non-vaccinating targets. And in fact, we saw this in a large proportion of the patients, and actually, this phenomenon tracked with prolonged progression-free survival, as you can see here on the right side.
As I mentioned, in terms of path response, we had 14 patients where we had serial tumor biopsies across the three time points. So prior to PD-1 inhibition, prior to vaccine, post-vaccine, and five of these patients had a complete path response right after the PD-1 inhibition but prior to the vaccine, versus nine of the 14 patients actually did not have a path response after PD-1 inhibition, but then developed a path response after the vaccine, which is, I think, quite remarkable.
Although with one caveat is that these, when I call them path responses that were from core biopsy and not from surgical samples. But nevertheless, this phenomenon also tracked with prolonged progression-free survival.
So those are what I just went over now in terms of the vaccine, was like the initial Dana-Farber experience in melanoma, and then, like, a larger trial with Neon Therapeutics. Yeah, and then I also alluded to the sort of signals of activity that we saw in these trials. There were other signals from two additional trials that I don't have the time here to go over. One was from the initial BioNTech study, also in melanoma, where they saw a decreased rate of recurrence after personalized RNA vaccine.
And then there's a study from Gritstone, where they saw decrease of ct DNA in patients that were vaccinated, that correlated with improved survival. I just wanted to go over two really exciting studies that were both published or reported this year that we're all very excited about.
One is an effort from Sloan Kettering by Vinod Balachandran, who used the BioNTech RNA liposomal vaccine, targeting up to 20 neoantigens of nodes that has intrinsic adjuvant activities, given its properties as a TLR 7 agonist. I'm not gonna go into all the specifics of the trial, but it's basically done. It was done in pancreatic cancer, resected. The patients received one dose of atezolizumab, and then the vaccines, nine different vaccines every week, and then adjuvant chemotherapy. And what was exciting about this study was that they had two immune assessments, types.
One was ELISpot, so they looked at vaccine-specific interferon gamma ELISpot responses, and then they also looked at TCR clones going up after vaccination. Then patients who did have both ELISpot responses and TCR expansion were considered immune responders.
As you can see here on the left side, there were, in the 16 patients that were treated, 8 had immune responses and 8 didn't, and the 8 patients who did not, the 8 patients who did have immune responses did not recur, versus, like, 6 out of the 8 who did not have immune responses, had a recurrence. So quite intriguing. Not a randomized study suggesting that, there is a direct, therapeutic benefit, but nevertheless, quite suggestive that it's... so not directly showing, I should say, that it was a therapeutic benefit, but, but quite, indicative.
Then, of course, there's the Moderna study done in stage three high-risk melanoma patients, where there was randomized two-to-one, where about 100 patients received RNA vaccine targeting up to 34 neoantigens, plus pembrolizumab, versus pembrolizumab alone. And really excitingly shows a quite remarkable recurrence-free survival difference of about 15%, which is actually pretty similar to the benefit of PD-1 inhibition versus placebo in this population.
And so this is really absolutely, I find exciting for the field because it could really suggest that these vaccines are effective not only in melanoma, but potentially in other cancers as well. So where are we now, in terms of what are the challenges and opportunities?
I just wanted to point out again, time and cost is an issue, but there's many things that we can still work on, including the magnitude and quality of the immune responses. So we can certainly improve the formulation and the immune adjuvants in order to enhance T cell priming. We need to look at approaches where we can manage the tumor, the immunosuppressive tumor microenvironment better.
And then there's a lot of discovery and science that can still be done to really hopefully improve neoantigen discovery, so we can actually immunize with the most immunogenic neoantigens, so select them better.
But we can also increase the space of neoantigens by taking advantage of different types of mutations, so not only SNVs and indels, but also other, you know, RNA level, different mutations, but also like alternative translation products. I'm not gonna go into all the details, but as essentially, this has been called the dark matter, because we so far have not been able to really take advantage of it, because whole exome sequencing simply doesn't, you know, discover those types of mutations.
But with that, I'd like to stop and just acknowledge the team at Dana-Farber and the other Boston institution, and just to point out that these efforts really require a village and have been funded by many different institutions. Thank you for having me today.
Thank you, very, very much, Dr. Ott. This was a very interesting presentation, giving us an overview of where we are with the development of cancer vaccine and how this approach fits with other approaches in oncology. Khursheed, if you would like to take us through our development programs and what we have currently in our pipeline.
Great, sure. Thank you, Corinne. Let's see. Okay. All right, thank you, Dr. Le Goff. Excellent presentation by Dr. Ott. Clearly, with the approval of checkpoint inhibitors, the interest in immunotherapy has surged. Cancer vaccines have seen a lot of failures in the past, but with the advent of nucleic acid-based approaches, there's a resurgence in cancer vaccine, and especially with the use of neoantigen approach, clearly, there has been a difference. But as we saw in Dr. Ott's presentation, a combinatorial approach is probably valuable, you know, combining vaccines with other immunotherapy approaches.
Well, getting back to my program, you had seen, I talked about our DNA-based platform for vaccines against infectious diseases. We have now expanded that platform into cancer vaccines. We already had immuno-oncology program in place at a clinical stage. So I'll talk about our immuno-oncology and cancer vaccine platforms in this set of slides.
So, there are three platforms in immuno-oncology at Imunon. TheraPlas is the most advanced one, where expressing a potent immunocytokines locally at the site of tumor using a plasmid DNA that expresses IL-12, a powerful anticancer immunocytokines, with a synthetic delivery system that does not require a device or virus. So that's the lead product is IMNN-001, that is in phase II randomized clinical trial in ovarian cancer at this stage. Then we have these cancer vaccine platforms, FixPlas and IndiPlas. FixPlas is targeting tumor-associated antigen in this respect, and the IndiPlas is neoantigens.
Of course, tumor-associated antigens are overexpressed in, tumor tissue, but also have, some expression in normal cells as well, while neoantigens are more, personalized and specifically expressed in a, in an individual or a small group of individuals. So I'll talk about a little bit of TheraPlas, since that has been-- that is our, lead product, in advanced stage, immuno-oncology, and then I'll talk about our FixPlas, program. So Imunon, IMNN-001, as I said earlier, persistent local delivery of IL-12 with a formulated plasmid.
This is targeting epithelial ovarian cancer, disease of unmet need, late-stage diagnosis, high recurrence rate, and hence, poor survival. And novel approaches are certainly warranted beyond chemotherapy and radiation. IMNN-001 is a gene therapy product, for safe and effective delivery of IL-12, which is a powerful immunocytokines.
A safe alternative to recombinant IL-12 therapy that is short-lived and exerts serious systemic toxicity. We have done a few clinical trials with 001 in different patient population, platinum-resistant, and more recently into newly diagnosed, neo-adjuvant population. We've seen some encouraging results in clinical efficacy, some biological activity, and certainly good safety data from these trials. A phase II trial, Ovation-02, is underway.
We will be sharing some interim data this quarter and next year, more final analysis from that study, where chemotherapy alone versus chemotherapy plus IMNN-101 is being examined. So let's move to cancer vaccine, the FixPlas.
FixPlas is the targeting tumor-associated antigens that overexpress in in cancer, both monovalent and bivalent, means either targeting one antigen or more than one antigen. Our approach, like in COVID-19, for infectious diseases, DNA-based vaccines. Clearly, we, we saw some rationale for why DNA is a good candidate for infectious agent vaccine. Similar thing applies here for cancer vaccines. First of all, DNA gives durable antigen expression, so you can get a durable immune responses against cancer antigens, plus memory T cells could be long-lasting with that exposure of the antigen.
DNA is known to elicit very strong cellular responses, and that's really key to cancer therapy. So durability advantage over mRNA and strong cellular response, that's the advantage of a protein-based vaccine.
So clearly, DNA-based vaccines are well suited for cancer therapy if effectively and safely delivered, and certainly we do not use a virus or devices for that purpose, but synthetic delivery systems... so this is a more recent program where we have initiated proof-of-concept studies with a bivalent vaccine in a mouse melanoma model. Of course, melanoma is an attractive target for immunotherapy, but still a lot of melanoma patients who do not benefit from current approaches. So new approaches in immunotherapy or vaccines for melanoma is certainly warranted.
In an experimental way for proof of concept, we're targeting NY-ESO-1 and TRP-2 in a mouse melanoma model, and using two approaches, a proof of concept, to see if DNA-based synthetic delivery system approach works, using a prophylactic approach, where we vaccinated animals and then challenged with the tumor or treated the already existing established tumor with the vaccine. It's a little bit busy slide, but I'll walk you through. This is looking at a prophylactic approach with FixPlas.
And on the very left side column, top panel is a tumor growth rate with a monovalent vaccine that targets TRP-2 antigen. And you see that green ones are the vaccinated animals, the red ones are control, and you can see a delay in growth that translates into survival and benefit.
This is a very aggressive model, and the benefits in survival you're seeing are pretty consistent with what you normally see with a good approach in an animal model. So that's with a single antigen, TRP2, and then middle column with the graphs is a combination vaccine, TRP2 and NY-ESO combination. And here you can see that further extension or delaying of the tumor growth, again, the green bars, as opposed to the control, which are red, and that also correspondingly translates into better survival in a combination approach.
That gets to prove that a single antigen approach that has been used for many years in the past may not be sufficient. You have to target tumor with combination combination antigen approaches. The third column shows that there are T cell responses also with these vaccines, which is very critical because you want to generate CD4, CD8 cells to be able to engulf and specifically kill the tumors. So but this, like I said, this is an early program in cancer vaccine.
This demonstrate that a DNA-based approach with synthetic delivery system does have an efficacy responses in a very challenging, aggressive mouse melanoma model. Then we moved on to a therapeutic approach with the same vaccine bivalent TRP-2 and NY-ESO. Here, the tumors were established, and then they were treated intramuscular with the vaccine approach, and here also we see benefit in tumor growth rate and survival.
So, again, these studies, there are at least enough evidence that there is a direction to move forward with this program. Clearly, we have to optimize the antigen. There are ways to optimize the antigen, stabilize the structure, you know, secretion, expression of the member, surface, increase expression with the MHC class, but molecule to get T cell responses, adjuvancy. Some of those optimization studies have to go on, but clearly, we are going looking at this program into further product development.
Selection of the disease target, melanoma is an interesting and attractive target. As I mentioned, that is a great target for immunotherapy, highly immunogenic tumor, yet there's still a need for therapies that are effective in melanoma. So we do like to create a program around melanoma, selection of an optimization of the antigen targets. You saw TRP2 and NY-ESO-1, but that's not the end of the story. That's the proof of concept of our formulation.
But we'll be plugging in a best candidate as a target for antigens, and then again demonstrate robust anticancer activity. And around this time next year or before that start IND-enabling studies, and we target a clinical trial with the FixPlas first quarter 2025. In parallel, we're also developing an animal model for neoantigen approach, a mouse model where we can take neoantigens, multiple neoantigens, and that's the advantage of plasmid DNA.
You can pack into a single product, multiple epitopes, and being able to deliver that and go after cancer with that approach. So, I think it's pretty exciting, as I said, going into clinic with the infectious disease vaccine early spring next year and going into phase II instantly or very quickly. It's very exciting for us. Now with DNA cancer, a cancer vaccine also, it's very promising to use DNA where it has a lot of promise and has not been fully capitalized.
And we feel that Imunon is in a position to use these non-viral, non-device-based system to make an impact in immuno-oncology cancer vaccines. Thank you very much for your patience. With this, I would like to now transfer to Dr. Le Goff.
Thank you very much, Dr. Anwer. It was very interesting, and thank you for, you know, your enthusiasm as I think you're as enthusiastic as I am on the potential of DNA in areas of immuno-oncology and infectious diseases. Now, we have time for questions, so I'd like to open up the Q&A portion of our discussion today.
You'll see that unfortunately, Dr. Ott cannot be with us for the Q&A, so we'll do our best to answer questions that are addressed to him, and if we can't, we'll make sure that we obtain the answers directly from him and communicate that to you. I would like also to introduce Kim Golodetz from LHA, who will actually let us know if we already have some questions in the queue for us.
Okay. Thank you, everybody. And yes, we do have some questions in the queue, and as a reminder, there is a chat function on this video that will allow you to submit some additional questions. We have two questions from Emily Bodner at H.C. Wainwright, and I'll do one at a time. The first is: Can you discuss your T cell results more specifically, particularly CD8 T cells? And now that we know more about mRNA vaccination, which doesn't induce high amounts of CD8 T cells, how important is it to see a high CD8 T cell response?
Thank you very much, Emily, and I think this is a question for you, Khursheed.
Yeah, yeah. Thank you, Emily, for your question. Yes, the CD8 cell response is important for... let's see, once the virus has entered the cell, and I'm speaking from an infectious disease point of view, then antibodies are not as effective. Also, antibody-directed cell killing is a mechanism.
Clearly, you need a T cell response for that to completely eliminate the virus. We have looked at different effector CD8 cells, memory T cells. Of course, for the sake of time, we're not able to share some of that facts, data with you, but besides ELISpot data that I've shared with you, and for gamma response, we do see subsets of CD8 cells post vaccination in infectious disease model.
We are also looking at CD8 cells, where it's even more important, cancer vaccine subtypes in our analysis of cancer vaccine. So yes, it is important, especially to completely eliminate the virus from the system. And memory T cells, of course, you know, they play a pivotal role in in keeping you protected for a long time and from reinfection.
Okay. The second question from Emily is: We've seen data from BioNTech's mRNA vaccine cancer vaccines and also Gritstone's cancer vaccines, which have had lackluster data. Why do you think that a DNA approach could be superior to these approaches?
Yeah. So once again, a good question. As I mentioned earlier, that clearly both from Dr. Permar's talk and Dr. Ott's talk, that the new approaches with nucleic acid-based approaches are the way to go. Clearly, mRNA is ahead of the game, especially with COVID-19. The approval of the mRNA vaccine really gave it an edge.
But DNA has a more durable expression, and that could potentially translate into longer immunity and more memory T cells. So we think DNA, from that point of view, in terms of immunology, has an advantage over mRNA, and of course, it has to be proven in human data. Clearly, that would be the next step in the DNA field to get that recognition.
But at least knowing from the, durability of expression, which is the antigen exposure, it's important. We have done experiments where we see, expression of protein from mRNA, peaks about one or two days and then comes back to within three to four days. Maybe, in infectious disease, that early exposure is important, but certainly maintaining it, especially in cancer vaccine, you need to have durability.
So it's good that you have, some positive data from mRNA, and we believe that DNA has, some edge in some areas, in immunological that would perhaps even capitalize, further capitalize on the gains that the mRNA has made, and of course, the storage of vaccine and, plug-and-play rapid production is also an advantage.
Okay, we also have a three-part question on IndiPlas and FixPlas. How would you describe the differences between IndiPlas and FixPlas? How do you go about personalizing a cancer vaccine? How can a personalized cancer vaccine be made in a cost-effective way, especially given the constraints on reimbursement that we are seeing?
These are great questions. Thank you. Maybe I'll start, and then I hand it to Khursheed. You know, I gave, like, maybe a crude definition of those modalities, of FixPlas, saying that's more of an off-the-shelf approach and IndiPlas, a more personalized approach. I'm sure Khursheed will have what to say about this. And then we go to the next part on the costs.
Yeah, clearly a good question. So, fixed plas is targeting tumor-associated antigens that are overexpressed in tumor, and, and they, they are overexpressed in many different tumor types as well. So in that sense, if you develop a vaccine, under fixed supplies, that could be effective, as Corinne said, off the shelf, could be given to a larger patient population. But we also know that, there are differences from individual to individual in tumor genetic makeup.
So, the fixed plas is really going individual, specifically, individual where, a tumor may have, very different types of mutation that's not overall in general population, maybe a small subset of patients or that individual patient.
So FixPlas is targeting the neoantigens that are found in a specific patient or a subgroup of patients. So those are the two differences between fixed... I mean, that's the difference between FixPlas and IndiPlas. How do you go about, how do you go about personalized medicine? Of course, since it is about a personal person, individual specific, you have to collect the tumor tissue and do the genomic sequencing of the tumor genome and the normal tissue and identify mutations.
And then from those mutations, you, using algorithms, identify the epitopes of high affinity that would be reactive to the T cells, and then make vaccines from a combination of epitopes into a one vaccine. That's where the DNA plasmid has advantage, because you can put dozens of epitopes, neoantigen in a specific vector.
So once you put those epitopes in the vector, high affinity, then you formulate, if it is the our system, and then give that to that individual. So that vaccine will be very specific to those mutated antigens that are in that individual. One of the reasons why cancer vaccines have not been very successful over the years because the tumor is different, different antigens are expressed in different individuals.
And maybe briefly, because I want to make sure that we have also questions for Dr. Permar, but briefly on the cost. You know, our, our focus is on developing innovative approaches, but the definition of innovation is that it's only innovation if it ends up in the hands of patients, right? And if the costs are too high or whether it's in oncology or in other therapeutic areas, and if they don't correlate with the burden of disease, that, that is problematic for, for society in general.
So our focus, our strategic focus, is really to make sure that as we go forward and develop therapeutics, we are cost-conscious on, on. And we understand how our therapeutics will be used, whether they will be used in combination or not.
I would say here that DNA might have an advantage over other technologies that are more complex and longer to develop. You know, DNA basically uses your body's machinery to produce your therapeutic, right? And in that sense, and because I talked already about the flexibility of the manufacturing of nucleic acids, in that sense, I think we can develop a cost-effective, a very efficient therapeutics.
Okay, so, we have some infectious disease questions. Could you discuss the differences between a potential DNA-based vaccine that's used in an adult versus one that's used in a pregnant woman or a newborn, if any?
Thank you. I can address that. Yes, I think one of the biggest questions first is safety. And each of the populations does need to be studied in particular. There, at this point, have been slow introduction of a testing in those populations, which I think we need to have innovative approaches to improve on. Something like, do we really need age de-escalation in children versus can different ages be tested at the same time?
Also, to think about preclinical systems that can better predict any safety events. But actually, the vaccines at this point have not had a more events, safety events with the recent mRNA vaccines in those populations, children or pregnant women. The one major difference, I think, when it comes to what vaccines we're actually putting in arms, is dosing for children, and that's something that clearly had to be worked out with the mRNA-based vaccines.
I think there's some ways that we could be more prepared with preclinical models that would grease the wheels for the human phases, that would, you know, maybe reduce the amount of time that would be needed to do all the dosing studies. But that's one where does not impact the pregnancy setting as much as the children's setting, because it's the immune system that's developing in the child, less so the per kilogram size. And so that's what really has to be dose-adjusted.
Okay. Thank you. And we also have some combination infectious disease questions here. So related to COVID, given the rapid mutations of COVID, is your plug-and-play strategy fast enough? You also mentioned Lassa and Marburg viruses. Are these quickly mutating viruses? Does the market size warrant commercial development?
Right. So I'll stop there, and maybe Dr. Permar, you have a perspective on this as well. Well, COVID, for sure, mutates a lot, and very fast. And what we have learned through the pandemic is that you needed to have a technology that could adapt quickly to the different mutations. So what Dr. Anwer described as a plug-and-play strategy for all DNA technology, which is essential because it allows us to basically change the DNA cassette, right? If there is a mutation, to get the sequence, send a DNA cassette, the backbone is already characterized, and put this into the clinic.
you know, through our discussions with the regulators, and BARDA and others, it is clear that there is this mandate of being able to develop a commercial vaccine in 100 days. We can do that, and we tested it. We will be able to deliver on this.
Yeah, and I can just add that speed is of the essence, and, you know, especially for these RNA viruses of which Lassa and Marburg are as well, where we know that mutations can evolve rapidly. However, they're not... you don't always need an additional design variant that keeps up with the evolution. For some viruses, the response to any one of the variants may be enough to provide protection, at least against severe disease.
So I think that that's the hope with some of the pandemic viruses that if we could have prototype vaccines that are designed based on the sequences that are already available and if it's in a rapidly modifiable platform, then you know the current sequence that's spreading around the world could be put into an already developed vaccine and really needs very little additional testing and immunogenicity studies because it's already been through the gamut of those studies prior to that.
Yeah, with respect to the market, if I may add, currently, Lassa is more into West Africa and Latin America, but there's prediction in new market analysis that the market would increase, and there's potential to have western countries through migration. So, yeah, we have to just watch and, in terms of its spread, currently, it's confined in a couple of areas.
And I can also add that is a virus that is more severe in pregnant women and can cause deleterious fetal outcomes. So, it's gonna be... if it becomes a virus that's more easily spread, it's gonna be like a Zika pandemic, and we know how much attention there was because the effects were not just on, you know, the person who's initially infected, and so that is something that we have to be ready for.
We have another question that now goes back to the cancer vaccines. There seems to be a lot of work in melanoma with respect to vaccines. What other therapeutic areas do you think IndiPlas and FixPlas could be directed towards?
Yeah, so let's... thank you. Maybe I'll start, you know, I've worked over the years. I've worked a lot in melanoma. In fact, Dr. Ott mentioned the targeted therapies, targeting BRAF and those approaches, which actually launched. So now what we have seen as well is that there's still, despite those improvements in the therapies, it's still like there's still a great unmet need in melanoma. You know, when you use targeted therapies, patients tend to become resistant a year into treatment, then the PD-1, PD-L1 inhibitors have been approved as well in melanoma, but they don't work in all the patients. So there is...
I think the vaccinal approach seems to be very promising, and is, and I believe that DNA has a role to play there as well. Now, to the question, yes, could we look at other tumor types? Absolutely. I mean, I think, you know, it makes sense to envision other possibilities for cancer vaccines, which I strongly believe will be immense there in the treatment of cancer, in...
Now, maybe the reason for picking melanoma as the first indication, and as we study this, and develop those vaccinal approaches, is the fact that melanoma is a very immunogenic tumor type. And, you know, it's a good tumor to start working with. I don't know, Khursheed, if you have an opinion on this.
Yeah, I mean, our approach is more generic, right? So it's not specific to any particular antigen or disease. So initially, we are to demonstrate proof of concept in melanoma, but we could expand into other diseases.
For example, it could be a hot versus cold tumor. There's a hot tumor, you know, that's very good candidate for, say, T-cell therapies or checkpoint inhibitors. Cold tumor may need an immune environment where you may need to prop the immune system through vaccination. Even hot tumors also, some of the cell therapies don't work because highly immunosuppressive environmen t.
So there's an application to other disease areas as well. It's just that you can plug in any antigen to the plasmid. If there's a right environment in terms of the immunogenicity condition, that should be a good target for IndiPlas or FixPlas.
Okay. Great. We just have a couple more questions that have been submitted. With respect to synergistic M&A, what kinds of technologies do you view as being synergistic?
Yeah, so I mentioned this earlier in my presentation, saying that we're always on the lookout for potential acquisition. And what we're looking for are technologies that could complement our approaches in immuno-oncology or infectious diseases, or, of course, interested in nucleic acids, of course, interested in adoptive cell therapies. So, you know, it's where we can complement our efforts, be synergistic with where we do, and also de-risk our pipeline.
Okay. We have a question on intellectual property. What kind of intellectual property do you have around IndiPlas and FixPlas, and have any patents issued?
Yeah. So, of course, you know, intellectual property is at the core of our business model, so we, of course, protect the work that we do. But I'll let Khursheed answer this question.
Yes, of course, as Corinne said, you know, you have to protect your innovation. So we have filed multiple family of patents covering these technologies, both for composition of the matter, use of the composition, disease targets, and so several applications have been filed over the last few years.
Okay. We have one last question that's come in: What's your manufacturing strategy for your facility in Huntsville?
All right. So we just unveiled in June our cGMP manufacturing in Huntsville, and we now have the capacity for producing our own plasmids and facilitating agents for our vaccine programs, at least in the early phases, right? So that's a great development for us. It's a way for us to control costs and to control quality. So for now, that's where we are, but we'll see moving forward as we go towards the later phases of development, you know, if we need to partner with someone or not. So that's not out of the question, of course.
Okay. There appear to be no more questions that have come in.
Very good. Thank you very much, Kim. Listen, I'd like to thank everyone who were on the call today. Thank you for attending our first R&D Day. I want to thank Dr. Sallie Permar very much for her presentation and insights into the future developments of vaccinology and what we should expect in the coming years as we think of the next generation of vaccines. Dr. Khursheed Anwer, thank you very much for telling us all about our clinical programs. You know, I will thank Dr. Patrick Ott for being with us for the first part of this presentation.
I just want to conclude by saying that we are, you know, very optimistic and enthusiastic about this technology. I think, this can be transformative across many disease areas, and, we'll keep you updated on our progress. Thank you very much.
Thank you.
Conference is now concluded. Thank you for attending today's presentation, and you may now disconnect.