I think we can get started. Good afternoon, everyone. It's a great day to be indoors today. Welcome to the Precigen presentation at the 41st annual JP Morgan Healthcare Conference. My name is John Hill, and I'm from the JP Morgan Healthcare Investment Banking group. It's my pleasure today to be introducing you to President and CEO of Precigen, Helen Sabzevari. Before we get started, I just wanted to highlight two ways to submit questions. For those of you online, feel free to submit questions on the webcast. For those of you joining us today in person, we'll be hosting a Q&A session after the presentation in this room. Thank you. Over to you, Helen.
Thank you so much. Thank you very much. First of all, I wanted to thank the organizers at JP Morgan, and it's great to be back in person this year. With that, also, I would like to start the presentation. Before I start actual slides, I would like to mention that we are making some forward-looking statements and which are captured in this slide, and you can also look at our SEC disclosure. Well, in regard to Precigen, we are a cell and gene therapy company that we have really focused on two major platform and have differentiated ourselves from the rest. One is our UltraCAR platform, which is an overnight manufacturing platform, and it's quite differentiated and changed the paradigm of manufacturing.
The other one is our AdenoVerse immunotherapy platform, which is a gene therapy platform that actually allows the immune system to educate itself internally in the patient, and then you develop the specific immunity for various indication. We believe at Precigen that 2023 is a transformational year for us in the sense of really advancing our programs in the clinic, and specifically two programs that I will be highlighting here that have a possibility to for a rapid movement from regulatory pathways and also toward the commercialization. With that in mind, in the next slide, we are looking at our clinical pipeline. Clearly, we are a company that has number of shots on goal, and we have advanced the program on our UltraCAR-T programs in the clinic from phase one to phase 1B, both in hematological and solid tumors.
On our AdenoVerse platform, we have advanced two programs to phase two in the past, three years since the inception of the Precigen, both in HPV-specific cancer indication as well as in PRGN-2012, which is in our recurrent respiratory papillomatosis. I will go through these programs more. Every year, we have a tradition of setting our goals for the year to come, and after we finish the year, we look at what did we accomplish actually in that setting. As you can see here, for Precigen, 2020 has been a great year. We have a significant clinical advancement in our portfolio. On our UltraCAR-T platform, as you can see, our PRGN-3006, we presented the data at ASH, a positive safety and efficacy data. It's quite exciting by our investigators and the attention that was received.
We have moved to phase 1B. In our PRGN-3005, which is our UltraCAR-T in ovarian cancer in solid tumors, we also achieved finishing the phase 1B, actually both arms, because of the preliminary data that we had on the efficacy. FDA allowed us clear that we move to a arm of IV injection and bypass number of doses and also go to redosing and lymphodepletion. We are very excited about this, and we did the tech transfer of our next generation PRGN-3007, which currently enrolling patients. In regard to our AdenoVerse platform, I would like to highlight our PRGN-2012, which targets the recurrent respiratory papillomatosis patients. In this platform, I just wanna give a little bit of history.
We started the IND and the trial in April of 2021, in the midst of COVID. We finished the phase 1 and expansion cohort by December of 2021. We have started the phase 2 in 2022 and up to this point, and I will report on that. We have expanded, and we are very excited about the data that we will be showing in January. Finally, our PRGN-2009, which we have done the enrollment and dosing, has been completed in the phase one mono as well as in combination therapy, and we have moved to phase two arm in a newly diagnosed patients with head and neck. On a corporate side, this has been very exciting for us because we had a overhang of $200 million convertible notes.
By the sale of the subsidiary of our Trans Ova, which we maximize this value, we basically were able to cover the convertible notes. The deal was for $170 million upfront and $10 million upside. I'm happy to report that up to date, we have actually retired $157 million of that debt and have saved close to $6 million in savings. We have taken care of that overhang, basically, and that's very important for our company and for our investors.Talking about our UltraCAR platform, and the reality is there are a lot of companies that they are in this field, and they talk about each one of them a differentiation.
I don't know how many of you were at ASH, but I think it was a really awakening moment for everyone because there is a hype around everyone had realized that manufacturing is the issue. We realized this four years ago when we started actually really putting the platform that we refer to as UltraCAR together to address the issues that the field were facing at that time. Over the years, as it became more evident how difficult the manufacturing has been and the cost of classical CARs, classical TCRs, and there were a huge hopes for off-the-shelf, people started saying, "Yes, we are developing and manufacturing rapidly, two days, one week," so on and so forth. As an article that came out at ASH and also in discussions with the KOLs of some of these trials, it became evident that actually this was a hype.
Unfortunately, neither the manufacturing time were reduced that much or the costs were reduced. With that in mind, in the next slide, this is a direct comparison of our platform and why we really use the term paradigm-shifting. That's a term that I know is very chic. A lot of people use it. What we need to address is when you look at our UltraCAR versus autologous CAR-Ts or off-the-shelf allogeneics, we truly manufacture overnight in one day. From the T-cell separation to the infusion of the patient is 24 hours. Not a week, not two days, not 10 days, not 50 days. 24 hours. We believe we are the only company that currently is capable of doing that. This is not a hope and a dream to do. This is currently happening across the sites in U.S.
We have multiple sites at Moffitt, Mayo, Fred Hutch, University of Washington, and number of other sites that are joining as we speak to be running this. The quality control release assays are done on the same day of the release, the same day of infusion, which is overnight after we have used, produced our UltraCAR. Obviously, because we don't do any centralized manufacturing and expand manufacturing for weeks outside, you can imagine that our cost is significantly lower than the others. I just wanted to show this slide and make it very clear, when everybody talks about fast CARs, rapid, vein to vein, ours is the only one that has one day manufacturing and next day infusion. This is the process that currently our patients are going through in hospitals.
I would like to highlight that no one from Precigen is present at these centers. Our manufacturing is not at the hospital. This is done at the clean room of the hospital with technicians at the hospital doing this. The T-cells are separated. They are using our non-viral system, and that is the reason that we can do this in a hospital, is they have been transfected by usage of our UltraPorator. In discussions that we have had with the FDA, we developed this device ourself in order to be able to scale up and for commercialization. You can transfect four billion T-cells under 12 minutes using this UltraPorator. The cells, this is a semi-closed system that the bag is left overnight. There's no activation, there's no addition of cytokine, there's nothing to be done to it.
Next day, the cells are QC'd and infused back to the patient directly within 24 hours. We have a mechanism here, our membrane-bound IL-15, that allows actually majority of expansion and persistence of these cells, which I refer to as second point of the manufacturing directly in a patient, as opposed to be in a centralized manufacturing facility. With that in mind, I would like to take you through some of the work that we have done. First of all, our PRGN-3006, which addresses the AML patients. Why AML patients? These patients, they have very few months to live. None of the cell and gene therapies really have the ability to get to these patients as fast, especially the classical CAR-Ts. This is I think it's a very telling slide in comparison of our platform versus what the other platforms are.
On a left-hand side, this is the expansion and persistence of our UltraCAR-T that targets CD33 for the AML patient. First of all, I like to take a pay attention to the scale, the logs of expansion that you see in the this left-hand side. Also, the doses. We have doses as low as 4 million, and the top dose that we have was up to 83 million. One dose was given. On the right-hand side, this is the two major off-the-shelf that in the AML patient population. On the top, you see that they are giving a one billion cell three times, and now actually this company has gone up to three billion. On the lower half also, you have three doses of 300 million, so close to one billion.
Please pay attention to the expansion of these cells, but more importantly, persistence of these cells. You spend hundreds of thousands on the manufacturing of this, come up with billions of cells, you put them in a patient, and at the end, 20 days or less than that, the cells are gone. This is by the way, in the exact patient population, in the AML patient population. This shows the strength of the platform of our UltraCAR platform and overnight. Not only we can manufacture it overnight, these cells are capable of expanding and persisting directly in a patient. The next question comes, are they biologically active? We showed this data at ASH, which was received extremely well.
You can see on the left-hand side, given the dose levels as low as four million cells, we have nine out of our 15 patients, 60% of the patients, they had a decrease in a bone marrow blast. On the right-hand side, you see the objective responses from our phase one dosing, and you can see that almost 30% of these patients, they had objective response, complete response or partial responses. One of them that chose to bridge, because usually these patients, they don't receive any transplant, they are not eligible for transplant, has been now living close to two years post UltraCAR-T receiving it, and is doing perfectly fine. One other important factor here is the safety. These UltraCARs have a very, very favorable safety profile as compared to the others.
Because it's regulated in such a fashion that you don't introduce billions, you don't see those issues that you might see in a classical thing. With that, we are very excited and we are expanding. Now we are in phase 1B and moving this for the efficacy. I should mention, because of the safety and preliminary data that we have shown, the FDA has granted us the Fast Track in this. Now on to our PRGN-3005, which is a solid tumor. To be honest, majority of people in oncology and gene therapy don't even get close to the solid tumors because there has been 0 success. Again, we have targeted the MUC16, the unshed portion of MUC16.
You can see on the right-hand side, very similar to what you saw in the PRGN-3006, the expansion kinetic as well as the persistence in these patients, which is quite compelling. More importantly, it's the clinical activity and the safety that you see. The patients that enrolled in this trial, they have had between six-nine prior failed therapy. They are a stage four ovarian cancer, and as you know, for the past 20 years, we haven't done at all well in this indication. 10% response rate. This is what we have after 20 years of working. What you see on the right-hand side is the scan of some of our patient baseline. We're pointing to the metastasis. This patient received 7 million T-cells intraperitoneum. That's all. 1 dose, no lymphodepletion.
You can see that there was a complete response in the metastasis. Similarly, in the second case study, this is a partial response on the lesion, and this was a large lesion in bladder, which allows and actually points to the fact that these cells do traffic. Unlike what everyone says that CAR-T don't traffic. They don't traffic classical ones because they die before they can traffic, because they are exhausted. These cells, on the other hand, they are more stem-like. You can see that obviously there is effect and there is a change in the sum of all the diameters of target lesion, which is very exciting, and that has allowed us to move into the next phase one B. Now on to our AdenoVerse platform, which is also a very exciting platform. I would like to show you a video for a minute.
I think that explains how this works much better than I can do it, and I can do it justice. For those online, I apologize you hear it, but we will have this, basically video on our website and through YouTube will be available.
Precigen discovered and developed the AdenoVerse immunotherapy platform. AdenoVerse is a library of potent proprietary adenovectors engineered for large genetic payload and repeat administration. To ensure the AdenoVerse vectors do not cause disease, they are genetically modified to be replication-incompetent. AdenoVerse vector technology allows us to engineer gene therapies that can express multiple genes in a controlled manner, creating a large genetic payload capacity, able to deliver up to 12 kilobase pairs of genetic material in vivo. Gorilla adenovectors, part of the AdenoVerse library, have very low seroprevalence in humans, which is a major advantage over current human-derived adenoviral gene therapies that are easily neutralized by a patient's own immune system. Since a patient's immune system will not recognize and neutralize it, AdenoVerse immunotherapies have the advantage of being suitable for repeat administration.
Once in the host cell, the genetic material from AdenoVerse vectors can produce a desired therapeutic response, such as expressing an antigenic protein. This can generate a high level of durable antigen-specific immune responses and elicit therapeutic T-cell activation. Importantly, Precigen's AdenoVerse vectors can be used as therapeutic vaccines to treat patients with a variety of diseases. AdenoVerse investigational therapies have been shown to promote strong antigen-specific response to direct an influx of T-cells into the tumor microenvironment, enhancing the host's immune response and decreasing tumor growth rates in patients affected by human papillomavirus, HPV-associated diseases such as recurrent respiratory papillomatosis, or RRP, and malignant cancers. AdenoVerse vaccines are manufactured using proprietary cell lines as a delivery mechanism for off-the-shelf, easily scalable gene therapies for multiple clinical indications.
Precigen's cutting-edge AdenoVerse platform delivers therapeutic vaccines that are safe for repeat administration with a large genetic payload capacity to produce durable antigen-specific immune responses, providing tremendous advantages to patients.
As mentioned.
Precigen discovered and developed the AdenoVerse.
Okay, sorry. As I mentioned, we have obviously full IP around this platform, which is quite unique and differentiated than the others. We have applied it to develop PRGN-2012, which targets HPV 6 and 11 for a recurrent respiratory papillomatosis. This is a disease that is rare disease with papilloma reoccurring continuously in the airway as well as on vocal cords. Some of the patients, they go through hundreds of surgery through their lifetime. On January 24th, I'm really excited to say that we will be presenting the data from the first 15 patients from the RRP with the full follow-up of 1 year on safety and efficacy and the clinical translational data. We are really excited about this. Dr. Allen, our investigator, will be presenting this on January 24th.
With that in mind, in this slide, you see exactly on the left-hand side. I don't think I have to say that much. You see the issue that these patients have. A regular airway trachea on the right-hand side, what you see with this papilloma. These patients, they have to go through surgery to just be able to breathe, and there is no treatment for them whatsoever. With PRGN-2012, we have been able to treat these patients. The market, and the number of the patients, worldwide. In U.S., there is estimation up to 25,000. We have taken a sort of conservative estimate of 10,000 adults and 6,000 juveniles in U.S., and the projected market for this in U.S. is over one billion. In ex-U.S., approximately again, we only have numbers approximation for the adult is 60,000 cases.
Globally, we, our research studies have shown that the market will be close to two billion. These are based on the estimates that we have. The majority of issue with these patients, since there is no other treatment than surgery, it's the cost of surgery per year for these patients and indirect costs that the patients have to incur because majority of these patients actually cannot work. They can't use their voice, and every surgery actually makes their situation worse because of a scar tissue that's developed continuously. For that reason, this is, even as a rare disease, is extremely important unmet need, and we are really excited that we can provide a treatment for this patient population.
Here in November of 2021, we show a case study, whereas in January of 2023, we will show a full phase I and expansion cohort of 15 patients. You see from the baseline of the patient on the left and then after treatment. Obviously, at that point, we had a short follow-up, and now all of our patients that we will be presenting, they have been follow-up for a full year, and we will be presenting that data. On the right-hand side, you see that this off-the-shelf vaccine does exactly what it is supposed to do, initiate and expand a specific HPV T-cells. The basically red, green, and yellow that you see, these are T-cells. They are inside the papilloma, which they didn't exist before. That's the mechanism.
With that in mind, we are looking forward to our presentation, R&D presentation on January 24th with Dr. Allen. Finally, we have used our AdenoVerse platform in PRGN-2009, targeting HPV 16 and 18, which is prevalent in all of the HPV indications, especially cervical, head and neck, anal. As you see on the right-hand side, the disease snapshot, this is 5% of all cancers. They are estimated of 690,000 cases, and the estimated market opportunity growth for all the treatments in this field by 2030, it's estimated at more than $10 billion. What does that mean for our PRGN-2009?
What you see was we started a phase one and phase two study, and we have reported on immune phase one, which we had patients that they had a stable disease for almost two years. More importantly, when we went to the patients that they have failed checkpoint inhibitors. By the way, for cervical cancer, for head and neck, checkpoint inhibitors are the treatment, and the efficiency 15%. 85% of women with cervical cancer fail. Head and neck is 18%. 82% of the patient, they failed. What we did, we positioned the PRGN-2009 in these checkpoint inhibitor failure patients, and we followed them, and you see the numbers. We had a 40% overall disease control. These are stage four patients that they have failed everything. You can see that we had a 30% objective response.
In cervical cancer, two out of the two patients that they enrolled, they showed objective responses, and in head and neck, one out of the seven. Interestingly enough, we had durable responses. We have CR and PRs, our CR, actually, one of the patient, as you can see, is up to 400 days post-injection. We have the scan that shows that it's complete reduction of the tumor in this scan. This is quite exciting because currently, again, for this patient population and a large indication, there's really nothing out there. By the way, PRGN-2009, very similar to PRGN-2012, extremely safe. These patients, they have received upward of 16 injection per month. Every month, they have received one. Safety looks very similar to the flu vaccine that you get looks like. Some rash, some fatigue, and then you're fine.
We have reported on a preliminary data on a phase 1B. This first half of this year, we will be reporting on a complete combination. With that in mind, I would like to go to our summary and what is our major goals. I believe we have shown that we really had a very significant year in 2022 for our clinical trial and advancing it. For 2023, we are moving in continuing enrollment in PRGN-3006 in phase 1B across multiple centers, and we expect to report the full phase 1B data for 2024. This is important in regard to PRGN-3006. This patient population has nothing in front of them.
With the phase 1B data, if it's a solid data, this really allows us to start the discussion in regard to a rapid regulatory path, especially that FDA has already granted us the Fast Track for those discussions. PRGN-3005, very similar. Expansion to phase 1B, multiple centers, expectation for the data presentation is in 2024 when we have completed the enrollment and follow-up of this patient. We also initiate our dosing of PRGN-3007, we will report on a full set of data from phase one in 2024. As far as AdenoVerse, PRGN-2012 is we will be reporting, as I mentioned in January 24th, we are very excited about.
At the same token, we have been enrolling to our phase two, and up to date, we have enrolled close to 20 patients in our phase two currently. We will be finishing the enrollment in a phase two very early on this half of the year. We are in discussions with the FDA for a rapid regulatory path, and we are moving toward commercialization. In regard to our PRGN-2009, which targets HPV indications such as cervical and head and neck, the phase 1 monotherapy and combination therapy data will be presented the first half of this year. We expect that the first half of 2023. I'm sorry, the second half, we will be presenting the interim data from our phase two monotherapy in a newly diagnosed head and neck patients that we have.
With that, I'd like to thank the audience and the organizers for allowing us to present our advancement of our portfolio. Thank you.
Thank you, Helen, for such a great presentation. Just wanted to remind those online, please feel free to submit your questions through the webcast. Before I begin, passing it over to the floor, I just wanna kick off with a few questions. Helen, you mentioned the AdenoVerse platform and showed us a very informative video. You mentioned about the virtual R&D day that's coming up on January 24th. I'm sure we're all very excited about that. Can you just provide us a little more sort of details on what to expect for the upcoming readouts?
Absolutely. For our PRGN-2012, we actually waited until the last patient from the cohort, meet the 12 months because we did not wanna present a data that is not a complete set. What we will be presenting is the every single patient pretreatment, the history and number of surgeries that they have versus post-treatment and how our treatment has affected that, reduced or eradicated it. At the same token, we will present the full safety, efficacy, and the translational science of that, and this is presented by Dr. Allen, which is world-renowned in this field, and he will be presenting the full set of data. Fifteen patients in a rare disease, this is a very respectable number of patient because we are not talking about the oncology that they have hundreds of thousands of patients.
That would be very, I would say, highly relevant number of the patient for this kind of disease.
Perfect. Thank you. Just a follow-up question. You recently gave a data update on the sort of AML CAR-T, which is very helpful to understand, you know, your ongoing sort of clinical progress. This is understood to be a very clinically challenging population. Can you just provide a little more details on your update and then what the significance of this is?
Absolutely. One of the reasons that we went to the AML, everyone asked us, they said, "Why, why did you guys choose this indication?" The reality of the situation was we went to an indication that we knew that the patient can never receive a cell therapy, CAR therapy, because the time of the manufacturing would have been longer than the patient lived. Our platform that produces and generates the CAR-T within 24 hours the next day, we thought this is ethically it's our responsibility to do this. Yes, we did choose a very difficult challenging, basic indication.
However, the fact that we have been able to manufacture and present across the board, get to the patient within one day, and then have complete responses and partial responses in a patient population that actually some of them came out of hospice to receive this for us is extremely important because precision medicine has to be able to be tailor-made to the patient. It has to be able to be available for every patient, and the price tag should be at the point that can be used by physician and all patients. That was the reason.
I think the data of persistent kinetic manufacturing and finally objective responses is really spoke to that. That was why, for instance, we have sites such as Mayo Clinic coming on board, Moffitt and others because it's important. The importance of this to get to this patient rapid.
Thank you. I'll open it up to the floor. Any questions? Nope. with just five minutes left, I have one follow-up question.
Sure.
Helen, you mentioned a lot about 2022 being, you know, a great year of clinical and fiscal success, and seems like you have a lot of upcoming readouts that are very significant for obviously the company. What's the long-term vision for Precigen?
Definitely, I think for us it's very clear, bringing in good drugs to patients with the cost that it's applicable to everyone and precision medicine. Getting a cell and gene therapy to the point that it's not a dream of the 21st century, but it's a reality of our decade and we can get it to the patient. Our vision is to address the issues that are in solid tumors because we need that. As a woman, ovarian cancer is very close to my heart. Every time that I hear 10% of the patient only they can survive or benefit, this is clearly we have to do better than this. For Precigen, I think we have the tools to address this.
We have the platforms that we took great pain to, basically comprehensively move to the point that it can be a scale-up and get to the patients. Now it's time for Precigen to put this in, expanded trials.
Mm-hmm.
Also show the further efficacy of this platform and get to the patients and hopefully commercialization path that then every patient has access to that. That's our vision.
Thank you. Thanks again, Helen, for a great presentation and Q&A. Thanks to you, joining us online and in person. Thanks a lot.
Thank you.