PGEN - NASDAQ

Good evening and welcome to the Precigen’s Second Quarter and First Half 2024 Financial Results Call. At this time, all lines are in a listen-only mode. Following the presentation, there will be a question-and-answer session. [Operator Instructions] Please note, this event is being recorded. I would now like to turn the conference over to Steve Harasym, Vice President of Investor Relations. Please go ahead.

Thank you, Jenny, and thank you for everyone joining us this afternoon. With me today are Dr. Helen Sabzevari, President and CEO of Precigen; Harry Thomasian, our CFO; Phil Tennant, our Chief Commercial Officer, and our Chief Operating Officer, Rutul Shah. Before we begin, let me briefly review our forward-looking statements. During today's call, we will make various forward-looking statements. Investors are cautioned that our forward-looking statements are based on current expectations and are subject to risks and uncertainties that could cause actual results or outcomes to differ materially from those indicated by forward-looking statements. Please read the Safe Harbor Statement contained in our most recent SEC filings, as well as risk factors contained in Precigen’s filings. With that, I would like to now turn the call over to Dr. Sabzevari. Helen?

Thank you, Steve, And thank you to all joining us today. It is a pivotal time at Precigen, as we work hard to get what could be the first FDA approved treatment for the devastating recurrent respiratory papillomatosis disease, or as we know it, RRP, to the market. What I would like to do at the beginning is take you through some of the key programs and business highlights and then go through some of the strategic prioritization that has been communicated recently. Let me start by talking about PRGN-2012, which is the focus now of our portfolio. As you know, PRGN-2012 is our adenovirus gene therapy, that is designed to elicit immune responses directed to HPV6 and HPV11, infected tumors and to raise the immune system to both of these epitopes, both HPV6 and HPV11, for the treatment of recurrent respiratory papillomatosis. Let's establish some of the facts upfront in regard to our PRGN-2012. As I mentioned, it's delivered by our gorilla adenovectors and it's a gene therapy. It's delivered subcutaneously. It does not require any kind of a device. So it's an ease of administration that can be done at any office setting, for instance. The second important part of this gene therapy treatment is that our gorilla adenovectors platform in general and the viral vector that is used for delivery of PRGN-2012 is differentiated from other viral vectors. Even though there is this perception that all viral vectors are similar, and therefore they can be given a very limited number of times, perhaps only once or twice, and they cannot be used in redosing because humans have pre-immunity to them. This is not applying to the gorilla adenoviruses. And why do I say that? Simply, humans either have zero pre-immunity or very little pre-immunity to these vectors. And by the way, these vectors are designed in such a way that elicit a high affinity T-cells and they push toward the CD8 responses. And therefore, in a number of clinical trials that we have done across various indications, we have shown over a period of time you can keep re-dosing with these vectors and keep enhancing the immune responses and especially high affinity CD8 T-cell responses. So I just wanted to clarify that fact. This is one of the differentiating factors of our gorilla adenovirus platform in general compared to other AAV and viral delivery vectors. And also, these gorilla adenoviruses allows us to have a high payload that then we can put many epitopes and many genes. And therefore, when I say that we are targeting HPV6 and HPV 11 and raise immune responses to both, we have shown that and we have shown that in the clinical trial. Now with that in mind, what have we done with the PRGN-2012? As you are well aware, in the PRGN-2012, it's the first drug ever received a breakthrough designation and an accelerated path from FDA in June of 2023. And with that designation, we also had received the orphan drug designation from the FDA, as well as EMA. The interesting part of this was that because we had designed our clinical trial in such a way that, first of all, addressed the most advanced patients and most patients with the highest number of surgeries and also already put a very robust end point, not just reduction in the number of surgeries, but actually having safety and efficacy that leads to a complete response to the severe patient population that at least maintain for a whole year, that they do not require any surgery and beyond. As a result of that, the FDA agreed that our Phase I single arm trial, as well as our phase 2 single arm trial can serve as a pivotal trial and we did not have -- and we have not been required to do any kind of randomization or placebo control trial in that setting, and that is very important. And one other aspects that I want to stress here, it is, and FDA agrees that these patient populations, they are their own best control and therefore by having such a higher standard of not only in the number of -- being in a severe patient population, but also a robust endpoint that negated the need for having a randomization or placebo control. So let's just take a look at what happened as a result of our Phase 1 and Phase 2. We had enrolled 12 patients in our Phase 1 and 23 patients in our Phase 2 single arms. And we recently in June actually presented the full set of data, both from Phase 1 as well as Phase 2, the breakthrough session at ASCO. And what was there -- and it was received extremely well by investigators as well as our patients and patients in RRP for a number of reasons. First of all, if you look at the primary safety of this, it's extremely favorable and it's also the efficacy when you look at the end point for this trial, which was a complete response, meaning that the patient to go from number of surgery, which the average was 4.5 surgery prior year before the treatment to completely zero surgery requirement. 12 months follow-up and we have been, by the way, following these patients for a durability of response which we have seen quite adorable responses in this patient population. 18 out of 35 of these patients went to a complete response. That's 51% of the population. If you look at our secondary endpoint, which was the reduction in the number of surgeries, now we have 30 out of 35 patients. They reduced their number of surgeries. That's 86% of our population that was treated. This has been an unprecedented result by any treatment for this patient population. There has never been a data that was presented with this robustness of the endpoint as well as the safety and also being in the most severe patient population that clearly it -- really is the much tougher treatment to be treated, not only in this disease, in any disease in general, as we all agree. So I think this was quite exciting and, as I mentioned, in 2023, in June 2023, we received the accelerated approval path and the rolling BLA and our submission, we are on track to submit our BLA by the end of this year in 2024. We also -- what I'm very excited about is that we have initiated our enrollment in the confirmatory trial already and this we had reached an already agreement with the FDA that by the way our confirmatory trial are also single arm, no placebo requirement, no randomization, which as you can imagine it's going to make things extremely challenging for these patients if you have to randomize because each patient is their own best control. And the randomization is quite challenging, and this is what all the investigators believe as well. We already not only have initiated the confirmatory trial, which is part of submission of the BLA, but we have started the enrollment and I have to say that we are quite taken by the number of the patients that they already have shown excitement to participate in our confirmatory trial. On the side of our commercial scale for drug substance manufacturing, also our facility is operational. And we are quite confident that we can adequately provide the doses for both US and ex-US on a potential launch. And as part of our patient advocacy effort this year, we had the joint recurrent respiratory papillomatosis inaugural RRP awareness day on June 11, because this disease is actually as a result of infection by HPV6 and HPV11, therefore June 11. And we are really excited that we have been working very, very closely with RRP Foundation to advance this innovative treatment for the patients in this setting. So with that in mind, just to recap what we have done and why we are so excited and so focused on PRGN-2012 is we have established a well-differentiated innovative therapy that doesn't require any device. You can give it subcutaneously. It elicits immune responses to the root cause of these benign tumors which take place under trachea or the vocal cords of these patients and causes devastating scenario for these patients. And as a result of the mechanism of the action and the safety, advanced safety that we have shown, these patients we get 51% of these patients going to a complete response, 86% of them reducing their number of surgery. The durability of the response, the median has not been reached at this point is 20 months. Our Phase 1 patients that they have been obviously have a much longer follow-up have surpassed 32 months of the durable responses and have not required any surgery. So with that, we believe that this -- and we are extremely excited that this drug has the potential to be quite effective for RRP patients and the first drug has the potential to receive the first drug ever approved by the FDA. So in that process, we also have been preparing for the potential commercialization of the drug in 2025. And in that setting, I am thrilled to welcome Phil Tennant as the Chief Commercial Officer for our company and we have been very excited that Phil has joined the leadership and now currently leading all activities around the commercialization for PRGN-2012. And I would like to hand over actually to Phil to hear from him and his perspective on the commercial path of PRGN-2012. Phil?

Thank you, Steve, And thank you to all joining us today. It is a pivotal time at Precigen, as we work hard to get what could be the first FDA approved treatment for the devastating recurrent respiratory papillomatosis disease, or as we know it, RRP, to the market. What I would like to do at the beginning is take you through some of the key programs and business highlights and then go through some of the strategic prioritization that has been communicated recently. Let me start by talking about PRGN-2012, which is the focus now of our portfolio. As you know, PRGN-2012 is our adenovirus gene therapy, that is designed to elicit immune responses directed to HPV6 and HPV11, infected tumors and to raise the immune system to both of these epitopes, both HPV6 and HPV11, for the treatment of recurrent respiratory papillomatosis. Let's establish some of the facts upfront in regard to our PRGN-2012. As I mentioned, it's delivered by our gorilla adenovectors and it's a gene therapy. It's delivered subcutaneously. It does not require any kind of a device. So it's an ease of administration that can be done at any office setting, for instance. The second important part of this gene therapy treatment is that our gorilla adenovectors platform in general and the viral vector that is used for delivery of PRGN-2012 is differentiated from other viral vectors. Even though there is this perception that all viral vectors are similar, and therefore they can be given a very limited number of times, perhaps only once or twice, and they cannot be used in redosing because humans have pre-immunity to them. This is not applying to the gorilla adenoviruses. And why do I say that? Simply, humans either have zero pre-immunity or very little pre-immunity to these vectors. And by the way, these vectors are designed in such a way that elicit a high affinity T-cells and they push toward the CD8 responses. And therefore, in a number of clinical trials that we have done across various indications, we have shown over a period of time you can keep re-dosing with these vectors and keep enhancing the immune responses and especially high affinity CD8 T-cell responses. So I just wanted to clarify that fact. This is one of the differentiating factors of our gorilla adenovirus platform in general compared to other AAV and viral delivery vectors. And also, these gorilla adenoviruses allows us to have a high payload that then we can put many epitopes and many genes. And therefore, when I say that we are targeting HPV6 and HPV 11 and raise immune responses to both, we have shown that and we have shown that in the clinical trial. Now with that in mind, what have we done with the PRGN-2012? As you are well aware, in the PRGN-2012, it's the first drug ever received a breakthrough designation and an accelerated path from FDA in June of 2023. And with that designation, we also had received the orphan drug designation from the FDA, as well as EMA. The interesting part of this was that because we had designed our clinical trial in such a way that, first of all, addressed the most advanced patients and most patients with the highest number of surgeries and also already put a very robust end point, not just reduction in the number of surgeries, but actually having safety and efficacy that leads to a complete response to the severe patient population that at least maintain for a whole year, that they do not require any surgery and beyond. As a result of that, the FDA agreed that our Phase I single arm trial, as well as our phase 2 single arm trial can serve as a pivotal trial and we did not have -- and we have not been required to do any kind of randomization or placebo control trial in that setting, and that is very important. And one other aspects that I want to stress here, it is, and FDA agrees that these patient populations, they are their own best control and therefore by having such a higher standard of not only in the number of -- being in a severe patient population, but also a robust endpoint that negated the need for having a randomization or placebo control. So let's just take a look at what happened as a result of our Phase 1 and Phase 2. We had enrolled 12 patients in our Phase 1 and 23 patients in our Phase 2 single arms. And we recently in June actually presented the full set of data, both from Phase 1 as well as Phase 2, the breakthrough session at ASCO. And what was there -- and it was received extremely well by investigators as well as our patients and patients in RRP for a number of reasons. First of all, if you look at the primary safety of this, it's extremely favorable and it's also the efficacy when you look at the end point for this trial, which was a complete response, meaning that the patient to go from number of surgery, which the average was 4.5 surgery prior year before the treatment to completely zero surgery requirement. 12 months follow-up and we have been, by the way, following these patients for a durability of response which we have seen quite adorable responses in this patient population. 18 out of 35 of these patients went to a complete response. That's 51% of the population. If you look at our secondary endpoint, which was the reduction in the number of surgeries, now we have 30 out of 35 patients. They reduced their number of surgeries. That's 86% of our population that was treated. This has been an unprecedented result by any treatment for this patient population. There has never been a data that was presented with this robustness of the endpoint as well as the safety and also being in the most severe patient population that clearly it -- really is the much tougher treatment to be treated, not only in this disease, in any disease in general, as we all agree. So I think this was quite exciting and, as I mentioned, in 2023, in June 2023, we received the accelerated approval path and the rolling BLA and our submission, we are on track to submit our BLA by the end of this year in 2024. We also -- what I'm very excited about is that we have initiated our enrollment in the confirmatory trial already and this we had reached an already agreement with the FDA that by the way our confirmatory trial are also single arm, no placebo requirement, no randomization, which as you can imagine it's going to make things extremely challenging for these patients if you have to randomize because each patient is their own best control. And the randomization is quite challenging, and this is what all the investigators believe as well. We already not only have initiated the confirmatory trial, which is part of submission of the BLA, but we have started the enrollment and I have to say that we are quite taken by the number of the patients that they already have shown excitement to participate in our confirmatory trial. On the side of our commercial scale for drug substance manufacturing, also our facility is operational. And we are quite confident that we can adequately provide the doses for both US and ex-US on a potential launch. And as part of our patient advocacy effort this year, we had the joint recurrent respiratory papillomatosis inaugural RRP awareness day on June 11, because this disease is actually as a result of infection by HPV6 and HPV11, therefore June 11. And we are really excited that we have been working very, very closely with RRP Foundation to advance this innovative treatment for the patients in this setting. So with that in mind, just to recap what we have done and why we are so excited and so focused on PRGN-2012 is we have established a well-differentiated innovative therapy that doesn't require any device. You can give it subcutaneously. It elicits immune responses to the root cause of these benign tumors which take place under trachea or the vocal cords of these patients and causes devastating scenario for these patients. And as a result of the mechanism of the action and the safety, advanced safety that we have shown, these patients we get 51% of these patients going to a complete response, 86% of them reducing their number of surgery. The durability of the response, the median has not been reached at this point is 20 months. Our Phase 1 patients that they have been obviously have a much longer follow-up have surpassed 32 months of the durable responses and have not required any surgery. So with that, we believe that this -- and we are extremely excited that this drug has the potential to be quite effective for RRP patients and the first drug has the potential to receive the first drug ever approved by the FDA. So in that process, we also have been preparing for the potential commercialization of the drug in 2025. And in that setting, I am thrilled to welcome Phil Tennant as the Chief Commercial Officer for our company and we have been very excited that Phil has joined the leadership and now currently leading all activities around the commercialization for PRGN-2012. And I would like to hand over actually to Phil to hear from him and his perspective on the commercial path of PRGN-2012. Phil?

Great. Thank you, Helen. Thanks, everybody. Great to be here with you this afternoon. Please let me take a few moments to make some introductory comments about myself, and then some remarks about the commercialization efforts of PRGN-2012. So I'm now into my fourth decade in the industry. And a common theme for my experience across the industry has been launch activity, experience of global launches, launches in the UK, Europe, Japan, Australia, and now the US. And one of the common threads running through those launches has been the setting of new treatment paradigms and new standards of care, particularly in my most recent oncology experience. And many of those diseases have been rare diseases. They've been areas with high unmet need and few if any treatment options for patients. And so I'm aware of the impact that successful treatments can have on patients, on families, and on the broader healthcare system. And so PRGN-2012 absolutely fits into that category, which is why I'm excited to be here and I'm excited for the potential for launch. Helen, I think, did a great job in summarizing the compelling clinical offering that this drug has, you know, the reduction in the complete response rate of over 50%, the 86% of patients who see a reduction in surgeries. And we've actually heard from patients that the reduction of a single surgery is extremely meaningful. So we appear to have a very effective treatment, well tolerated, and it could reduce the burden on patients and the healthcare system quite considerably. The commercial team to date has been laying a lot of the groundwork for market access, for distribution. And now with me coming on board, we're beginning to really ramp up our full commercial launch preparation activities across marketing, sales, thought leader engagement, Congress activity, publications, and so on. So it is a very exciting time for the organization and a great moment for me to join. In terms of timelines, many of the commercial timelines are, of course, derived from the BLA submission timing, and so that's a very important milestone for us. There is a lot to do in, hopefully, a relatively short space of time, so that we can bring this treatment to patients in 2025. And in thinking about commercial build out, it is a rare disease, so the Salesforce footprint will need to be precise. But just as importantly, we need to think in parallel about our medical affairs organization, particularly the customer-facing component of the medical affairs team, so that we can deliver an integrated and seamless experience to our patients and our customers. And we look forward to making significant progress here during the remainder of this year and into 2025. So we continue to believe that this indication represents a significant market opportunity based upon the very high unmet need, the safety and efficacy results that we've seen, and the prescriber preference in our market research. So with that, Helen, I'll hand back to you.

Thank you very much, Phil. So what I would like to do in this part of the talk is really focus on our strategic prioritization. As a result of prioritizing PRGN-2012 for all the reasons that we mentioned and we are excited about for a potential commercial launch. Last week we announced a series of strategic initiatives. Before I go and explain this, first of all, I would like to thank our Chief Operating Officer, Rutul Shah, who is here today with us, for not only all the tireless work that he has done over the years for the buildup of this organization, but also especially the important role that he has played in really at this point for the strategic prioritization and some of the -- especially the operational aspects that we had to change and rapidly focus on our PRGN-2012. So, I really thank Rutul for all of the hard work. Let's start by pointing out that as part of this strategic prioritization, we had to make the difficult decisions to implement a reduction of over 20% of our workforce, which is always extremely difficult. However, in this sense, we had to redirect resources to our PRGN-2012. In the clinic, we have implemented also various cost-saving measures as well. For instance, for PRGN-2009, which is the treatment in a recurrent/metastatic cervical cancer as well as in head and neck related -- HPV related cancers. We have focused the trials through our CRADA at NCI, NIH and the PRGN-2009. It continues to advance through our CRADA partnership with National Cancer Institute. In regard to our UltraCAR-T, as you are aware, we had two – three clinical programs and what we have done is we have announced the complete enrollment of PRGN-3006, which is our UltraCAR-T acute myeloid leukemia, AML patients. Last year we had reported on our Phase 1 data of the AML patients that they were treated with PRGN-3006, and if you recall these are patients that they have failed number of treatments that unfortunately have very few months to live. And it was very exciting that we had reported more than 27% objective responses in a very, very challenging patient population with our PRGN-3006. Our patients had both complete responses as well as partial responses. And by the way, our PRGN-3006 has received the Fast Track designation from the FDA. So, I'm excited to announce that we have finished the phase 1b of this. And we are preparing to move forward for discussions with the FDA in regard to the strategies for next steps. In regard to our PRGN-3005 in ovarian cancer and 3007, our ROR1 CAR, the trials -- in order to minimize the spend, we have paused these trials currently. We are also looking at continuing to focus on a strategic partnership to further advance our UltraCAR-T platform. In addition, we also have all our pre-clinical programs across the company at this moment. Finally, we also have initiated a shutdown in ActoBio. It's our Belgium-based subsidiary. Their portfolio and IP remain available for prospective transaction, of course, as we move on. As I mentioned, with that -- what we have done is really try to focus our resources on the highest priority asset, which is our PRGN-2012, and prepare for a potential launch. And now, with having felt by our side that we are excited to prepare for a potential launch globally for this drug. So with that, I will now turn the call over to Harry for the financial update. Harry?

Thank you, Helen, And good afternoon to all of those on the call today. As Helen mentioned earlier, it is a pivotal time for Precigen with our recently announced asset prioritization and what could be the first FDA approved treatment for RRP patients in the near future. Before I talk about the company finances, I also want to publicly welcome Phil Tennant to the Precigen team. We're excited about the value that Phil has brought to the table in the short time that he's been with Precigen, and I look forward to working with him as we prepare for the anticipated commercial launch of PRGN-2012. I want to first touch on our recently announced prioritization of assets and the successful issuance, equity issuance, that we completed last week. Based on the prioritization of assets, which will result in streamlining of operations, the company expects to significantly reduce future operating costs. Last week's equity issuance netting $31.4 million plus our cash and investments on hand, which totaled $19.5 million at June 30th, will provide a runway into early 2025. I've had many investors ask the question as to why we did not raise more than the $31.4 million. The short answer is that our -- is our opinion that the company is fundamentally undervalued. In addition, the proceeds received last week allows us to focus on the advancement of PRGN-2012 in the near-term, while providing us the time to consider various financing options inclusive of non-dilutive options. Our focus has and always will be to utilize our resources to garner the highest value for our shareholders. With that being said, from a high level Q2 financial results perspective, our net loss for the quarter ended June 30th was $58.8 million or $0.23 per share compared to a net loss of $20.3 million or $0.08 a share in the period ended June 30, 2023. It should be pointed out that the 2024 period net loss includes $32.8 million of non-cash impairment charges net of tax benefit specific to our ActoBio business. We filed our 10-Q, as well as our quarterly press release on financial results and business update with the SEC just prior to this call. You can find more detailed financial information in those documents. With that said, I'd like to open the call up for Q&A. Operator?

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. [Operator Instructions] Your first question is from Ben Burnett from Stifel. Please ask your question.

Hello, good afternoon. This is Carolina Ibanez Ventoso for Ben Burnett. Thank you for taking our question. To start with, recently a close competitor has announced it has delayed its BLA filing. What are the gating factors for you to commence the rolling BLA submission of PRGN-2012? And this way ensure you keep a [lead in] (ph) RRP.

Hi, Carolina, and thank you for the question. So in regard to -- obviously we are laser-focused on our submissions. And as we have guided before and continue to guide, we anticipate to submit our BLA by the end of 2024 and we are on track for that. I think we're -- as I mentioned, We are really excited about our PRGN-2012 and the differentiation of this gene therapy treatment. For the ease of the treatment, which is a Sub-Q injection and does not require any kind of devices and the complexity there, as well as obviously the safety --favorable safety, supported by really outstanding efficacy that we see as far as complete responses followed by also secondary endpoints of reduction in the number of surgeries. So with that, I would just guide that we continue to focus our efforts on our drug treatment and really positioning it for potential launch in 2025.

Okay, understood. And then as a follow up, given that PRGN-2012 represents a novel therapeutic modality for RRP, do you think you will get an outcome meeting? And what can you do to prepare for it if there is one? Thank you.

Thank you. I think These are questions that obviously we cannot answer if there are outcome meetings. And in general, the way I look at these things, it's -- that it's always FDA has that call to have outcome meetings. But in general, when you look at the diseases, the outcomes come at the time that there are perhaps -- there are questions in the consistency of the data or in the various, let's say groups. And in this case, what I like to express is that if you look at our two pivotal data, it’s -- the consistency is actually really amazing. In a Phase 1, which we recruited -- which were 12 patients enrolled, we had 50% complete responders. And basically, in Phase 2, we had 52% complete responders. So, you cannot come any closer in a clinical trial at this kind of data. And same thing, by the way, for our secondary endpoints and immunological responders. So the way I usually answer this question [ad comps] (ph) are always at the discretion of the FDA, and it's not according to the companies, but also we believe that our clinical data has met both primary and secondary endpoints completely, And I think the data spoke for itself at ASCO.

Got it. Much appreciated.

Thank you. Your next question is from Jason Butler from Citizens JMP, please ask your question.

Hi. Thanks for taking the question. Just had one for Phil Tennant, as he joins the company. I'm wondering if you could just give us his high level thoughts on what attracted him to the opportunity, how he thinks about the opportunity and RRP and what the priorities will be in the coming months as the BLA is submitted and reviewed by FDA. And then I have a follow up, thanks.

Hi Jason, Phil?

Sure, Yeah, I think, thanks for the question. I think I alluded to that in some of my comments earlier. You know, given my history, particularly in oncology, some of the rare diseases that I've worked in, the rare tumors, the high unmet need, the lack of available treatment options for patients. You know, I am aware of where therapies can have such a significant impact on patient populations, on caregivers, on the healthcare system. And so, you know, this is one of those areas that I think fits into that category perfectly. A very high unmet need. Nothing other than surgery and multiple surgeries at that for most patients. And it's crying out for therapeutic alternatives. And so, you know, that's fundamentally the attractive nature of this disease for me. It's consistent with what sort of kept me going in my career to-date and it's an opportunity that I relish as we go forward. The priorities moving forward as you would expect, time is ticking so as I come on board it's really about right sizing the opportunity and then commensurate with that making sure our commercial footprint and our build is appropriate, that we understand who the treating healthcare professional is, we understand the multidisciplinary approach to the patient, we understand the patient journey, and we build our commercial and our medical affairs teams accordingly, so that we can best support the patient -- best support the customer, and make this as seamless as possible to get this new treatment to those patients who obviously are in need of it.

Great. Helpful. Thank you. And then, Helen, can you just talk about, in terms of the strategic prioritization, how we should think about the UltraCAR-T programs? I guess two-part question here one, for PRGN-3006, will we get a clinical update or an update on the clinical data this year? And how are you thinking about, or what is the interest level or prioritization already been on looking for partners for these programs?

Yeah. No, and thank you Jason for the question. So in regard to our UltraCAR-T, first of all, I have to mention we are extremely still very excited about this platform. As I have mentioned and I will continue to say that this is currently the only platform that it can deliver autologous CAR-T overnight in a setting of the hospital to the patient with substantially less cause. And not only doing that, the manufacturing is really, it's the paradigm shifting and we have been treated now more than 70 patients that it speaks to the ability to do this at the hospitals and treat the patients. And not only from a perspective of a safety which has shown a very favorable safety but also directly manufacturing these UltraCAR-Ts in the patients and also seeing objective responses. So we -- the reason for what we have done as far as pausing some of the two trials they were going, obviously, has been really focusing on PRGN-2012 and our basically commercial preparedness for potential launch for 2012 and next year. And that doesn't mean that we -- the value of our UltraCAR-T platform is any less than before our excitement about that. However, we had to take the tough decision and give the priority to what requires the priority at this moment. However, what we have done, and I'm very proud of our clinical team, is that we have finished actually our Phase 1b in our most advanced PRGN-3006, basically in AML indication. And we will be in -- as we move forward, then we will communicate about the data and the guidance on showing the data. However, what we are currently doing, as you know, we have received a Fast Track designation, which is very important especially in this setting where interactions with the FDA. So we are going to use that and prepare for a phase 1b meeting and then discuss the regulatory strategy for advancement of this in the upcoming months to next to 2025. So we are excited about that and we will continue with those activities. But at the meantime, since we have finished the enrollment of the patients for the Phase 1b, obviously we are not [occurring] (ph) the clinical cost that is related to this asset. And that, again further helps to put our resources on 2012.

Great. Thanks for taking the questions.

Sure. Thank you, Jason.

Thank you. [Operator Instructions] Your next question is from Swayampakula Ramakanth from H.C. Wainwright. Please ask your question.

Thank you. This is RK. Good afternoon, Helen, Rutul, Phil and team. So on the 2012 program, you know, would we see any additional data at all until you start talking about the confirmatory study. And I have a couple more questions after that.

Sure. Hi, RK. Thank you for the question. So we have shown both Phase I and Phase 2 data, especially at ASCO, all the data was presented including the safety, as well as the efficacy, tolerability, and durability, and immunological responses. So, and as I mentioned, we have met the requirement and actually exceeded the requirement for the meeting the endpoints of the both Phase 1 and Phase 2. We are currently, obviously as I have mentioned, we are preparing for a BLA submission and rolling BLA by the end of this year. So there would be no further data because the data is what FDA had asked us from Phase 1 and Phase 2 and that has been completed. Of course, one of the things that is ongoing with our patients is the durability of response and those patients that they have participated in a Phase 1 and Phase 2, they continue to be followed by their physicians, as they move on and that data will be followed and of course reported accordingly at times.

Okay. And then in terms of applications to regulatory authorities, is there any -- are you folks discussing a potential submission in Europe for the same indication?

Excellent question. So as I mentioned, we had already engaged with EU authorities and ex-US as we not only received the orphan drug designation, but we have obviously initiated our efforts globally. I don't go to all the details for strategic reasons, but we are very excited about the potential of PRGN-2012 in ex-US and Europe. And as I mentioned, our facility, commercial facility, as they have started their manufacturing, we have every confidence that by 2025 we will be in the position to provide the drug globally, both for US as well as ex-US. So we are excited about that and we look forward to that. And I leave it at that.

Okay. And then one last question. This is for Phil. Since this is a rare indication, what sort of a, you know -- what size of a commercial team do you need to set up before you get into the market?

Yeah, that's a great question. As I mentioned earlier, because it is a rare disease, we have to be precise in our thinking. The footprint doesn't need to be, we're not talking hundreds of sales team, for instance. We're talking tens. But the important thing that I would stress is that we combine that with our thinking on medical affairs. So we have a joined up approach from an internal perspective to our external environment. So it's going to be a small but perfectly formed team, hopefully, particularly in terms of the customer-facing aspect.

Perfect. Thank you. Thanks for taking all my questions.

Thank you.

Thank you. Your next question is from Brian Cheng from JPMorgan. Please ask your question.

Hi. Thanks for taking our question this afternoon. This is [Shawn] (ph), on for Brian. Could you remind us what the bar for response you have to see in your confirmatory trial is? And based on your conversations with the agency, do you need to complete enrollment in this confirmatory trial before you receive the approval?

Yes. Very good question. Thank you, Shawn. So the bars for confirmatory trial is similar to what we had for Phase 1 and Phase 2. The design is also exactly the same. As we have mentioned, we do not have to -- it's a single arm And no randomization, no placebo control required, which as you can imagine, that can be quite challenging enrollment to the placebo or randomizing these trials, the Phase 3 trials. And as far as part of the accelerated path, of course, there's a confirmatory trial, but it only needs to be initiated at the time of a BLA submission. And also, it's not a requirement for approval that you have finished the confirmatory trial. However, as I mentioned, we are really excited. Not only we have already initiated our confirmatory trial, we have enrolled to our confirmatory trial. And based on the reaction of the patients and what we hear from investigators, that there is a tremendous interest, especially based on the safety and the efficacy that was presented at ASCO by patients to enroll into these confirmatory trials, which obviously being single-arm, no randomization, and exact same designs as we had before. And with the patient population that is extremely interested in basically enrolling, we are really excited at what we can do with this innovative treatment for our patients.

Thanks for the additional color.

Thank you. Your next question is from Jennifer Kim from Cantor Fitzgerald. Please ask your question.

Hi. Thanks for taking my question. Maybe a follow-up to the last question on the confirmatory trial. Can you talk about what you would expect the pace of enrollment in that trial to look like, maybe in comparison to the prior trial?

Yeah. Hi, Jennifer. Excellent question. Actually, if you recall, the way our Phase 1, but maybe I give, if you allow me to give a little bit of the history of this. We started our Phase 1 arm in, I would, I think April or May of 2021 in the midst of COVID. And we have finished the enrollment of our patients by December of 2021 to our Phase 1. So you can imagine we had 30 patients in a dose level 1 and 12 patients in dose level 2 and 15 patients, we had already finished in the span of a little bit more than six months. We had started our Phase 2 single arm in January of 2022, And we finished in May of 2023, and that was 2023 patients that we again recruited in really a very short amount of time. And by the way, all of the 35 patients during the COVID, and at that point we had not really, in the middle of our Phase 2, we had started showing our Phase 1 data. So, you can imagine now after ASCO and basically the reception that PRGN-2012 got through the breakthrough session with hundreds of investigators being there was very clear. And the data and the consistency and safety of the data has added obviously to interest of all the patients with this devastating disease that they really have no treatment for. So we have currently many, many, many patients. We are not going to guide on the exact timing of this, but obviously you can imagine that we already have initiated, we have started enrollments, and we have a large patient population that they are asking to receive this drug. So we are confident that we can finish our confirmatory trials in a very orderly and [fast fashion] (ph), and we are looking forward to bring the value to our patients.

Thanks, Helen. And maybe one question for Phil. Phil, since your background seems to focus a lot on global development as well. I'm wondering, is that something you're exploring? And what are sort of the steps to understand what's required to look at XUS markets? Or when you're thinking about monetization or other strategies, is that something that you're considering? Thanks.

Yeah, thank you for that question. Absolutely. We have global ambition with PRGN-2012, so we would approach market sizing, opportunity assessment, you know, in much the same way that we would do for the US, for instance. And there is a sizable disease burden. Obviously, the unmet need is still high. Different countries have different vaccine programs, but the impact of those vaccine programs for the younger population to flow through into the adult population is probably 20 to 30 years out. So we still believe there is a significant commercial opportunity even in those countries where they do have the vaccine program for younger adults and adolescents. So, yeah, we're absolutely looking at all of those opportunities XUS to build a true global picture of the opportunity.

All right, thank you.

Thank you, Jen.

Thank you. There are no further questions at this time. I will now hand a call back to Dr. Helen Sabzevari for the closing remarks.

Thank you very much. First of all, I want to thank all of you for the thoughtful questions. As you can see, this is a very pivotal and exciting time for us at Precigen. We are one step closer to bringing in a first-ever treatment to a patient population that is desperate -- in desperate need of a treatment. I want to take this opportunity to truly thank our team at Precigen for their tireless work over the past several years. Without them, we would have not been where we are today. We could have not delivered what we are delivering for a patient. And I just want to highlight my gratitude and also say I'm -- it's been a privilege to stand next to this team at such a high caliber. So, thank every one of the members of this. Of course, we thank our patients for the trust and the enrollment and we are happy with the results that we are seeing for our patients. And finally, I want to thank all of our investigators and all of the physicians that are really treating these devastating diseases out there, which they are outstanding. And finally, thank you to all of our shareholders for their continued support. So with that, I thank you and wish you a great day.