Precigen, Inc. (PGEN) Earnings Call Transcript & Summary

Our final fireside chat of the day. I'm Jennifer Kim, a biopharma and biotech analyst here at Cantor. And I'm looking forward to hosting Helen Sabzevari, President and CEO of Precigen. Helen, thanks for joining us.

Thank you for having us.

Okay. Maybe we can start. Could you give a brief introduction of yourself and Precigen?

Sure. I'm Helen Sabzevari. As you mentioned, I'm the CEO and President of Precigen. And Precigen is a biotech company that focuses on cell and gene therapy that it specifically addresses the Precigen medicine by activating the immune system in various fashion and different indications.

Okay. And can you talk about the key points of differentiation of your therapeutic and technology platforms that support that pipeline of yours?

Absolutely. I think for the past few years, we have really focused on bringing in a differentiated platform that does 2 things; one, is to really address this and train the immune system directly from within patient body. And the second platform is really taking the immune cells out and activating them and training them, especially in the indications that patients have very, very few months to live or limit at times. And the combination of these 2 platforms in conjunction with the manufacturing that is very rapid and especially in cell and gene therapy, which has been one of the tasks that everyone has been having a problem with. We have overnight manufacturing that can accomplish retraining and reengineering autologous T cells of the patient and then the next day, returning them back to the patient. So I think from that perspective, we have differentiated on not only the technology but also the manufacturing and then eventually what it leads to a much lower cost.

Okay. You have quite a broad pipeline, and I want to give time to each. Let's start with PRGN-2012. Can you talk a bit about that asset, what it's targeting and the data that we've seen today?

Absolutely. So PRGN-2012, it's really targeting the HPV 6 and 11 in a recurrent respiratory papillomatosis. This is a rare disease that the patients, they develop benign tumors continuously and chronically. And the reason for this papilloma is really the infection with HPV virus 6 and 11. Now to date, there is no treatment whatsoever for this patient population. This is a rare disease. And the only treatment that they have is surgery upon surgery. Majority of these patients, if -- they really have surgery every 6 to 7 to 10 weeks. And some of them, when you speak to them, they have gone through hundreds of surgery over the period of their time. This disease can happen both in children and adult. And as I mentioned, it's -- currently there are 16,000 cases, 10,000 adults, 6,000 juvenile as well as 1,500 cases that every year gets added with no treatment and the continuous surgery and the appearance of this papilloma on the vocal cord and trachea, it really damages the vocal box and then upon surgery, the trachea eventually. So you can imagine how difficult it is for this patient to go through life with this kind of a severe disease and even worse when they have to see their children or they themselves as a child having gone through this.

Okay. And in terms of clinical data, what have you shown?

So we -- last year, we showed the Phase I data that with the expansion cohort in Phase I with our PRGN-2012. What was really striking? The first thing was, number one, the safety of this drug. This drug is administered subcutaneously like flu vaccines in the arm or in the leg. And patients, and this is the investigators telling us, basically they showed no toxicity, no DOTs. The grade of basically treatment adverse event was a grade 1 or 2, which basically comes down to a slight rash at the site that they receive their vaccination or somewhat level of fatigue that will go away in a day or 2. And what we also saw following that with a very great safety was really looking at the efficacy that we saw in the clinic. 50% of the patients that received the vaccine, they did not develop or require any surgeries within a year of the follow-up. And that was the endpoint. Specifically, we had gone to a much more severe population of patients that they at least had required 3 surgeries and above in the prior years. And some of our patients, at least a good amount of them, they had somewhere between 6 to 10 surgeries per year required. And what we saw that after receiving the vaccine, and the year of a follow-up, they did not require any surgery. And furthermore, what we have shown is that these patients now have been followed up more than 12 months, and they have passed actually majority 18 months, and the response is ongoing, and we have not seen any requirement of the surgery for this patient population.

Okay. And on the back of this data, you had a positive update recently with the FDA giving the green light for an accelerated approval pathway for 2012. Can you talk about the importance of the FDA's decision here?

Absolutely. So after the -- basically the data that we saw from a Phase I and expansion of the dose level 2 in the Phase I. We started discussions with the FDA. And what -- it was very important, especially in rare diseases and especially in diseases that they have 0 options for the patients. It became very evident that with the safety and with the clinical efficacy of 50% of the patients having a complete response in this after vaccination, we discussed the path. And also, was it required that we go through another Phase III -- randomized III. And our request was the consideration that our Phase 1 and Phase 2, which we had started in January of 2022, if that can be considered as a pivotal trial. And FDA, we are very grateful that after looking at the safety data and after looking at the clinical efficacy, which was also related to the immunological responses, which is directly raised against these papillomas by vaccination, the FDA concurred that they actually see the Phase I, Phase II as pivotal. And these are single on. They are not randomized, but also, there was no requirement for another Phase III randomization. And they agreed that not only we received the breakthrough designation for this, but also, they have agreed that this can serve as pivotal. And currently we are discussing all the other steps and the ongoing discussion and basically for a rolling BLA and accelerated approval, which, in this case, we have been allowed to file for. And I think why is this so important, first of all, for this patient population? This patient population have nothing in front of them, but surgeries. The KOLs, investigators, they do not like that because of the damage that the surgeries cause to the patient. It's dangerous. Every single time that the patient has to go through it. Can you imagine every 4 to 6 weeks, you receive a surgery. And the quality of the life of these patients clearly for themselves and their families, some of them and they have expressed that, that for instance, their children have not heard their voice all their life because they cannot speak or they can't breathe if they don't remove this papilloma. So it was very important that in a very comprehensive fashion, we bring forward a treatment for this patient and then really not having to run another randomized trial from a time perspective. This is very important that we currently have finished our Phase 2 enrollment, and we will be communicating on a full data from a Phase II also in the first half of 2024. So this put the program at a much more accelerated rate to move toward the commercialization and approval for the patients.

Okay. And in terms of the confirmatory trial, can you walk us through the steps for that?

Absolutely. Another thing that we are very happy about was the decision of the FDA in regard to the confirmatory trial. As you know, for accelerated approvals, there's always a confirmatory trial. However, the confirmatory trial has to be only initiated at the time that you submit your BLA. It doesn't mean that you have to finish or has to get started, enrolled and finished. So that is an important distinction, and we will be starting our confirmatory trial next year prior to the submission of our BLA. But more importantly, again, our confirmatory trial, FDA agreed that it can be exactly the same trial that we have run, for instance, in a Phase II, a single arm, not randomized, and with a similar number of patients. So again, this is important because it will be a rapid and nonrandomized trial.

Okay. And if we could touch a little more on the market opportunity for this kind of product, I think you talked about 16,000 patients in the U.S. How do you think about the patients who need the number of multiple surgeries that were enrolled in your trial? And then can you talk about those additional other opportunities in patients that might need fewer surgeries?

Absolutely. So first of all, in the U.S., it's 16,000 in ex U.S., just in adult, the estimation has been around 60,000, and we still have to look into the pediatric and juvenile population because that data is not available. And one of the things that we will be doing in the upcoming months is actually much more comprehensively communicate with the data from around the world and especially the cases and to the market opportunity. But the original research that independently has been done, it confirms that the market opportunity with at least the number of the patients that I mentioned, in U.S., we are looking at 1 billion and worldwide we are looking at close to 2 billion market valuation. And obviously, we will be communicating more further with more data on this, but currently, as it stands -- this is, we believe that it's very true to the research that has been done. From the perspective of also patients with lower number of surgeries. This was very interesting and actually has been the recommendation of FDA, which we welcome tremendously, because due to the excellent safety profile of this drug and because of the efficacy -- clinical efficacy, what we saw was actually 83% of the patients, they all benefited from vaccination, 50% they didn't require any surgery and the other 33%, they reduced the number of the surgeries significantly. And from the FDA perspective, the recommendation has been perhaps we can even add additional arm by enrolling some of the noncomplete responder or what we refer to as partial responders and basically redose, which that will be extremely important. And definitely, we are considering that, and that would be part of this. One other opportunity and also similarly for patients that they have less than 3 surgery, FDA again has asked us to consider an arm that enroll the patients that they require less than 3 surgery per year, so that can expand the label. One other aspect that I would like to discuss and is part of the future discussion is, for instance, the importance of PRGN-2012 and targeting HPV 6 and 11, not only in RRP, but in other indications, like in genital warts which is really a large millions of people, not only in the United States but across various continents. They suffer from this. And the cause of it is HPV 6 and 11 infection in these patients which is exactly what our vaccine targets. And obviously, the potential of this in that indication, it can be worldwide and quite high, and this is another thing that we have to consider.

And those are additional to the current market place.

Yes, absolutely.

Okay. And next year would you -- when do you expect to release the pivotal data? And what are you hoping to show?

So the -- as I mentioned, we have a single arm randomized -- nonrandomized , sorry, trial, which we have enrolled and now the patients in Phase II, are following up. We will be communicating the data by the end of the first quarter beginning of second quarter of next year. The full Phase II data will be presented. And obviously, part of the advantage of having a single arm is that we see the -- basically the efficacy in a patient as we follow each one of them and we see them throughout the year and this year and up to the next year. So we are very excited about this data, and I think it's going to be a very exciting year for Precigen and mainly for our patients.

Okay. In the data that includes the Phase II trial, are you hoping to show something comparable to what you've shown to date?

Absolutely. I think this is very -- the efficacy, it's a major part of this clinical efficacy. And also, one of the things that it usually does not happen is a lot of times, you have clinical efficacy, but not necessarily people can directly show the science with it. And this is one of those occasions that the clinical efficacy is followed by the immunological response, which is directly related to the vaccination. And we have been able to show that. So next year, we will show fully both of this hand in hand and as we report [indiscernible].

Okay. And once you report on that data, could you walk us through the time line and steps afterwards in terms of manufacturing or filing and all that?

So the manufacturing activities are ongoing as we speak. We have been using our own facility for commercial manufacturing and this is important. It gives us an advantage for a number of reasons. First of all, we have produced all of our clinical trial material in our own facility prior to that. So our team is very well versed and experienced with it. And secondly, having our own commercial manufacturing, of course, it allows us to have a control, especially in this environment, that all the manufacturing sites are having difficulties or time lines that people cannot necessarily adhere to. And this is now fully under our own control. And also even from a cost perspective, you can imagine that it will be much different than if we will go to the other facility. So as we speak, our manufacturing facility and -- for the past year, actually they have been preparing for this. Through our breakthrough designation with FDA, we have very close contact with FDA discussing various aspects of our manufacturing and commercial manufacturing. And the way we are anticipating the steps will take place is obviously through a rolling BLA. We will start submitting different parts of the BLA. And of course, the last -- one of the last parts would be the clinical in next year. And then our anticipation is that the full BLA will be submitted by second half of 2024, and then there is a 6 months of a review by FDA. And we anticipate that early 2025 we have the [ report ].

Okay. And I may have missed this before. Are the discussions for the plans for rolling NDA, you said those are ongoing? Or are you expecting feedback?

For them we are -- we have discussions and we have had some feedbacks, which we have incorporated and some -- we continuously go for guidances and -- to ensure that prior to submission of the parts of the BLA that you are in fully agreements. So there would be no surprises. And that's exactly what we are trying to do is to ensure that by the time that the full BLA is submitted, that all the requirements have been met. And this is a great opportunity it's interaction with the FDA, and we are very thankful to them for a very, very close interaction for our patients and also for the company.

Okay. And would you plan to commercialize this by yourself? Would you look for a partner? Any thoughts around that?

Absolutely. So currently, as I mentioned, we are moving towards commercialization by ourselves and our teams have been preparing for that. In the next few months, we will be discussing our commercial activities. So the way we take it is we are preparing for commercialization. However, as always, if there are opportunities that is appropriate and that will address the need and obviously always will be considered. But we definitely are moving with our own commercial activity.

Okay. And sort of related to the FDA feedback for 2012, you also highlighted some actions you've taken to realign your resources and prioritize your portfolio activities. What are you doing to balance management of those resources while also still investing behind the key programs?

Absolutely. For us it was very important to make sure that we extend our cash runway, so we will meet all the inflection points and the data points that are coming up. And in order to do that, what we have done is somewhat reprioritize the portfolio. As you know, and I'm sure we will get to it. Our UltraCAR programs are similarly very, very important to us. So our PRGN-3006, which is in AML, we continue pushing forward, also that is a very, very exciting program and asset for patients and for the company. What we communicated that in 2023 for our PRGN-3005, which targets the MUC16 in ovarian cancer, we will not be opening new sites. And the reason for that was the prioritization of the asset or cash more towards PRGN-2012. However, we continue with [indiscernible] and UW as our major sites, and I'm really excited to mention, and we will say that soon that NCI will be joining as a new site for PRGN-3005 and that is through our [ CRADA ] program, which again is very, very helpful. Similarly, we are continuing our Phase I in PRGN-3007, but there are no other sites being open. And I think this has allowed us to extend our cash runway into 2025, which really allows us to present our clinical data next year, submit our BLA, and it gives us a good cash runway.

Okay. And in terms of the UltraCAR-T programs 3006, like you mentioned, high-priority program there. Could you talk about the data you've shown so far, what you think the takeaways from that are and what you're hoping to show in interim data, I think you've guided to next year?

Absolutely. I think in the patient population that we are addressing the relapsed refractory AML patient population. I believe that we are the only cell and gene therapy. We are the head of the group. There is really other companies and unfortunately for the patient, but the reality is the programs have not resulted well, including off the shelves. What we have shown up to this stage in a very heavily pretreated patient population that they have no other option, and some of them have came out of hospice treatment. We have shown almost 30% objective responses, both partial and complete responses. And also, one of the things that we have been able to carve a niche for this patient -- these are patients that they were not eligible to receive any transplant at this point. And we have some of the patient that through our treatment with complete responses that they have had, they opted to receive because now they could receive a bone marrow transplant. And for instance, we have a patient that is up close -- getting close to almost 3 years post bone marrow transplant, and she is doing perfectly fine. So we are very excited about this program. FDA has granted us the Fast Track on PRGN-3006. We have communicated that this year we continue our expansion of a Phase Ib. Next year, we anticipate to report on that and we are hoping that, that would allow us to discuss the program and the regulatory path of that with FDA in a very specific patient population and the option that it's honestly, currently is nonexistent...

Okay. And any thoughts in the interim data in terms of number of patients? And also, where would you see 3006 fitting into the AML treatment landscape?

Yes. So currently, we position this in AML strategically because this patient population, they have very short period of time for any treatment. By definition, majority of them, they do not leave past 3 to 4 months. So you can imagine that the cell and gene therapy typical one, even the off the shelves, were not able to meet these patients and because we have overnight treatment. This has allowed us to get treatment to these patients very rapidly. And more importantly, so this is, of course, we have entered into the [ stage IV ] of this patient population, which is usually the investigational drugs are that stage. Our hope is, for instance, one of the ways that we can help these patients and the regulatory strategy will be is really bridge to transplant for these patients. It's very similar to what we have seen with our complete responders and they continue to have a normal life with -- post transplant. And so this would be part of the discussion, and I think this would be the immediate thing. As we move then the treatment to the frontline stages, for instance. Currently, we are treating these patients that they have failed everything. But can you imagine that we are now moved towards the second line or eventually a first line, meaning when the patient is diagnosed with AML, we can immediately treat and reengineer their own T cells and make UltraCAR for them and as a first line. So eventually, our goal is in that direction. But obviously, for the approval and regulatory strategy, we start with the data that we have in stage IV patients, and then we keep on moving to the frontline.

Okay. And you briefly talked about your other UltraCAR-T programs 3007, 3005, how should we think about where those programs stand and how those can progress?

One of the specific things about our platform, whereas every other platform in a cell and gene therapy at this point, they are mentioning that they are really best, they can address the hematological indication. Because of the design of our UltraCARs that, first of all, they are fresh, they expand and persist directly in a patient body. And they can traffic and they can get to the patient. We always felt that this can be used in solid tumors plus, of course, the hematological one. And the data that we have presented from a Phase I at ASCO this year, I think it spoke to that. It showed that in a -- again, a stage IV ovarian cancer patients that they have failed anywhere between 8 to 10 lines of therapy before, we were able to reduce the target lesion. We could get these cells directly to this site of metastasis. We -- these cells were able to expand and persist for a long period of time in these patients with a very, very favorable safety profile. And we could accomplish these things with as little cells as between 7 million to maybe 60 million or 70 million of these cells, which compared to all the other therapies is minimal amount. So we are excited about that, and we continue with our [ ovarian ] trial. And as I mentioned, it's just for this year, we have scaled back on opening new sites, but we will reevaluate in the upcoming year. But at the same token, we continue and we added actually one site, which will be NCI that will help us in keeping the momentum for Phase Ib and getting the data in the upcoming year. PRGN-3007 is another excellent example of our technology because not only in that one, we have all the technology, membrane bound IL-15, the kill switch and the CAR of interest that targets ROR1, which is on lung cancer, triple-negative breast cancer, CLL, but also we put in an intrinsic mechanism that down regulates PD-1. So you do not need to combine now a checkpoint inhibitor, which is the extra cost and extra toxicity on the patients. And this is huge, again, for differentiation of our platform because it not only we have an overnight manufacturing directly in the hospital and next day infusion to the patient, but our cost and COGS are at a significantly lower portion than what the current cell and gene therapy treatments are going. So now we also are trying to eliminate the need of any kind of a checkpoint inhibitor, which will be always an added cost of between $120,000 to $150,000. And these cells, they already have the mechanism -- not to require that. We are excited about that. It's an umbrella trial in Phase I. We're currently keeping it as Moffitt Cancer Research. And obviously, next year, we will be reporting the data from Phase I, and then we will be addressing the expansion.

Okay. We're out of time. So thank you, Helen, and Precigen again for a wonderful conversation. And everyone, for attending, thank you and enjoy the rest of the conference.

Thank you very much.