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

Good afternoon, and thanks for tuning into the 40th Annual JPMorgan Healthcare Conference. I'm Eric Joseph, senior biotech analyst with the firm. Our next presenting company is Precigen. And it's my pleasure to welcome Helen Sabzevari to talk to us a little bit about the company. There is a Q&A session after the presentation. So just click the icon, and I'll work in questions where appropriate. With that, Helen, thanks very much for sharing some of your time with us to speak.

Absolutely. Thank you so much, Eric, for having us. And we are really -- it's a pleasure always for us to present at JPMorgan presentation series. So with that, what I would like to do is, today, take a few minutes to take you through the updates that we had presented over the last year and also the goals and what we are going to do in the upcoming year. With that in mind, if we move to the second slide is our forward-looking slides, which clearly, I highly recommend everyone to read it as I will be making some forward-looking statements in our presentation. In the next slide, what I'd like to do is focus on our clinical portfolio, especially, which is, as you can see, it's quite extensive. We have been working on 3 platforms, our UltraCAR-T platform as well as our AdenoVerse platform and Microbial platform. And I will be touching on a number of the programs on what we have accomplished last year and where we are going to prioritize and go next year. At the same token, one of our therapeutics, the INX-4001, which we have finished the Phase I and has shown an excellent safety and preliminary efficacies, which is quite exciting, basically asset for us. And as we have mentioned before, we have been engaging in partnership discussions, and we will be updating on that program in the upcoming Q calls that we have. With that in mind, let's take a look at what we have done in 2021 as a company. In regard to our UltraCAR-T programs, our PRGN-3006 UltraCAR-T, we completed the dose escalation and we have presented the positive interim data from Phase I trial in the AML. With our solid tumors PRGN-3005 UltraCAR-T, we initiated an IV arm in the Phase I trial. We have completed the enrollment of the dose level 3 in the IP arm, and we have presented the encouraging interim data from the IP arm, both on not only the manufacturing, expansions and kinetic but also early signs of activity. And we also brought a new next-generation of the CAR-T PRGN-3007, which incorporate an intrinsic mechanism that lowers the checkpoint inhibitor, and I will discuss this as we go through the program. We received the IND clearance from the FDA last year. And for the Phase I, not only just in hematological and a number of them, but also in the solid tumors as an umbrella trial. With PRGN-2012, we have had a very exciting year. We dosed the first patient in March, April, and we were able to finish the dose escalation and enrollment of the expansion. And we reported the -- basically, interim data in our R&D. PRGN-2009, which is also relies on our AdenoVerse platform immunotherapy, we basically and targets the HPV positive indications. We initiated a Phase I in combination with the checkpoint inhibitor, started the Phase II monotherapy, and we have shown the Phase I safety as well as the interim data from a combination therapy with the checkpoint inhibitors. Our PRGN-2013, which also relies on our AdenoVerse platform, and it's basically targets the HBV, and it's a vaccine for infectious diseases, we have initiated the IND-enabling studies per goals that we had. And finally, for our ActoBiotics and microbial platform, AG019, in the first half of last year, we presented the positive data from a Phase I/IIa and have now completed these trials. So with that in mind, I would like to take you through some of the programs, the highlights and also discuss what we are going to do on 2022. Starting with our UltraCAR-T platform, PRGN-3006. As you know, it targets the CD33 in AML, that patient population, which is a patient population that basically have very little in front of them. The patients that we have been treating, they have felt basically every other therapy, all the monoclonal, our conjugated therapies. And these are the patients that they have very few months in front of them. That would not even allow the regular cell therapies or conventional CAR or TCR therapies, they cannot address from a manufacturing perspective, these patients. 85% to 90% of the tumor cells in these patients, they express CD33, and that's one of the reasons that this makes such a good target as a CAR. In the next slide, what we have reported this year was data both in 2 arms, the nonlymphodepleted as well as the lymphodepleted patients. And just recently, what we showed we have completed the enrollment in the Level 3 of lymphodepletion, and we are following these patients. We have shown an excellent safety data. No DLTs to date. No neurotoxicities as we dose escalated, and the result, not only we have shown a feasibility of manufacturing overnight directly at the cancer center, but also very solid and robust expansion of cells and persistence of these cells in both arms, lymphodepletion and non-lymphodepletion. And finally, both in our R&D and at ASH, we showed on the 2 lowest dose cohort, 1 and 2, which when you look at the number of cells that depletion received, somewhere between 4 million to 28 million cells, 1 time, 1 dose comparison to the competitors that they have been injecting hundreds of millions, if not billions, multiple doses with extensive other therapies, we showed at ASH, 50% objective responses in these patients. We have patients that they have complete responses and partial responses. And we have patients that they have reached to transplant. And now after a year later, they are doing perfectly fine. So the data obviously has created a lot of excitement in the field, especially in the field of AML because this patient population don't have anything in front of them. And this has positioned us now as a leader with the UltraCAR-T therapies. As the first company that actually has achieved this and pushing this forward, it allows us now as we have dose escalated and finished the dose escalation, to initiate a multicenter expansion centers and this year, a number of very, very high-power centers will be coming on. And what we are going to do is incorporate the PRGN-3006 obviously, expansion and, if need to be, a redosing with these clinical trials. And also what we will be doing in 2022 is reporting on further data from the expansion. So we are looking forward to this as this allows us also to start the discussions with the FDA of how we can move this rapidly in an unmet disease patient population that requires treatment and have filed everything else. So we are really excited, and we are moving rapidly with the expansion phase. In the next slide, I would like to address our PRGN-3005, which, as you know, has been targeting the unshed portion of MUC16. And this is in the ovarian cancer and ovarian tumors, in general, express high levels of MUC16. But also importantly, other indications such as pancreatic cancer and lung cancer, they also expressed very high levels of MUC16, and therefore, this allows us to basically use the data that we get from the dose escalation and for the expansions to other indication as well. Clearly, ovarian cancer is a disease that currently -- as you know, there are 10% response rates in these patients. We have been treating patients that they have at least received 6 to 8 prior treatments and have failed every single one of them. In the next slide, what have we shown in the past year and what have we [ done ]? Clearly, one of the aspects that we have always pointed out in regard to our platform is the ability not only to overnight manufacture much more younger and stem-like cells, and the cells that have a capability to expand directly in the patient and persist for a long period of time, which we believe it's a necessity for addressing the metastatic site, especially in solid tumors. And this is something that all of the other current therapies are missing with the solid tumors, and there are reasons for the failures in solid tumors. With that, we not only finished the 3 dose at the IP level and have shown a clear expansion and persistence of these cells. We also showed a preliminary interim data of activity at lesion sites. But more importantly, because of the excellent safety profile that we have shown with these patients, and with our UltraCAR-T PRGN-3005, no DLTs and no neurotoxicities, what FDA has cleared for us was to concurrently move to the IV arm of this trial. But more importantly, to jump to those levels -- to dose level 3 of the IV arm. We currently have finished that, and we are following these patients. And for -- as you can see, we also have very clearly showed excellent expansion and persistence of these cells as part of this manufacturing. And in 2022, we are looking forward to incorporating the lymphodepletion, which, by the way, FDA has already approved and we are allowed to do. And as soon as we have finished our follow up of the dose level 3, this gets incorporated. Also, we incorporate redosing if needed and initiate a multicenter expansion phases in 2022. And finally, our PRGN-3007, which is our next generation of our UltraCAR-T. We received IND approval last year. And this is quite exciting because with the ability now to incorporate an intrinsic mechanism to down-regulate the PD-1, we are further addressing a number of issues that, especially in the solid tumors become major, the tumor microenvironment and also in hematological. We now can down-regulate the PD-1 and basically avoid the need of a checkpoint inhibitor. Why is this important? It's important because CAR-Ts, regular Ts, any kind of a T cell therapy, it's exposed to all the tumor micro environment challenges, including the checkpoint inhibitions. Now if you continuously do a systemic combination of checkpoint inhibitor with the CAR-T therapies, which some of the companies, they have seen the need for that, and especially in solid tumor that is one of the major issues. What happens is you have a systemic toxicity of checkpoint inhibitor, plus also with other conventional CAR-Ts or TCRs have. And then on top of that, you are adding an extensive cost to another very highly cost treatment. What we have done in our next generation, we have addressed. As we mentioned with our UltraCAR-Ts, we always have done the overnight manufacturing to decrease the cost tremendously and the access for the patients rapidly. But also now with introduction of the regulation of the PD-1, it basically makes the combination with the anti-PD-1s for checkpoint inhibitors irrelevant here. And not only helps the further safety, but also the cost that we'll be running. We have targeted the role 1, which is an excellent target because it's mainly expressed only on the tumor cells. And it's expressed on a variety of tumor cells, hematological as well as solid tumor like CLL, CML, ALL and a number of solid tumors like triple-negative breast cancer, lung cancer, pancreatic cancer. And this is the first umbrella trial that under the same trial, now we are treating all these various indications, and this allows us to get a step closer to our vision for the library treatment that we have discussed on a number of times. And of course, on the ROR1, it has become now some of the favorite basically targets for many of the competitors. And obviously, here, we have the edge as we started working on this years ago, and we have gotten it to the position that is in the clinic. And I think this is quite an exciting target, and we are looking forward to dosing our first patient this year. So with that, that has been a sort of a little bit of summary of our UltraCAR-T platform. But we also have a quite exciting year with our AdenoVerse platform. This was another platform that we brought for the first time to the clinic. As the advantage of AdenoVerse, these are gorilla vectors that humans have either -- they have zero positivity to or very little because they have not been exposed to. And we have done these studies in Africa and in the United States and have shown that. But more importantly, what is different in this AdenoVerse platform is we have now Adeno virus that you can give a number of times. Unlike [indiscernible], unlike retroviruses, lentiviruses that you can only give one and a lot of the other competitions -- competitors, they have those in their portfolios. For the first time, we were able to bring this forward and show that you can give this number of times. We have been following 2 programs in the clinic, PRGN-2012, which basically we built an off-the-shelf vaccine that directly targets HPV6 and 11 plus some other epitopes. One of the advantages that we have with the gorilla Adeno virus is the payload capacity that we can go up to 12 to 14, which means we can put a number of genes, epitopes and switches in there, and that's what we have done. Our preliminary data, preclinical showed that we could raise a great T cell immunity to the various epitopes that we have had in this. And if we go to the next slide, Slide #11, we positioned this in the patients with a recurrent respiratory papillomas. This patient population -- this is a rare disease that the patient population really has nothing in front of them, except surgeries. This disease happens in both adults and children. And you can imagine the devastations that the patients feel for recurrent surgeries, which is always, from a safety perspective, it's difficult. It's expensive. People have to be out of work. And then seeing your child that every, sometimes 4 to 6 weeks, has to go through a surgery. So what we did, we started -- we dosed our first patient last year in end of March, April of 2021. And we finished the dose escalation and enrollment in the expansion by December of 2021. What did we show in our R&D and up to this date? We have shown an excellent safety profile. In some of the presentation with Dr. Allen, he showed that basically this is an injection in the arm or on the leg. And the worst safety profile was redness around the area of the injection. That's number one. Number two. We showed what we had presented preclinically that upon redosing, and giving a number of doses of this, you can increase the T cell immunity. And that was very exciting as well. We have shown that our -- we have kept the neutralizing antibodies at bay, which supports the repeated administration of PRGN-2012 and also for AdenoVerse platform, which makes it unique from every other platform in order to actually generate -- educate the T cells directly in a patient body and keep expanding them over time. And finally, in our R&D, we showed the preliminary data, which has been extremely encouraging. And on the patients that they had RRP, and we showed a number of cases. On the right-hand side, you see one of these cases of the patient that every 6 weeks, for 3 years, this patient had required surgery every 6 weeks. And after receiving full vaccination of PRGN-2012, you see the pictures. The baseline pictures, you see the papillomas. These benign tumors that are basically in the trachea and it's on top of a vocal cords. And what you see is almost it's really narrowing the trachea. And then 12 weeks following the last vaccination, now we have 18 weeks of follow-up of this patient. And you can see that the vocal cords, there is no evidence of the disease there. And this is one of the cases and we have many cases as we have finished enrollment of expansion. As I mentioned in December, we are following this patient, and we are looking forward in 2020, first of all, to present additional data on our Phase I and our expansion cohort. But more importantly, we are seeking the FDA guidance on a rapid regulatory strategy for approvals. As you know, this is a rare disease that the patient have no other options, and there is no other therapy. And we feel that this is quite exciting for this patient population and our investigators feel similarly. And therefore, the discussions with the FDA and regulatory path for a rapid BLX. In the next, basically, target that we have used our AdenoVerse platform is PRGN-2009. Now PRGN-2009, obviously, the backbone of our Gorilla adeno virus is similar with the high capacity of expressing a number of genes, which we have used by the way. We have targeted the HPV16 and 18 epitopes, which all of the other competitors have, but we have gone a step further because we have the ability to put a much more epitopes and bioinformatics group have identified those epitopes. We have the design of multi-epitopes that we have for PRGN-2009 is very different and it's much more extensive than the competitors. On the right-hand side of this Slide #12. What you can see is the number of indications that is related to the HPV infection, from all the way cervical cancers and the number of cases per year that you see, vaginal, the head and neck, anal cancers. So this is a very, very extensive population in need of a treatment here. If we go to the next slide, Slide #13. We brought PRGN-2009 into the clinic. And what did we show in the clinic? Number one thing, we finished the dose escalation last year. We showed excellent safety data of PRGN-2009, extremely favorable. We have shown that we can vaccinate patients. Over the years, we have patients that they have received over 15 to 16 vaccination over 1.5 years. And not only they have tolerated extremely well, the safety has been extremely well but we continue to educate their immune system, expand their T cells to their epitopes and enhance their immunity. On top of that, we also, in 2021, showed that we can combine it with the checkpoint inhibitor in the combination arm in Phase I that we have. I'm going to stress this point. These were patients that they have received checkpoint inhibitors prior, and they had failed. When we added the PRGN-2009, for the first time, we showed. In this patient population, 40% objective response rate. Patients that showed complete responses. And by the way, as we are following them, are still showing that and patients that they had shown partial responses. Now I want to basically just set the scenario here. At the moment, for head and neck patients, the standard of care is Keytruda anti-PD-1 with 18% response rate, meaning 82% of the patients fail the frontline treatment. Cervical cancer is between 15% to 20%. Now with the data that we have generated here with the safety profile that we have with our PRGN-2009, currently, we are seeking the FDA guidance on the rapid regulatory path for approvals and the HPV indications, and this is part of our major goals for this year. And we will be initiating a Phase II study in advanced HPV patients in combination with anti-PD-1. And why that? Because this is the way that we can move these assets in the front line, the standard of care because in the best scenario, 15% to 18% of these patients are only responsing to the Keytruda. And if you know, we can increase that, this becomes a standard of care and our preliminary data points to that. So I think this is quite an exciting time for this platform as well as these assets as we are moving them forward. And then the next and finally, the program, AG019, which is our microbial. In the first half of 2021, we reported Phase Ib/IIa positive data. We have finished this trial has shown an excellent safety and especially has shown that our monotherapy with AG019, it stabilized the C-peptide levels, which was a biomarker for T1D disease. Also, it has a stabilized HbA1c and 1DAA. These are the long-term indicators for glycemic control of type 1 diabetes. And also from a mechanism of action, we have shown exactly what we have shown in preclinical, which affects the tolerance in conjunction with the reduction of the disease-specific T cells. What are we looking forward in 2022 is we are currently basically making the commercial-grade manufacturing, a scale up.And we are in discussions with the FDA and EMA for a Phase II/III clinical trial designs. So with that in mind, where are we going in 2022? First of all, in regard to our UltraCAR-Ts, PRGN-3006, as I mentioned, we are going to initiate the multicenter expansions and present additional data in 2022. In regard to our PRGN-3005, we're going to incorporate a lymphodepletion and redosing, if needed, and go through initiate of the expansion cohorts in a multicenter across, and this is going to be quite exciting for a solid tumor. This is a year that can be quite exciting. PRGN-3007, we will be initiating the dosing of both patients in hematological settings as well as in solid tumors, specifically the triple-negative breast cancer, which is first time that the next-generation UltraCAR-T is going in that indication. AdenoVerse inverse platform, PRGN-2012, in RRP. We will be presenting additional data from Phase I and expansion cohort. And actually, we are very much looking forward to this as it comes up. And we are going to be in discussions with our regulatory agencies for a rapid path for approvals. Same thing for PRGN-2009. We are positioning it to move into frontline in combination with anti-PD-1 and discussions with FDA to get a rapid regulatory strategy to move this forward. And finally, our AG019, ActoBiotics, after showing a solid positive Phase Ib/IIa, as I mentioned, we are in the process of commercially scaling up material as well as discussions as we speak with the EMA and FDA for a Phase II/III clinical trial as a monotherapy, which is also quite exciting. Finally, I'd like to finish the talk with this slide that we see here. Obviously, we have been extremely privileged with the team that have pushed number of platforms, number of programs and clinical trial. And across the 2021, we have reported positive data on 5 clinical trials. And I think this is something that I am proud of the team at Precigen. What it becomes very clear, now after having preliminary data in these platforms, we are obviously prioritizing our portfolio with the assets that have a very rapid path towards regulatory approvals versus PRGN-2009, 2012, PRGN-3006 and [ 5 ] especially also with the expansion data and the unmet need for this patient population, it will be also extremely important. And we are moving that to the expansion cohort to get further data that we should have those discussions with the FDA. And finally, on the right-hand side, which is very important, and we are always get asked our financial strength. As we finished 2021, we have a very comfortable cash runway that can support our priorities in the clinic all the way to the end of 2023, and we will be discussing this more at our quarterly call. We continue our fiscal discipline. And with operational efficiencies that we have put across the organization, even in our subsidiaries that, for instance, has led to the really becoming a substantial cash contributors to Precigen, and therefore, the value has become tremendously higher. And we -- also, in this year, we are obviously looking at various strategic pathway non-dilutive funding opportunities that will continue to provide strength to our portfolio and our financial strength. With that, I thank you for your attention, and I'd be happy to take any questions.

Thanks, Helen. I think the first place to start, based on the incoming questions, would be to address the balance sheet. The guidance that you provided there, runway out through '23. How does that incorporate obligations on the balance sheet, particularly the convertible bond coming due in '23, I believe? And you speak to confidence in executing across the pipeline, not having to really prioritize. That being said, I think some are interested to know sort of how the ActoBio vertical fits in with the overall future Precigen. And how to weigh that versus competing demands with the oncology basket of assets?

Yes. So actually, what I said was that we definitely are prioritizing and focusing on the assets, and we are putting the assets that they have a very rapid path forward and, therefore, the discussions with the regulatory agency that you might not need to go through the classical development pathways that would take extensive number of years. And that is one of the reasons. We clearly are focusing on and prioritizing this, and as I mentioned, on AdenoVerse the 2 programs that have the ability for fast tracking as well as in our UltraCAR-T. And with AG019, we are in discussion currently with the EMA and also FDA exactly for the design of a trial that allows a rapid movement here, but also from a monotherapy setting because originally, when we went these trials, we have both monotherapy arm and combination, and we have clearly shown that our monotherapy treatment is quite strong. And I think we will be advancing that arm into the clinic, as we speak. But one thing about our cash -- as we spoke, our cash runway, by the end of the past year, and we will be talking our CFO, will be giving a much more detailed analysis of our cash, but we are standing fairly well as what we said, based on what we are providing and moving the programs to 2023. In regard to our convertible debt, and there will be further guidance in our Q1 calls as we are going forward. And what I mentioned here is we have a number of now strategic path in front of us, not only in regard to the assets that we have and they are quite valuable at this point. But also in regard to the data that we have shown across platforms, which allows for discussions on partnerships and moving forward. So we are actually looking forward to have these discussions in the upcoming quarter.

With 2012 for RRP, curious to get a sense of the types of endpoints that you might propose with FDA that would pursue a fairly rapid development strategy for that asset?

Excellent question. I think for this patient population, clearly, there's nothing to compare or randomize against, correct? You need to mainly look within the same patient as we showed some of the data that -- same patient that every 6 weeks for 3 years had requirement for surgery. Now all of a sudden, 18 weeks, 20 weeks later and has not had one surgery. And I think some of the -- our KOLs and, of course, our PI, Dr. Clint Allen, who are expert in this field, they are putting basically end points. You can imagine one aspect could be the number of the surgeries that is required or the intervals of the surgeries that's required. Also the quality, for instance, from the appearance of these blind tumors, the extend of them as well as the vocal cord situation and what it gets done. And one thing that people -- especially if no one has seen a patient such as this, I have been talking to a number of these patients. And not only the expenses, the amount of time of their life that they have lost. And also the dangers that they have to see, continuously going 6 weeks for surgery and what can happen if there is something goes wrong. I think these are also part of the discussions with the FDA from the patient's perspective. And it's very extremely valuable because you have a treatment here that basically these patients receive 4 injection, with no safety issue with no complication, no adverse effects. And their own immune system is educated to basically eradicate this [indiscernible]. So we are really excited about this for the patient -- for the patient and possibility that we have here.

Okay. Okay. Great. Fortunately, we'll have to leave it there for time. So thanks, again, for participating in the conference this year. And thanks, everybody, for joining this session.

Thank you very much, Eric, for having us. And thank you, everyone.