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

Greetings, and thanks for joining us to have a conversation with Helen Sabzevari, Chief Executive Officer; and Phil Tennant, Chief Commercial Officer of Precigen. Precigen is a biopharmaceutical company specializing in advancement of innovative precision medicines to address difficult-to-treat diseases, which are -- which have high unmet need. Recently, the company received approval for PAPZIMEOS, which is the first and only drug approved for treating adults with a rare and debilitating and potentially fatal disease, recurrent respiratory papillomatosis. The drug is a nonreplicating adenoviral vector-based immunotherapy against HPV 6 and 11 that are believed to be the cause of the disease. FDA has granted a full approval to the drug on August 15, almost 2 weeks ahead of the PDUFA date of August 27. And management is planning to launch the drug in early fourth quarter of this year. So to know more about the drug and the commercial strategy and welcome Helen and Phil to this fireside chat. Good morning, Helen and Phil. Glad to see you both, and appreciate you accepting our invitation to talk to our audience today.

Good morning, RK. It's great being with you and the audience.

Helen, so just for starters and for those people who are not yet aware of Precigen, what's the business plan here for the company? And also, how successful have you been in executing the plan to date?

So first of all, thank you for the opportunity. And the business plan, we are an innovative, as you mentioned, biotech company that has been really focusing on bringing innovative platform with the right indication and right regulatory strategy. So from the very beginning. And with that as our business plan at the core of it, what we have done in the past few years to advance two platforms forward. One is our AdenoVerse platform, which is a very unique and differentiated platform, which Precigen has a full IP around it. And the other is our overnight CAR-T cells that is manufactured at the side of the hospitals, and it's really autologous CAR-T overnight. What we had done originally was really, first of all, make sure that the both platforms come to clinic and show its capability for scaling up and commercialization, which we have been very successful in showing the power of both platform. And especially for AdenoVerse, which we moved that very, very rapidly, as you are aware. Even during a pandemic, starting the program, starting the IND in the middle of the pandemic in 2021. And receiving, as you mentioned, a full approval by the August of 2025, which is an unprecedented, really, speed for a drug development. It doesn't matter which organization, you are part of it as big pharma or biotech. This has been an incredible journey with a lot of effort from the teams involved. So -- and part of really, our business development, I will go back, is on really understanding the science and the platform and applying it to the right indication with the right -- basically regulatory strategy from the very beginning. And this has allowed us to move very rapidly despite of all the challenges that globally, all of the companies have been -- had to face. But we have been very successful. And as you are aware, quarter-after-quarter, we have delivered or exceeded our goals for that quarter, which I'm very proud of the accomplishments of Precigen.

Yes. Congratulations on that. I should underscore the 4-year effort which went in to bring this drug to the market and potentially should be in the market by the end of this year. So just so that people understand a little bit more, can you describe the platforms at a high level? Obviously, we'll go more into the AdenoVerse platform, so PAPZIMEOS, but at least a little bit more on the CAR-T part of the platform?

Absolutely. Our CAR-T part of the platform is an autologous CAR-T that basically, we have initiated a very unique and differentiated platform. It's a nonviral platform that -- because of that, you do not need an extensive manufacturing that is required with viruses and also the cost that is associated. The way it works is very simply, the patients, they come. They have their apheresis done. And their own T cells are -- basically, we have a platform and UltraPorator with our ultra vectors that generate a specific autologous T cell overnight in the hospital. And then the next day, the patients are capable of receiving their own autologous CAR-Ts. We have done an extensive Phase I, both in hematological as well as solid tumors. And it's end of Phase Ib, especially in AML, which we reported a very significant 27% to 28% complete responses as well as partial responses in the patient population that basically had 2 to 3 months to live. And we have finished our Phase Ib, and we are in the process of having to go for the end of Phase Ib, meeting with FDA and discussions for pivotal studies for Phase II.

Fantastic. So going straight to the topic for our fireside chat today. What is RRP? And how big of a patient population suffer from this indication?

RRP, as you mentioned at the beginning, or recurrent respiratory papillomatosis, is a rare disease, it's debilitating and devastating. It's -- the root cause of this is infection of HPV 6 and 11. And this can -- basically, on take of RRP can happen during childhood as children pass through the birth canal of the mothers and they get infected, so they can start having this benign tumor developed on vocal cord or trachea as early as age of 1 and continue for the rest of their life. Or you can basically get infected as an adult through sexual interactions, and as a result of that, be infected and develop these tumors. As you mentioned, for the past 100 years, this disease have been known, but unfortunately, did not have any FDA-approved therapy that addresses the root cause of this, which is the chronic infection of HPV 6 and 11. And now for the first time with using our AdenoVerse platform, which is differentiated than all the other platform in the sense of not having much higher capacity to express number of epitopes and genes in our gorilla adenoviral vectors that are nonreplicating, but also the ability to be repeat dosing it and keep enhancing the specific CD8 responses, which is at the core of the mechanism of action of this drug, which directly now targets the infected cells. And they can also maintain, and by giving a redosing of this, you can enhance the immune responses. And this is very, very important for people to understand that some of these patients, they go -- up to before the approval of PAPZIMEOS, the only thing that was available to them was really repeated surgeries. And the studies have shown that by the -- almost the fifth surgery, more than 76%, 80% of these patients have now irreversible damage either to their vocal cords or to their trachea. So it's quite debilitating. And in some cases, as you mentioned, it can also metastasize and lead to the fatal disease. So we are very excited that now, PAPZIMEOS is the first and only treatment, FDA-approved treatment for this patient population, which has been set a very high clinical bar out there in regard to the treatment.

So regarding the disease itself, in terms of progression of the disease. So for example, you said at some point, patients could go through 5 to 7 surgeries in a year. So is this something that progresses over time? Or how does -- I'm just trying to figure out, like if I find out that I'm suffering from this, should I first go straight to the medicine? Or can I wait? How does that work?

Yes. No, absolutely. It's very, very important to the -- upon the diagnosis really to go to the physicians. And now with PAPZIMEOS being approved and for a broad label which is for all adult RRP, the patients, upon really diagnosis, they can directly go to receive this drug. And this is very, very important. And the fact of this broad label, it allows -- as you mentioned, some of our patients, actually, even in our clinical trial, they had, per year, 10 surgeries. Can you imagine? Every 4 to 6 weeks, you have to go under a surgery in order just to be able to speak or breathe at this point. And it -- obviously with the data that came out of John Hopkins, it has shown very clearly, as I mentioned, by fifth surgery, you have done irreversible damage. So clearly, neither the patients nor the physician wants this to happen. Because once that damage is done, you cannot reverse it. And the risks of every surgery, it keeps adding up. And this is one of the reasons that physicians really do not like to do these surgeries. And now with the approval of PAPZIMEOS for all adult RRP patients, patients can receive it at any stage of the disease that they are. If they are just diagnosed or they have had a number of surgeries, all of them are -- can be receiving the PAPZIMEOS for treatment.

So for patients who get infected, unfortunately, through their mother during -- as they pass through their birth canal, as you said, do the HPV vaccines like CERVERIX and GARDASIL that have been approved for almost a decade or more now, can they help these patients out in terms of progression of the disease? Or that really -- those vaccines don't really -- those prophylactic vaccines really don't work for this particular indication?

As you mentioned, the GARDASIL is a prophylactic vaccine, which means that you -- like many other vaccines, you get vaccinated prior to getting infected. And the effect is really -- it's effective in that setting. But once you are infected, actually, GARDASIL does not have the same effect. And I can tell you, some of our patients that they have been diagnosed with RRP before entrance to our trials, they have received GARDASIL, and it didn't have any effect. So for our pediatric population, it also -- FDA has been very, very interested in because of the safety, efficacy and durability of response that we have shown with PAPZIMEOS that this really be used in the pediatric population. And currently, part of our immediate plans is to move in that direction as well and expand the indication for the pediatric patient population.

RK, just to add to that. In our discussions with thought leaders, there's a general sense that it's going to take a few generations before any significant vaccination in a preventative sense would have an impact in the adult population, and that's in the 2040s and beyond.

Okay. And Phil, in terms of the patient population, both in the United States and Europe, I know you have done some work on that. So what's the number that we can think that is real? Because that has been changing over the last couple of years.

Yes. Yes. I'll let Helen comment on the literature, but I'll speak to the work that we did. We think it was pretty innovative and pioneering and the most robust look at the patient numbers that's ever been done in the U.S. Because there's no ICD-10 code. So you can't go into claims data and electronic health records and just pluck these patients out. So what we did is we worked with a company that provided access to tens of millions of electronic health records and hundreds of millions of claims data. And we were able to definitively identify patients in their electronic health records because the physician had basically typed in something, like this patient has RRP. But based -- what we did, we built algorithms around those patients based upon the diagnostic codes and the surgical codes that they had and used AI algorithms to then lift and shift what those patients look like, the definitive patients, into the broader database. And that estimated 27,000 adults in the U.S. alone. Now if you extrapolate that -- obviously, we don't have access to claims data and such ex-U.S. or not in the same way. But if you were to extrapolate that to ex-U.S., then you're looking at 100,000, 120,000 or more patients in the top markets ex-U.S. as well. So it's still a rare disease, but there's still a significant burden on patients in the health care system.

Okay. No, that's good. And in terms of starting off to talk about commercialization. I know you were not expecting -- I don't know if you were expecting the full approval, but we were not expecting it. So since you got the full approval, how do you regard the label? And were there any surprises in the label itself that you got?

Helen, do you want to go?

So from a full approval, clearly, FDA has granted us accelerated path, as you know, with the confirmatory trial. And throughout the interactions with the FDA, we have been updating our clinical data, which is -- not only it included the safety, which was Grade 1, Grade 2 and nothing more than that and no DLTs, but also a very robust efficacy, 51% complete responders, which means that they didn't require any surgery for a minimum of 1 year. And 86% overall responses, which patients that they reduced the number of surgeries. As you know, RK, we had a very, very robust endpoint. We didn't go just for a reduction in the number of surgery, but really to eliminate the surgeries at least for 1 year. And then with the durability of a response, which -- the minimum has been 24 months, and we have patients that they have passed 3 years, and we will be reporting on those fairly soon. In meetings and publications, that was also updated. And as a result of that, this is -- was something that the FDA, based on a very robust prospectively -- prospective -- statistically significant data powered pivotal Phase I, Phase II. And durability, plus the efficacy, plus the basically safety, FDA, I think, took into consideration all of that for the patients with this debilitating disease. And instead of having accelerated with confirmatory trial, they gave a full approval, which now has set the PAPZIMEOS as really a standard of care for RRP [ and health ] patients. So with that, I hand it back to Phil.

I would just say, RK, I think the broad label just speaks to the illogical nature of trying to treat a chronic infection with risky surgeries. And I think through the great work my colleagues did, we were able to work with the FDA to pull through that logic and secure a broad label, which obviously, from a commercial perspective, is great news.

Yes. So Helen, you just was -- were speaking a little bit earlier regarding the severity of the disease, how severe it can get and in terms of getting to the fifth surgery and almost getting into a very bad situation by then. So in your clinical trial, I'm sure we'll get all these details a bit later in the year. But in general, can you talk to the patient population itself and the mix of the patient population that were in the trial? Were there any patients where you -- or where they had to be debulked a little bit before vaccination, I mean, before giving the PAPZIMEOS? Or is it irrespective of how severe the disease is when they come in, they can be given PAPZIMEOS?

So the way that our trial, pivotal Phase I and Phase II was designed is basically the severe patient population, they will come in. And usually, this patient population is very simple. They go to their doctors when they cannot speak or they cannot breathe. And the reason for that is that the benign tumors have grown on a vocal cord or trachea. And as a result, there is this [indiscernible] on the patient. So the first thing is what these benign tumors, if they were obstructing a vocal cord or trachea, the physicians, they removed it. And then they started the treatment, which is considered a 4 -- a subcu injection is a very easy to administer -- 4 subcu injection over 3 months period. And then the patients were followed for a minimum of the 1 year. Of course, all of our patients have been followed for much longer than that. But the endpoint was no requirement of surgery for a minimum of 1 year. And that's the way that the trial was designed.

Yes. So it doesn't matter at what stage of the disease progression they are in, they can be taken in and be given the treatment without additional surgery?

Yes. And I think what becomes important as we were talking about the broad label, now the patients that -- they are just diagnosed with the disease, they can go in and get treated with PAPZIMEOS. Or patients that have had the disease for many years, they can go in and get it. So the severity of the disease is not the issue, it's as soon as the patient is diagnosed or requires, then they can go in and receive this.

So a follow-up to that question is, let's say, a patient goes in, gets the surgery done. Can you -- can that patient be dosed with PAPZIMEOS immediately after the surgery so that they don't have the next surgery?

Absolutely. And that's the whole plan. That the moment that they are diagnosed or if they have had already the disease for many years, but then they have required to go in, they go in, and then they can receive their PAPZIMEOS immediately.

Okay. All right. No, those are good. And -- but Phil, when you were looking into the patient numbers, you -- I know that you had looked into the claims as well. So were there any of these patients where they were in a -- once we start taking into this neoadjuvant settings and other patients, will that patient number start to grow? Or is that -- it doesn't matter because all of them were taken into account in the numbers that you have?

Yes, the 27,000 that I mentioned was based upon a combination of diagnostic and surgical codes that we looked at around these patients. So that patient population is fixed as it were, but we have seen a phenomenon in other rare disease launches where there have been no treatments available or approved treatments, and then you have 1 or maybe 2 come to the market in quick succession. You do see an increase in diagnosed prevalence. So we do expect there to be an increasing diagnosed prevalence over and above the numbers that we've quoted.

Okay. No, that's good. So Helen, as we're going into this PDUFA date, you had an ongoing Phase III study as well. So what's happening with those patients? And a part of that trial was also to include redosing phase. So how will that be taken care of as you launch the drug?