Precigen, Inc. ($PGEN)

Great. So first, welcome to the 47th Annual Goldman Sachs Healthcare Conference. Very pleased to be joined by Helen and Phil from Precigen. First, welcome. Maybe to start things for those who maybe might be a little bit less familiar with Precigen and overall story as it stands today. Maybe Helen, if you could give a brief overview of the company.

Sure. First of all, thank you for having us here. Precigen is a cell and gene therapy company. It works on a really innovative, differentiated platforms, with combining it really for fit our technology to the right indication with the right regulatory pathway. And this is very important from the very beginning because it allows the focus and allows us to move very rapidly, which a good example of this, we have a portfolio of 2 technology platform. One is our AdenoVerse platform, which is a very unique and differentiated basically delivery platform that allows that you can repeat those patients with very specific adenovirus vectors that are not similar to what you have seen in the field. And the reason for that, it has a large capacity, and it allows for continuous repeat dosing. And without very little or no neutralizing antibodies. And the good part of that is that you can repeat those as many times, which we have shown in our clinical trial. And the front runner of that using this platform is our PAPZIMEOS drug that has been now approved in the rare disease space for recurrent respiratory PAPZIMEOS [indiscernible] RRP, which for the past 100 years have not had any kind of approved treatment. And these patients basically as a result of HPV infection with either HPV 6 or 11, they develop these tumors, benign tumors in the throat or on the vocal chord. And as a result of that, they continuously -- the only thing that physicians could offer them up to the last year was continuous surgery. Some of our patients have had over 300 surgery. Some of them have to receive a surgery every practically month. And this disease can be basically established either as a child by a child passing to the birth canal or and getting infected from the under or in at all transition [indiscernible] it's a devastating disease. And for the first [indiscernible] in a very, very with a very exciting data that we are able now to treat 51% of these patients go to a complete response not requiring any basically surgery or any other treatment, which is unheard of in this sale. So on the back of the same platform, we have our PRGN-2009, which we are very excited. And again, it's applies to the cancers ahead of HPV-related cancers, such as head and neck and cervical cancer, which we will be actually looking forward to sharing our data in early Q4 of this year on head and neck cancer. And then we also have our cellular therapy, which is our ultra CAR-T cells, which is this is truly an overnight with the manufacturing directly in patient. And with that, we have finished our basically Phase Ib, and we are moving now to setting up the pivotal for the phase II. And so as a result of having this platform, it allows the -- to come up with very innovative treatments for the patients, which not only has a very good safety profile, but also have a very unique efficacy and a durability of response that we will be touching based on that, for instance, in regards to PAPZIMEOS, which now well over into the 40-year post treatment.

Great. You mentioned upcoming data, but maybe near- and medium-term catalysts that investors should keep in mind in the coming quarters.

Absolutely. First of all, our PAPZIMEOS is, as we mentioned, we received under accelerated top from FDA last year in August, full approval actually, it became a full approval and currently, as Phil will be speaking, we are very excited about the commercial revenues and the path that is coming in. But at the same token, we have started the redosing the trial for this, which becomes very important as we mentioned, not only we had the 51% complete response in this patient population that they never had any treatment before, but we have an 86% overall response. And based on that, actually, FDA was very interested and safety that we showed that those partial responders that should also be redosed. And they perhaps will benefit from this. So we have started those studies of redosing. We also will be studies in a pediatric population. Again, because of the safety and efficacy and durability of response that we see with PAPZIMEOS, this was highly encouraged, but FDM, we are extremely excited because this is a unique platform that it will lend itself to the pediatric trials. At the same token, we have already submitted for the approval for the European and EMA. So we will be waiting in the upcoming quarters to communicate in regard to that. And it's -- our application is under review from the PAPZIMEOS side. And also one of the other aspects is that currently, our PRGN-2009, which I mentioned is the drug that is on the same backbone of the viral vector with PAPZIMEOS, it's in the clinic on Phase II for head and neck and cervical cancer. And we are very, very excited about the trial reporting on a trial in fall, probably by Q4, early Q4. The result of the head and neck. As you know, this is actually 2 on trial in the patients that they have head and neck. The response rate of the patients in these settings are between 15% to 18%, even with all the checkpoint inhabitor. And in a Phase I, what we show was the objective responses of 30%. And currently, obviously, we -- this is an open trial that we have a view to the data, and we are very excited to be sharing that in Q4 of this year and I think this will be very relevant for the investors.

Great. You recently got orphan drug exclusivity. Can you talk about the importance of that to the company overall?

Absolutely. So we had originally received the orphan drug designation when we submitted our application. And as part of that, if you receive approval, then you become qualified for the orphan drug market exclusivity, it doesn't mean that every company will receive that. It's just that they will be qualified, especially in rare diseases. This is a special program that FDA had basically put forward for the innovative treatments. And what they have done is to encourage the company to work on a rare diseases. Now with receiving the orphan drug market exclusivity we have 7 years of market exclusivity that basically similar type of drugs are not going to be approved by FDA. So you can imagine and Phil will speak to this more that this now allows PAPZIMEOS and Precigen have the full 7 years of basically having the marketing of the PAPZIMEOS and the drug for RRP. And it's very, very important because similar drugs cannot be receiving approval from FDA and also they have to meet the same efficacy as well as durability as well as basically the safety. So it puts the bar very, very high for 7 years and allows us to move very rapidly. So that's quite exciting.

Great. Maybe turning to the commercial side and maybe Phil. Obviously, early innings still, and I'm not going to try pindown on Q2. But has the launch going so far? And any update you can give investors there?

Sure. Well, we've covered a lot of the dynamics that are leading to our excitement launch you're right. We won't go into Q2 in any great detail, but we look forward to sharing the Q2 in August. But a lot of the building blocks have launched have exceeded expectations. We had a rapid increase in payer coverage to well over 200 commercial lives within 6, 8 months of north. When you include Medicare, Medicaid and the others, we've got over 90% of insured lives covered. And as you can imagine, for any rare disease launch without that, our launch is going to be in trouble for them. So to get the payer coverage has been phenomenal. Our prelaunch work told us that there was a concentration of patients in the academic centers. So we estimate there were 27 [indiscernible] in the U.S. with this condition. And most of those because of the cyclical nature of surgery, they were concentrated in the academic centers, the IDN. And that is indeed the case. But one of the things that we're also seeing through launch is the community interest in the drug and the community uptick. And that makes sense for a number of reasons. It's closer to home for the patient. And it -- and we've put in place simple low-cost solutions because our drug is ultra cold chain, but freeze lease programs and just-in-time shipping mean that basically we can ship the drug and patients can get treated anyway. So that community uptake has been very important -- we had a paper published under the [indiscernible] of the foundation in January, where 16 thought leaders basically -- their name to the fact that PAPZIMEOS is the standard of care for all adult patients with RRP irrespective of surgical burden. And then in April, we got the permanent J code, which is an important piece of the jigsaw puzzle as you're launching a drug. That just takes a lot of the drama out of the whole patient journey to access. And we were aware of certain institutions that were waiting for the permanent J code and now we've got the permanent J code. So as in other rare disease launches that we've looked at, we expect that to help with our acceleration in [indiscernible].

And maybe I can just add to what Phil mentioned. In regard to our label from FDA, we have a very broad label that covers all patients at all patients -- adult patients, RRP. And that becomes -- has become very important because now we see that a patient across the spectrum are being treated. And 1 of the reasons for the community centers is because they are the first line and when patients actually start the journey with this disease, they go first to their community doctors. And we are seeing the uptake not only just in severe patient population, but as early as just being diagnosed, the patients now started receiving excellent for the patient because this is a kind of a disease that by fifth surgery, these patients have irreversible damage. And the sooner that you get to them, the better.

Great. In terms of real-world usage, what are you seeing from a compliance standpoint in the initial innings?

Yes, pretty much what we saw in our registrational studies where all patients -- all 35 patients took doses of the treatment. We are seeing very good observance of that regimen in [indiscernible], which reflects the safety and the promise of durability that we've seen in the data, and we continue to see in the extended follow-up. So yes, we're very pleased. We're not seeing anything untoward in the real-world use of the drug.

Okay. Phil, you mentioned a little bit ago, economic first community centers, especially on other side of J-code, maybe a little bit more detail in terms of how you're seeing usage patterns and how that may inform things going forward?

Yes. So we have -- we've talked a lot about hub, our manufacturers -- so this is a site where basically patients can register and physicians can register patients with the intent of getting them onto drug. That's 1 source of the top of the funnel as it were -- some institutions are very well versed in their own patient support services, and they don't use our hub. So it's only part of the story. But 5% of the patients registered in our hub from the community, which gives you an idea of what I talked about earlier in terms of the community uptake of PAPZIMEOS. So both sides of that coin, the academic and the community centers are embracing the drug and basically treating patients. To Helen's point, early on in launch, you would expect at the academic institutions, the severe patients, those who have multiple surgeries, those have highest unmet need to be treated. But now with the community and even at the IDNs, we're seeing that now expand into less severe patients, which is important for the long-term growth and continued growth.

Okay. Helen, you mentioned earlier that your recent ASCO data. Can you give a little bit more detail in terms of updated durability data you gave and especially how that's going to inform the [indiscernible] product?

No, absolutely. I think this is the most -- one of the most important indicator for this drug is not only the safety and efficacy that we saw in the pivotal trial, which was looking at a very robust endpoint of not having any surgery or requiring any treatment for the first year. But now we have gone well over that, the median of the patients had past 36 months. And we have at ASCO, we showed the number of patients that they have past 4 years. And these were the most severe patient population and imagining a patient that they require the surgery, practically some of them every month and to go now more than 40 years, not requiring not only any surgery, no treatment at all. This is quite with what some of our investigators and the physicians say out there is really outstanding. They have never seen anything like this. And with the safety that it has. So -- and as I mentioned, the total response rate is 86% in this patient population. And this has put this standard now for the treatment that is really outstanding as the standard of care for [indiscernible].

And [ Rob ], I mentioned that we're in a great position with payers, but in this increasing durability just adds to that confidence that a lot of patients are going to be treated with this drug and have a great durable response and payers like that sort of thing.

Certainly helps with the health economics. That is for sure. Maybe back to kind of the practicalities of commercial launch. Can you walk us through the steps involved from getting scripts to treatment. And maybe along similar lines, any characteristics of treated patients in terms of [Audio Gap]

we operate in a complex talk about site activation internally and there are a number of things that have to happen. But basically, when a doctor registers the patient, that's an intention to prescribe. That's a prescription. They may or may not be within our hub, as I mentioned -- but that triggers, if they are in our manufacturers have a benefit verification process to make sure the patient has the insurance and coverage and everything else. Once that is done, it's really up to the institution then to help get the prior authorization through dialogue with the payers. And then the patient is ready when those 3 things come together, you get the treatment. And that should take a matter of weeks that entire process once those things are in place. So we have put dedicated resources in field to help the institutions get through that prior authorization step because a lot of these ENT sites, they've never had to do this before. So we have the expertise now, and we've dedicated that resource to make sure that those patients are accelerating prior to treatment. In terms of the characteristics of the patients, we talked earlier, initially, as you would expect, the more severe patients, but we have a broad label, and it's important now to stress that we are seeing the use beyond those severities and that needs to continue and our marketing programs are designed to make sure that every single patient with this condition as a conversation about PAPZIMEOS with their treating physician. That has to be our goal.

Excellent. And on the label, I guess, how are you seeing things regarding the label and potential for an opportunity for redosing?

So from the label, as we mentioned, when we received the full approval from FDA and very also we received a broad label, which meant that regardless of severity of the disease, the patients are qualified to receive this treatment. And also based on the original discussions with FDA, it was very clear based on the safety and efficacy that we were seeing that the immunological data that we showed that the patients that also had reduced their number of surgeries but have not gone to they perhaps can benefit from reducing. And so as part of that, we have already started our redosing and actually patients are enrolling in that program currently. So we very rapidly move with that concept. At the same token, our label is not really restricted in the -- already in the redosing. So it's at the discretion of the physicians. But obviously, we are generating also further data on redosing. This will be very important because it adds the 36%, which are the 5% of the patients that they have partial responders that have benefited and we showed that data as well that they reduced their number of surgery. And as the patients they say, even reduction with 1 surgery for them is very relevant. So we would be moving very rapidly with that.

That's great. Especially early in the launch, things can be lumpy and not always the easiest to track. I guess, from an investor standpoint, what's the best way to think about tracking the launch on the forward?

Well, Revenue, is quite the indicator -- how we -- share -- yes. We shared our Q1 revenue, which not favorable responses, which is an indicator of all the work that we've done in the platform that we've set in Q4 into Q1. And as I said, we're very excited about sharing -- we still got the best part of a month to go of the second quarter, but we are already looking forward to sharing that information. So I'd say revenue is a pretty big cove. But we'll continue to share information on how patient hub numbers because that represents the intention to prescribe both in our hub and from elsewhere. We've talked about payer numbers, which are very healthy. So not going to be too much more to say on that because we're in such a great position, but we continue to reinforce that. And we'll continue to talk about the community and the IDN sort of split. And I think that the community side of the business and we would expect that to be a more prominent part as we go forward of our overall business opportunity, and we'll continue to share that.

Makes sense. We've talked about the patient hub a few times. Can you give us a sense of the conversion you're seeing and also a sense of how you think that might evolve?

Yes. Well, first and foremost, our ambition is to make sure that all of those patients in our manufacturers have get onto treatment. And we have the resources in place to help with that conversion. The revenue that we shared in Q1, obviously gives us a big clue as to how we're doing in terms of that conversion. And now we have the permanent J code as of April. I think that will help provide a little bit more momentum. So we expect that conversion to continue to even accelerate and to be represented in the revenues that we'll share in Q2.

Yes. And maybe I can just add to what Phil mentioned. In regard to our hub, as we have seen from last year to this year, continuous increase in the number of hundreds in the hub, just our hub. And this, as Phil mentioned, is not really talking about the patients that are in the other hubs of the institute. But also, I think one of the things that I'm going to address more is really how fast the treatment has been picked up by the payers. Both Phil and I, we have quite a long experience in the drug development. And this is one of the factors space that we have seen, especially for rare diseases, which are necessarily very low pay and this for the payers and insurers, but to be able to approve it and approve it so rapidly and get to more than 90% of the payers agreeing with a label and also agreeing with the payment. This has helped tremendously, and it would get reflected as has been reflected in the revenue.

Great. Switching gears to the Europe side. So you filed last year, late last year. Can you give an update on regulatory [indiscernible]?

So we have already submitted the application. Our application is under review by EMA, and we are looking forward, obviously, to the results from there. And this is a similar application that we had submitted to the FDA. And I think we have also communicated, we are looking in the path for the commercialization, which a major part of that is with the partnership in Europe and perhaps as soon as we hopefully get approval. Then within the right strategy, we also will start the treatment in Europe. And one of the things that our team has done over the years, again, looking in the numbers of the patients in Europe. And very interestingly, Europe and Japan probably have similar or more of the patients in the United States. So it's quite a large market there as well. And of course, China is even a much bigger market, which we will be paying our extension.

Great. Makes sense. We talked a little bit about the expansion opportunities for redosing. Can you talk a little bit about pediatric opportunity?

Absolutely. I think pediatric opportunity, as I mentioned, some of the patients, actually, a lot of adult patients, they come -- they are infected as a child and as early as age of 1, we have had a patient at 1 year old was infected. And can you imagine basically taking a 1-year-old to OR every month or every other month. So there is a continuous population, some are estimated by FDA that between 1,000 to 1,500 cases per year. And unfortunately, with, I think, without taking the vaccine preventive that this might become even larger population. For children, the safety of the drug, it becomes the side effects. It's extremely important, as you can imagine, because the threshold of the tolerance of the adult is different than a child and it becomes very important. FDA based on the results that we have shown, they have been extremely excited. And so as we -- take the pediatric population end of this year Q4, we will be basically opening our trial for the pediatric. And we look forward to having a similar at least or even hopefully more in pediatric because we are now intervening at a much earlier stage of the disease. And so we look forward to that. And I think PAPZIMEOS is the only drug that has the ability to go very rapidly in the pediatric.

Okay. We talked a little bit about it earlier, but you have a similar same platform in the [indiscernible] for HPV-associated head and neck as well as cervical. Can you talk in a little bit more detail in terms of when we would expect to read out and expectations going into it in terms of what you might see?

So PRGN-2009 is our basically second molecule that is exactly on the backbone of the vector that has PAPZIMEOS built on. So first of all, as you can imagine, it's very important under also the new guidance from FDA. We are going towards applying for the platform designation. This platform designation allows now all of the basically the next drugs that comes with the same platform with the same record they receive this -- and they will have the same safety and manufacturing, which from a regulatory perspective, it makes it much easier and faster to move. So PRGN-2009, [indiscernible] of cervical cancer and head and neck. These are in patients that they have failed practically -- well, on the cervical cancer everything on head and neck, we have gone to various stages of head and neck, not only Stage 4 in Phase I, but also in Phase II, we have gone through even earlier stages. This -- just to give you a perspective, checkpoint inhibitor in these settings, they have had between 15% to 20%. And when they -- in the head and neck when they combine the checkpoint inhibitors with the standard of care in the earlier stages of head and cancer, there was no benefit whatsoever. What we have done now is in conjunction with pembro, we have gone in to both cervical cancer and head and neck. And we showed that actually quite a substantial increase to 30% objective responses, complete responder, partial responders that they went well over, for instance, complete responders over 2 years and some of them continues. And now in head and neck, we will be reporting on the data in early Q1, which is going to be very exciting in the different stages in conjunction with pembro. And in that space, really the standard of care has been really harsh. You have surgeries followed by extensive chemo radiation, which really the patients become devastated as a result of that. And we are looking forward to show that data. I think it will be -- in my opinion, it will change the paradigm.

That's great. Such a high unmet need and then in both patient populations. Maybe in closing in the last couple of minutes, what do you think is the most underappreciated aspect of present you want investors to take away?

Absolutely. I think I have heard from a lot of investors that they have [indiscernible] we missed this and Precigen we missed Precigen -- was under the radar. And first of all, to say that if still there is a huge potential for Precigen as it's going up. And this is the just a tip of iceberg for us. So we are looking forward to this portfolio and the next molecules. As we have shown, Precigen really the start as the company in 2020. And if you can imagine in the middle of a pandemic and then the global markets crashing. What we have done, our PAPZIMEOS drug entered to a Phase I in 2021 by -- end of 2021, we had finished the Phase I. It started the Phase II in 2022. We receive a full approval in 2025. This is unprecedented for drug development, even by a biggest pharma left alone by a small biotech. We have been very focused from basically financially and strategically, we position our assets with our technology and regulatory path, not just basically hoping and wishing for a miracle. This is not our style. We are very focused on that. And I think people, they really didn't understand that differentiated the technology at the beginning. And also, I think the discipline that we have shown over the years on our portfolio and advancement and having a team that a management team that is well worked not only in discovery and development but also in commercial. And at various stages, there has been always question, especially going in a rare disease, that there was well, what is the market value of this and basically how fast can you get the approval? Would the payers pay for this -- all those questions were all along, and I think that has led to under appreciation. But I think 1 by 1, we have taken this obstacle. And we have answered them, and we have moved the assets forward and the portfolio. So I think, hopefully, the investors see the evolution of our company. And also, as I mentioned, this is just the tip of iceberg for us. We are looking forward in the upcoming quarters, not only from our pastimes commercialization, but also the next generation of the molecules in the oncology indication.

Wonderful. Well, that is a great place to close. Thank you, Helen and Phil, for joining.

Thank you very much for having us.