PRECIGEN, INC. Q2 FY2023 earnings call

Positive Regulatory Developments

• FDA confirmed the ongoing single-arm Phase 1/2 study for PRGN-2012 will serve as the pivotal study to support BLA submission for accelerated approval in RRP, with no additional randomized control study required. Endpoints include complete response rate (percentage of patients with no surgical intervention needed in 12 months) and immunological surrogate marker for HPV specific T cell responses.

Portfolio Prioritization

• Focus on accelerating development of PRGN-2012 towards commercialization while advancing other key programs and extending cash runway to 2025.

PRGN-2012 Details

• Phase 1 completed, Phase 2 enrollment and dosing complete; follow-up data collection for Phase 2 to finish by Q2 2024. 50% of Phase 1 patients at dose level 2 had complete response, and ongoing follow-up shows these patients remain surgery-free. The drug has a mechanism of action targeting HPV 6 and 11, favorable safety profile (Grade 1/2 flu-like), reduces surgeries, and has an attractive subcutaneous administration route.

Cost-Saving Measures

• Reduced CRO costs, SG&A; redirected R&D team to focus on CMC and translational clinical research. Divested Exemplar, discussed non-dilutive funding for AG019 and UltraCAR-T programs. Plan to present interim Phase 1b data for PRGN-3006 UltraCAR-T in 2024, activate NCI site for PRGN-2009 Phase 2 study to reduce costs.

No specific product segment financial performance with absolute revenue and contribution % provided in the transcript.

Cash Runway

• Cash runway extended to 2025, allowing time for PRGN-2012 BLA submission and non-dilutive funding.

UltraCAR-T Program

• Plan to present interim Phase 1b data for PRGN-3006 UltraCAR-T in 2024; no new sites for Phase 1 in 2023.

PRGN-2009

• Activating NCI site for Phase 2 study to reduce clinical costs, with update in early 2024 on other sites.

• Uncertainties in regulatory approval processes for PRGN-2012 and other programs.
• Dependence on successful execution of portfolio prioritization and non-dilutive funding efforts.
• Risks associated with clinical trial outcomes and market acceptance of new therapies.

Q: Hi. Thanks for taking the question. Congrats on the progress. A couple on PRGN 2012. Just was there any discussion with FDA about the magnitude of benefit and a complete response rate you would need to show in the Phase 2 portion to support accelerated approval? And then can you just remind us what the patient population baseline characteristics in the Phase 2 portion look like versus Phase 1? And then I have a follow-up. Thank you.

A: Sure. Thank you, Jason. So in regard obviously, we have had discussions in regard complete responses. And we are happy that the FDA has agreed with our endpoints, as I mentioned as far as the complete responders with a follow-up of 12 months. One of the things that we are very, very thankful and grateful to the FDA leadership is the fact that recognition that our Phase 2 is the exact same design as of our Phase 1 in the same patient population, which are basically minimum of three surgery and above. And both of Phase 1 and 2 have enrolled patients with the same characteristics. We have the same endpoint. And this is part of the reason that the FDA also has confirm that we can combine the results from our dose level two of Phase 1 and the Phase 2, which is all dose level two together. Also, what is also very exciting and in part of the discussions that we have had with the FDA, the possibility to have additional on one dose are not necessarily part of the confirmatory it can be additional that we can expand the label by going to, first of all patients that they have less than three surgeries, obviously, as little as one surgery even per year and also for repeat dosing. One thing that, we clearly showed in our data presentation in January, we have the overall 83% response rate in this patient population. 50% of our patients had the complete responses, and 33% of our patient we reduced the number of surgeries. And FDA definitely recognizes the mechanism of action here and the value of the immunological enhancement of the T-cell against the HPV and has actually encouraged us, to have another arm added that we can address those partial responders by repeat dosing, which we are very thankful for that. And I think, it's excellent for the future expansion of the label of this drug product. So, yes, we have had discussion and yet we have the agreement -- and by the way as I mentioned, and I will mention again, the end points for the Phase 1 and Phase 2 and what we have confirmed with the FDA are the same end points.

Q: Hi. Good morning. Thanks for taking my… A: Hi, Jennifer.

Q: Hi and congrats on a lot of good progress this quarter especially with 2012. Maybe to start off on 2012, is there a way we should think about the time line between the positive phase or if there's positive Phase II data in the second quarter, starting the confirmatory study and then BLA submission. And I know you just said that the exploratory arms aren't required for BLA submission, but would you want to submit something on that point in conjunction, with the submission, or what is your thinking currently? And I have a few more after. Thanks.

A: Yes. Obviously, we are laser focused first on getting our -- all of the ducks in a row and moving towards the BLA submission. As you know, and we have mentioned and that's why, it's one of the exciting part. The Phase 1/2 their single arm is an open label, it's not randomized. And as the data comes in, we have the data and clearly, we can assort the preparation. We also have a plan through our breakthrough designation to move and ask for a rolling BLA. And this is part of our strategy. So for further rapid. And finally, the last is -- as we mentioned, our Phase II follow-up will be done by the second quarter of 2024. So we have all the intention to be prepared and move as fast as we can for the submission of our BLA in regard to the confirmatory trial, clearly our confirmatory trial and part of the agreement is going to be, again, a single-arm trial, very similar to what we have done. And that has to be just initiated, and we are already in the process of that. As you can imagine, there is really not that much discussion around the design of this or what needs to be done. As far as the arms for the extension of the label and inclusion of the patients with the lower burden of the disease or for the repeat dosing, this is something that currently we are discussing and of the design. Clearly, we will see how that can be done. But the first priority for us is, to put the confirmatory in initiate that as we submit the BLA because it's every entry intention for us to submit the BLA as soon as possible as we know that these patients have no other options, and we are looking forward to get this to the commercial path as soon as cost.

Q: Hi. Good morning. Thanks for taking my questions. Just a technical difficulty, I apologize, if the question has been asked before. So regarding the 2012 program, I'm just curious, from your perspective regarding the efficacy data endpoint, what is kind of efficacy you think is the approval threshold -- and what kind of data you think is more commercially favorable?

A: I think, from a perspective of commercially favorable, as you can see there is nothing there. There is no other therapeutic and from that currently exists for this patient except number of surgeries over and over and over again in the last time of this. And if you can imagine, that if you have this disease from childhood, it means a lifetime of surgeries and challenges with this. So in that regard, we hope to be the first therapeutic on the market for this disease on patient population. In regard to the efficacy, as we have said, we have currently shown what as far as 50% of our patients from Phase 1 as they are a complete responder. And one thing that we have discussed with FDN is very clear that surgeries alone doesn't lead to the regression of these patients. And because if it was then all the years that these patients had the surgeries they should have been cured by now, which unfortunately that is not the case. And therefore, we have the – the automatic regression it's not there. But even if you consider that it's going to be above 10%, you will be benefiting this patient population but we are currently standing at 50% response rates. So we are very excited. And by the way this is a very deep response. Not only we have completed our 12 months of a response. But as I mentioned, from a Phase 1, or patients' responses the complete responses are ongoing and none of them have required any surgeries.

Q: Hey. Thank you very much. And I will throw in my congrats on the progress this quarter. I would ask sticking with PRGN 2012, -- in the past you provided efficacy on a number of different endpoints in addition to the 12-month CR rate. I guess what is kind of the totality of the data that the FDA is going to look at? Are they focused on those other endpoints that you've shown? And I guess maybe how focused are they on durability versus response rate?

A: I think very good question. First of all the part of the endpoints that we put forward, which was very meaningful, was we didn't go for a reduction in a number of surgeries. What we went for upfront and we provided was that no surgeries required and we made that for 12 months, which is quite a long period of time. It was not for three months or six months. And one other thing that we did which I believe it was seen as a very positive point was we went to a very severe patient population, which they require three surgeries and higher. So all those elements together, it not only shows the durability of the immune response, especially now that we continue obviously following all of our patients. And especially with our responders, we are showing they are well past 12 months and they continue to be in full response. So that speaks to the durability of that response that 12-month follow-up and beyond. On the other hand the fact that we showed a mechanism of action associated with this. And I think this is again was appreciated by the FDA leadership, because clearly we have clinical data from the patients that are in full response that they have generated a specific HPV 6 and 11 responses and that obviously, this is due to the treatment as this patient did not have these responses prior to entering to the trial. So I think that has become very, very important. And the fact that the mechanism of action, it relates to the ability to redose with the AdenoVerse platform. Again that's a huge differentiation and difference between us and others, because with this you allow now to give a number of in this case is the course of over 85 days. And by the way it's subcutaneously event. And it allows, obviously, without having increase neutralizing antibodies or tremendously increased neutralizing antibodies, which will hinder the usually the T-cells and we don't see that at all opposite. It allows all of that to be considered as the uniqueness of this product and also the FDA confirmation for accepting the endpoints that we had plus the immunological markers that we have currently have put in the trials and therefold.

Q: Hi team. Thanks for taking my question this morning. From your discussion of the FDA, have they talked about how long of a safety follow-up do you need in the ongoing study before filing? And then on the preparation work for filing, can you talk about whether there are any additional preclinical work that you need to tee up between now and filing that you have to work on? And then I have a couple of follow-ups. Thank you.

A: Sure. So in regards to the safety profile, it's similar to the endpoints that we have for efficacy one-year safety follow-ups. Of course, we have -- we will be following these patients regardless as they move on. So those are part of the endpoints. And as we have mentioned and I will repeat, this product -- drug product has a very favorable safety profile in all of the patients that we have treated very, very similar and very favorable. As far as -- in regard to the preclinical discussions, obviously, the preclinical work has been already taken place prior to us going to a Phase I, Phase II, but obviously is as part of any BLA submission, we have to meet all the criteria that the FD is asking for. This is part of a typical of submission for the BLA, which includes obviously the Phase II data has to be similar and to what we have seen up to this point. It has to meet the clinical end point, we also are in discussion with the FDA for a manufacturing comparability and using our commercial material in our manufacturing, in the confirmatory trial. So those discussions are ongoing. And when we submit our BLA, of course, it has to have all those components in for the rapid review and approval, which we are hoping that we will moving towards that way rapid.