Precigen (NASDAQ:PGEN) is a biotech to keep an eye on because of its phase 1/2 study it is advancing using its lead immunotherapeutic vaccine known as PRGN-2012, which is being used to treat patients with recurrent respiratory papillomatosis [RRP] in an ongoing phase 1/2 trial. That’s because there has been several positive developments as it relates to this program. The first and most important advancement would be the positive talk that it had with the FDA. That is, the agency is allowing the currently ongoing phase 1/2 single-arm study could be used as a pivotal one, whereby an Accelerated Approval Filing could be made. Given this development, it is in the process of initiating a pivotal confirmatory study before the submission of a Biologics Licensing Application [BLA] for this program. A BLA filing of PRGN-2012 for the treatment of patients with RRP is expected to take place in the 2nd half of 2024.
Not only that, but this federal agency has also already given PRGN-2012 Orphan Drug Designation and Breakthrough Therapy Designation as well. ODD was also given from the EMA in Europe as well on January 16th of 2024. This program is in good shape, because full results from the phase 1 portion were already published in a peer-reviewed medical journal. The Phase 2 portion of this phase 1/2 study is expected to complete enrollment with 35 patients in Q2 of 2024, whereby a phase 2 data presentation will be released. PRGN-2012 makes use of the company’s AdenoVerse technology, which has several advantages of being deployed as an immunotherapeutic vaccine over others.
PRGN-2012 Provides Basis For AdenoVerse Technology Advancement
As I stated above, PRGN-2012 is an immunotherapeutic vaccine, which makes use of the company’s off-the-shelf AdenoVerse technology platform. This platform utilizes its gorilla adenovector technology that helps it to target human papillomavirus [HPV] 6 or HPV 11 for the treatment of patients with recurrent respiratory papillomatosis [RRP]. RRP is a disorder whereby recurrent growths appear on the vocal cords or the tissues that surround the vocal cords. This technology, plus AdenoVerse is highly ideal compared to other therapeutic vaccine approaches. Why is that? That’s because it may be safe enough for repeat administration without any undue toxicities. Secondly, it has the ability to deliver a large genetic payload, which could possibly increase efficacy. Lastly, the inability to replicate in vivo means reduced risk of exposure to healthy human cells. Besides the fact that this modified therapy doesn’t cause cytopathic or cytotoxic effects in healthy normal cells in a patient’s body. There is no cure for RRP and the current standard of care [SOC] is not ideal, because it involves repeated endoscopic debulking with ablation or excision of the lesion itself.
This is where the phase 1/2 study comes into play, in that it is using PRGN-2012 as an adjuvant to be given to these patients with RRP. By adjuvant, I mean that this therapy is going to be given via subcutaneous injection before standard of care [SOC] debulking surgery. As I stated above, where I believe value can be unlocked here is because Precigen already had a highly positive meeting with the FDA with respect to the data it had achieved thus far. During the meeting it had, it was established that the ongoing phase 1/2 study could serve as a pivotal one. This is huge in my opinion, because this means that upon completion of this trial, the company would be allowed to file a Biologics Licensing Application [BLA] to the FDA of PRGN-2012 for the treatment of patients with RRP. Matter of fact, it believes that it is on track to report phase 2 data presentation in Q2 of 2024 and then a BLA filing being done by the 2nd half of 2024. I think the reasoning for having such a productive meeting with the U.S. FDA is because of the data it was able to obtain from this early-stage study. It was shown that patients given Dose Level 2 of PRGN-2012 had helped 50% of patients achieve a complete response [CR]. This is very good, because these are patients who would need recurrent surgeries. With this treatment, such patients didn’t require post-treatment surgeries to remove lesions. All this that was accomplished was done so in a very safe manner. That is, no treatment related adverse events [TAEs] > Grade 2 were shown to be exhibited for the patients given this exact Dose Level. One key question to ask is if these patients didn’t need surgery after treatment, how long has their CR been ongoing? There is good news on this front as well, because with average follow-up range of 18 to 24 months after PRGN-2012 treatment, it was noted that all those who responded were still surgery free.
Another good aspect to consider here would be the market opportunity that is possible for RRP. The company believes that it could obtain $2 billion in peak annual sales globally for PRGN-2012 for RRP. However, it won’t come easy, because another biotech by the name of Inovio Pharmaceuticals (INO) was given the ability to file a BLA after only having completed a phase 1/2 study. That is, it expects to file its BLA of INO-3107 by the 2nd half of 2024 and request for Priority Review as well. Regardless, both companies are going to be required to start confirmatory studies before being able to submit a BLA. The good news is they don’t have to get such pivotal studies completed to receive Accelerated Approval for RRP. There is an ongoing phase 2 study by the NCI using Avastin [bevacizumab] for the treatment of patients with RRP. However, this study is not expected to complete until November of 2025. Another study being done is a phase 2 one, whereby LENVIMA [Lenvatinib] is being combined with Keytruda [pembrolizumab] for the treatment of patients with HPV-associated recurrent respiratory papillomatosis [RRP]. Things bode well for Precigen’s PRGN-2012, because it was just granted Orphan Drug Designation from the European Commission. In addition, to the fact that this AdenoVerse treatment was given this status along with Breakthrough Therapy Designation from the FDA.
Financials
According to the 10-Q SEC Filing, Precigen had cash, cash equivalents, short-term and long-term investments of $79 million as of September 30th 2023 It believes that it has enough cash on hand to fund its operations into 2025. The reason why it is able to extend its cash runway for this extended period of time is because it has been able to reduce its expenses. In particular Selling, general, and administrative [SG&A] costs have decreased by 9% and 17% for the 3 months and 9 months ending 2023, respectively. If it does need to raise cash, then it will likely do so towards the end of 2024. However, what is encouraging is that management not only reprioritized its business but it intends to seek out other means to raise cash. That’s because the BLA, along with starting to prepare for commercialization of PRGN-2012, means it needs to start finding ways to raise significant capital. To accomplish this goal, it wants to extend its runway even further, which could be by means of developing a strategic partnership. A partnership being made with respect to PRGN-2012 or any other clinical candidate in the pipeline could mean a way to obtain non-dilutive capital.
Risks To Business
There are several risks that investors should be aware of before investing in Precigen. The first risk to consider would be with respect to the possible BLA submission of PRGN-2012 for the treatment of patients with RRP. Even though the company received guidance that it could submit a BLA, there is no assurance that the filing will be accepted by the FDA. A second risk to then consider would be upon the review of the BLA filing if it is ultimately accepted by the agency. There is no assurance that it will be given U.S. marketing approval for the treatment of this patient population upon completion of this review.
A third risk to then consider would be with respect to competition. Even if Precigen receives regulatory approval of this therapy for RRP, it may have to ultimately compete against Inovio, with its treatment of INO-3107. The fourth and final risk to consider would be with respect the confirmatory study of PRGN-2012 for RRP. That’s because if Accelerated Approval is given for it, that will only be the beginning. In order for Precigen to keep its drug on the market, it needs to meet the primary endpoint for a phase 3 confirmatory study. Should this late-stage confirmatory trial fail, then there is a good chance that the FDA could pull the drug off of the market.
Conclusion
Precigen has a shot at receiving Accelerated Approval from the FDA of PRGN-2012 for the treatment of patients with recurrent respiratory papillomatosis [RRP]. However, it still has a lot of work that needs to be done in order to achieve this end goal. First, it has to submit and the FDA has to accept its regulatory application of PRGN-2012 for review. Secondly, it must receive U.S. marketing approval for it. I believe there is value here, because peak global sales for targeting this indication could be $2 billion globally. It has another item in its pipeline, which is PRGN-2009, which is an off-the-shelf AdenoVerse immunotherapy being developed to target HPV-associated positive solid tumors.
There was a phase 1 study completed using PRGN-2009 as a monotherapy or in combination for the treatment of patients with recurrent or metastatic HPV-associated cancers. Data from this particular study was presented at the 2023 ASCO Annual Meeting. It was shown that when PRG-2009 was combined with bifunctional fusion protein targeting PD-L1 and TGF-beta [bintrafusp alfa] for the treatment of patients with recurrent/metastatic HPV-associated cancers, that there was a 30% objective response rate [ORR] observed. Having said that, the company is already exploring the use of PRG-2009 + KEYTRUDA for the treatment of patients with newly diagnosed oropharyngeal squamous cell carcinoma [OPSCC] in a phase 2 study, with plans to initiate another one in 2024 to use PRGN-2009 + KEYTRUDA to treat patients with recurrent or metastatic cervical cancer.
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