What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-03-19 compared with 2024-03-19 · 164 added, 242 removed, 510 unchanged (44% of the section changed)

6 unchanged sentences

Our therapeutic platforms, including UltraCAR-T, AdenoVerse immunotherapy, and ActoBiotics, are designed to allow us to precisely control the level and physiological location of gene expression and modify biological molecules to control the function and output of living cells to treat underlying disease conditions.

We are actively advancing our lead clinical programs, including:

PRGN-3005, PRGN-3006, and PRGN-3007, which are built on our UltraCAR-T platform;

PRGN-2009 and PRGN-2012, which are based on our AdenoVerse immunotherapy platform.

In addition, we have completed a Phase 1b/2a study of AG019, which is built on our ActoBiotics platform.

We also have a robust pipeline of preclinical programs that we are pursuing in order to drive long-term value creation.

We have developed a proprietary electroporation device, UltraPorator, designed to further streamline and ensure the rapid and cost-effective manufacturing of UltraCAR-T therapies.

UltraPorator has received FDA clearance for manufacturing UltraCAR-T cells in clinical trials, and we have been dosing patients with UltraCAR-T cells manufactured with UltraPorator in our clinical trials.

Our clinical pipeline includes PRGN-2012 and PRGN-2009, which are based on our AdenoVerse immunotherapy platform;

and PRGN-3005, PRGN-3006 and PRGN-3007, which are built on our UltraCAR-T platform.

We have completed enrollment in the Phase 1b clinical trial of PRGN-3006.

As part of the strategic prioritization of our pipeline, we have paused enrollment in the PRGN-3005 and PRGN-3007 clinical trials.

In addition, we have completed a Phase 1b/2a study of AG019, which is built on our ActoBiotics platform, which we have completed the shut-down of, as discussed below under our Biopharmaceuticals segment (Precigen ActoBio, Inc.).

We have reduced our focus on preclinical programs, while continuing select projects that we believe could provide further near-term validation of our technology platforms.

In August 2024, we announced strategic prioritization of our pipeline to focus on development of our lead program, PRGN-2012.

We plan to minimize UltraCAR-T spending and focus on strategic partnerships to further advance UltraCAR-T programs.

As part of this restructuring, we have paused enrollment in PRGN-3005 and PRGN-3007 UltraCAR-T clinical trials.

In addition, we plan to continue PRGN-2009 Phase 2 clinical trials under a cooperative research and development agreement ("CRADA") with the National Cancer Institute ("NCI") in recurrent/metastatic cervical cancer and in newly diagnosed HPV-associated oropharyngeal cancer.

We have reduced our focus on preclinical programs, while continuing select projects that we believe could provide further near-term validation of our technology platforms.

We have completed the shutdown of our ActoBio subsidiary operations, including the elimination of all ActoBio personnel.

In conjunction with this shutdown, ActoBio's portfolio of intellectual property is available for prospective transactions.

These strategic changes are designed to enable us to focus on the pre-commercialization efforts on PRGN-2012, including supporting regulatory approval, conducting the confirmatory clinical trial, and manufacturing of commercial products.

Additionally, we will continue acceleration of commercial readiness efforts for a potential launch.

We have completed submission of a Biologics License Application ("BLA") for PRGN-2012 for the treatment of adults with Recurrent Respiratory Papillomatosis ("RRP") and the FDA has granted priority review with a Prescription Drug User Fee Act ("PDUFA") target action date set for August 27, 2025.

We exercise discipline in our portfolio management by systematically evaluating data from our preclinical programs in order to make rapid "go" and "no go" decisions.

15 unchanged sentences

• Strategically pursuing our preclinical programs.

We have a robust pipeline of preclinical programs that we are pursuing in order to drive long-term value creation.

We are strategically focusing on selecting preclinical programs to create long-term value.

We exercise discipline in our portfolio management by systematically evaluating data from our preclinical programs in order to make rapid "go" and "no go" decisions.

19 unchanged sentences

UltraVector-enabled matrices facilitate rapid identification of components that yield desired gene expression.

Our library of characterized genetic components and associated functional characterization data enable construction of gene programs for optimized expression of multiple effector genes.

Our library of characterized genetic components and associated functional characterization data enables construction of gene programs for optimized expression of multiple effector genes.

Expression of our membrane-bound interleukin-15, or mbIL15, gene improves functional characteristics of certain immune cells, including T-cells, by enhancing their potential for expansion and persistence.

4 unchanged sentences

Precigen has made significant improvements to the Sleeping Beauty system by optimizing gene elements, genetic payload capacity, and efficiency of delivery, which provides a system tailored to our multigenic UltraCAR-T platform.

Our AttSite recombinases, which break and rejoin DNA at specific sequences in a unidirectional, irreversible fashion to direct integration of a transgene into the host cell genome, allow for stable, site-specific gene integration.

Our AttSite recombinases, which break and rejoin DNA at specific sequences in unidirectional, irreversible fashion to direct integration of a transgene into the host cell genome, allow for stable, site-specific gene integration.

The UltraPorator system includes proprietary hardware and software solutions and potentially represents major advancements over current electroporation devices by significantly reducing the processing time and contamination risk.

9 unchanged sentences

Precigen's Therapeutic Platforms

"Off-the-shelf" AdenoVerse Immunotherapy

Our AdenoVerse immunotherapy platform utilizes a library of proprietary adenovectors for the efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens.

We have established proprietary manufacturing cell lines and production methodologies from our AdenoVerse immunotherapy platform, which we believe are scalable for commercial supply.

Our AdenoVerse platform utilizes a library of proprietary adenovectors for the efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens.

We have established proprietary manufacturing cell lines and production methodologies from our AdenoVerse platform, which we believe are scalable for commercial supply.

We believe that our proprietary gorilla adenovectors, part of the AdenoVerse technology, have superior performance characteristics as compared to current competition, including standard human adenovirus serotype 5, or Ad5, rare human adenovirus types and other non-human primate adenovirus types.

The key advantages of AdenoVerse immunotherapy platform include:

The key advantages of AdenoVerse platform include:

Large genetic payload capacity

19 unchanged sentences

We are able to execute drug substance manufacturing at this facility in an expedited manner at reduced cost compared to contract manufacturing organizations.

We are expanding our drug substance cGMP manufacturing capabilities at this facility with an aim to support the possible commercial launch of our PRGN-2012 asset.

We have expanded our drug substance cGMP manufacturing capabilities at this facility with an aim to support the possible commercial launch of our PRGN-2012 asset.

We will continue to evaluate internal and external strategies to support cGMP manufacturing needs of our AdenoVerse-based therapeutics .

Precigen's most advanced programs based on the AdenoVerse immunotherapy platform include:

(i) PRGN-2012, a first-in-class, investigational "off-the-shelf" AdenoVerse immunotherapy designed to elicit immune responses directed against cells infected with HPV type 6, or HPV6, or HPV type 11, or HPV11, which is in a Phase 1/2 trial in patients with recurrent respiratory papillomatosis, or RRP;

and (ii) PRGN-2009, a first-in-class, investigational "off-the-shelf" immunotherapy utilizing the AdenoVerse platform, is designed to activate the immune system to recognize and target human papillomavirus-positive, or HPV+, solid tumors, which is in two Phase 2 clinical trials for patients with HPV-associated cancers.

PRGN-2012 is a first-in-class, investigational "off-the-shelf" AdenoVerse immunotherapy for the treatment of RRP.

PRGN-2012 is an innovative therapeutic vaccine with optimized antigen design that uses our gorilla adenovector technology, part of our proprietary AdenoVerse platform, to elicit immune responses directed against cells infected with HPV6 and HPV11.

(i) PRGN-2012, a first-in-class, investigational "off-the-shelf" AdenoVerse gene therapy designed to elicit immune responses directed against cells infected with HPV type 6, or HPV6, or HPV type 11, or HPV11, for which BLA is submitted to the FDA for adults with recurrent respiratory papillomatosis, or RRP;

and (ii) PRGN-2009, a first-in-class, investigational "off-the-shelf" treatment utilizing the AdenoVerse platform, is designed to activate the immune system to recognize and target human papillomavirus-positive, or HPV+, solid tumors, which is in two Phase 2 clinical trials for patients with HPV-associated cancers.

PRGN-2012 is an investigational "off-the-shelf" AdenoVerse gene therapy for the treatment of RRP.

PRGN-2012 is engineered with an optimized antigen design and uses our gorilla adenovector technology, part of our proprietary AdenoVerse platform, to elicit immune responses directed against cells infected with HPV6 and HPV11.

Gorilla adenovectors have numerous advantages, including the ability for repeat administration, the inability to replicate in vivo , which may improve safety, and the ability to deliver large payload capacity.

1 unchanged sentence

RRP is classified based on age of onset as juvenile or adult.

RRP prevalence is estimated to be approximately 15,000 to 20,000 patients in the U.S and more than 125,000 patients outside the U.S., based on our commissioned research.

RRP prevalence is estimated to be approximately 27,000 adult patients in the U.S and more than 125,000 patients outside the U.S., based on our commissioned research.

There is no approved therapeutic treatment for RRP and the current standard-of-care is repeated endoscopic debulking with ablation or excision of papillomatous lesions.

5 unchanged sentences

In preclinical models, PRGN-2012 has demonstrated strong HPV6 and HPV11-specific T-cell response in RRP patient samples in vitro .

PRGN-2012 is currently under evaluation in a Phase 1/2 clinical trial.

The clinical trial evaluates PRGN-2012 as an immunotherapy following standard-of-care surgery in adult patients with RRP.

We have completed Phase 1 dose escalation and dose expansion portion of the PRGN-2012 Phase 1/2 trial.

The Phase 1 clinical trial evaluated safety and efficacy of PRGN-2012 as an immunotherapy following standard-of-care RRP surgery.

Trial design included a 3+3 dose escalation cohort followed by a dose expansion cohort to enroll additional patients at the recommended Phase 2 dose (RP2D).

Adult patients with severe, aggressive RRP, defined as greater than or equal to 3 surgeries in the prior 12 months, were eligible for the clinical trial.

The Phase 1 study enrolled a total of 15 patients at one of the following dose levels with patients receiving four PRGN-2012 administrations (on days 1, 15, 43 and 85) via subcutaneous injection at one of the two dose levels:

(i) Dose Level 1:

1 x 10 11 particle units (PU)/dose;

or (ii) Dose Level 2:

5 x 10 11 PU/dose;

Baseline patient characteristics included a median age of 51 years (range:

Ten patients were male and five were female.

Patients had an average of 6.2 surgeries (range:

3 to 10) in the prior 12-months before enrolling in the trial.

The Phase 1 data demonstrated that the repeated administrations of PRGN-2012 were well-tolerated with no DLTs.

There were no TRAEs greater than Grade 2.

All patients received four administrations of PRGN-2012 at the intended dose level.

TRAEs were all mild and reduced in frequency over the treatment interval.

The most common TRAE was injection site reaction, which occurred in all of the patients.

Most other TRAEs occurring in more than one subject were similar to seasonal vaccines and the most common were fatigue, fever, and chills.

There was a low-level increase in neutralizing antibodies against gorilla adenovector after first administration and lack of significant neutralizing antibody response to gorilla adenovector over time with subsequent vaccinations highlights the ability to deliver repeated administrations of PRGN-2012.

The Phase 1 efficacy data for Dose Level 1 showed that PRGN-2012 treatment reduced the need for surgeries for 100% (3 out of 3) severe, aggressive RRP patients.

Patients in Dose Level 1 had a 33% (1 out of 3) Overall Response Rate (ORR), defined as greater than or equal to 50% reduction in the surgeries in 12-months post PRGN-2012 treatment completion compared to 12-months pre-treatment.

Additionally, PRGN-2012 treatment at Dose Level 1 resulted in improvement in average time to recurrence (TTR), which is defined as time from start of treatment to first RRP surgery, post treatment.

The Phase 1 efficacy data for Dose Level 2 showed PRGN-2012 treatment significantly reduced the need for surgeries for severe, aggressive RRP patients.

At Dose Level 2, 50% (6 out of 12) patients had a Complete Response, which is defined as no surgeries needed during the 12-month period following PRGN-2012 treatment completion.

Patients in Dose Level 2 had a 58% (7 out of 12) ORR.

83% (10 out of 12) of patients treated at Dose Level 2 had reduced RRP surgeries in 12-months post PRGN-2012 treatment compared to pre-treatment.

The number of RRP surgeries in the patients (N=12) in Dose Level 2 reduced from a median of 5 surgeries (range:

3-10) in the 12-months pre-treatment to 0.5 surgeries (range:

0-6) in 12-months post PRGN-2012 treatment completion.

In addition, there was a significant improvement in TTR for patients treated with PRGN-2012 at Dose Level 2.

We announced in January 2024 that all Complete Responses from Phase 1 trial remain durable ongoing at more than 2 years after PRGN-2012 treatment.

Additionally, PRGN-2012 treatment at Dose Level 2 showed significant improvement in anatomical Derkay scores, a tool used for research purposes to quantify RRP severity based on involvement of laryngeal structures, and voice quality, evaluated using the validated Vocal Handicap Index-10 (VHI-10), at 24-weeks post PRGN-2012 treatment completion compared to baseline.

The Phase 1 data showed that PRGN-2012 treatment resulted in an increase in HPV 6/11-specific T-cell response in the peripheral blood of RRP patients.

A significantly greater expansion of HPV-specific T cell responses after PRGN-2012 treatment were observed in responders compared to non-complete responders.

We have completed enrollment and dosing in the Phase 2 study of PRGN-2012 with 23 patients enrolled.

The Phase 2 trial is anticipated to be completed in the second quarter of 2024.

We have announced that the FDA has confirmed that the ongoing Phase 1/2 single-arm study will serve as pivotal and that no additional randomized, placebo-controlled trial will be required to support submission of a BLA under an accelerated approval pathway.

The FDA has confirmed that the current primary endpoint for the ongoing Phase 1/2 study, which is Complete Response rate (percentage of patients with no surgical interventions during the 12 months following treatment with PRGN-2012), along with an immunological surrogate marker demonstrating an induction of HPV-specific T cell responses following PRGN-2012 treatment, is acceptable for the accelerated approval request.

Based on the FDA guidance, we plan to initiate a confirmatory study prior to submission of the BLA.

We have completed Phase 1/2 pivotal clinical trial of PRGN-2012 in adults with RRP.

Phase 1/2 pivotal study met the primary safety and efficacy endpoints.

The Phase 1/2 clinical trial (clinical trial identifier:

NCT04724980) evaluated safety and efficacy of PRGN-2012.

The study design included an initial 3+3 dose escalation cohort to identify the recommended Phase 2 dose (RP2D).

Adult RRP patients who had three or more surgeries in the prior 12 months were eligible for the study.

The Phase 1/2 study enrolled a total of 38 patients.

Of these, 3 patients received four administrations of PRGN-2012 at 1x 10 11 particle units (PU)/dose and 35 patients received four administrations of PRGN-2012 at RP2D (5 x 10 11 PU/dose) over a 12-week treatment period via subcutaneous injection.

Primary endpoints included safety and Complete Response rate defined as the percentage of patients who require no RRP surgeries in the 12-month period after PRGN-2012 treatment completion.

Key secondary endpoints included HPV-specific immune responses, extent of papilloma growth as measured by Derkay scoring, and quality of life measurement as measured by Vocal Handicap Index-10 (VHI-10).

Baseline patient characteristics of the 35 adult patients included a median age of 49 years (range:

20 of the patients were male and 15 were female.

Patients had a median of 4 surgeries (range:

3-10) in the 12 months before PRGN-2012 treatment initiation.

Average years since RRP diagnosis was 20 (range:

1-65) with 12 and 23 patients with juvenile and adult onset RRP, respectively.

PRGN-2012 treatment was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events, or TRAEs, greater than Grade 2.

All patients received four administrations of PRGN-2012 at the intended dose levels.

TRAEs were mostly mild with no treatment-related serious adverse events reported.

The most common TRAE was injection site reaction.

Other common TRAEs occurring in more than one subject were fatigue, chills, and fever.

There was no meaningful anti-drug antibody response with repeat administrations of PRGN-2012.

Primary efficacy endpoint analysis demonstrated that 51% (18 out of 35) (95% CI:

34-69) patients treated at RP2D achieved Complete Response.

The Complete Response rate was 50% (6 out of 12) and 52% (12 out of 23) in the Phase 1 and Phase 2 portions of the study, respectively.

Complete Responses were durable with median durability of response yet to be reached.

PRGN-2012 treatment significantly (p < 0.0001) reduced the need for surgeries in RRP patients compared to pre-treatment history.

PRGN-2012 treatment reduced the need for RRP surgeries in 86% (30 out of 35) of patients compared to their pre-treatment history.

RRP surgeries were reduced from a median of 4 (range:

3-10) in the 12 months pre-treatment to 0 (range:

0-7) in the 12 months post PRGN-2012 treatment completion .

PRGN-2012 treatment showed a significant (p < 0.0001) improvement in anatomical Derkay scores, a tool used for research purposes to quantify RRP severity based on involvement of laryngeal structures, with mean Derkay scores reducing from 9 (range:

5-19) at baseline to 1 (range:

0-5) at 24 weeks post-treatment in patients with Complete Response.

Quality of life, as evaluated using the validated VHI-10, significantly (p < 0.0001) improved from a mean of 25 (range:

12-38) at baseline to 7 (range:

0-30) at 24 weeks post PRGN-2012 treatment in patients with Complete Response.

PRGN-2012 treatment induced HPV 6/11-specific T cell responses in RRP patients with a significantly greater expansion of peripheral HPV-specific T cells observed in responders compared with non-responders.

PRGN-2012 has been granted Breakthrough Therapy Designation and Orphan Drug designation for the treatment of RRP by the FDA.

PRGN-2012 has received Orphan Drug Designation for the Treatment of RRP from the European Commission as well.

PRGN-2012 Phase 2 pivotal trial data are anticipated in the second quarter of 2024.

We plan to submit a BLA under an accelerated approval pathway in the second half of 2024.

We are preparing for commercial readiness for a potential launch, if approved, of PRGN-2012 in 2025.

PRGN-2009, a first-in-class, "off-the-shelf" investigational immunotherapy, is designed to activate the immune system to recognize and target HPV+ solid tumors.

We have completed the submission of, and received priority review for Precigen's BLA for PRGN-2012, which is intended for treating adults with RRP.

The PDUFA target action date is set for August 27, 2025.

PRGN-2009, an "off-the-shelf" investigational AdenoVerse gene therapy, is designed to activate the immune system to recognize and target HPV+ solid tumors.

PRGN-2009 leverages our UltraVector and AdenoVerse platforms to optimize HPV type 16, or HPV16, and HPV type 18, or HPV18, antigen design for delivery via a proprietary gorilla adenovector with a large genetic payload capacity and the ability for repeat administrations.

9 unchanged sentences

Recent studies indicate that about 70 percent of cancers of the oropharynx also may be related to HPV.

PRGN-2009 is in a Phase 1/2 clinical trial for patients with HPV-associated cancers in collaboration with NCI pursuant to a Cooperative Research and Development Agreement (CRADA).

We have completed the Phase 1 portion of the trial.

The Phase 2 portion of the study is designed to evaluate PRGN-2009 as a monotherapy in patients with newly-diagnosed stage II/III HPV16-positive oropharyngeal cancer and patients with newly diagnosed operable stage II/III/IVA/IVB HPV+ sinonasal squamous cell cancer.

We have completed enrollment in the Phase 2 monotherapy arm with twenty evaluable patients.

In June 2023, the Principal Investigator of the PRGN-2009 clinical study presented Phase 1 data at the 2023 American Society of Clinical Oncology, or ASCO, Annual Meeting.

Phase 1 study enrolled a total of seventeen adult patients (N=6 Arm 1A, N=11 Arm 1B).

In the monotherapy arm, patients (N = 6) were enrolled in two sequential dose level cohorts with PRGN-2009 delivered via subcutaneous injection.

PRGN-2009 at 5x10 11 particle units (PU) per dose was selected as the recommended phase 2 dose (RP2D).

In the combination arm, PRGN-2009 was administered at the RP2D in combination with bintrafusp alfa.

Patients received up to 20 doses of PRGN-2009 for a duration of 1.8 to 17.9 months in the monotherapy arm and 0.5 to 23.0 months in the combination arm.

The median age in both arms was 61.

The median number of prior lines of therapies in the metastatic setting was 2.5 for the monotherapy arm and 2 for the combination arm.

All patients in the monotherapy arm (N=6) and 10 of 11 patients in the combination arm received prior immune checkpoint blockade (ICB) therapy.

PRGN-2009 treatment in both monotherapy and combination arms was well-tolerated.

In both study arms, there was a low incidence of PRGN-2009 treatment-related adverse events (TRAEs) with only Grade 1 or 2 TRAEs in the monotherapy arm.

TRAEs reported in the combination arm were in line with the safety profile reported for bintrafusp alfa and TRAEs attributable to PRGN-2009 in the combination arm were Grade 1 or 2.

Tumor responses were observed in patients after treatment with PRGN-2009 in combination with bintrafusp alfa (Arm 1B), including in ICB-resistant patients.

The majority (6/6 Arm 1A, 8/10 Arm 1B) of patients developed HPV-16 and/or HPV-18 specific immune responses after treatment with PRGN-2009 in both monotherapy and combination arms.

There was a lack of significant neutralizing antibody response to gorilla adenovector over time with subsequent vaccinations.

PRGN-2009 combined with bintrafusp alfa resulted in a 30% objective response rate (ORR) in patients with pretreated recurrent or metastatic (R/M) HPV-associated cancers that were naïve or resistant to checkpoint blockade.

A Phase 2 clinical trial designed to evaluate PRGN-2009 in combination with anti-PD1 antibody, pembrolizumab, in adult patients with newly-diagnosed HPV-associated oropharyngeal cancer is ongoing in collaboration with NCI pursuant to a CRADA.

We have completed a Phase 1 clinical trial of PRGN-2009 as a monotherapy or in combination with bintrafusp alfa, or M7824, an investigational bifunctional fusion protein, for patients with HPV-associated cancers in collaboration with the National Cancer Institute, or NCI, pursuant to a cooperative research and development arrangement, or CRADA.

PRGN-2009 is being evaluated in two Phase 2 clinical trials in combination with anti-PD1 monoclonal antibody, pembrolizumab, for patients with HPV-associated cancers in collaboration with NCI pursuant to a CRADA.

The first Phase 2 clinical trial is designed to evaluate PRGN-2009 in combination with anti-PD1 antibody, pembrolizumab, in adult patients with newly-diagnosed HPV-associated oropharyngeal cancer is ongoing in collaboration with NCI pursuant to a CRADA.

The primary objective of the study is to determine if there is an increase in CD3+ tumor infiltrating T cells post treatment compared with pre-treatment.

Secondary objectives include safety and overall survival (OS).

In addition, we have received FDA clearance of an Investigational New Drug Application, or IND, to initiate a Phase 2 randomized, open-label clinical trial of PRGN-2009 in combination with pembrolizumab to treat patients with R/M cervical cancer.

The second Phase 2 clinical trial is randomized, open-label clinical trial of PRGN-2009 in combination with pembrolizumab to treat patients with recurrent or metastatic, or R/M, cervical cancer.

Patients in the Phase 2 trial will be randomized 1:1 to the combination of PRGN-2009 and pembrolizumab (cohort 1) or pembrolizumab monotherapy (cohort 2).

5 unchanged sentences

The Phase 2 trial in R/M cervical cancer is enrolling patients.

As part of the strategic prioritization of our pipeline announced in August 2024, we plan to enroll patients in the PRGN-2009 clinical trials only at NCI under a CRADA.

Recent technological advances have revolutionized the field of immunotherapy for the treatment of cancer.

5 unchanged sentences

We believe such an ex vivo expansion process can result in the exhaustion of CAR-T cells prior to their administration, limiting their potential for persistence in patients after administration.

Furthermore, lengthy and complex manufacturing of current CAR-T approaches results in high manufacturing costs and long delays in providing the CAR-T treatment to cancer patients.

Furthermore, the lengthy and complex manufacturing of current CAR-T approaches results in high manufacturing costs and long delays in providing the CAR-T treatment to cancer patients.

Time is of the essence for advanced cancer patients and even modest delays in treatment can adversely affect outcomes.

Our UltraCAR-T platform is differentiated from the competition, and we believe it has the potential to address the shortcomings of current technologies and disrupt the CAR-T treatment landscape by increasing patient access through shortening manufacturing time from weeks to days, decreasing manufacturing-related costs, and improving outcomes.

We advanced the UltraCAR-T platform to address the inhibitory tumor microenvironment by incorporating intrinsic checkpoint blockade without

the need for complex and expensive gene editing techniques.

We advanced the UltraCAR-T platform to address the inhibitory tumor microenvironment by incorporating intrinsic checkpoint blockade without the need for complex and expensive gene editing techniques.

The next generation of UltraCAR-T utilizes a single multicistronic transposon DNA and our overnight, decentralized manufacturing process of UltraCAR-T.

10 unchanged sentences

This design achieves intrinsic CPI blockade without gene editing and is aimed at avoiding systemic toxicity and the high cost of combining CPI antibodies.

The next generation UltraCAR-T cells simultaneously express CAR, mbIL15, and a kill switch, and incorporates intrinsic CPI blockade using a single multicistronic non-viral transposon.

This design differentiates our UltraCAR-T platform from the approaches used by our competitors and, we believe, reduces the

developmental risk as compared to those approaches because product homogeneity is a critical consideration for later stages of clinical development and subsequent commercialization.

We utilize our protein engineering and immunology expertise to optimize antigen binding, hinge, and signaling domains of each CAR based on the target antigen expression profile and cancer indication.

The next generation UltraCAR-T cells simultaneously express CAR, mbIL15, and a kill switch, and incorporate intrinsic CPI blockade using a single multicistronic non-viral transposon.

This design differentiates our UltraCAR-T platform from the approaches used by our competitors and, we believe, reduces the developmental risk as compared to those approaches because product homogeneity is a critical consideration for later stages of clinical development and subsequent commercialization.

We utilize our protein engineering and immunology expertise to

optimize antigen binding, hinge, and signaling domains of each CAR based on the target antigen expression profile and cancer indication.

We have also included our proprietary kill switch technology in our UltraCAR-T cells to improve the safety profile.

11 unchanged sentences

We have developed a proprietary electroporation device, UltraPorator, designed to further streamline and ensure the rapid and cost-effective manufacturing of UltraCAR-T therapies.

The UltraPorator system, intended to be a viable scale-up and commercialization solution for decentralized UltraCAR-T manufacturing, includes proprietary hardware and software solutions and potentially represents major advancements over current electroporation devices by significantly reducing the processing time and contamination risk.

The FDA has cleared UltraPorator as a manufacturing device for clinical trials of our UltraCAR-T investigational therapies.

1 unchanged sentence

We believe development of rapid and successful overnight manufacturing of UltraCAR-T therapies at medical centers signifies a paradigm shift in CAR-T therapy by eliminating manufacturing and timing risks associated with conventional CAR-T therapies, and our intent is for it to take place directly in numerous treatment centers, which can improve the accessibility of our therapies for patients.

Precigen's most advanced programs based on the UltraCAR-T platform include PRGN-3005, which is in a Phase 1b clinical trial for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer;

PRGN-3006, which is in a Phase 1b clinical trial for patients with relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes, or MDS;

and PRGN-3007, based on the next generation UltraCAR-T, which has received FDA clearance to initiate a Phase 1/1b clinical trial for patients with advanced receptor tyrosine kinase-like orphan receptor 1-positive, or ROR1 + , hematological and solid tumors.

PRGN-3005 is a first-in-class, investigational autologous CAR-T therapy that utilizes our UltraCAR-T platform to simultaneously express a CAR targeting the unshed portion of the Mucin 16 antigen, or MUC16, mbIL15, and kill switch genes.

Precigen's most advanced programs based on the UltraCAR-T platform include PRGN-3006, which has completed enrollment in a Phase 1b clinical trial for patients with relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes, or MDS;

PRGN-3005, which is in a Phase 1b clinical trial for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer;

and PRGN-3007, based on the next generation UltraCAR-T, which is in a Phase 1/1b clinical trial for patients with advanced receptor tyrosine kinase-like orphan receptor 1-positive, or ROR1 + , hematological and solid tumors.

PRGN-3005 is an investigational autologous CAR-T therapy that utilizes our UltraCAR-T platform to simultaneously express a CAR targeting the unshed portion of the Mucin 16 antigen, or MUC16, mbIL15, and kill switch genes.

MUC16 is an extremely large, type I transmembrane cell surface glycoprotein that plays a key role in the pathogenesis of ovarian cancer by promoting an increase in cell proliferation, metastasis, resistance to chemotherapy and immune system evasion by cancer cells.

4 unchanged sentences

In order to eliminate binding to circulating CA125, we have designed our MUC16 CAR using an antigen binding domain that specifically binds the unshed portion of MUC16 and optimized its affinity to preferentially target PRGN-3005 to tumor cells.

PRGN-3005 is being evaluated for the treatment of advanced ovarian, fallopian tube, and primary peritoneal cancers.

Advanced ovarian cancer is often fatal, with Stage IV survival rates as low as 20 percent, and has limited treatment options.

Patients with ovarian cancer represent a large population, with approximately 300,000 patients diagnosed worldwide annually, including 22,000 in the United States alone.

In preclinical in vitro studies, PRGN-3005 UltraCAR-T cells have shown robust MUC16-specific cytotoxicity of ovarian cancer cell lines, a stem-cell like memory phenotype and significant improvement in their longevity even in the absence of exogenous cytokines as compared to conventional CAR-T cells.

PRGN-3005 UltraCAR-T cells have shown significantly superior anti-tumor response in mouse models of ovarian cancer compared to mice treated with a saline solution or

conventional MUC16 CAR-T cells lacking mbIL15 expression.

Specifically, a single administration of PRGN-3005 one day after non-viral gene transfer showed significantly superior expansion and preferred memory phenotype of UltraCAR-T in vivo and significantly superior efficacy compared to traditional CAR-T resulting in all PRGN-3005 treated mice becoming tumor-free.

Furthermore, rechallenging these tumor-free mice three months later with ovarian tumors for a second time (to simulate tumor relapse) led to the elimination of tumor burden without additional PRGN-3005 UltraCAR-T treatment.

In preclinical in vitro studies, PRGN-3005 UltraCAR-T has shown robust MUC16-specific cytotoxicity of ovarian cancer cell lines, a stem-cell like memory phenotype and significant improvement in their longevity even in the absence of exogenous cytokines as compared to conventional CAR-T cells.

PRGN-3005 UltraCAR-T cells have shown significantly superior anti-tumor response in mouse models of ovarian cancer compared to mice treated with a saline solution or conventional MUC16 CAR-T cells lacking mbIL15 expression.

These data demonstrated the potential of UltraCAR-T cells to persist long-term in vivo , prevent CAR-T cell exhaustion, and mount a durable anti-tumor response with the ability to continue to respond upon tumor rechallenge.

The Phase 1/1b clinical study of PRGN-3005 is designed to enroll in two phases, an initial dose escalation phase (Phase 1) followed by a dose expansion phase (Phase 1b).

PRGN-3005 is in a 1/1b clinical trial designed to enroll in two phases, an initial dose escalation phase (Phase 1) followed by a dose expansion phase (Phase 1b).

We have completed the Phase 1 dose escalation portion of the PRGN-3005 Phase 1/1b study.

The Phase 1 portion of the study is a dual-arm, non-randomized, open-label clinical trial in patients with advanced, recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.

Patients in the Phase 1 dose escalation trial receive either intraperitoneal, or IP (Arm 1), or intravenous, or IV (Arm 2), administration of PRGN-3005 without prior lymphodepletion.

Previously we had announced FDA clearance to incorporate a cohort with lymphodepletion at Dose Level 3 of the IV arm in the Phase 1 study.

The primary objectives of the Phase 1 trial are to assess the safety and maximum tolerated dose, or MTD, of PRGN-3005.

In June 2023, the Principal Investigator of the PRGN-3005 clinical study presented Phase 1 data at the 2023 American Society of Clinical Oncology, or ASCO, Annual Meeting.

The presentation included the complete data set for the Phase 1 dose escalation portion of the study.

Patients in the Phase 1 dose escalation trial received either intraperitoneal, or IP (Arm 1), or intravenous, or IV (Arm 2), administration of PRGN-3005 without prior lymphodepletion.

After receiving FDA clearance, we also incorporated a cohort with lymphodepletion at Dose Level 3 of the IV arm in the Phase 1 study.

The primary objectives of the Phase 1 trial included assessment of safety and maximum tolerated dose, or MTD, of PRGN-3005.

The Phase 1 study enrolled a total of 27 patients (N=12 IP;

and N=9 IV with lymphodepletion).

The mean age of patients in the study was 57.4 in the IP arm without lymphodepletion, 67.3 in the IV arm without lymphodepletion and 62.7 in the IV arm with lymphodepletion.

Patients were heavily pretreated with a median of greater than or equal to 8 prior lines of therapy across all arms.

Patients had significantly advanced stage disease with a high baseline tumor burden with most patients having distant metastases, including liver, spleen, bladder and lung.

Patients treated in the non-lymphodepletion cohort and lymphodepletion cohort received a single administration of 1.8 to 50 x 10 6 and 4.4 to 83 x 10 6 UltraCAR-T cells via IV infusion, respectively.

PRGN-3005 was well-tolerated with low incidence of treatment related adverse events (TRAEs), no dose limiting toxicities (DLTs), and no neurotoxicity.

PRGN-3005 treatment was well-tolerated with low incidence of treatment related adverse events (TRAEs), no dose limiting toxicities (DLTs), and no neurotoxicity.

The most common side effects for the IV and IP arms without lymphodepletion were abdominal pain, fever and decreased absolute lymphocyte count (ALC).

Serious Adverse Events included five incidences of Cytokine Release Syndrome (CRS), with no incidence of CRS greater than Grade 2.

One patient with CRS required specific intervention which resolved following standard CRS management after 24 hours.

One patient with CRS required specific intervention which was resolved following standard CRS management after 24 hours.

There was no use of tocilizumab or dexamethasone or kill switch.

PRGN-3005 administered via either IP or IV infusion resulted in a dose-dependent expansion and encouraging persistence in peripheral blood.

Best responses in patients treated without lymphodepletion were stable disease with complete responses observed in certain individual target lesions.

Incorporating lymphodepletion prior to IV infusion led to an encouraging anti-

tumor activity with a decrease in tumor burden in 67% (6/9) of patients and stable or partial response in 90% of the individual target lesions in these patients.

Subsequently, we have initiated the Phase 1b dose expansion study of PRGN-3005 UltraCAR-T at Dose Level 3 with lymphodepletion prior to IV infusion.

We previously communicated, based on portfolio reprioritization efforts, that we will not add an extensive number of new clinical sites for the Phase 1b study.

Instead, we anticipate to activate a new site under the CRADA with the National Cancer Institute (NCI) to continue the advancement of the Phase 1b dose expansion study without incurring major clinical/contract research organization (CRO) costs.

PRGN-3006 is a first-in-class, investigational autologous CAR-T therapy that utilizes our UltraCAR-T platform to express a CAR to target CD33, mbIL15 and a kill switch for better precision and control.

Best responses in patients treated without lymphodepletion were stable disease with complete responses

observed in certain individual target lesions.

Incorporating lymphodepletion prior to IV infusion led to an encouraging anti-tumor activity with a decrease in tumor burden in 67% (6/9) of patients and stable or partial response in 90% of the individual target lesions in these patients.

Subsequently, we initiated the Phase 1b dose expansion study of PRGN-3005 UltraCAR-T at Dose Level 3 with lymphodepletion prior to IV infusion.

As part of the strategic prioritization of our pipeline announced in August 2024, we have paused enrollment in the Phase 1b clinical trial of PRGN-3005.

PRGN-3006 is an investigational autologous CAR-T therapy that utilizes our UltraCAR-T platform to express a CAR to target CD33, mbIL15 and a kill switch for better precision and control.

CD33, also known as Siglec-3, is a single pass transmembrane glycoprotein and a member of the sialic acid-binding immunoglobulin-like lectin super-family.

15 unchanged sentences

PRGN-3006 demonstrated engraftment and significantly higher expansion and persistence in mice compared to conventional CAR-T cells, which lack mbIL15 expression.

The Phase 1/1b clinical study of PRGN-3006 is designed to enroll in two phases, an initial dose escalation phase (Phase 1) followed by a dose expansion phase (Phase 1b).

We have completed Phase 1 dose escalation portion of the PRGN-3006 Phase 1/1b study.

PRGN-3006 is in a Phase 1/1b clinical trial designed to enroll in two phases, an initial dose escalation phase (Phase 1) followed by a dose expansion phase (Phase 1b).

We have completed Phase 1 dose escalation portion and completed enrollment in Phase

1b portion of the trial.

The Phase 1 portion of this study is a dual-arm, non-randomized, dose-escalation clinical trial where PRGN-3006 is delivered via intravenous infusion.

The patient population includes relapsed or refractory AML, or r/r AML, higher-risk MDS, and CMML.

The patient population included patients with relapsed or refractory AML, or r/r AML, higher-risk MDS, and CMML.

In the Phase 1 3+3 dose escalation portion, patients are treated in one of the two arms:

patients in Cohort 1, or No Lymphodepletion arm, receive UltraCAR-T cell infusion without prior lymphodepletion, and patients in Cohort 2, or Lymphodepletion arm, receive lymphodepleting chemotherapy prior to UltraCAR-T infusion.

The primary objective of this trial is to assess the safety of PRGN-3006 and determine the MTD.

The Principal Investigator of the PRGN-3006 clinical study presented complete Phase 1 data at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition.

The presentation included the complete data set for the Phase 1 dose escalation portion of the study.

The study enrolled a total of 26 patients (N=10 non-lymphodepletion;

The primary objective included assessment of safety of PRGN-3006 and determination of the MTD.

The Phase 1 study enrolled a total of 26 patients (N=10 non-lymphodepletion;

N=16 with lymphodepletion) and included 21 patients with r/r AML, 2 patients with chronic myelomonocytic leukemia (CMML), and 3 patients with MDS.

7 unchanged sentences

Incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was rare with one Grade 1 event and one Grade 2 event in Cohort 1 and Cohort 2, respectively.

No patients experienced a significant increase in serum IL-15, demonstrating that mbIL15 remains tethered to the UltraCAR-T cells as designed and is not released.

Excellent dose-dependent expansion and persistence of PRGN-3006 in peripheral blood and bone marrow was observed following a single infusion in both the non-lymphodepletion and lymphodepletion cohorts highlighting the ability of UltraCAR-T cells to engraft and survive even in the absence of lymphodepletion.

1 unchanged sentence

In the lymphodepletion cohort (Cohort 2), an objective response rate (ORR) of 27% (3 out of 11) was reported for heavily pre-treated r/r AML patients with poor prognosis (median prior treatments:

Responders received a single PRGN-3006 dose ranging between 4.4 to 28 x 10 6 cells following lymphodepletion.

A disease control rate (DCR) of 45% (5 out of 11) at day 28 for r/r AML patients and 100% of MDS patients, respectively.

One patient with CRi was bridged to allo-HSCT at three months post treatment and remains in a measurable residual disease-negative CR 18 months post-transplant.

A disease control rate (DCR) of 45% (5 out of 11) was reported at day 28 for r/r AML patients and 100% of MDS patients, respectively.

Additionally, of the 15 evaluable patients in the lymphodepletion cohort (Cohort 2), 60% (9 out of 15) heavily pre-treated patients had a reduction in bone marrow blasts following a single PRGN-3006 infusion, with 4 patients experiencing a substantial decrease to ≤5%.

1 unchanged sentence

There was an increase in cytotoxicity, costimulatory signaling, and lymphoid compartment and decreased apoptosis pathway scores in the lymphodepletion cohort on Days 14 and 28 post PRGN-3006 treatment compared to baseline.

We have initiated a Phase 1b dose expansion study where PRGN-3006 is being evaluated following lymphodepletion.

The Phase 1b dose expansion study of PRGN-3006 UltraCAR-T was expanded to Mayo Clinic in Rochester, Minnesota, joining the existing Moffitt Cancer Center, Tampa, Florida site enhancing the decentralized manufacturing model.

Based on the results of correlative studies of the patient samples from the Phase 1/1b study, we have identified clinical biomarkers that correlate to objective responses after PRGN-3006 treatment in r/r AML patients.

This advancement may further enable patient stratification and positively impact efficacy.

We have completed enrollment in the Phase 1b dose expansion study.

We are preparing for an end of Phase 1b meeting with the FDA to discuss the results and next steps.

We plan to focus on strategic partnership opportunities to advance PRGN-3006 UltraCAR-T program in AML.

PRGN-3006 has been granted Orphan Drug designation in patients with AML and Fast Track Designation in patients with r/r AML by the FDA.

PRGN-3007 is a first-in-class, investigational autologous CAR-T therapy that utilizes the next generation UltraCAR-T platform to express a CAR to target ROR1, mbIL15, kill switch, and a novel mechanism for the intrinsic blockade of the programmed death 1, or PD-1, gene expression.

PRGN-3007 is an investigational autologous CAR-T therapy that utilizes the next generation UltraCAR-T platform to express a CAR to target ROR1, mbIL15, kill switch, and a novel mechanism for the intrinsic blockade of the programmed death 1, or PD-1, gene expression.

ROR1 is a type I orphan-receptor that is expressed during embryogenesis and by certain hematological and solid tumors but is undetectable on normal adult tissues.

8 unchanged sentences

Single-cell cytokine proteomics showed that the downregulation of PD-1 expression on PRGN-3007 resulted in a significantly higher number of polyfunctional CAR-T cells compared to Control ROR1 CAR-T.

Expression of mbIL15 on PRGN-3007 UltraCAR-T, with or without downregulation of PD-1 expression, resulted in robust expansion in presence of ROR1 antigen, lack of autonomous expansion in absence of ROR1, and durable persistence even in absence of exogenous cytokines in vitro.

PRGN-3007 showed robust expansion in presence of ROR1 antigen, lack of autonomous expansion in absence of ROR1, and durable persistence even in absence of exogenous cytokines in vitro.

PRGN-3007 was selectively and effectively eliminated by the kill switch activator treatment demonstrating functionality of the kill switch, which is intended to improve the safety profile of PRGN-3007.

1 unchanged sentence

Blood analyses demonstrated sustained downregulation of PD-1 expression, rapid expansion, long-term persistence, and a predominant central memory phenotype of PRGN-3007 in tumor bearing mice.

The Phase 1/1b clinical trial is an open-label study designed to evaluate the safety and efficacy of PRGN-3007 in patients with advanced ROR1 + hematological (Arm 1) and solid (Arm 2) tumors.

The Phase 1/1b clinical trial is designed as an open-label study designed to evaluate the safety and efficacy of PRGN-3007 in patients with advanced ROR1 + hematological (Arm 1) and solid (Arm 2) tumors.

The target patient population for Arm 1 includes relapsed or refractory CLL, relapsed or refractory MCL, relapsed or refractory B-ALL, and relapsed or refractory DLBCL.

The target patient population for Arm 2 includes locally advanced unresectable or metastatic histologically confirmed TNBC.

will enroll in two parts:

The study will enroll in two parts:

an initial 3+3 dose escalation in each arm followed by a dose expansion at the maximum tolerated dose.

Arm 1 and Arm 2 will enroll in parallel.

The Phase 1 trial is being conducted in collaboration with Moffitt Cancer Center, a pioneer in CAR-T clinical development.

PRGN-3007 manufacturing technology transfer to Moffit Cancer Center was completed for initiation of the Phase 1 study.

We have initiated dosing in the Phase 1 dose escalation portion of the Phase 1/1b study.

As part of the strategic prioritization of our pipeline announced in August 2024, we have paused enrollment in the Phase 1 clinical trial of PRGN-3007.

Preclinical Programs

4 unchanged sentences

Precigen ActoBio (ActoBio)

ActoBio is pioneering a proprietary class of microbe-based biopharmaceuticals that enable expression and local delivery of disease-modifying therapeutics.

We refer to these microbe-based biopharmaceuticals as ActoBiotics.

Precigen ActoBio's Therapeutic Platforms

Our ActoBiotics platform is a unique delivery platform precisely tailored for specific disease modification with the potential for superior efficacy and safety.

ActoBiotics combine the advantages of highly selective protein-based therapeutic agents with local delivery by the well-characterized and food-grade bacterium Lactococcus lactis , or L.

ActoBiotics can be delivered orally in a capsule, through an oral rinse or in a topical solution.

We believe ActoBiotics have the potential to provide superior safety and efficacy via the sustained release of appropriate quantities of select therapeutic agents as compared to injectable biologics, while reducing the side effects commonly attributed to systemic delivery and corresponding peaks in concentration.

ActoBiotics work via genetically modified bacteria that deliver proteins and peptides at mucosal sites, rather than the insertion of one or more genes into a human cell by means of a virus or other delivery mechanism.

By foregoing this insertion, ActoBiotics allow "gene therapy" without the need for cell transformation.

The key advantages of ActoBiotics include:

Food-grade bacterium with easy genetic manipulation

ActoBiotics combine the advantages of highly selective protein-based therapeutic agents with local delivery by the well-characterized and food-grade bacterium with L.

lactis , which has a long history of safe use.

ActoBiotics are generated by genetically modifying L.

lactis via chromosomal integration through targeted double homologous recombination to express and release a variety of highly versatile biological moieties.

Multiple therapeutic agents, such as proteins, peptides, and antibodies, can be incorporated into a single ActoBiotics therapeutic, enabling the simultaneous targeting of multiple pathways in one disease.

lactis host is also engineered for environmental containment, thus preventing the spread of bacteria outside the human body.

Cost-effective and scalable manufacturing

We have established an efficient and reliable cGMP manufacturing process for the production of ActoBiotics that we believe is easily scalable for commercial supply.

The manufacturing process involves fermentation of genetically modified L.

lactis to generate significant quantities of the therapeutic agent, followed by concentration and freeze-drying.

The process does not require the costly purification required to produce conventional biologics.

Convenient delivery method

ActoBiotics can be delivered to the oral cavity through a mouthwash, intestinally via a capsule, or through a topical formula.

Physiological dosing is low, and our ActoBiotics product candidates have been well-tolerated in preclinical and clinical studies.

As compared to conventional biologics, we believe ActoBiotics have the potential to provide superior safety and efficacy via the sustained release of appropriate quantities of select therapeutic agents while reducing the side-effects commonly attributed to systemic delivery and corresponding peaks in concentration of conventional biologics.

ActoBio's most advanced internal pipeline candidate, AG019, is a first-in-class disease modifying antigen-specific, investigational immunotherapy for the prevention, delay, or reversal of type 1 diabetes mellitus, or T1D.

AG019 is an easy-to-take capsule formulation of ActoBiotics engineered to deliver the autoantigen human proinsulin, or hPINS, and the tolerance-enhancing cytokine human interleukin-10 to the mucosal lining of gastro-intestinal tissues in patients with T1D.

We believe this design can reduce T1D pathology by reestablishing immunological tolerance to islet antigens via the production of regulatory T, or Treg, cells.

T1D represents a highly unmet medical need, with approximately 132,000 patients, most commonly children and young adults, diagnosed each year.

In T1D, the immune system destroys insulin-producing beta cells in the pancreas, creating a blood glucose imbalance and numerous symptoms, including polyuria, polydipsia, polyphagia, weight loss, lassitude, nausea and blurred vision.

The current treatment standard for T1D consists of exogenous insulin along with diet and lifestyle modification, but no disease-modifying treatment is available.

We believe that AG019 has the potential to address the unmet medical need for disease modifying treatment in T1D.

Preclinical studies in mice have shown that AG019, in association with a short-term treatment with a low-dose anti-CD3 monoclonal antibody, induced stable reversion to normal blood sugar levels and reversed the disease in diabetic mice treated at an early stage.

Furthermore, AG019 treatment induced accumulation and proliferation of PINS-specific FoxP3 + Treg cells in the pancreas and peripheral lymph nodes.

ActoBio has developed a proprietary class of microbe-based biopharmaceuticals that enable expression and local delivery of disease-modifying therapeutics.

We refer to these microbe-based biopharmaceuticals as ActoBiotics.ActoBio’s lead asset is AG019, a disease modifying antigen-specific, investigational immunotherapy for the prevention, delay, or reversal of type 1 diabetes mellitus, or T1D.

We have completed a Phase 1b/2a clinical trial of AG019 for the treatment of early-onset T1D.

The Phase 1b open-label portion of the study evaluated the safety and tolerability of AG019 monotherapy administered as a single dose and repeated daily doses in adult and adolescent patients.

The Phase 2a double-blind portion of the study investigated the safety and tolerability of AG019 in combination with teplizumab, or TZIELD.

The primary endpoint of both the Phase 1b AG019 monotherapy and the Phase 2a AG019 combination therapy was met.

AG019 was well-tolerated when administered to adults and adolescents either as monotherapy or in combination with teplizumab.

A single 8-week treatment cycle of oral AG019 as a monotherapy and in combination with teplizumab showed stabilization or increase of C-peptide levels during the first 6 months post treatment initiation in recent-onset T1D.

In an independent analysis performed in a subset of adult and adolescent patients by the Immune Tolerance Network (ITN), a leading independent research group sponsored by the United States National Institutes of Health, AG019 monotherapy and combination therapy induced antigen-specific tolerance in conjunction with the reduction of disease-specific T-cell responses.

The extent of these antigen-specific immune modulatory effects in the combination therapy patients was similar to what was seen in AG019 monotherapy patients indicating that this effect may be attributed to the single 8-week treatment cycle of oral AG019.

As part of our strategic prioritization, we have completed the shutdown of our ActoBio subsidiary operations, including the elimination of all ActoBio personnel.

In conjunction with this shutdown, ActoBio's portfolio of intellectual property is available for prospective transactions.

Precigen Exemplar

8 unchanged sentences

Healthcare Business

While we believe that our novel approach to developing the next generation of gene and cell therapies utilizing our UltraCAR-T, AdenoVerse immunotherapy or ActoBiotics platform to target the most urgent and intractable challenges in immuno-oncology, autoimmune disorders, and infectious diseases provides us with competitive advantages, our industry is highly competitive and subject to rapid and significant technological change.

While we believe that our novel approach to developing the next generation of gene and cell therapies utilizing our AdenoVerse and UltraCAR-T platforms to target the most urgent and intractable challenges in immuno-oncology, autoimmune disorders, and infectious diseases provides us with competitive advantages, our industry is highly competitive and subject to rapid and significant technological change.

Many of our competitors have significantly greater financial, technical, and human resource capabilities than we do, and certain of our competitors may also benefit from local government subsidies and other incentives that are not available to us.

6 unchanged sentences

Key product features that would affect our ability to effectively compete with other therapeutics include the efficacy, safety and convenience of our products, as well as the availability of intellectual property protection.

AdenoVerse Immunotherapy

For our product candidate PRGN-2012 for the treatment of RRP, while we believe our approach for PRGN-2012 is novel based on the design of antigen targeting HPV6 and HPV11 and use of our gorilla adenovector, we face competition in the treatment of RRP.

We believe our main competitor in the field is INOVIO Pharmaceuticals with their investigational DNA vaccine INO-3107 targeting HPV6 and HPV11 antigens.

For our PRGN-2009 candidate in HPV-associated cancers, we believe that INOVIO Pharmaceuticals, BioNTech SE, PDS Biotechnology, Hookipa Pharma, Transgene S.A.

and Nykode Therapeutics are developing immunotherapies that are in clinical testing.

TG4001 is an investigational therapeutic cancer vaccine candidate using an attenuated and modified poxvirus, or MVA, as a vector expressing the HPV16 E6 and E7 proteins and interleukin-2.

We believe TG4001 is in a clinical trial in combination with anti-PD-L1 antibody avelumab for anogenital HPV+ cancers.

INOVIO's lead investigational candidate VGX-3100 is a plasmid DNA based vaccine designed to increase T cell immune responses against the E6 and E7 antigens of HPV16 and HPV18.

VGX-3100 is in clinical trials for precancerous cervical dysplasia, vulvar dysplasia, and anal dysplasia.

INOVIO is also developing INO-3112, a DNA medicine candidate targeting HPV 16/18, combined with a DNA plasmid for IL-12 in combination with an anti-PD1 monoclonal antibody for locoregionally advanced, high-risk, HPV16/18 positive oropharyngeal squamous cell carcinoma.

We believe BioNTech is developing BNT113, an investigational HPV16 E6/7 mRNA vaccine.

We believe BNT113 in combination with an anti-PD1 monoclonal antibody is in a clinical trial for HPV16+PD1+ Head and Neck squamous cell carcinoma.

We believe PDS Biotechnology is developing Versamune® HPV (previously PDS0101), an investigational HPV16 peptide vaccine for various HPV-associated cancers.

We believe Versamune HPV is in clinical trials as monotherapy and combination therapy for recurrent/metastatic HPV16+ head and neck cancer, pre-metastatic HPV-associated oropharyngeal cancer, and HPV+ anal, cervical, head and neck, penile, vaginal, vulvar cancers.

We believe Hookipa is developing Eseba-vec (HB-200), based on two single-vector compounds with arenaviral backbones based on lymphocytic choriomeningitis virus and pichinde virus expressing the same transgene encoding an HPV16 E7E6 fusion protein, which is in a clinical trial for HPV16+ head and neck cancers.

Cellid is developing BVAC-C, which is based on CeliVax technology that uses patient-derived B cells and monocytes transfected with E6/E7 recombination gene of HPV16 and HPV18 and loaded with an adjuvant for HPV-associated cancers.

Nykode Therapeutics is developing VB10.16, a DNA-based therapeutic vaccine targeting malignancies caused by HPV16, which is being evaluated in multiple clinical trials.

In addition to our direct competitors developing vaccines for treatment of HPV-associated cancers, various development-stage companies are involved in different vaccine and immunotherapy technologies, including Bavarian Nordic.

We also face competition from non-vaccine based approaches being developed by companies such as Kite, Iovance, Bristol-Myers Squibb, and Merck.

Our lead product candidates include PRGN-3005, PRGN-3006, and PRGN-3007, each of which are built on our UltraCAR-T platform.

3 unchanged sentences

We believe that Lyell Immunopharma, and Oncternal Therapeutics are developing ROR1 CAR-T cells for treatment of ROR1-positive cancers.

We believe that INOVIO Pharmaceuticals, AstraZeneca, Transgene SA, PDS Biotech, and Advaxis Immunotherapies are developing immunotherapies against HPV-associated cancers.

Anixa Biosciences is developing an autologous CAR-T treatment targeting follicle stimulating hormone receptor (FSHR) for ovarian cancer, which we believe is in a clinical trial.

3 unchanged sentences

For the treatment of AML using cell therapies, we believe that Kite, 2seventy bio and Nkarta have product candidates in the most advanced clinical trials.

Kite is developing KITE-222, an investigational autologous T-cell therapy engineered with a CAR that specifically targets CLL-1 for treatment of AML.

We believe that 2seventy bio is developing DARIC33, a pharmacologically controlled CD33-targeted CAR-T therapy which is in a clinical trial for pediatric AML.

Nkarta is developing NKX101, an investigational allogeneic NK cell therapy expressing a CAR target NKG2D ligands and mbIL-15.

We believe NKX101 is in a clinical trial for AML and MDS.

Amgen is developing AMG 553, an FMS-like tyrosine kinase 3, or FLT3, CAR-T cell therapy utilizing autologous T-cells genetically modified ex vivo to express a transmembrane CAR to target FLT3 protein on the surface of AML cells irrespective of FLT3 mutational status.

Cellectis S.A.

is also developing UCART123, an allogeneic anti-CD123 CAR-T cell therapy, which utilizes lentivector transduction followed by TALEN-mediated gene editing to eliminate expression of TCRαβ from donor T-cells.

Vor Biopharma is developing VOR33, an investigational hematopoietic stem cell (HSC) therapy with elimination of CD33 expression via gene-editing, in combination with Mylotarg TM , an anti-CD33 antibody drug conjugate (ADC).

Vor Biopharma is also developing VCAR33, an autologous anti-CD33 CAR-T as a monotherapy and in combination with VOR33.

Vor Biopharma is developing Trem-cel (VOR33), an investigational hematopoietic stem cell (HSC) therapy with elimination of CD33 expression via gene-editing, in combination with Mylotarg TM , an anti-CD33 antibody drug conjugate (ADC).

Vor Biopharma is also developing VCAR33, an autologous anti-CD33 CAR-T as a monotherapy and in combination with Trem-cel.

We believe Autolus is developing AUTO09, an autologous CAR-T targeting CD33, CD123 and CLL-1, is in preclinical development.

Finally, Allogene Therapeutics' allogeneic CAR-T therapies ALLO-316 and ALLO-819, targeting FLT3 and CD70, respectively, which we believe are in preclinical and discovery stage of

development respectively, are manufactured using healthy donor T-cells that are engineered using lentiviral transduction to express CAR followed by gene editing to eliminate expression of TCR to reduce the potential of rejection of therapy by a patient's immune system.

Lyell Immunopharma is developing LYL797, a ROR1-targeted CAR T-cell product, which we believe recently received FDA clearance to initiate Phase 1 clinical trial for patients with relapsed/refractory ROR1+TNBC or non-small cell lung cancer, or NSCLC, and other solid tumors.

We believe that Lyell is also developing another ROR1 CAR-T candidate, LYL119, which is in preclinical development for ROR1+ solid tumors.

Oncternal Therapeutics is developing ONCT-808, a ROR1 targeted autologous CAR-T cell therapy, which we believe is currently in a Phase 1/2 study in patients with relapsed/refractory aggressive B cell malignancies.

In addition to our direct competitors that are using CAR-T therapies specifically for the treatment of ovarian cancer and AML, the CAR-T technology space has significant other competition including from multiple companies and their collaborators, such as Novartis and University of Pennsylvania, Kite and Gilead, Bristol-Myers Squibb, Janssen and Legend Biotech, Adaptimmune, Autolus Therapeutics, Poseida Therapeutics, Gracell and AstraZeneca, and Bellicum Pharmaceuticals.

We believe Arcellx is developing ACLX-002, CAR-T targeting CD123 based on ARC-SparX platform.

We believe Allogene Therapeutics' allogeneic CAR-T therapy ALLO, targeting CD70 is manufactured using healthy donor T-cells that are

engineered using lentiviral transduction to express CAR followed by gene editing to eliminate expression of TCR to reduce the potential of rejection of therapy by a patient's immune system.

Oncternal Therapeutics is developing ONCT-808, a ROR1 targeted autologous CAR-T cell therapy, which we believe is in a clinical trial in patients with relapsed/refractory aggressive B cell malignancies.

In addition to our direct competitors that are using CAR-T therapies specifically for the treatment of ovarian cancer and AML, the CAR-T technology space has significant other competition including from multiple companies and their collaborators, such as Novartis and University of Pennsylvania, Kite and Gilead, Bristol-Myers Squibb, Janssen and Legend Biotech, Adaptimmune, Autolus Therapeutics, Roche and Poseida Therapeutics, and Gracell and AstraZeneca.

We also face competition from non-cell based cancer treatments offered by other companies such as Amgen, AstraZeneca, Incyte, Merck, Abbvie, and Roche.

See "Precigen's Therapeutic Platforms" for a discussion of the features that we believe differentiate our UltraCAR-T treatments from our competitors.

AdenoVerse Immunotherapy

We believe our main competitor in the field is INOVIO Pharmaceuticals with their investigational DNA vaccine INO-3107 targeting HPV6 and HPV11 antigens.

For our PRGN-2009 candidate in HPV-associated cancers, we believe that INOVIO Pharmaceuticals, BioNTech SE, PDS Biotechnology, Hookipa Pharma and Transgene S.A.

are developing immunotherapies that are in clinical testing.

TG4001 is an investigational therapeutic cancer vaccine candidate using an attenuated and modified poxvirus, or MVA, as a vector expressing the HPV16 E6 and E7 proteins and interleukin-2.

We believe TG4001 is in a clinical trial in combination with anti-PD-L1 antibody avelumab for anogenital HPV+ cancers.

INOVIO's lead investigational candidate VGX-3100 is a plasmid DNA based vaccine designed to increase T cell immune responses against the E6 and E7 antigens of HPV16 and HPV18.

VGX-3100 is in clinical trials for precancerous cervical dysplasia, vulvar dysplasia, and anal dysplasia.

Inovio is also developing INO-3112, a DNA medicine candidate targeting HPV 16/18, combined with a DNA plasmid for IL-12 in combination with an anti-PD1 monoclonal antibody for locoregionally advanced, high-risk, HPV16/18 positive oropharyngeal squamous cell carcinoma.

We believe BioNTech is developing BNT113 , an investigational HPV16 E6/7 mRNA vaccine.

We believe BNT113 in combination with an anti-PD1 monoclonal antibody is in a clinical trial for HPV16+PD1+ Head and Neck squamous cell carcinoma.

We believe PDS Biotechnology is developing PDS-0101, an investigational HPV16 peptide vaccine for various HPV-associated cancers.

We believe PDS0101 is in clinical trials as monotherapy and combination therapy for recurrent/metastatic HPV16+ head and neck cancer, pre-metastatic HPV-associated oropharyngeal cancer, and HPV+ anal, cervical, head and neck, penile, vaginal, vulvar cancers.

We believe Hookipa is developing HB-200, based on two single-vector compounds with arenaviral backbones based on lymphocytic choriomeningitis virus and pichinde virus expressing the same transgene encoding an HPV16 E7E6 fusion protein, which is in a clinical trial for HPV16+ head and neck cancers.

We also face competition from non-vaccine based approaches being developed by companies such as Kite, Iovance, Bristol-Myers Squibb, and Merck.

We are using our suite of proprietary and complementary synthetic biology technologies for the preclinical and clinical development of product candidates for the treatment of autoimmune disorders, including T1D.

While we believe AG019 is the first disease-modifying treatment for T1D, there are a number of competitors pursuing immunotherapy product candidates to treat T1D.

We believe that our primary competitors with respect to the development of immunotherapies for T1D are Sanofi,

Midatech Pharma, and MerciaPharma.

Precigen Exemplar is providing porcine research models and services that aid scientists in the understanding of human disease mechanisms and development of new therapeutics.

We use precise genome modification to recapitulate numerous human diseases in our Yucatan MiniSwine platform, which are utilized by our industry and academic clientele for the development of new small molecule, gene, and cell therapies.

Precigen Exemplar provides porcine research models and services that aid scientists in the understanding of human disease mechanisms and development of new therapeutics.

We believe that the primary competitors of Exemplar are smaller privately owned entities.

16 unchanged sentences

and our portfolio around various genetic componentry such as specialized vectors containing these genetic componentry and their use, with a last to expire patent in 2044.

Although we have no certainty that these patents will not be subject to challenge in the future, as of this filing, there are currently no material contested proceedings and/or third-party claims with respect to any of these patent portfolios.

Although we have no certainty that these patents will not be subject to challenge

in the future, as of this filing, there are currently no material contested proceedings and/or third-party claims with respect to any of these patent portfolios.

Additionally, we complement our intellectual property portfolio with exclusive and non-exclusive patent licenses and options for licenses to third-party technologies.

2 unchanged sentences

Because we rely on trade secrets, know-how, and continuing technological advances to protect various aspects of our technology, we require our employees, consultants and scientific collaborators to execute confidentiality and invention assignment agreements with us to maintain the confidentiality of our trade secrets and proprietary information.

Our confidentiality agreements generally provide that the employee, consultant or scientific collaborator will not disclose our

confidential information to third parties.

Our confidentiality agreements generally provide that the employee, consultant or scientific collaborator will not disclose our confidential information to third parties.

These agreements also provide that inventions conceived by the employee, consultant or scientific collaborator in the course of working for us will be our exclusive property.

33 unchanged sentences

The FDA licenses biological products, or biologics, through its authority under the Public Health Service Act, or PHSA, and implementing regulations.

The development processes for obtaining FDA

approval for a non-biological drug product under the FDCA and for biologic licensure under the PHSA are generally similar but have product-related differences reflected in regulations and in FDA guidance documents.

The development processes for obtaining FDA approval for a non-biological drug product under the FDCA and for biologic licensure under the PHSA are generally similar but have product-related differences reflected in regulations and in FDA guidance documents.

United States pharmaceutical development process

21 unchanged sentences

An IRB is charged with protecting the welfare and rights of trial participants and considers, among other things, whether the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits.

The sponsor of a clinical trial, the investigators, and IRBs each must comply with requirements and restrictions that govern, among other things, obtaining informed consent from each study subject, complying with the protocol and investigational plan, adequately monitoring the

clinical trial, and timely reporting adverse events.

Clinical trials involving recombinant or synthetic nucleic acid molecules, such as DNA, conducted at institutions that receive any funding from the National Institutes of Health also must be reviewed by an institutional biosafety committee, an institutional committee that reviews and oversees basic and clinical research that utilizes recombinant DNA at that institution.

16 unchanged sentences

The results of the preclinical tests and clinical trials, together with detailed information relating to the product's CMC and proposed labeling, among other things, are submitted to the FDA as part of an application requesting approval to market the product for one or more uses, or indications.

When an application is submitted, the FDA makes an initial determination as to whether the application is sufficiently complete to be accepted for review.

When an application is submitted, the FDA makes an initial determination as to

whether the application is sufficiently complete to be accepted for review.

If the application is not, the FDA may refuse to accept the application for filing and request additional information.

6 unchanged sentences

An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

A complete response letter

generally outlines the deficiencies in the submission and may require substantial additional testing or information for the FDA to reconsider the application.

A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing or information for the FDA to reconsider the application.

If those deficiencies have been addressed to the FDA's satisfaction in a resubmission of the application, the FDA may issue an approval letter.

47 unchanged sentences

Changes to the product, manufacturing process, or facility often require prior FDA approval before being implemented and other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review and approval.

Additionally, the FDA may require postmarketing studies or clinical trials, changes to a product's approved labeling, including the addition of new warnings and contraindications, or the implementation of other risk management measures, including distribution restrictions, if new safety information emerges.

Additionally, the FDA may require postmarketing studies or

clinical trials, changes to a product's approved labeling, including the addition of new warnings and contraindications, or the implementation of other risk management measures, including distribution restrictions, if new safety information emerges.

Failure to comply with the applicable requirements may result in administrative, judicial, civil or criminal actions and adverse publicity.

36 unchanged sentences

The CCPA and its implementing regulations have already been amended multiple times since their enactment.

Similarly, there are a number of legislative proposals in the United States, at both the federal and state level that could impose new obligations or limitations in areas affecting our business.

Similarly, numerous other states have enacted, or are considering enacting, comprehensive data privacy laws that share similarities with the CCPA, and there are a number of legislative proposals in the United States at the federal level, in each case which could impose new obligations or limitations in areas affecting our business.

These laws and regulations are evolving and subject to interpretation, and may impose limitations on our activities or otherwise adversely affect our business.

7 unchanged sentences

Certain provisions of the Affordable Care Act have been subject to judicial challenges, as well as efforts to repeal, replace, or otherwise modify them or to alter their interpretation or implementation.

For example, the Tax Cuts and Jobs Act, or Tax Act, enacted in December, 2017 eliminated the tax-based payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code of 1986, as amended, commonly referred to as the "individual mandate," effective January 1, 2019.

For example, the Tax Cuts and Jobs Act, or Tax Act, enacted in December 2017 eliminated the tax-based payment for individuals who fail to maintain minimum essential coverage under section 5000A of the Internal Revenue Code of

1986, as amended, commonly referred to as the "individual mandate," effective January 1, 2019.

Additional legislative changes, regulatory changes, and judicial challenges related to the Affordable Care Act remain possible.

3 unchanged sentences

It is possible that the Affordable Care Act, as currently enacted or may be amended in the future, as well as other healthcare reform measures that may be adopted in the future, and their implementation may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, and new payment methodologies and in additional downward pressure on coverage and payment and the price that we receive for any approved product.

Any reduction in reimbursement

from Medicare or other government programs may result in a similar reduction in payments from commercial payers.

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from commercial payers.

The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products.

18 unchanged sentences

Our compensation packages include a competitive base salary and bonus, the issuance of equity incentives, a 401(k) plan, and health and wellness benefits, including a health insurance plan with a Platinum actuarial value.

We pride ourselves on a diverse workforce as evidenced by our international subsidiaries and 76% of our domestic employees identifying as ethnic, racial, and/or gender minorities.

Worldwide 49% of our research and development employees are female.

Our 2024 employee development initiatives included employee training targeting specific areas of interest, executive and manager coaching, and performance management, which encompass performance goals and competency evaluations.

12 unchanged sentences

Reports filed with the SEC may be viewed at www.sec.gov .

are available free of charge to shareholders and the public through the "Corporate Governance" section of our website.

In addition, our Corporate Governance Guidelines, Code of Business Conduct and Ethics, and charters for the Audit Committee, the Compensation and Human Capital Management Committee and the Nominating and Governance Committee are available free of charge to shareholders and the public through the "Corporate Governance" section of our website.

Printed copies of the foregoing are available to any shareholder upon written request to our Communications Department at the address set forth on the cover of this Annual Report or may be requested through our website, www.precigen.com.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business