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Item 1. Business

2026-03-25 compared with 2025-03-19 · 237 added, 208 removed, 466 unchanged (49% of the section changed)

We are a dedicated discovery and clinical-stage biopharmaceutical company advancing the next generation of gene and cell therapies with the overall goal of improving outcomes for patients with significant unmet medical needs.

We are a commercial-stage biopharmaceutical company specializing in the advancement of innovative precision medicines to improve the lives of patients.

We are leveraging our proprietary technology platforms to develop product candidates designed to target urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases.

We have developed an extensive pipeline of therapies across multiple indications.

We believe that our array of technology platforms uniquely positions us among other biotechnology companies to advance precision medicine.

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Our proprietary and complementary technology platforms provide a strong foundation to realize the core promise of precision medicine by supporting our efforts to construct powerful gene programs to drive efficacy, deliver these programs through viral, non-viral, and microbe-based approaches to drive lower costs, and control gene expression to drive safety.

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.

Our therapeutic platforms, including AdenoVerse immunotherapy, and UltraCAR-T, 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 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;

In August 2025, the FDA granted full approval to our product, Papzimeos (zopapogene imadenovec-drba, PRGN-2012), for the treatment of adults with recurrent respiratory papillomatosis (RRP).

RRP is a rare, debilitating, and potentially life-threatening disease caused by chronic human papillomavirus (HPV) 6 or HPV 11 infection, which results in recurrent benign tumors in the respiratory tract.

Papzimeos is a non-replicating adenoviral vector-based immunotherapy designed to express a fusion antigen comprising selected regions of HPV types 6 and 11 proteins.

Papzimeos is designed to generate an immune response directed against HPV 6 and HPV 11 proteins in patients with RRP.

Our clinical pipeline includes PRGN-2009, which is 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.

As part of the strategic prioritization of our pipeline we announced in August 2024 that we have paused enrollment in the PRGN-3005 and PRGN-3007 clinical trials.

In addition, we announced a 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 exercise discipline in our portfolio management by systematically evaluating data from our preclinical programs in order to make rapid "go" and "no go" decisions.

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• Advancing our lead clinical stage programs and seeking opportunities to maximize their value.

We are actively advancing our lead programs that we believe have significant potential value.

We are actively

advancing our lead programs that we believe have significant potential value.

We intend to efficiently pursue these programs toward clinical proof-of-concept and commercialization, whether independently or with collaborators.

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We continually assess the application of these technologies across therapeutic areas to determine where we can develop and provide unique solutions to challenges facing existing therapies.

We have strategically focused our efforts on developing an innovative pipeline of therapies based on our transformative UltraCAR-T and AdenoVerse immunotherapy therapeutic platforms.

We have strategically focused our efforts on developing an innovative pipeline of therapies based on our transformative AdenoVerse immunotherapy and UltraCAR-T therapeutic platforms.

A core focus of our research and development programs has been an effort to address the drawbacks associated with conventional cell and gene therapy manufacturing approaches.

To this end, we are developing therapeutic candidates that reduce manufacturing risk by eliminating the need for centralized cell therapy manufacturing and have invested in internal manufacturing capabilities to de-risk our clinical and, in certain cases, commercial production.

Our Clinical Pipeline

Our Healthcare Business

Our Biopharmaceuticals reportable segment is primarily comprised of the Company's legal entities of Precigen and ActoBio, as well as royalty interests in therapeutics and therapeutic platforms from companies not controlled by us.

Our Exemplar reportable segment is comprised of Exemplar Genetics LLC, doing business as Precigen Exemplar, or Exemplar, our wholly owned subsidiary focused on developing research models and services for healthcare research applications.

Biopharmaceuticals

Precigen is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target urgent and intractable diseases in immuno-oncology, autoimmune disorders and infectious diseases.

Precigen's Technology Platforms

We leverage a diverse portfolio of proprietary technology platforms to accelerate research and development efforts to deliver the promise of precision medicine.

Our Technology Platforms

We leverage a diverse portfolio o f proprietary technology platforms to accelerate research and development efforts to deliver the promise of precision medicine.

Precigen's innovative technology platforms enable us to construct powerful, multigenic programs that we believe will drive efficacy, deliver multigenic constructs using viral and non-viral approaches that we believe will drive lower costs, and control expression of genes and performance of therapeutics in vivo for precise targeting of complex malignancies.

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We have leveraged our proprietary and complementary technology platforms discussed above and our expertise in immunology to develop key therapeutic platforms, including UltraCAR-T and AdenoVerse, to address multiple pathways of complex disorders with significant unmet medical needs and to realize our core promise of precision medicine.

Precigen's Therapeutic Platforms

Our Therapeutic Platforms

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

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

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 expanded our drug substance cGMP manufacturing capabilities at this facility to support the commercial launch of Papzimeos.

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 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.

RRP is a rare, difficult-to-treat and sometimes fatal neoplastic disease of the upper and lower respiratory tracts that is caused by infection with HPV6 or HPV11.

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

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.

Surgeries are not curative and recurrence of papilloma after surgical removal is very common and repeated procedures are required to debulk and monitor the disease, which exposes patients to anesthetic and surgical risks, and emotional distress.

Patients with aggressive RRP can undergo hundreds of lifetime surgeries to control their disease.

RRP morbidity and mortality results from the effects of papilloma mass on the vocal cords, trachea, and lungs, which may cause voice changes, stridor, airway occlusion, loss of lung volume, and/or post-obstructive pneumonia.

Although rare, RRP has the potential for malignant transformation in three to seven percent of adult patients.

In addition, more than 90 percent of genital warts are related to HPV6 and HPV11 infection.

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

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.

(i) Papzimeos, a non-replicating adenoviral vector-based immunotherapy designed to generate an immune response directed against HPV 6 and HPV 11 proteins in patients with RRP;

and (ii) PRGN-2009, an investigational off-the-shelf AdenoVerse immunotherapy designed to activate the immune system to recognize and target HPV-associated cancers, which is in Phase 2 clinical trials for patients with HPV-associated cancers.

Papzimeos (zopapogene imadenovec-drba, PRGN-2012) - Our FDA Approved Commercial Product

Papzimeos (zopapogene imadenovec-drba, PRGN-2012) is a non-replicating adenoviral vector-based immunotherapy designed to express a fusion antigen comprising selected regions of HPV types 6 and 11 proteins—the root cause of RRP.

RRP is a rare, debilitating, and potentially life-threatening disease of the upper and lower respiratory tract caused by chronic HPV 6 or HPV 11 infection.

RRP can lead to severe voice disturbance, compromised airways, and recurrent post-obstructive pneumonia.

Although rare, RRP has the potential for transformation to malignant cancer and can be fatal.

Management of RRP has primarily consisted of repeated surgeries, which do not address the underlying cause of the disease and can be associated with significant morbidity as well as significant patient and health system burden.

As the number of lifetime surgeries increases,

the risk for irreversible iatrogenic laryngeal injury increases with each surgery, and patients may undergo hundreds of these surgeries over their lifetimes.

RRP can impact patients' work and social lives, financial stability, and mental health.

Patients with RRP can experience substantial impacts to daily living with decreased quality of life and high health care utilization.

In August 2025, FDA granted full approval to Papzimeos for the treatment of adults with RRP.

The Papzimeos approval marks a historic milestone for the RRP patient community as the first and only FDA-approved therapy for the treatment of adults with RRP.

We completed submission of the rolling Biologics License Application (BLA) in December 2024 under an accelerated approval pathway;

however, the FDA has granted Papzimeos full approval.

As a result of Papzimeos receiving full FDA approval, a confirmatory clinical trial is no longer required.

The Papzimeos FDA approval was supported by data from the open-label, single-arm, pivotal study in adult patients with RRP:

• The pivotal study successfully met its primary safety and pre-specified primary efficacy endpoints.

• 51% (18 out of 35) of study patients achieved Complete Response, requiring no surgeries in the 12 months after treatment with Papzimeos.

These Complete Responses remained durable for over 12 months.

Of the 18 patients with a Complete Response in the ongoing study, 15 patients have demonstrated continued Complete Response at median follow-up duration of 36 months.

• Papzimeos was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2.

• Papzimeos induced HPV 6/11-specific T cell responses in RRP study patients with a significantly greater expansion of peripheral HPV-specific T cells in responders compared with non-responders.

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

NCT04724980) evaluated safety and efficacy of Papzimeos.

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.

The study enrolled a total of 38 patients who were treated with subcutaneous injections of Papzimeos over a 12-week period.

Of the 38 patients, 3 patients were treated with Papzimeos at a dose of 1×10 11 particle units ("PU") per injection.

Thirty-five patients were treated at a dose of 5×10 11 PU per injection and were included in the efficacy evaluation.

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.

The demographic characteristics of the population were as follows:

the median age was 50 years (range 20 to 88 years), 15 patients (39%) were female, 33 patients (87%) were White, 1 patient (3%) was Asian, 1 patient (3%) was African American, 1 patient (3%) was of “other” race, 2 patients (5%) were of unknown race, and 32 patients (84%) were non-Hispanic or Latino.

The mean (Standard Deviation) BMI was 28 (6) kg/m 2 .

The median number of baseline surgical procedures performed in the 12 months prior to treatment was 4 (range 3 to 10).

Papzimeos treatment was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events ("TRAEs") greater than Grade 2.

All patients received four administrations of Papzimeos 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.

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.

The most common adverse reactions (incidence ≥5%) included injection site reaction, fatigue, chills, pyrexia, myalgia, nausea, headache, tachycardia, diarrhea, vomiting and hyperhidrosis.

At a dose of 5×10 11 PU per injection, 18 out of 35 patients achieved a complete response at 12 months resulting in a complete response rate of 51% [95% confidence interval ("CI") 34 to 69%].

Complete responses after Papzimeos treatment have been durable.

Of the 18 patients with a complete response in the ongoing study, 15 demonstrated continued complete response with median duration of follow-up at 36 months (range:

27 to 37) as of September 19, 2025 data cutoff date.

Median durability of response has yet to be reached.

Papzimeos 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.

In 28 patients evaluated at completion of treatment, the induction of HPV 6- and HPV 11-specific T cell responses was higher in RRP patients demonstrating a clinical response to treatment, i.e.

reduction in or elimination of the requirement for surgical debulking during the 12 months following completion of treatment, with mean fold-change from baseline of 164.9 versus 5.1 (p<0.018).

This difference persisted at 12 weeks post-treatment, with mean fold-change of 61.5 in responders versus 11.5 in non-responders.

Following the FDA-approval, we launched Papzimeos in the United States as the first and only FDA approved treatment for adults with RRP.

We estimate that there are approximately 27,000 adults patients in the United States living with RRP.

Commercial readiness efforts had been underway prior to the FDA approval of Papzimeos.

We had selected Eversana, a leading provider of commercialization services to the global life sciences industry, to support launch strategy and commercialization of Papzimeos in the United States.

In the United States, prior to FDA approval and Papzimeos launch, our Medical Science Liaisons had been interacting with health care professionals (“HCPs”) for appropriate scientific exchange related to RRP.

Additionally, a team of National Account Directors and Key Account Directors organized many Pre-Approval Information Exchange (PIE) meetings with payers and population health decision makers at large hospital systems, in order to help prepare

for ultimate market entry.

We have established Papzimeos Support, a comprehensive patient support program to offer personalized services, including insurance navigation, financial assistance, and ongoing access support.

Our field sales team was onboarded and fully deployed immediately following FDA approval, and continues to engage with large Integrated Delivery Networks (IDNs) as well as community physicians treating RRP patients.

Our market access team has successfully secured private health plan coverage with approximately ~215 million lives covered to date, including the majority of leading insurers.

Papzimeos is also covered under Medicare and Medicaid.

Papzimeos early demand is consistent with internal expectations, with patients being treated nationwide within IDN and community settings.

Papzimeos had been granted Breakthrough Therapy Designation and Orphan Drug designation for the treatment of RRP by the FDA.

In addition, zopapogene imadenovec-drba has received Orphan Drug Designation for the Treatment of RRP from the European Commission as well.

We submitted a Marketing Authorization Application (“MAA”) for zopapogene imadenovec-drba for the treatment of adults with RRP to the European Medicines Agency (“EMA”) in November 2025.

The MAA has been validated by the EMA and is currently under review.

PRGN-2009, an investigational non-replicating adenoviral vector-based immunotherapy, based on our AdenoVerse platform, 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.

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HPV infections account for 5 percent of all cancers globally, and 690,000 new cancer cases are attributable to HPV infections per year.

HPV infects the squamous cell carcinoma.

Some cervical cancers come from HPV infection of gland cells in the cervix and are referred to as adenocarcinomas.

HPV-related cancers include cervical, oropharyngeal, anal, penile, vaginal, and vulvar.

Nearly 44,000 HPV-associated cancers occur in the United States each year.

Of these, approximately 25,000 occur in women and 19,000 occur in men.

HPV is considered responsible for more than 90 percent of anal and cervical cancers, about 70 percent of vaginal and vulvar cancers, and more than 60 percent of penile cancers.

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

Approximately 39,000 HPV-associated cancers are estimated to occur in the United States each year.

HPV is considered responsible for more than 90% of anal and cervical cancers, approximately 75% of vaginal cancers, 70% vulvar cancers, more than 60% of penile cancers, and approximately 70% of cancers of the oropharynx.

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.

PRGN-2009 is being evaluated in two Phase 2 clinical trials for patients with newly-diagnosed HPV-associated oropharyngeal cancer 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.

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).

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.

Secondary objectives include safety and overall survival.

The second Phase 2 clinical trial is designed to evaluate PRGN-2009 in combination with neoadjuvant chemotherapy in adult patients with newly-diagnosed HPV-associated oropharyngeal cancer.

The primary objective of the study is to determine the rate of pathological complete response rates in patients receiving neoadjuvant chemotherapy alone or in combination with PRGN-2009.

Secondary objectives include safety and recurrence free survival.

PRGN-2009 is also being evaluated in a randomized, open-label Phase 2 clinical trial of 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).

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The primary objective of the Phase 2 trial in R/M cervical cancer is to assess the objective response rate (ORR) per RECIST v1.1 following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab monotherapy.

Secondary objectives include the evaluation of safety and tolerability, progression-free survival (PFS), overall survival (OS), best overall responses (BOR), Disease Control Rate (DCR), time to response and duration of response.

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.

Secondary objectives include the evaluation of safety and tolerability, progression-free survival (PFS), overall survival (OS), best overall

responses (BOR), Disease Control Rate (DCR), time to response and duration of response.

The Phase 2 trial in R/M cervical cancer is enrolling patients with two additional clinical sites active in addition to NCI.

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

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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.

Our UltraCAR-T platform differentiates 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.

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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 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.

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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-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.

MUC16 is overexpressed on more than 80 percent of ovarian tumors but has limited expression in healthy tissues, making it an attractive CAR-T target for ovarian cancer.

Other cancers with known overexpression of MUC16 include pancreatic, breast, endometrial, lung, and bladder cancers.

MUC16 undergoes proteolytic cleavage in the extracellular domain resulting in shedding of a large portion of extracellular domain, termed CA125, from the cell surface and leaving only a short, unshed extracellular domain tethered to the cell surface.

Therapies that target the region of MUC16 that is shed from the cell surface may have limited effectiveness due to their binding to CA125 in circulation which is not associated with tumor cells.

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.

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 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.

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 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).

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.

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 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 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.

Precigen's most advanced program based on the UltraCAR-T platform is PRGN-3006, which has completed enrollment in a Phase 1b clinical trial for patients with relapsed or refractory acute myeloid leukemia, or AML.

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.

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Due to the aggressive nature of AML progression, rapid availability of treatment is of even greater importance in this patient population, and our non-viral UltraCAR-T manufacturing process would represent a significant potential advantage over current approaches that require long lead times for manufacturing.

In preclinical studies, PRGN-3006 demonstrated robust expansion in the presence of CD33 antigen, lack of autonomous expansion in the absence of CD33 and prolonged persistence in the absence of exogenous cytokines.

PRGN-3006 exhibited target-specific killing of CD33 + tumor cells as well as a significant release of inflammatory cytokines such as IFNγ, upon co-culture with AML tumor cells.

PRGN-3006 cells were specifically eliminated by kill switch activator treatment, displaying functionality of the kill switch, which is intended to improve the safety profile of PRGN-3006.

In vivo , a single administration of PRGN-3006 UltraCAR-T cells only one day after gene transfer effectively eliminated the tumor burden and significantly improved overall survival of tumor bearing mice compared to CAR-T cells lacking mbIL15 expression (conventional CAR-T) in an aggressive xenograft model of AML.

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

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.

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.

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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.

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.

T cells to engraft and survive even in the absence of lymphodepletion.

Higher peak expansion (> 10 fold) in peripheral blood was observed in the lymphodepletion cohort compared to non-lymphodepletion cohort at the same dose level.

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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.