Precigen Announces Positive Phase 1 Dose Escalation and Expansion Cohort Data for Investigational Off-the-Shelf PRGN-2012 AdenoVerse Immunotherapy in Patients with Recurrent Respiratory Papillomatosis - Repeated administ

Precigen Announces Positive Phase 1 Dose Escalation

and Expansion Cohort Data for Investigational Off-the-Shelf PRGN-2012 AdenoVerse Immunotherapy in Patients with Recurrent

Respiratory Papillomatosis

- Repeated administrations of PRGN-2012 were well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than

data show strong response in RRP patients with 50% of patients in Complete Response, requiring no post-treatment surgeries,

following PRGN-2012 treatment at Dose Level 2; All complete responders remain surgery-free post-treatment with a minimum 12-months

- PRGN-2012 treatment at Dose Level 2 significantly reduced the need for surgeries in severe, aggressive RRP patients; Median number of RRP surgeries in 12-month period reduced from 6.5 pre-treatment to 0.5 post-treatment -

study is enrolling patients with a total of 32 patients enrolled at Dose Level 2 to date -

- Company to outline regulatory strategy in RRP as US Food and Drug Administration (FDA) discussions advance -

- Precigen to host R&D Day virtual event today at 4:30 PM ET -

Germantown, MD, January 24, 2023 -

Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies

to improve the lives of patients, today announces positive Phase 1 dose escalation and expansion cohort data as of the January 12, 2023

cutoff for the investigational, potential first-in-class PRGN-2012 off-the-shelf (OTS) AdenoVerse immunotherapy in patients with

recurrent respiratory papillomatosis (RRP).

The company will host an R&D Day virtual

event today at 4:30 PM ET to showcase the data and will feature presentations by Clint T. Allen, MD, Senior Investigator, Surgical Oncology

Program, Center for Cancer Research, National Cancer Institute (NCI) and lead associate investigator for the PRGN-2012 clinical trial,

and Precigen's President and CEO, Helen Sabzevari, PhD. Participants may register and access the live webcast through Precigen's

investor relations website in the Events & Presentations section.

"As a patient and an advocate on behalf

of the RRP community, the potential for a therapeutic alternative to surgical intervention would be nothing short of life changing,"

said Kim McClellan, President, Recurrent Respiratory Papillomatosis Foundation (RRPF). "There has never been a therapeutic option

for the RRP patient community and we are incredibly hopeful that this will change in the near future. Our community faces ongoing risks

from hospitalizations and repeat surgeries, coupled with daily quality-of-life challenges, such as obstructed breathing, difficulties

swallowing, and impaired speech, and our community bears a tremendous financial burden from the significant lifetime costs to patients

and their families affiliated with this disease."

"RRP is a rare disease with no cure. The

current standard-of-care is repeated surgery to treat symptoms, which exposes patients to surgical risks, emotional distress and poses

a significant economic burden to families and the healthcare system overall. We are thrilled to present these Phase 1 results today as

PRGN-2012 has the potential to improve the lives of patients with severe, aggressive RRP through reduced surgeries," said Helen

Sabzevari, PhD, President and CEO of Precigen. "Any treatment that reduces the burden of surgeries in RRP is considered meaningful

and in the PRGN-2012 Phase 1 study, 50% of patients had a Complete Response, requiring no surgeries as of the data cutoff more than 12

months following treatment."

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 HPV 6 or HPV 11.1-4 RRP

is classified based on age of onset as juvenile or adult. 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.3,4 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.5 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.6 Although rare, RRP has potential for malignant transformation in three to seven percent of adult patients.7

About PRGN-2012 AdenoVerse

PRGN-2012 is an innovative therapeutic vaccine

with optimized antigen design that uses Precigen's gorilla adenovector technology, part of Precigen's proprietary AdenoVerse platform,

to elicit immune responses directed against cells infected with HPV 6 or HPV 11. 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. In preclinical models, PRGN-2012 has demonstrated strong and specific immune response against HPV

6 and HPV 11. PRGN-2012 has been granted Orphan Drug Designation in patients with RRP by the FDA.

About the Phase 1 Clinical Trial

The Phase 1 clinical trial (clinical trial identifier:

NCT04724980) evaluated safety and efficacy of PRGN-2012 as an immunotherapy following standard-of-care RRP surgery. Trial design

included initiation of 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 three surgeries in the prior 12

months, were enrolled to the clinical trial. A total of 15 patients were enrolled in the Phase 1 dose escalation and expansion cohorts

at Dose Level 1: 1 x 1011 viral particles (vp)/dose (N=3) or Dose Level 2: 5 x 1011 vp/dose (N=12) with patients receiving four PRGN-2012 administrations (on days 1,15, 43 and 85) via subcutaneous injection.

Patient Characteristics

Baseline patient characteristics of the 15 adult

patients included a median age of 51 years (range: 30-73). Ten patients were male and 5 were female. Patients had an average of 6.2 surgeries

(range: 3-10) in the last 12 months before enrolling in the trial. Patients were diagnosed with RRP for an average of 15 years prior to

Repeated administrations of PRGN-2012 were well-tolerated

with no dose-limiting toxicities and no treatment-related adverse events (TRAEs) greater than Grade 2 (TABLE 1). All patients received

four administrations of PRGN-2012 at the intended dose levels. 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 (TABLE 2). The lack of a significant neutralizing

antibody response to gorilla adenovector over time with subsequent additional vaccinations highlights the ability to deliver repeated

administrations of PRGN-2012, a differentiating feature of the AdenoVerse platform.

TABLE 1: Treatment-related Adverse Events

Total Patients (N=15)

TABLE 2: Treatment-related Adverse Events by

Total Patients (N=15)

Clinical Efficacy Summary

Clinical data show PRGN-2012 treatment

significantly reduced the need for surgeries for severe, aggressive RRP patients treated at Dose Level 2. 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 (TABLE 3). All complete responders remained surgery-free as of the cutoff date post PRGN-2012

treatment.Patients in Dose Level 2 had a 58% (7 out of 12) Overall Response Rate, 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. 83% (10 out of 12) of

patients treated at Dose Level 2 had reduced surgeries post PRGN-2012 treatment. The number of RRP surgeries in the patients (N=12)

in Dose Level 2 reduced from a median of 6.5 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.

Further, PRGN-2012 treatment 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.

Phase 1 data show that PRGN-2012

treatment resulted in an increase in HPV 6/11-specific T-cell response in the peripheral blood of RRP patients. Furthermore, the

T-cells infiltrating papillomas from patients who had an objective response and a biopsy sample available showed an increase in HPV

6/11-specifc T-cells in papillomas after PRGN-2012 treatment.

TABLE 3: Clinical Efficacy Summary

Total Patients (N=15)

Case studies will be presented for three of

the six complete responders. For each case study, papilloma growth, as measured by the Derkay score, decreased to zero following

completion of PRGN-2012 treatment. An example case study included subject #5, a 40 year old male who required eight surgeries in the

12-months prior to treatment to control papilloma growth. This patient has been in Complete Response after completing PRGN-2012

treatment, and has been surgery-free up to 18-months as of the cutoff date (FIGURE 1). Consistent with the disease response, the