CRISPR Therapeutics Provides Broad Update on Zugocaptagene Geleucel (Zugo-cel; formerly CTX112™) in Autoimmune Diseases and Hematologic Malignancies

Rhea-AI Summary

CRISPR Therapeutics (Nasdaq: CRSP) provided a broad update on zugocaptagene geleucel (zugo-cel), an allogeneic anti-CD19 CAR T, across autoimmune diseases and B-cell malignancies on Dec 22, 2025. Key clinical readouts include deep B-cell depletion and drug-free DORIS remission through Month 6 in an SLE patient at the 100 million cell dose, and in R/R large B-cell lymphoma an ORR 90% and CRR 70% at the 600 million cell RP2D. Safety findings: Grade 3 CRS and ICANS each at 17% and serious infections 8% at the RP2D. A Phase 1 basket study in ITP and wAIHA has started and a collaboration with Lilly will evaluate zugo-cel plus pirtobrutinib. Additional data expected H2 2026.

Positive

• ORR 90% at 600 million cell dose in R/R LBCL (9/10)
• CRR 70% at 600 million cell dose in R/R LBCL (7/10)
• Drug-free DORIS remission through Month 6 in first SLE patient at 100M dose
• RP2D endorsed at 600 million cell dose for LBCL cohort
• Phase 1 trial initiated in ITP and wAIHA
• Collaboration with Lilly to test zugo-cel plus pirtobrutinib

Negative

• Grade 3 CRS rate 17% at RP2D
• Grade 3 ICANS rate 17% at RP2D
• Serious infection rate 8% at RP2D
• Durability data limited: 67% (2/3) in CR at 12 months in small cohort

Key Figures

Autoimmune patients treated 4 patients Phase 1 basket trial in rheumatologic autoimmune diseases at data cut-off Dec 17, 2025

Autoimmune dose level 100 million cells Dose used in autoimmune basket trials with no high-grade CRS or ICANS observed

LBCL RP2D dose 600 million cells Recommended Phase 2 dose for R/R large B-cell lymphoma cohort

LBCL ORR 90% (9/10) Overall response rate at 600 million cell dose with ≥1 month follow-up

LBCL CRR 70% (7/10) Complete response rate at 600 million cell dose in R/R LBCL

12-month CR durability 67% (2/3) R/R LBCL patients remaining in complete response at 12 months

Total patients treated 39 patients All dose levels in ongoing Phase 1/2 B-cell malignancies trial

Grade 3 CRS/ICANS rates 17% / 17% Rates among all LBCL patients treated at RP2D (n=12)

Market Reality Check

$56.46 Last Close

Volume Volume 2,931,033 is 1.55x the 20-day average of 1,891,384, indicating elevated trading interest before this update. high

Technical Shares traded above the 200-day MA, with price at 55.86 versus the 200-day MA of 51.1 ahead of the news.

Peers on Argus

Key biotech peers like PTCT, TGTX, and LEGN showed modest gains (e.g., PTCT up 4.36%), but no peers appeared in the momentum scanner and CRSP’s move of 1.86% looks more company-specific to this zugo-cel update.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 10	Q3 earnings update	Neutral	-1.0%	Reported Q3 loss with strong cash and ongoing clinical/commercial progress.
Oct 10	Preclinical data	Positive	-2.5%	SyNTase CTX460 preclinical AATD data showed high correction and serum AAT levels.
Oct 02	Partnership news	Positive	+10.1%	Monash Boston Hub launch highlighting extensive licensing and CRSP collaborations.
Oct 01	Conference presentation	Positive	+2.1%	Announcement of SyNTase gene editing presentation at ESGCT with strong editing data.
Sep 22	Clinical trial start	Positive	-0.3%	First patient dosed in Phase 2 SRSD107 FXI siRNA trial for thromboembolic disorders.

Pattern Detected

Recent history shows positive reactions to partnership/innovation headlines, while some clinical and earnings updates have seen flat-to-negative moves despite constructive scientific data.

Recent Company History

Over the past six months, CRISPR Therapeutics reported multiple R&D and collaboration milestones. On Sep 22, a Phase 2 trial of SRSD107 began with prior Phase 1 data showing 93% FXI reduction, but shares slipped slightly. In early October, SyNTase AATD data with up to 95% editing and >70% mRNA correction coincided with mixed price reactions. A Monash partnership headline on Oct 2 saw a 10.07% gain. Q3 results on Nov 10 highlighted a cash position of $1,944.1M and a net loss of $106.4M. Today’s broad zugo-cel update fits the pattern of data-rich clinical communications.

Market Pulse Summary

This announcement highlighted robust early data for zugo-cel across autoimmune disease and hematologic malignancy settings, including a 90% overall response rate and 70% complete response rate in R/R LBCL at the 600 million cell dose. It also introduced a new collaboration with Lilly and additional Phase 1 work in ITP and wAIHA. In context of past updates on the SyNTase platform and SRSD107, investors may watch for longer-term durability, safety, and expanded patient numbers in the second half of 2026.

Key Terms

car t medical

"its investigational allogeneic CAR T targeting CD19, in development"

CAR T is a type of immunotherapy that reprograms a patient’s own white blood cells to recognize and attack cancer cells, like giving immune cells a custom GPS to find and destroy tumors. It matters to investors because CAR T therapies can offer durable responses for hard-to-treat cancers, but they also involve complex manufacturing, high costs, regulatory hurdles and market access challenges that affect a company’s revenue potential and risk profile.

cytokine release syndrome (crs) medical

"no high-grade cytokine release syndrome (CRS) or immune-effector cell-associated"

An excessive immune reaction in which the body’s defense system releases large amounts of inflammatory signals (cytokines) all at once, like an overactive alarm system that triggers too many responders and causes collateral damage. It matters to investors because this side effect can halt clinical trials, prompt safety warnings or recalls, and increase development costs and regulatory scrutiny for drugs or therapies, affecting a company’s valuation and future revenue prospects.

immune-effector cell-associated neurotoxicity syndrome (icans) medical

"no high-grade cytokine release syndrome (CRS) or immune-effector cell-associated neurotoxicity syndrome (ICANS)"

Immune-effector cell-associated neurotoxicity syndrome (ICANS) is a potentially serious brain-related side effect that can occur after treatments that strongly activate a patient’s immune cells, producing symptoms from mild confusion and trouble speaking to seizures, severe disorientation, or swelling of the brain. It matters to investors because ICANS shapes a therapy’s safety record, can trigger extra monitoring, clinical hold or labeling requirements, raise treatment costs and legal risk, and therefore affect regulatory approval, market adoption and commercial prospects — similar to how a rare but severe defect can stall a product launch.

overall response rate (orr) medical

"demonstrated an overall response rate (ORR) of 90% (9/10) and a complete"

Overall response rate (ORR) is the percentage of trial participants whose disease measurably improves—typically tumor shrinkage or disappearance—according to predefined medical criteria. Investors watch ORR because it provides an early, concrete signal of a therapy’s effectiveness and commercial potential, similar to seeing what share of products in a test batch actually work before deciding to back wider production.

complete response (cr) medical

"67% (2/3) of patients in complete response (CR) after one year on study"

A complete response (CR) is when a company or individual fully satisfies a specific requirement or condition, indicating that the issue or task has been resolved completely. For investors, it signals that a problem has been fully addressed, which can influence decisions about trust, future actions, or the company's overall status. Think of it as a full "checkmark" showing everything has been successfully handled.

complete response rate (crr) medical

"overall response rate (ORR) of 90% (9/10) and a complete response rate (CRR) of 70%"

Complete response rate measures the share of patients in a medical trial whose signs of disease disappear entirely after treatment and remain undetectable by the tests used. For investors, a high complete response rate is a clear signal that a therapy may be highly effective—like a treatment that removes all visible weeds from a garden—which can improve chances of regulatory approval, stronger market demand, and better commercial prospects.

phase 1/2 trial medical

"advancement of zugo-cel into the Phase 2 portion of the ongoing Phase 1/2 trial"

A phase 1/2 trial combines the earliest human safety testing with an initial look at whether a treatment works, typically starting by checking tolerability and side effects and then expanding to measure early signs of benefit and the best dose. For investors, results from these trials are an early indicator of a drug’s clinical promise and regulatory path: positive data can materially increase a company’s value and reduce development risk, while negative data can sharply lower expectations.

lymphodepletion medical

"Zugo-cel was administered after a standard course of lymphodepletion with fludarabine"

Lymphodepletion is a short medical treatment that lowers a patient’s lymphocytes, the immune cells that can interfere with certain cell-based therapies, to create a more supportive environment for the new therapy to work. Think of it like clearing a crowded garden bed before planting seeds: by temporarily reducing competing cells, the engineered therapy can take hold more effectively. Investors watch lymphodepletion because it affects clinical trial results, safety profiles, treatment adoption, and overall commercial potential.

AI-generated analysis. Not financial advice.

-Four autoimmune patients treated to date demonstrate deep B-cell depletion sustained for at least 28 days; initial efficacy data suggest significant clinical improvement in patients dosed at the 100 million cell dose, with the first systemic lupus erythematosus (SLE) patient achieving Definitions of Remission in SLE (DORIS) remission through Month 6-

-An additional Phase 1 basket trial has been initiated for zugo-cel in refractory primary immune thrombocytopenic purpura (ITP) and warm autoimmune hemolytic anemia (wAIHA)-

-Single-agent activity with zugo-cel demonstrated an overall response rate (ORR) of 90% (9/10) and a complete response rate (CRR) of 70% (7/10) in patients dosed at the 600 million cell dose, with 67% (2/3) of patients in complete response (CR) after one year on study in relapsed or refractory (R/R) large B-cell lymphoma (LBCL)-

-Announces a collaboration and clinical supply agreement with Lilly to evaluate zugo-cel in combination with pirtobrutinib for aggressive B-cell lymphomas-

-Additional updates across autoimmune disease and hematological malignancies are expected in the second half of 2026-

ZUG, Switzerland and BOSTON, Dec. 22, 2025 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today provided updates on zugocaptagene geleucel (zugo-cel), formerly known as CTX112™, its investigational allogeneic CAR T targeting CD19, in development for autoimmune disease and hematologic malignancies.

“Preliminary data from zugo-cel in patients with rheumatologic autoimmune diseases have been encouraging, and the therapy has been well tolerated to date. We have also initiated an additional Phase 1 basket study in immune thrombocytopenia purpura (ITP) and warm autoimmune hemolytic anemia (wAIHA), two autoimmune hematologic diseases,” said Naimish Patel, M.D., Chief Medical Officer of CRISPR Therapeutics. “In hematologic malignancies, clinical experience to date supports continued advancement of the program. Together with our recently established collaboration with Lilly to evaluate zugo-cel with pirtobrutinib in aggressive B-cell lymphomas, these developments reflect the breadth of opportunity for zugo-cel. We look forward to sharing additional data at future scientific meetings.”

Autoimmune Disease

Zugo-cel, targeting CD19, is in an ongoing Phase 1 basket trial in autoimmune rheumatologic diseases, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myositis. Patients in the study may have active SLE (with or without renal involvement), SSc, or idiopathic inflammatory myopathy (IIM) despite the use of standard therapies.

Preliminary clinical data from the Phase 1 study has been encouraging, and zugo-cel has been well tolerated to date.

As of the data cut-off on December 17, 2025, four patients (2 SLE and 2 immune-mediated necrotizing myopathy (IMNM) with interstitial lung disease) have been treated at a dose of 100 million cells and followed for at least 28 days post-infusion:

• Zugo-cel cell expansion is comparable to that observed at the same dose in patients in the ongoing B-cell lymphomas trial.
• Rapid and deep B-cell depletion in the periphery was observed within the first 1-2 days and maintained over the first month of treatment, with repopulating B-cells demonstrating a shift toward an unswitched, naïve repertoire.
• All patients demonstrated significant clinical improvement at the Day 28 assessment.
• The first patient with SLE, refractory to 9 prior therapies with a baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 8, has maintained drug-free DORIS clinical remission through Month 6 following CAR T therapy.
• Treatment has been well-tolerated, with no high-grade cytokine release syndrome (CRS) or immune-effector cell-associated neurotoxicity syndrome (ICANS) observed.
  

Clinical trials in autoimmune disease remain ongoing across indications. The Company expects to provide additional updates in the second half of 2026. In addition, a Phase 1 clinical trial for zugo-cel has been initiated in ITP and wAIHA.

Immuno-Oncology

Positive clinical data generated to date support the advancement of zugo-cel into the Phase 2 portion of the ongoing Phase 1/2 trial in patients with (R/R) CD19-positive B-cell malignancies. Eligible disease subtypes include large B-cell lymphoma (LBCL), follicular lymphoma (FL) grade 1-3a, marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL).

Zugo-cel was administered after a standard course of lymphodepletion with fludarabine and cyclophosphamide. A total of 39 patients have been treated across all 4 dose levels. The recommended Phase 2 dose (RP2D) was recently endorsed at the 600 million cell dose for the large B-cell lymphoma (LBCL) cohort.

As of the data cut-off of November 20, 2025, 10 patients with R/R LBCL have been treated at the RP2D of 600 million cell dose and have had at least one month of follow-up, with the following observations:

• An overall response rate (ORR) of 90% (9/10) and a complete response rate (CRR) of 70% (7/10) were observed, including a complete response (CR) in a patient who relapsed following autologous CAR T cell therapy.
• Among patients who have completed 12-months of follow-up, 67% (2/3) remained in CR at the 12-month evaluation.
• Peak mean CAR T cell expansion of approximately 1,700 cells/µL was observed at the RP2D, representing approximately a four-fold higher expansion compared with patients receiving 300 million cells.
• Rates of Grade 3 CRS, ICANS and serious infections were 17%, 17%, and 8%, respectively, among all LBCL patients treated at the RP2D (n=12).
• No Grade 3 ICANS or CRS has been observed at the 100 million cell dose, which is the dose currently being studied in the autoimmune basket trials.
  

The Phase 1/2 clinical trial in R/R B-cell malignancies is ongoing. The Company expects to provide additional updates in the second half of 2026. CRISPR Therapeutics has also established a new collaboration and clinical supply agreement with Lilly to evaluate zugo-cel together with pirtobrutinib in aggressive B-cell lymphomas, further expanding the program’s development in oncology.

About Zugocaptagene Geleucel (zugo-cel; formerly CTX112) 
Zugocaptagene geleucel (zugo-cel) is a wholly-owned, allogeneic chimeric antigen receptor (CAR) T cell therapy product candidate targeting Cluster of Differentiation 19 (CD19), in development for both autoimmune and immuno-oncology indications. Zugo-cel is an off-the-shelf allogeneic CAR T that utilizes CRISPR Cas9 for targeted gene knockout and CAR insertion for immune evasion and enhanced T effector cell potency. Zugo-cel is given following a standard lymphodepletion regimen without the need for HLA matching. Zugo-cel is being investigated in ongoing clinical trials in adult patients with systemic lupus erythematosus, systemic sclerosis, and inflammatory myositis and in adult patients with relapsed or refractory B-cell malignancies.

About CRISPR Therapeutics 
Founded over a decade ago, CRISPR Therapeutics is a leading gene editing company focused on developing transformative medicines for serious diseases. The Company has evolved from a pioneering research-stage organization into an industry leader, marking a historic milestone with the approval of CASGEVY^® (exagamglogene autotemcel [exa-cel]), the world’s first CRISPR-based therapy, approved for eligible patients with sickle cell disease and transfusion-dependent beta thalassemia. CRISPR Therapeutics is advancing a broad and diversified pipeline across hemoglobinopathies, oncology, regenerative medicine, cardiovascular and autoimmune, and rare diseases. The Company continues to expand its leadership in gene editing through the development of SyNTase™ editing, a novel and proprietary gene-editing platform designed to enable precise, efficient, and scalable gene correction. To accelerate and expand its impact, CRISPR Therapeutics has established strategic collaborations with leading biopharmaceutical partners, including Vertex Pharmaceuticals. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California. To learn more, visit www.crisprtx.com.

CRISPR THERAPEUTICS^® standard character mark and design logo, SyNTase™ and CTX112™ are trademarks and registered trademarks of CRISPR Therapeutics AG. CASGEVY^® and the CASGEVY logo are registered trademarks of Vertex Pharmaceuticals Incorporated. All other trademarks and registered trademarks are the property of their respective owners. 

CRISPR Special Note Regarding Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements made by Dr. Patel in this press release, as well as regarding any or all of the following: (i) CRISPR Therapeutics preclinical studies, clinical trials and pipeline products and programs, including, without limitation, manufacturing capabilities, status of such studies and trials, potential expansion into new indications and expectations regarding data, safety and efficacy generally; (ii) data included in this press release, as well as the ability to use data from ongoing and planned clinical trials for the design and initiation of further clinical trials; (iii) the expected benefits of its collaborations; and (iv) the therapeutic value, development, and commercial potential of gene editing technologies and therapies, including CRISPR/Cas9 and SyNTase, as well as other technologies. Risks that contribute to the uncertain nature of the forward-looking statements include, without limitation, the risks and uncertainties discussed under the heading “Risk Factors” in its most recent annual report on Form 10-K and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. We disclaim any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

This press release discusses investigational therapies and is not intended to convey conclusions about efficacy or safety as to those investigational therapies or uses of such investigational therapies. There is no guarantee that any investigational therapy will successfully complete clinical development or gain approval from applicable regulatory authorities.

Investor Contact:
+1-617-307-7503
ir@crisprtx.com

Media Contact:
+1-617-315-4493
media@crisprtx.com

FAQ

What were the key zugo-cel efficacy results reported by CRSP on Dec 22, 2025?

At the 600 million cell RP2D in R/R LBCL, zugo-cel showed an ORR 90% and CRR 70% (9/10 and 7/10 patients).

What safety risks did CRISPR report for zugo-cel at the RP2D (600M) in CRSP update?

Reported rates at the RP2D included Grade 3 CRS 17%, Grade 3 ICANS 17%, and serious infections 8%.

What autoimmune results did CRSP announce for zugo-cel on Dec 22, 2025?

Four autoimmune patients at the 100 million cell dose showed rapid, deep B-cell depletion and the first SLE patient achieved DORIS remission through Month 6.

Has CRSP set a recommended Phase 2 dose for zugo-cel and what is it?

Yes; the recommended Phase 2 dose (RP2D) for the LBCL cohort was endorsed at 600 million cells.

What new trials and collaborations did CRISPR announce for zugo-cel?

A Phase 1 basket trial in ITP and wAIHA was initiated and a collaboration with Lilly will evaluate zugo-cel plus pirtobrutinib.

When does CRSP expect additional zugo-cel updates?

CRISPR plans to provide additional updates in the second half of 2026.