Press Release

-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.

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Source: CRISPR Therapeutics AG