CRISPR Therapeutics (NASDAQ:CRSP) executives highlighted progress across its oncology and autoimmune cell therapy pipeline during Citi’s Virtual Oncology Leadership Summit, emphasizing updates on its allogeneic CAR-T program zugo-cel (formerly CTX112) and outlining a strategy that includes combination approaches and potential global commercialization.
Company overview and oncology focus
Chief Executive Officer Sam Kulkarni said the company is active across multiple disease areas, including a commercial product in sickle cell disease and thalassemia with Vertex, cardiovascular programs, an autoimmune “franchise” built around allogeneic CAR-Ts, regenerative medicine efforts in type 1 diabetes, and oncology programs.
Zugo-cel design: knock-in/knock-out strategy and “potency” edits
Kulkarni and Chief Medical Officer Naimish Patel detailed a multi-edit engineering strategy intended to increase both activity and persistence versus earlier allogeneic CAR-T designs.
- Targeted CAR insertion: The CAR is inserted into the T-cell receptor (TCR) locus, which Kulkarni said both knocks down TCR to reduce graft-versus-host disease risk and places CAR expression under endogenous regulatory control, in contrast to viral approaches.
- Immune evasion/persistence: An edit in the beta-2 microglobulin (beta-2M) locus reduces MHC Class I presentation, which Kulkarni said can lessen recognition and clearance by the host immune system and extend persistence.
- Proprietary “potency” edits: Kulkarni said two additional edits are designed to reduce exhaustion and improve functional activity during the persistence window:
- Regnase-1 knockout to retain a more naïve phenotype, support expansion, reduce exhaustion, and increase cytotoxicity.
- TGF-beta receptor 2 knockout to blunt TGF-beta-mediated suppression and exhaustion.
Kulkarni said CRISPR’s experience with CTX110 indicated that while persistence could be extended, cells could become exhausted around day 11–12, limiting effective activity. He described the objective for zugo-cel as increasing “activity under the area” during the period the cells remain in patients.
Clinical approach: no HLA matching, standard lymphodepletion, and redosing experience
Patel said the company’s studies to date have not required HLA matching. While CRISPR measures HLA subtypes in patients, Patel said the company has not observed a correlation between HLA and cell expansion. He also said some patients have been redosed to deepen responses after partial response, with no evidence to date of an immune response preventing redosing—an outcome he attributed to the platform’s immune evasion edits.
On lymphodepletion, Patel said the company uses standard chemotherapy lymphodepletion regimens similar to those used with autologous CAR-T in oncology, rather than increasing immunosuppression or adding biologics to deepen depletion. He added that, dose-for-dose, zugo-cel shows significantly greater expansion than CTX110, and at the highest doses being advanced to phase II, expansion is “akin” to what is seen with autologous CAR-T.
Parallel development in autoimmune and oncology, with regulatory discussions as a key decision point
Kulkarni said CRISPR is pursuing zugo-cel in both autoimmune disease and oncology in parallel, with the scale and direction of investment expected to be shaped by regulatory discussions. He cited the importance of pathways that allow ongoing dialogue with regulators and said the company hopes to engage regulators by year-end to determine whether single-arm registrational trials may be feasible in both settings or whether randomized studies would be required, particularly in oncology.
In autoimmune disease, Kulkarni argued allogeneic CAR-T could be a “winner” due to scalability and a lower cost of goods (which he said is under $10,000), as well as logistical advantages such as not needing to stop background therapy to harvest a patient’s T cells. He also suggested that eventual elimination of allogeneic cells could reduce certain risks, including ICANS, while still enabling an “immune reset.”
Patel described an ongoing rheumatology basket trial in systemic lupus erythematosus (SLE), inflammatory myositis, and scleroderma, with active recruitment across all three. He said CRISPR has reported two SLE patients achieving zero disease activity (SLEDAI of zero). In one patient, Patel said follow-up extends to nine months off background therapy with complete remission, with biomarkers consistent with immune reset, including complete B-cell depletion at day 28 and CAR-T expansion.
Patel also said the company has initiated a separate study in immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (WAIHA), citing published case reports (including from China) showing durable responses in heavily pretreated patients. He characterized these as areas where fewer CAR-T developers are actively advancing programs and said CRISPR expects data in the second half of the year.
Regarding dosing in autoimmune studies, Patel noted the initial SLE patients received 100 million cells and said the company is assessing both T-cell expansion and B-cell depletion as earlier indicators, with both appearing strong at that dose. He added the company is evaluating whether the same dose will be appropriate across different autoimmune indications.
Oncology strategy: combination with pirtobrutinib and niche-focused commercialization
For oncology, Kulkarni said the key question is durability of complete responses. He contrasted CTX110—where he said the initial complete response rate was around 40% but fell to about 20% at six months—with zugo-cel, where he said the initial complete response rate has been “almost 70%.” He also said the company has observed deep reductions in disease, describing results as “almost MRD negative” in most cases, and suggested that could support improved durability.
Both executives discussed a combination strategy with a BTK inhibitor, pirtobrutinib (in collaboration with Eli Lilly). Patel said interest in the combination was influenced by an investigator-sponsored study presented at ICML combining an autologous CAR-T with ibrutinib in LBCL that reported complete response rates above 80%. He also cited preclinical data suggesting BTK inhibition may enhance CAR-T activity during expansion. Patel said the CRISPR study is ongoing in largely third-line-plus patients and that the company does not yet have data to share.
Kulkarni said that in oncology, CRISPR may prioritize pathways that enable approval without large, expensive head-to-head randomized trials against established standards in earlier lines. He suggested potential initial approaches could include seeking a label in third-line-plus relapsed/refractory settings while also considering “pockets” such as patients ineligible for CAR-T or other therapies, including some elderly patients. He also emphasized opportunities outside the U.S., including Europe and other markets where he believes lower pricing could drive adoption; he said the company is dosing patients in India and discussed the affordability advantages of allogeneic approaches.
On pricing, Kulkarni said autologous CAR-T therapies in oncology are priced around $350,000 to $400,000, and he said market “chatter” suggests autoimmune CAR-T pricing could be higher, potentially $700,000 to $800,000. He said CRISPR may be able to price allogeneic CAR-T in the $200,000 range or slightly lower in Western markets while preserving margins and expanding access, with potentially lower pricing in parts of Asia tied to lower-cost manufacturing strategies.
In vivo CAR-T: transient and permanent LNP-based approaches
Kulkarni also outlined CRISPR’s emerging in vivo CAR-T platform, differentiating between transient and permanent approaches and emphasizing the company’s focus on lipid nanoparticle (LNP) delivery rather than viral vectors, citing manufacturing and safety considerations.
He said the transient approach involves LNP delivery of mRNA encoding a CAR engineered for longer detectability than some competitors, potentially exceeding 10 days, which he suggested could be suited for autoimmune indications. For oncology, he described work on “permanent” in vivo CAR-T in which the CAR donor template and editing machinery would enable integration in vivo, potentially enabling a “one injection” approach without conditioning, though he said data will determine feasibility and safety. Kulkarni and Patel noted safety considerations around over-potentiating permanent CARs, with Kulkarni suggesting different engineering tactics may be used rather than the full set of edits used in allogeneic programs.
The session concluded with the company indicating it would provide additional updates later, including on areas not covered in detail during the discussion, such as cardiovascular and diabetes programs.
About CRISPR Therapeutics (NASDAQ:CRSP)
CRISPR Therapeutics AG is a biopharmaceutical company specializing in the development of gene-editing therapies based on the CRISPR/Cas9 platform. The company applies its proprietary technology to modify genes in human cells, aiming to create durable treatments for a range of serious diseases. Its research and development efforts focus on both ex vivo and in vivo applications, enabling targeted correction or disruption of disease-causing genes.
Among its lead programs is CTX001, an ex vivo edited cell therapy designed to treat sickle cell disease and transfusion-dependent β-thalassemia in collaboration with Vertex Pharmaceuticals.
