On February 11, 2025 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the fourth quarter and full year ended December 31, 2024 (Press release, CRISPR Therapeutics, FEB 11, 2025, View Source [SID1234650168]).

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"With continued advancements across our commercial and clinical portfolio, CRISPR Therapeutics is poised to make meaningful strides in transforming the landscape of medicine. As we continue to expand our portfolio and deliver on our mission to bring life-changing treatments to patients, 2025 stands as a milestone-rich year for CRISPR Therapeutics. In addition to the continued launch progress of CASGEVY, we expect several key milestones across our pipeline, including updates on our lead in vivo, cardiovascular programs in the first half of 2025. We also anticipate a broad update on CTX112 in oncology and autoimmune diseases in mid-2025, and additional updates across our pipeline. We remain deeply committed to advancing our technology platform to tackle some of the most challenging diseases and improving patient lives."

Recent Highlights and Outlook

Hemoglobinopathies and CASGEVY (exagamglogene autotemcel [exa-cel])
CASGEVY is approved in the U.S., Great Britain, the EU, the Kingdom of Saudi Arabia (KSA), the Kingdom of Bahrain (Bahrain), Canada, Switzerland and the United Arab Emirates (UAE) for the treatment of both SCD and TDT, and launches are ongoing. Building on the strong foundational launch in 2024, significant strides are being made to bring this transformative therapy to patients worldwide.
Vertex recently announced a reimbursement agreement with NHS England for SCD patients to access CASGEVY, consistent with the reimbursement agreement reached in August 2024 with NHS England for eligible TDT patients to access CASGEVY.

As of the end of 2024, more than 50 authorized treatment centers (ATCs) have been activated globally, including centers in all regions where CASGEVY is approved, and more than 50 patients have already had at least one cell collection across all regions. The number of new patients initiating cell collection is expected to grow significantly throughout 2025.
Enrollment has been completed in two global Phase 3 studies of CASGEVY in children 5 to 11 years of age with SCD or TDT, and dosing of this age group is expected to be completed in 2025.
CRISPR Therapeutics has two next-generation approaches with the potential to significantly expand the addressable population with SCD and TDT. The Company continues to advance its internally developed targeted conditioning program, an anti-CD117 (c-Kit) antibody-drug conjugate (ADC), through preclinical studies. Additionally, the Company is conducting ongoing research to enable in vivo editing of hematopoietic stem cells. This work could eliminate the need for conditioning altogether, expand geographic reach, and enable the treatment of additional other diseases beyond SCD and TDT.

Immuno-Oncology and Autoimmune Diseases

Clinical trials are ongoing for the Company’s next-generation CAR T product candidates, CTX112 and CTX131, targeting CD19 and CD70, respectively, across multiple indications. CTX112 and CTX131 both contain novel potency edits which can lead to significantly higher CAR T cell expansion and cytotoxicity, potentially representing best-in-class allogeneic CAR T products for these targets. CRISPR Therapeutics is advancing CTX112 for both hematologic malignancies and autoimmune indications, with an emerging best-in-class profile. The company’s next-generation allogeneic CAR T candidates reflect its commitment to continuous innovation, aiming to deliver potentially transformative medicines to patients as quickly as possible.

In December, CRISPR Therapeutics presented positive data from its ongoing Phase 1/2 trial of CTX112 in relapsed or refractory B-cell malignancies at the 2024 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The data demonstrated strong efficacy comparable to autologous therapies, a tolerable safety profile and robust cell expansion. The latest data, presented in January, highlight responses in patients who have received prior T-cell engager-based therapies (TCEs), with responses observed in all 6 patients, including 3 with large B-cell lymphoma (LBCL), who either relapsed post-TCE treatment or were refractory to TCEs. Based on these compelling preliminary data, CTX112 was awarded Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma. The Company plans to engage with regulatory authorities to align on the path forward for CTX112 in B-cell malignancies, with an update expected in mid-2025.

CRISPR Therapeutics has formed a strategic partnership with Nkure Therapeutics Private Limited ("NKure") to co-develop and co-commercialize CTX112 in India. This alliance aims to accelerate the global development of CTX112 in countries with significant unmet medical needs, while also highlighting the potential for lower costs associated with allogeneic cell therapy platform.

CTX112 is also in an ongoing Phase 1 clinical trial in systemic lupus erythematosus (SLE), systemic sclerosis and inflammatory myositis. Preliminary safety, pharmacokinetic, and pharmacodynamic data from oncology trials highlight the potential of CTX112 in autoimmune indications. Based on favorable oncology data, CRISPR Therapeutics expanded the CTX112 trial in SLE to include patients with systemic sclerosis and inflammatory myositis in a basket study, with updates expected in mid-2025.
Clinical trials are ongoing for CTX131 in both solid tumors and hematologic malignancies, with updates expected in 2025. Additionally, we are advancing an autologous, gene-edited CAR T therapy targeting glypican-3 (GPC3) for the potential treatment of solid tumors and expect to initiate a clinical trial in the first half of 2025.
In Vivo
CRISPR Therapeutics continues to make significant progress in advancing its proprietary LNP delivery technologies for gene editing in the liver, with ongoing development in both clinical and preclinical stages. The first two in vivo programs utilizing this proprietary platform, CTX310 and CTX320, are directed towards validated therapeutic targets associated with cardiovascular disease.
CTX310 is in an ongoing Phase 1 clinical trial targeting ANGPTL3 in patients with homozygous familial hypercholesterolemia (HoFH), severe hypertriglyceridemia (SHTG), heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemias. ANGPTL3 loss-of-function mutations are linked to reduced LDL-C, triglycerides, and a lower risk of atherosclerotic cardiovascular disease (ASCVD), without adverse effects on overall health. This program has the potential for approval based on validated biomarkers, pending regulatory discussions. Dose escalation is ongoing, with an update expected in the first half of 2025.
CTX320 is in an ongoing Phase 1 clinical trial targeting LPA in patients with elevated lipoprotein(a) [Lp(a)], a genetically determined cardiovascular risk factor linked to major adverse cardiovascular events (MACE). Elevated Lp(a) affects up to 20% of the global population. Dose escalation is ongoing, with an update expected in the first half of 2025.
CRISPR Therapeutics continues to advance two preclinical programs: CTX340, targeting angiotensinogen (AGT) for the treatment of refractory hypertension, and CTX450, targeting 5’ aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias (AHP). Both programs are currently in IND/CTA-enabling studies, with clinical trials expected to begin in the second half of 2025.
Regenerative Medicine
Progress in regenerative medicine continues with the ongoing clinical trial for CTX211 in Type 1 diabetes (T1D), along with the development of next-generation programs. These initiatives focus on allogeneic, gene-edited, stem cell-derived beta islet cell precursors, which have the potential to make T1D patients insulin-independent without the need for chronic immunosuppression. The Company expects to provide an update in 2025.
Other Corporate Matters
In January, CRISPR Therapeutics announced its proposal to elect Briggs Morrison, M.D., to its Board of Directors at the Company’s upcoming 2025 annual general meeting. With his extensive experience in the pharmaceutical industry and deep expertise in clinical development, Dr. Morrison will be an invaluable asset as CRISPR Therapeutics continues advancing its innovative platform and pipeline, aiming to develop transformative therapies for patients with serious diseases.

Fourth Quarter and Full Year 2024 Financial Results

Cash Position: Cash, cash equivalents, and marketable securities were $1,903.8 million as of December 31, 2024, compared to $1,695.7 million as of December 31, 2023. The increase in cash was primarily driven by proceeds from the $280.0 million February 2024 registered direct offering, milestone payments received from Vertex Pharmaceuticals in connection with our license and collaboration agreements, proceeds from ATM activity and employee option exercises, as well as interest income, offset by operating expenses.
R&D Expenses: R&D expenses were $82.2 million for the fourth quarter of 2024, compared to $95.1 million for the fourth quarter of 2023. The decrease in R&D expense was primarily driven by reduced variable external research and manufacturing costs.
G&A Expenses: General and administrative expenses were $18.1 million for the fourth quarter of 2024, compared to $16.5 million for the fourth quarter of 2023.
Collaboration Expense: There was no collaboration expense, net for the fourth quarter of 2024 due to reaching the deferral limit on costs related to the CASGEVY program in the third quarter of 2024. Collaboration expense for the fourth quarter of 2023 was $20.0 million.
Net Loss: Net loss was $37.3 million for the fourth quarter of 2024, compared to net income of $89.3 million for the fourth quarter of 2023.

About CASGEVY (exagamglogene autotemcel [exa-cel])
CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate recurrent vaso-occlusive crises (VOCs) for patients with SCD and transfusion requirements for patients with TDT. CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients.