Crispr Therapeutics announces 2024 outlook

CASGEVY: Received regulatory approvals for CASGEVY in the fourth quarter of 2023 in the U.S. for sickle cell disease and in Great Britain and Bahrain for the treatment of SCD and transfusion-dependent beta thalassemia; also received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use for CASGEVY for both SCD and TDT from the European Medicines Agency. Exa-cel is the first therapy to emerge from a strategic partnership between CRISPR Therapeutics and Vertex Pharmaceuticals. Vertex leads global development, manufacturing, regulatory and commercialization of CASGEVY with support from CRISPR Therapeutics. The FDA has assigned a Prescription Drug User Fee Act action date of March 30, 2024, for CASGEVY in TDT. Additional regulatory submissions for CASGEVY are currently under review in Switzerland and the Kingdom of Saudi Arabia, with the submission in Canada planned for the first half of 2024. Completed enrollment in two global Phase 3 studies of CASGEVY in patients 5 to 11 years of age with SCD or TDT. Vertex is engaging with experienced hospitals to establish a network of authorized treatment centers throughout the U.S. to offer CASGEVY to patients. Nine ATCs have been activated in the U.S. and three in Europe, with the goal of activating approximately 50 ATCs in the U.S. and 25 in the EU. Additionally, Vertex announced an agreement with a major medication contracting organization, Synergie Medication Collective, which covers nearly 100 million lives in the U.S., to provide access to CASGEVY through an outcomes-based contract. Hemoglobinopathies CRISPR Therapeutics has two next-generation research focuses that each have the potential to expand the addressable population with SCD and TDT significantly. First, the Company continues to advance its internal targeted conditioning program, an anti-CD117 antibody-drug conjugate, through preclinical studies. Second, the Company has ongoing research efforts to enable in vivo editing of hematopoietic stem cells. This work, supported in part by a $14.5 million grant from the Bill & Melinda Gates Foundation, could obviate the need for conditioning altogether, expand geographic reach, and enable the treatment of multiple additional other diseases beyond SCD and TDT. Immuno-Oncology and Autoimmune Disease CRISPR Therapeutics’ next-generation allogeneic CAR T candidates reflect the Company’s mission of innovating continuously to bring potentially transformative medicines to patients as quickly as possible. Clinical trials are ongoing for CRISPR Therapeutics’ next-generation CAR T product candidates, CTX112 and CTX131, targeting CD19 and CD70, respectively. Emerging pharmacology data, including pharmacokinetics, indicate that the novel potency gene edits in CTX112 and CTX131 can lead to significantly higher CAR T cell expansion and functional persistence in patients compared to the first-generation candidates. Focusing efforts on these candidates will enable the Company to advance these potentially best-in-class CAR T therapies more efficiently and rapidly. The Company expects to provide a clinical update in 2024 for these next-generation candidates. CRISPR Therapeutics plans to initiate a clinical trial of CTX112 in systemic lupus erythematosus in the first half of 2024, with the potential to expand into additional autoimmune indications in the future. Early clinical studies have shown that CD19-directed autologous CAR T therapy can produce long-lasting remissions in multiple autoimmune indications. CRISPR Therapeutics is expanding trials of CTX131 into hematologic malignancies, including T- and B-cell malignancies, in addition to the ongoing clinical trial in solid tumors. In Vivo CRISPR Therapeutics is advancing a pipeline of in vivo gene editing programs using lipid nanoparticle delivery of Cas9 mRNA and a guide RNA to the liver. Its first two in vivo programs, CTX310 and CTX320, each aim to reduce expression of a validated target for cardiovascular disease. Beginning with these programs, CRISPR Therapeutics aims to transform the treatment paradigm for cardiovascular indications and beyond with potential one-time therapies that could recapitulate the proven benefit of targets validated by natural human genetics and other therapeutic modalities. A Phase 1 clinical trial is ongoing for CTX310, targeting angiopoietin-like 3 protein. In humans, naturally occurring loss-of-function variants in ANGPTL3 are associated with reduced levels of serum lipids and reduced risk of atherosclerotic cardiovascular disease. The Phase 1 trial is enrolling patients with mixed dyslipidemias, homozygous familial hypercholesterolemia, and severe hypertriglyceridemia. CRISPR Therapeutics has initiated a Phase 1 clinical trial for CTX320, an investigational program targeting lipoprotein. Elevated Lp(a), which is associated with an increased risk of atherosclerotic cardiovascular disease, is present in approximately one in five people in the United States and around the world. CRISPR Therapeutics expects to nominate additional in vivo programs targeting both rare and common diseases this year, to be disclosed in mid-2024. Regenerative Medicine CRISPR Therapeutics announced today that ViaCyte has elected to opt-out of the collaboration with CRISPR Therapeutics for the co-development and co-commercialization of gene-edited stem cell therapies for the treatment of diabetes. Per the opt-out terms, the on-going collaboration assets will now be wholly owned by CRISPR Therapeutics, subject to a royalty on future sales owed to ViaCyte. The opt-out will become effective in early February. The ViaCyte collaboration assets include CTX211, an allogeneic, gene-edited, immune-evasive, stem cell derived product candidate that is transplanted into patients in a device and intended to produce insulin in a glucose-dependent manner. CRISPR Therapeutics continues to advance a Phase 1 clinical trial for CTX211 for the treatment of Type 1 Diabetes . CRISPR Therapeutics remains committed to its goal of developing a beta-cell replacement product that does not require chronic immunosuppression. Separate from the ViaCyte collaboration, Vertex continues to have non-exclusive rights to certain CRISPR Therapeutics’ CRISPR/Cas9 technology to accelerate development of potentially curative cell therapies for T1D. Vertex paid $170 million to CRISPR Therapeutics in upfront and milestone payments in 2023 as part of that licensing agreement, and CRISPR Therapeutics remains eligible for an additional $160 million in research and development milestones and would receive royalties on any future products resulting from this agreement. Manufacturing CRISPR Therapeutics’ state-of-the-art Good Manufacturing Practice facility located in Framingham, MA is fully operational, and continues to support the production of the Company’s various investigational therapies. Potential benefits of this facility include significantly lower cost of goods, increased flexibility and greater scalability. The Company’s next-generation allogeneic CAR T candidates manufactured at its internal GMP facility exhibit increased manufacturing robustness, yield and scalability.