-Regulatory submissions complete for exagamglogene autotemcel (exa-cel) in Europe for transfusion-dependent beta thalassemia (TDT) and sickle cell disease (SCD); U.S. rolling Biologics Licensing Application (BLA) submission on track for completion by end of Q1 2023-
-Enrollment and dosing ongoing for CTX110®, targeting CD19+ B-cell malignancies, and CTX130™, targeting CD70 for the treatment of T cell lymphomas-
-Initiating Phase 1/2 clinical trials for next generation CAR T products, CTX112™ targeting CD19+ B-cell malignancies andCTX131™, targeting CD70+ solid tumors-
-Enrollment and dosing ongoing in a Phase 1/2 clinical trial of VCTX211™ for the treatment of Type 1 Diabetes (T1D)-
-Expects to advance its lead in vivo program, CTX310™, targeting angiopoietin-related protein 3 (ANGPTL3) into clinical trials this year-
ZUG, Switzerland and BOSTON, Feb. 21, 2023 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today reported financial results for the fourth quarter and full year ended December 31, 2022.
“2022 marked a significant year of progress toward our goal of delivering innovative gene edited therapies to patients. Exa-cel has the potential to be the first approved CRISPR-based therapy in the world, with regulatory submissions complete in Europe and underway in the United States,” said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. “At the same time, we continue to expand our pipeline and drive forward our programs across the immuno-oncology, diabetes and cardiovascular disease verticals. Based on encouraging data reported in 2022 at EHA and ASH conferences, we continue to advance both CTX110 and CTX130 in larger clinical trials. We are also initiating clinical trials for our next generation CAR T cell programs, CTX112 and CTX131, which have the potential to be best-in-class cell therapies. We continue to progress our regenerative medicine portfolio with the advancement of VCTX211, an immune-evasive cell replacement therapy designed to enable patients with T1D to produce their own insulin, to the clinic following clearance of our CTA by Health Canada. Finally, we expect to move our first in vivo program, CTX310, into the clinic this year, while advancing additional in vivo programs into IND-enabling studies. We are well-positioned to continue expanding our portfolio of transformative medicines while continuously improving our editing and delivery platform throughout 2023.”
Recent Highlights and Outlook
Fourth Quarter and Full Year 2022 Financial Results
About exagamglogene autotemcel (exa-cel)
Exa-cel, formerly known as CTX001™, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with TDT or SCD characterized by recurrent VOCs, in which a patient’s own hematopoietic stem cells are edited to produce 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. The elevation of HbF by exa-cel has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021.
Based on progress in this program to date, exa-cel has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA for both TDT and SCD. Exa-cel has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.
Among gene-editing approaches being evaluated for TDT and SCD, exa-cel is the furthest advanced in clinical development.
About CLIMB-111 and CLIMB-121
The ongoing Phase 1/2/3 open-label trials, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after exa-cel infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial.
About CLIMB-131
This is a long-term, open-label trial to evaluate the safety and efficacy of exa-cel in patients who received exa-cel in CLIMB-111, CLIMB-121, CLIMB-141 or CLIMB-151. The trial is designed to follow participants for up to 15 years after exa-cel infusion.
About CLIMB-141 and CLIMB-151
The ongoing Phase 3 open-label trials, CLIMB-141 and CLIMB-151, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 2 to 11 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years of age and will plan to extend to patients 2 to less than 5 years of age at a later date. Each trial will enroll approximately 12 patients. Patients will be followed for approximately two years after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up- trial.
About the CRISPR-Vertex Collaboration
CRISPR Therapeutics and Vertex Pharmaceuticals entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. Exa-cel represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development, manufacturing and commercialization of exa-cel and split program costs and profits worldwide 60/40 with CRISPR Therapeutics.
About CTX110 and CTX112
CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON clinical trial, which is designed to assess the safety and efficacy of CTX110 in adult patients with relapsed or refractory CD19-positive B-cell malignancies who have received at least two prior lines of therapy. CTX110 has been granted RMAT designation by the FDA. In addition, CTX112, a next-generation allogeneic CAR T cell therapy targeting CD19, is being investigated in a clinical trial. CTX112 includes two additional edits beyond CTX110 that are designed to enhance the potency of the CAR T cells.
About CTX130 and CTX131
CTX130, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being developed for the treatment of relapsed or refractory T-cell hematologic malignancies in the COBALT-LYM trial. CTX130 has been granted Orphan Drug designation for the treatment of T-cell lymphoma by the FDA and RMAT designation for the treatment of relapsed or refractory Mycosis Fungoides and Sézary Syndrome (MF/SS), types of cutaneous T-cell lymphoma (CTCL). In addition, CTX131, a next-generation allogeneic CAR T cell therapy targeting CD70, is being assessed for safety and efficacy in a clinical trial investigating a basket of select solid tumors. CTX131 includes two additional edits beyond CTX130 that are designed to enhance the potency of the CAR T cells.
About VCTX210 and VCTX211
VCTX210 is an investigational, allogeneic, gene-edited, immune-evasive, stem cell-derived investigational therapy for the treatment of T1D. VCTX210 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and ViaCyte, Inc. VCTX211 is an allogeneic, gene-edited, stem cell-derived investigational therapy for the treatment of T1D, which incorporates additional gene edits that aim to further enhance cell fitness. This immune-evasive cell replacement therapy is designed to enable patients to produce their own insulin in response to glucose.
About CRISPR Therapeutics
CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. 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, and business offices in London, United Kingdom. For more information, please visit www.crisprtx.com.
CRISPR Therapeutics Forward-Looking Statement
This press release may contain a number of “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements made by Dr. Kulkarni in this press release, as well as statements regarding CRISPR Therapeutics’ expectations about any or all of the following: (i) its preclinical studies, clinical trials and pipeline products and programs, including, without limitation, status of such studies and trials, expected timing of data releases, timing of regulatory submissions and the regulatory filings for exa-cel; (ii) the sufficiency of its cash resources; (iii) the expected benefits of its collaborations; and (iv) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words “believes,” “anticipates,” “plans,” “expects” and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the potential for preliminary data from any clinical trial not to be indicative of final trial results; the potential that clinical trial results may not be favorable; that one or more of its internal or external product candidate programs will not proceed as planned for technical, scientific or commercial reasons; that future competitive or other market factors may adversely affect the commercial potential for its product candidates; uncertainties inherent in the initiation and completion of preclinical studies for its product candidates and whether results from such studies will be predictive of future results of future studies or clinical trials; uncertainties about regulatory approvals to conduct trials or to market products; it may not realize the potential benefits of its collaborations; uncertainties regarding the intellectual property protection for its technology and intellectual property belonging to third parties, and the outcome of proceedings (such as an interference, an opposition or a similar proceeding) involving all or any portion of such intellectual property; and those risks and uncertainties described under the heading "Risk Factors" in CRISPR Therapeutics’ most recent annual report on Form 10-K, quarterly report on Form 10-Q and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at www.sec.gov. 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. CRISPR Therapeutics disclaims 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. CRISPR THERAPEUTICS® standard character mark and design logo, COBALT™, CTX001™, CTX110®, CTX112™, CTX130™, CTX131™, CTX310™, VCTX210™, VCTX211™ are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.
Investor Contact:
Susan Kim
+1-617-307-7503
susan.kim@crisprtx.com
Media Contact:
Rachel Eides
+1-617-315-4493
rachel.eides@crisprtx.com
CRISPR Therapeutics AG
Condensed Consolidated Statements of Operations
(Unaudited, In thousands except share data and per share data)
| Three Months Ended December 31, | Year Ended December 31, | |||||||||||||||
| 2022 | 2021 | 2022 | 2021 | |||||||||||||
| Revenue: | ||||||||||||||||
| Collaboration revenue | $ | 6 | $ | 12,348 | $ | 436 | $ | 913,081 | ||||||||
| Grant revenue | — | 551 | 762 | 1,882 | ||||||||||||
| Total revenue | $ | 6 | $ | 12,899 | $ | 1,198 | $ | 914,963 | ||||||||
| Operating expenses: | ||||||||||||||||
| Research and development | 103,555 | 103,095 | 461,645 | 340,567 | ||||||||||||
| General and administrative | 21,169 | 23,678 | 102,464 | 99,690 | ||||||||||||
| Collaboration expense, net | 6,823 | 31,824 | 110,250 | 101,178 | ||||||||||||
| Total operating expenses | 131,547 | 158,597 | 674,359 | 541,435 | ||||||||||||
| Total operating expenses | (131,541 | ) | (145,698 | ) | (673,161 | ) | 373,528 | |||||||||
| Total other income, net | 11,490 | 2,197 | 22,661 | 6,003 | ||||||||||||
| Net (loss) income before income taxes | (120,051 | ) | (143,501 | ) | (650,500 | ) | 379,531 | |||||||||
| Benefit (provision) for income taxes | 9,476 | 2,253 | 325 | (1,870 | ) | |||||||||||
| Net (loss) income | (110,575 | ) | (141,248 | ) | (650,175 | ) | 377,661 | |||||||||
| Foreign currency translation adjustment | 115 | 3 | (80 | ) | (11 | ) | ||||||||||
| Unrealized loss on marketable securities | 6,501 | (4,300 | ) | (10,500 | ) | (4,973 | ) | |||||||||
| Comprehensive (loss) income | $ | (103,959 | ) | $ | (145,545 | ) | $ | (660,755 | ) | $ | 372,677 | |||||
| Net (loss) income per common share — basic | $ | (1.41 | ) | $ | (1.84 | ) | $ | (8.36 | ) | $ | 4.97 | |||||
| Basic weighted-average common shares outstanding | 78,336,506 | 76,649,727 | 77,746,575 | 75,948,686 | ||||||||||||
| Net (loss) income per common share — diluted | $ | (1.41 | ) | $ | (1.84 | ) | $ | (8.36 | ) | $ | 4.70 | |||||
| Diluted weighted-average common shares outstanding | 78,336,506 | 76,649,727 | 77,746,575 | 80,393,496 | ||||||||||||
CRISPR Therapeutics AG
Condensed Consolidated Balance Sheets Data
(Unaudited, in thousands)
| As of | ||||||||
| December 31, 2022 | December 31, 2021 | |||||||
| Cash | $ | 211,885 | $ | 923,031 | ||||
| Marketable securities | 1,603,433 | 1,456,098 | ||||||
| Marketable securities, non-current | 53,130 | — | ||||||
| Working capital | 1,731,919 | 2,297,630 | ||||||
| Total assets | 2,243,057 | 2,751,877 | ||||||
| Total shareholders' equity | 1,875,479 | 2,399,460 | ||||||