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- More than 70 patients have been dosed with CTX001™ across CLIMB-Thal-111 and CLIMB-SCD-121 to date; enrollment complete and regulatory submissions planned for late 2022-
-Initiated and began dosing patients in the pivotal trial of CTX110™, targeting CD19+ B-cell malignancies; additional data expected to report in 2022-
-Top-line data expected to report in 1H2022 for ongoing CTX120™ and CTX130™ clinical trials-
-First patient dosed in Phase 1 clinical trial of VCTX210 for the treatment of type 1 diabetes (T1D)-
“2021 was a productive year for
Recent Highlights and Outlook
- Beta Thalassemia and Sickle Cell Disease Programs
- More than 70 patients have been dosed with CTX001 across both trials to date. Target enrollment has been achieved in the ongoing clinical trials for CTX001 in transfusion-dependent beta thalassemia (TDT) and severe sickle cell disease (SCD), with planned regulatory submissions in late 2022.
June 2021, data from 22 patients with at least three months of follow-up after CTX001 infusion were presented at the Annual European Hematology Association Virtual Congress(EHA) and continued to build the profile of a potentially functional cure for patients with TDT and SCD, showing consistent and durable benefit with longer term data from a larger population of patients.
April 2021, CRISPR Therapeuticsand Vertex announced an amendment to their collaboration for CTX001. In connection with the completion of the transaction in June, Vertex made a $900 millionupfront payment to CRISPR Therapeutics.
April 2021, CRISPR Therapeuticsand Vertex announced that the European Medicines Agency(EMA) granted Priority Medicines (PRIME) designation to CTX001 for the treatment of TDT. CTX001 was granted PRIME designation for the treatment of SCD in 2020.
- Immuno-Oncology Programs
CRISPR Therapeuticshas begun dosing patients in the pivotal trial of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19+ B-cell malignancies. Enrollment is ongoing and the Company expects to report additional data in 2022. The U.S. Food and Drug Administration(FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX110 in November 2021.
October 2021, CRISPR Therapeuticsannounced positive results from its ongoing Phase 1 CARBON trial evaluating the safety and efficacy of CTX110. The data showed early evidence of a dose dependent response to CTX110, with overall response rates (ORR), complete response rates (CR) and durability similar to approved autologous CD19 CAR-T therapies on an intent-to-treat (ITT) basis. A single dose of CTX110 at DL2 and above resulted in a 58% ORR and 38% CR rate in large B-cell lymphoma (LBCL) patients on an ITT basis. The pharmacokinetic data provide a strong rationale that consolidation dosing can improve on an already competitive profile for CTX110. Based on the safety and efficacy profile, the Company has expanded the current trial into a pivotal trial that incorporates consolidation dosing and has begun dosing patients in this pivotal arm. The Company expects to report additional data in 2022.
- In addition to CTX110,
CRISPR Therapeuticshas ongoing Phase 1 clinical trials assessing safety and efficacy of several dose levels for the following CAR-Ts: (i) CTX120, its wholly-owned allogeneic CAR-T investigational therapy targeting B-cell maturation antigen for the treatment of relapsed or refractory multiple myeloma; and (ii) CTX130, its wholly-owned allogeneic CAR-T investigational therapy targeting CD70 for the treatment of both solid tumors and certain hematologic malignancies. The Company expects to report top-line data in the first half of 2022.
May 2021, CRISPR Therapeuticsand Nkarta, Inc. announced a strategic partnership to research, develop, and commercialize CRISPR/Cas9 gene-edited cell therapies for cancer. Under the agreement, the companies will co-develop and co-commercialize two CAR-NK cell product candidates, one targeting the CD70 tumor antigen and the other target to be determined. In addition, the companies will bring together their complementary cell therapy engineering and manufacturing capabilities to advance the development of a novel NK+T product candidate harnessing the synergies of the adaptive and innate immune systems.
- Regenerative Medicine and In
- Earlier this month,
CRISPR Therapeuticsand its partner ViaCyteannounced the first patient had been dosed in the Phase 1 clinical trial of VCTX210 for the treatment of T1D. VCTX210 is an investigational, allogeneic, gene-edited, stem cell-derived product developed in collaboration by applying CRISPR Therapeutics’ gene-editing technology to ViaCyte’s proprietary stem cell capabilities for the generation of pancreatic cells designed to evade recognition by the immune system. This immune-evasive cell replacement therapy is designed to enable patients to produce their own insulin.
June 2021, CRISPR Therapeuticsand Capsida Biotherapeutics, Inc.announced a strategic partnership to research, develop, manufacture and commercialize in vivo gene editing therapies delivered with engineered AAV vectors for the treatment of familial amyotrophic lateral sclerosis (ALS) and Friedreich’s ataxia. Under the agreement, CRISPR Therapeuticswill lead research and development of the Friedreich’s ataxia program and perform gene-editing activities for both programs, and Capsida will lead research and development of the ALS program and conduct capsid engineering for both programs.
- The Company continues to make progress with its in vivo approaches for liver gene editing utilizing both viral and non-viral delivery vehicles. The Company expects to move multiple programs utilizing in vivo approaches into the clinic in the next 18 to 24 months.
- Earlier this month,
- Other Corporate Matters
- Under the
June 2019collaboration agreement with Vertex to discover and develop gene editing therapies for the treatment of Duchenne Muscular Dystrophy (DMD) and Myotonic Dystrophy Type 1 (DM1), CRISPR Therapeuticsreceived a payment of $12.5 millionfrom Vertex related to the achievement of a research milestone in the DM1 program. CRISPR Therapeuticsis eligible to receive additional milestone payments from Vertex of up to $775 millionfor these two programs.
- Under the
Fourth Quarter and Full Year 2021 Financial Results
- Cash Position: Cash, cash equivalents and marketable securities were
$2,379.1 millionas of December 31, 2021, compared to $1,690.3 millionas of December 31, 2020. The increase in our cash position of $688.8 millionwas primarily driven by an upfront payment of $900.0 millionin connection with the Amended and Restated Joint Developmentand Commercialization Agreement with Vertex. Additionally, cash provided by financing activities was $250.9 million, primarily related to common shares issued in connection with utilizing the Company’s at-the-market (ATM) financing facility as well as option exercises. These increases were offset by continuing operating expenses to support ongoing research and development of the Company’s clinical and pre-clinical programs as well as capital investments in our manufacturing facility.
- Revenue: Total collaboration revenue was
$12.3 millionfor the fourth quarter of 2021 compared to $0.2 millionfor fourth quarter of 2020, and $913.1 millionfor the year ended December 31, 2021, compared to $0.5 millionfor the year ended December 31, 2020. The increase in collaboration revenue is primarily attributable to revenue recognized in connection with the aforementioned payments received from Vertex.
- R&D Expenses: R&D expenses were
$134.5 millionfor the fourth quarter of 2021 compared to $82.4 millionfor the fourth quarter of 2020, and $438.6 millionfor the year ended December 31, 2021, compared to $266.9 millionfor the year ended December 31, 2020. The increase in expense for the year was driven by development activities supporting the advancement of the hemoglobinopathies program and wholly-owned immuno-oncology programs, as well as increased headcount and supporting facilities-related expenses.
- G&A Expenses: General and administrative expenses were
$24.1 millionfor the fourth quarter of 2021 compared to $25.8 millionfor the fourth quarter of 2020, and $102.8 millionfor the year ended December 31, 2021, compared to $88.2 millionfor the year ended December 31, 2020. The increase in general and administrative expenses for the year was driven by headcount-related expense.
- Net Income / Loss: Net loss was
$141.2 millionfor the fourth quarter of 2021 compared to a net loss of $107.0 millionfor the fourth quarter of 2020, and net income was $377.7 millionfor the year ended December 31, 2021, compared to a net loss of $348.9 millionfor the year ended December 31, 2020.
CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate or eliminate transfusion requirements for patients with TDT and reduce or eliminate painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published as a Brief Report in
Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the
Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.
About the CRISPR-Vertex Collaboration
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.
This is a long-term, open-label trial to evaluate the safety and efficacy of CTX001 in patients who received CTX001 in CLIMB-111 or CLIMB-121. The trial is designed to follow participants for up to 15 years after CTX001 infusion.
CTX110, a wholly owned program of
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies.
CTX120, a wholly-owned program of
CTX130, a wholly-owned program of
VCTX210 is an investigational, allogeneic, gene-edited, immune-evasive, stem cell-derived therapy for the treatment of T1D. VCTX210 is being developed under a co-development and co-commercialization agreement between
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) the safety, efficacy and clinical progress of CRISPR Therapeutics’ various clinical programs, including CTX001, CTX110, CTX120, CTX130, and VCTX210; (ii) the status of clinical trials (including, without limitation, expectations regarding the data that is being presented, the expected timing of data releases and development, as well as completion of clinical trials) and development timelines for CRISPR Therapeutics’ product candidates; (iii) the data that will be generated by ongoing and planned clinical trials, and the ability to use that data for the design and initiation of further clinical trials, including expectations regarding the CTX001 and CTX110 data that was previously presented; (iv) its in vivo programs; (v) the actual or potential benefits of regulatory designations; (vi) the intellectual property coverage and positions of CRISPR Therapeutics, its licensors and third parties as well as the status and potential outcome of proceedings involving any such intellectual property; (vii) the sufficiency of CRISPR Therapeutics’ cash resources; (viii) the expected benefits of CRISPR Therapeutics’ collaborations; and (ix) 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 initial and preliminary data from any clinical trial and initial data from a limited number of patients not to be indicative of final trial results; the potential that clinical trial results may not be favorable; that one or more of CRISPR Therapeutics’ 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 CRISPR Therapeutics’ product candidates; uncertainties inherent in the initiation and completion of preclinical studies for CRISPR Therapeutics’ product candidates (including, without limitation, availability and timing of results and whether such results will be predictive of future results of the future trials); uncertainties about regulatory approvals to conduct trials or to market products; the potential impacts due to the coronavirus pandemic such as (x) delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; (y) the timing and progress of clinical trials, preclinical studies and other research and development activities; and (z) the overall impact of the coronavirus pandemic on its business, financial condition and results of operations; uncertainties regarding the intellectual property protection for CRISPR Therapeutics’ 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® word mark and design logo, CTX001™, CTX110™, CTX120™, and CTX130™ are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.
Condensed Consolidated Statements of Operations
(Unaudited, In thousands except share data and per share data)
|Three Months Ended
|Research and development||134,470||82,365||438,633||266,946|
|General and administrative||24,127||25,766||102,802||88,208|
|Total operating expenses||158,597||108,131||541,435||355,154|
|(Loss) income from operations||(145,698||)||(107,761||)||373,528||(354,435||)|
|Total other income, net||2,197||575||6,003||6,379|
|Net (loss) income before income taxes||(143,501||)||(107,186||)||379,531||(348,056||)|
|Benefit (provision) for income taxes||2,253||147||(1,870||)||(809||)|
|Net (loss) income||(141,248||)||(107,039||)||377,661||(348,865||)|
|Foreign currency translation adjustment||3||37||(11||)||40|
|Unrealized loss on marketable securities||(4,300||)||14||(4,973||)||(130||)|
|Comprehensive (loss) income||$||(145,545||)||$||(106,988||)||$||372,677||$||(348,955||)|
|Net (loss) income per common share — basic||$||(1.84||)||$||1.50||$||4.97||$||(5.29||)|
|Basic weighted-average common shares outstanding||76,649,727||71,282,096||75,948,686||65,949,672|
|Net (loss) income per common share — diluted||$||(1.84||)||$||1.50||$||4.70||$||(5.29||)|
|Diluted weighted-average common shares outstanding||76,649,727||71,282,096||80,393,496||65,949,672|
Condensed Consolidated Balance Sheets Data
(Unaudited, in thousands)
|Total shareholders' equity||2,399,460||1,664,234|
Source: CRISPR Therapeutics AG