CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical
company focused on creating transformative gene-based medicines for
serious diseases, today reported financial results for the third
quarter ended September 30, 2023.
“The third quarter marked significant progress
across our broad clinical pipeline of potentially curative gene
edited therapies,” said Samarth Kulkarni, Ph.D., Chief Executive
Officer and Chairman of the Board of CRISPR Therapeutics. “We are
excited about the upcoming PDUFA date for exa-cel, which could
potentially bring a transformative therapy to patients living with
sickle cell disease. If approved, exa-cel would be the first
CRISPR-based medicine available to patients in the U.S.,
highlighting the groundbreaking opportunity of this technology to
treat people with serious diseases. Additionally, we are excited to
initiate clinical trials for our in vivo programs, adding a new
pillar to our clinical portfolio. We remain well positioned and
well capitalized to bring several transformative medicines for
patients suffering from serious diseases.”
Recent Highlights and
Outlook
- Hemoglobinopathies
- In October, the U.S. Food and Drug Administration’s (FDA)
Cellular, Tissue, and Gene Therapies Advisory Committee completed
their meeting for exagamglogene autotemcel (exa-cel) for the
treatment of sickle cell disease (SCD) in people ages 12 and older
with recurrent vaso-occlusive crises (VOCs). Exa-cel is the first
potential therapy to emerge from a strategic partnership between
CRISPR Therapeutics and Vertex Pharmaceuticals.
- In November, it was announced that two abstracts (details
below) on exa-cel clinical data have been accepted for oral
presentations at the 2023 American Society of Hematology (ASH)
Annual Meeting and Exposition. The updated clinical data will
include additional patients with longer follow-up duration from
pivotal Phase 3 trials demonstrating exa-cel’s potential as a
one-time functional cure for SCD and transfusion-dependent beta
thalassemia (TDT). The accepted abstracts are available online on
the ASH website.
- Abstract #1052 entitled
“Exagamglogene Autotemcel for Severe Sickle Cell Disease” will be
an oral presentation on Monday, December 11 at 4:45 pm PST.
- Abstract #1053 entitled
“Exagamglogene Autotemcel for Transfusion-Dependent
Βeta-Thalassemia” will be an oral presentation on Monday, December
11 at 5:00 pm PST.
- CRISPR Therapeutics and Vertex
Pharmaceuticals previously announced that the FDA accepted the
Biologics License Applications (BLAs) for exa-cel for severe SCD
and TDT. The FDA has granted Priority Review for SCD and Standard
Review for TDT and assigned Prescription Drug User Fee Act (PDUFA)
target action dates of December 8, 2023, and March 30, 2024,
respectively. In the U.S., exa-cel has been granted Fast Track,
Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug and Rare
Pediatric Disease designations.
- A marketing authorization
application for exa-cel has also been submitted to the Saudi Food
and Drug Authority (SFDA). Exa-cel is the first investigational
medicine to receive Breakthrough Designation from the SFDA,
reflecting the high unmet need for patients with SCD
and TDT in the Kingdom of Saudi Arabia.
- The Phase 1/2/3 CLIMB-111 and
CLIMB-121 studies and the CLIMB-131 long-term follow-up study are
ongoing in patients 12 years of age and older.
- Two global Phase 3 studies of
exa-cel are ongoing for patients 5 to 11 years of age with TDT or
SCD.
- CRISPR Therapeutics continues to
advance its anti-CD117 (c-Kit) antibody-drug conjugate (ADC), its
internal targeted conditioning program, in preclinical studies.
This targeted conditioning agent has the potential to significantly
expand the patient population that can benefit from exa-cel.
- Immuno-Oncology
- Clinical trials are ongoing for CTX110® and CTX112™, CRISPR
Therapeutics’ first and next-generation allogeneic chimeric antigen
receptor T cell CAR T) investigational therapies targeting CD19 in
B-cell malignancies. Based on encouraging preliminary data, CTX110
was granted RMAT designation by the FDA.
- Clinical trials are ongoing for CTX130™ and CTX131™, CRISPR
Therapeutics’ first and next-generation allogeneic CAR T
investigational therapies targeting CD70 in T cell malignancies and
solid tumors. Based on encouraging preliminary data, CTX130 was
granted RMAT designation by the FDA.
- Earlier this month, CRISPR Therapeutics presented new
preclinical data at the Society for Immunotherapy of Cancer (SITC)
38th Annual Meeting demonstrating the continued advancement of its
immuno-oncology programs and platform.
- Regenerative
Medicine
- CRISPR Therapeutics and ViaCyte
continue to collaborate on their existing gene-edited allogeneic
stem cell therapies for the treatment of diabetes under the terms
of their collaboration. The clinical trial for VCTX211™ for
the treatment of T1D is ongoing.
- In Vivo
- CRISPR Therapeutics continues to progress its in vivo platform,
focused on lipid nanoparticle (LNP)-based delivery to the liver and
extrahepatic tissues. The Company continues to advance multiple in
vivo programs directed towards cardiovascular indications and
beyond.
- CRISPR Therapeutics initiated a
Phase 1 clinical trial for CTX310™, targeting angiopoietin-like 3
protein (ANGPTL3). Natural history studies have shown that
individuals with natural loss-of-function variants of ANGPTL3 have
lower triglyceride levels, lower LDL-C levels, and a lower risk of
coronary artery disease, validating targeting ANGPTL3 for the
treatment of atherosclerotic cardiovascular disease (ASCVD).
- Additionally, CRISPR Therapeutics
continues to advance CTX320™, an investigational program targeting
lipoprotein(a) (Lp(a)) and remains on track to enter the clinic in
the first half of 2024. High levels of Lp(a) are an independent and
causal risk factor for ASCVD. CTX310 and CTX320 have the potential
to shift the treatment paradigm for ASCVD with a single-dose,
potentially life-long durable editing approach.
- In November, CRISPR Therapeutics
announced preclinical data from the Company’s investigational
programs for the treatment of cardiovascular disease at the
American Heart Association (AHA) Scientific Sessions 2023. The data
will be presented on Saturday, November 11, 2023, in two oral
sessions, entitled “CTX310: An Investigational in vivo CRISPR-Based
Therapy Efficiently and Durably Reduces ANGPTL3 Protein and
Triglyceride Levels in Non-Human Primates After a Single Dose” and
“CTX320: An Investigational in vivo CRISPR-Based Therapy
Efficiently and Durably Reduces Lipoprotein(a) Levels in Non-Human
Primates After a Single Dose.”
- Beyond CTX310 and CTX320, CRISPR
Therapeutics is advancing additional programs utilizing in vivo
delivery to address both rare and common diseases.
- In October, CRISPR Therapeutics
received a new grant from the Bill & Melinda Gates Foundation
to research in vivo gene editing of hematopoietic stem and
progenitor cells (HSPCs). The grant builds upon CRISPR
Therapeutics’ proprietary gene editing technology and expertise in
editing HSPCs and contributes to efforts to accelerate
transformative medicines for global health.
- Other Corporate Matters
- In October, CRISPR Therapeutics announced its proposal to elect
Sandy Mahatme, LL.M. to its Board of Directors at the Company’s
upcoming annual general meeting to be held in 2024. Mr. Mahatme,
LL.M., brings a considerable breadth of experience to CRISPR
Therapeutics gained from his senior roles at industry-leading
companies and has a strong track record of success in finance,
business development and corporate strategy.
Third Quarter 2023 Financial
Results
- Cash Position: Cash, cash equivalents, and
marketable securities were $1,739.8 million as of September 30,
2023, compared to $1,868.4 million as of December 31, 2022. The
decrease in cash of $128.6 million was primarily driven by
operating expenses, offset by payments received from Vertex in
connection with a non-exclusive license agreement and related
milestone, as well as interest income.
- R&D Expenses: R&D expenses were $90.7
million for the third quarter of 2023, compared to $116.6 million
for the third quarter of 2022. 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 $18.3 million for the third quarter of 2023, compared
to $27.0 million for the third quarter of 2022. The decrease in
G&A expense was primarily driven by a decrease in external
professional costs.
- Collaboration Expense: Collaboration expense,
net, was $23.4 million for the third quarter of 2023, compared to
$38.9 million for the third quarter of 2022. The decrease of
approximately $15.5 million in collaboration expense, net, was due
to the fact that we reached the $110.3 million deferral limit on
costs related to the exa-cel program in the third quarter of 2023,
whereas the limit was not reached until the fourth quarter of
2022.
- Net Loss: Net loss was $112.2 million for the
third quarter of 2023, compared to a net loss of $174.5 million for
the third quarter of 2022.
About exagamglogene autotemcel
(exa-cel)Exa-cel is an investigational,
autologous, ex vivo CRISPR/Cas9 gene-edited cell therapy
that is being evaluated for patients with SCD or TDT, 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 reduce or eliminate painful and debilitating VOCs
for patients with SCD and alleviate transfusion requirements for
patients with TDT. Earlier results from these ongoing trials were
published in The New England Journal of Medicine in
January of 2021 and presented at the American Society of Hematology
Annual Congress in 2022 and the European Hematology Association
Annual Meeting in 2023.
Exa-cel has been granted Regenerative Medicine
Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare
Pediatric Disease designations from the U.S. FDA for both TDT and
SCD. The FDA has accepted the Biologics License Applications (BLAs)
for exa-cel and assigned Prescription Drug User Fee Act (PDUFA)
action dates of December 8, 2023, for SCD and March 30, 2024, for
TDT.
In the EU, exa-cel has been granted Orphan Drug
Designation from the European Commission, as well as Priority
Medicines (PRIME) designation from the European Medicines Agency
(EMA), for both SCD and TDT. In the U.K., exa-cel has also been
granted an Innovation Passport under the Innovative Licensing and
Access Pathway (ILAP) from the Medicines Healthcare products
Regulatory Agency (MHRA). In Europe, the Marketing Authorization
Applications (MAAs) for exa-cel were submitted in December 2022 and
validated by the EMA and MHRA in January 2023.
About CLIMB-111 and
CLIMB-121The 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-131The ongoing
long-term, open-label trial, CLIMB-131, is designed to evaluate the
safety and efficacy of exa-cel in patients who received exa-cel in
CLIMB-111, CLIMB-121, CLIMB-141, CLIMB-151 or CLIMB-161. The trial
is designed to follow participants for up to 15 years after exa-cel
infusion.
About CLIMB-141 and
CLIMB-151The 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 with the plan to extend to ages 2 to less than 5 years
at a later date. Each trial will enroll approximately 15 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 CLIMB-161The ongoing
Phase 3b trial, CLIMB-161, is to support expansion of our
manufacturing footprint after initial potential approval and
launch. This trial will enroll approximately 12 patients with
either TDT or with SCD, characterized by recurrent VOCs, ages 12 to
35 years. Patients will be followed for approximately one year
after infusion. Each patient will be asked to participate in
CLIMB-131, a long-term follow-up trial.
About the CRISPR Collaboration and
Vertex CRISPR Therapeutics and Vertex 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 an amended collaboration agreement, Vertex
now leads global development, manufacturing and commercialization
of exa-cel and splits program costs and profits worldwide 60/40
with CRISPR Therapeutics.
About CD19
Candidates CTX110 is a wholly-owned, healthy
donor-derived gene-edited allogeneic CAR T investigational therapy
targeting cluster of differentiation 19, or CD19, and CTX112, a
next-generation, wholly-owned, investigational, allogeneic CAR T
product candidate targeting CD19, which incorporates additional
edits designed to enhance CAR T potency and reduce CAR T
exhaustion. Both CTX110 and CTX112 are being investigated in
ongoing clinical trials designed to assess the safety and efficacy
of the applicable product candidate 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.
About CD70
Candidates CTX130 is a wholly-owned, 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, and
CTX131, a next-generation, wholly-owned, investigational allogeneic
CAR T product candidate targeting CD70 in a basket of solid tumors,
which incorporates additional edits designed to enhance CAR T
potency and reduce CAR T exhaustion. The safety and efficacy of
CTX130 is being evaluated in two independent clinical trials, one
for the treatment of relapsed or refractory T or B cell
malignancies and on for the treatment of relapsed or refractory
clear cell renal cell carcinoma. CTX131 is being investigated in a
clinical trial designed to assess the safety and efficacy of the
product candidate in adult patients with relapsed or refractory
solid tumors. 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).
About VCTX211VCTX211 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
TherapeuticsCRISPR 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
cardiometabolic 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® standard character mark and
design logo, CTX110®, CTX112™, CTX130™, CTX131™, CTX310™,
CTX320™, and VCTX211™ are trademarks and registered trademarks
of CRISPR Therapeutics AG. All other trademarks and registered
trademarks are the property of their respective owners.
CRISPR Therapeutics Forward-Looking
StatementThis 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, data,
expected timing of data releases, timing of regulatory submissions
and the regulatory filings for exa-cel; (ii) the potential benefits
of exa-cel for patients; (iii) plans to and the pre-clinical and
clinical data that are being presented during oral presentations at
the 2023 ASH Annual Meeting and Exposition and AHA Scientific
Sessions 2023; (iv) Mr. Mahatme’s election to the Board of
Directors and the expected benefits thereof; (v) the sufficiency of
its cash resources; (vi) the expected benefits of its
collaborations; and (vii) 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 efficacy and safety results from ongoing
clinical trials, including of exa-cel, will not continue or be
repeated in ongoing or planned clinical trials or may not support
regulatory submissions; the FDA or other regulatory authorities may
not approve exa-cel on a timely basis or at all; adequate pricing
or reimbursement may not be secured to support continued
development or commercialization of exa-cel following regulatory
approval; clinical trial results may not be favorable; one or more
of its product candidate programs will not proceed as planned for
technical, scientific or commercial reasons; future competitive or
other market factors may adversely affect the commercial potential
for its product candidates; initiation and completion of
preclinical studies for its product candidates is uncertain and
results from such studies may not be predictive of future results
of future studies or clinical trials; regulatory approvals to
conduct trials or to market products are uncertain; 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.
Investor Contact:Susan
Kim+1-617-307-7503susan.kim@crisprtx.com
Media Contact:Rachel
Eides+1-617-315-4493rachel.eides@crisprtx.com
CRISPR Therapeutics AG |
Condensed Consolidated Statements of
Operations |
(Unaudited, In thousands except share data and per share data) |
|
|
Three Months Ended September 30, |
|
|
Nine Months Ended September 30, |
|
|
2023 |
|
|
2022 |
|
|
2023 |
|
|
2022 |
|
Revenue: |
|
|
|
|
|
|
|
|
|
|
|
Collaboration revenue |
$ |
— |
|
|
$ |
94 |
|
|
$ |
170,000 |
|
|
$ |
430 |
|
Grant revenue |
|
— |
|
|
|
— |
|
|
|
— |
|
|
|
762 |
|
Total revenue |
$ |
— |
|
|
$ |
94 |
|
|
$ |
170,000 |
|
|
$ |
1,192 |
|
Operating expenses: |
|
|
|
|
|
|
|
|
|
|
|
Research and development |
|
90,698 |
|
|
|
116,622 |
|
|
|
292,188 |
|
|
|
358,090 |
|
General and administrative |
|
18,291 |
|
|
|
27,001 |
|
|
|
59,683 |
|
|
|
81,295 |
|
Collaboration expense, net |
|
23,422 |
|
|
|
38,859 |
|
|
|
110,250 |
|
|
|
103,427 |
|
Total operating expenses |
|
132,411 |
|
|
|
182,482 |
|
|
|
462,121 |
|
|
|
542,812 |
|
Loss from operations |
|
(132,411 |
) |
|
|
(182,388 |
) |
|
|
(292,121 |
) |
|
|
(541,620 |
) |
Total other income, net |
|
20,671 |
|
|
|
7,264 |
|
|
|
51,819 |
|
|
|
11,171 |
|
Net loss before income taxes |
|
(111,740 |
) |
|
|
(175,124 |
) |
|
|
(240,302 |
) |
|
|
(530,449 |
) |
(Provision) benefit for income taxes |
|
(412 |
) |
|
|
575 |
|
|
|
(2,655 |
) |
|
|
(9,151 |
) |
Net loss |
|
(112,152 |
) |
|
|
(174,549 |
) |
|
|
(242,957 |
) |
|
|
(539,600 |
) |
Foreign currency translation adjustment |
|
(49 |
) |
|
|
(100 |
) |
|
|
12 |
|
|
|
(195 |
) |
Unrealized gain (loss) on marketable securities |
|
2,160 |
|
|
|
(1,820 |
) |
|
|
8,838 |
|
|
|
(17,001 |
) |
Comprehensive loss |
$ |
(110,041 |
) |
|
$ |
(176,469 |
) |
|
$ |
(234,107 |
) |
|
$ |
(556,796 |
) |
Net loss per common share —
basic |
$ |
(1.41 |
) |
|
$ |
(2.24 |
) |
|
$ |
(3.07 |
) |
|
$ |
(6.96 |
) |
Basic weighted-average common
shares outstanding |
|
79,414,098 |
|
|
|
78,021,520 |
|
|
|
79,063,415 |
|
|
|
77,547,771 |
|
Net loss per common share —
diluted |
$ |
(1.41 |
) |
|
$ |
(2.24 |
) |
|
$ |
(3.07 |
) |
|
$ |
(6.96 |
) |
Diluted weighted-average common
shares outstanding |
|
79,414,098 |
|
|
|
78,021,520 |
|
|
|
79,063,415 |
|
|
|
77,547,771 |
|
CRISPR Therapeutics AG |
Condensed Consolidated Balance Sheets Data |
(Unaudited, in thousands) |
|
|
As of |
|
|
September 30, 2023 |
|
|
December 31, 2022 |
|
Cash and cash equivalents |
$ |
527,765 |
|
|
$ |
211,885 |
|
Marketable securities |
|
1,212,061 |
|
|
|
1,603,433 |
|
Marketable securities,
non-current |
|
— |
|
|
|
53,130 |
|
Working capital |
|
1,649,352 |
|
|
|
1,731,919 |
|
Total assets |
|
2,086,830 |
|
|
|
2,243,057 |
|
Total shareholders'
equity |
|
1,727,794 |
|
|
|
1,875,479 |
|
CRISPR Therapeutics (NASDAQ:CRSP)
Gráfica de Acción Histórica
De Abr 2024 a May 2024
CRISPR Therapeutics (NASDAQ:CRSP)
Gráfica de Acción Histórica
De May 2023 a May 2024