ANGPTL3

Preclinical and translational pipeline program data for AX-0810 for Cholestatic Diseases targeting NTCP and AX-1412 for Cardiovascular Disease targeting B4GALT1 anticipated in 2024, building further momentum toward the clinicAccelerated development of Axiomer™ for CNS applications via new research partnership with Rett Syndrome Research TrustCompleted divestment of sepofarsen and ultevursen ophthalmic programs to Laboratoires Théa€118.9 million cash and cash equivalents as of December 31, 2023 providing runway into mid-2026 LEIDEN, Netherlands & CAMBRIDGE, Mass., March 13, 2024 (GLOBE NEWSWIRE) -- ProQR Therapeutics NV. (Nasdaq: PRQR) (ProQR), a company dedicated to changing lives through transformative RNA therapies based on its proprietary Axiomer™ RNA editing technology platform, today reported its financial and operating results for the year ended December 31, 2023, and provided a business update. “Over the past year as we exclusively focused our strategy on RNA editing, ProQR made important progress with Axiomer, our ADAR-mediated RNA editing technology platform,” said Daniel A. de Boer, Chief Executive Officer of ProQR. “We announced our initial pipeline programs, AX-0810 and AX-1412, targeting NTCP and B4GALT1, respectively, and presented preclinical platform data across a variety of targets. Our platform has demonstrated robust editing, including reporting up to 70% editing of ACTB in the liver of non-human primates, as well as functional protein data with the liver target ANGPTL3 in mice. Additionally, we further strengthened our leading global IP estate for ADAR-mediated RNA editing, which was upheld when challenged by multiple parties in various jurisdictions. We continued to execute and build on the successes achieved during the first two years of our collaboration with Eli Lilly, and formed a new partnership with the Rett Syndrome Research Trust. We also completed the divestment of late-stage ophthalmic assets, sepofarsen and ultevursen, to Laboratoires Théa who will continue the development of these therapies for patients, as ProQR continues to focus exclusively on advancing our RNA editing platform and pipeline.” De Boer continued, “In 2024, we anticipate sharing in vitro, in vivo, and translational data for our initial pipeline programs using Axiomer, and remain on track to enter the clinic in late 2024/early 2025. Along with our extensive body of preclinical proof of concept data for the platform, partnership with Eli Lilly, leading IP position, and strong cash position providing runway into mid-2026, we believe that ProQR is well positioned to continue to execute on our strategy and advance our mission of changing lives through transformative RNA therapies.” Recent Progress In February, ProQR announced that it further strengthened its leading intellectual property estate for ADAR-mediated RNA editing by successfully defending against an opposition filed in Japan by a strawman against ProQR’s granted patent JP 7244922, which is related to the broad concept of using chemically modified oligonucleotides to target specific adenosines within target RNA using endogenous enzymes. The Japanese Patent Office rejected the strawman’s opposition and indicated that all claims were to be maintained as granted to ProQR.In January, ProQR highlighted its continued progress in advancing its Axiomer™ RNA editing technology platform, with new data presented at the 5th International Conference on Base Editing, Prime Editing & Related Enzymes (Deaminet 2024), including: Platform demonstrates robust in vivo editing capabilities reporting up to 70% editing of ACTB in the liver of non-human primates (NHPs) and mice; andFunctional effect demonstrated in mice in vivo via modulation of ANGPLT3 protein properties leading to favorable increase in LPL enzymatic activity and meaningful impact of biomarkers. In January, ProQR and the Rett Syndrome Research Trust (RSRT) formed a partnership focused on utilizing ProQR’s Axiomer™ RNA editing technology platform to design and develop editing oligonucleotides targeting an underlying genetic variant that causes Rett syndrome. RSRT awarded ProQR approximately $1 million as a research grant for the initial phase of the project, which encompasses editing oligonucleotide design and optimization, including evaluation in in vivo models for editing efficiency and MECP2 protein recovery. It is the intent of the partnership to be continued by an expanded co-funding arrangement following the initial discovery work.In December, ProQR completed the divestment of sepofarsen and ultevursen to Laboratoires Théa, who will continue the development of these programs for patients with LCA10 and Usher syndrome. The transaction agreement provided ProQR with an initial payment of €8 million and the Company may be eligible for up to €165 million in further development, regulatory, and commercial earn-out payments upon related achieved milestones, as well as double-digit royalties based on commercial sales in the US and EU. Anticipated Upcoming Events Additional Axiomer™ platform data updates throughout 2024.Preclinical and translational pipeline program data for AX-0810 for Cholestatic Diseases targeting NTCP and AX-1412 for Cardiovascular Disease targeting B4GALT1: In vitro and in vivo data for AX-0810 for Cholestatic Diseases targeting NTCP in mid 2024, and In vitro and in vivo data for AX-1412 for Cardiovascular Diseases targeting B4GALT1 in the second half of 2024. Continue to progress on key steps required to advance AX-0810 and AX-1412 to clinical trials with translational data updates ahead of entry to clinic, which is on track for late 2024/early 2025.Potential initial Trident preclinical data in late 2024 – Trident is ProQR’s early stage RNA editing pseudouridylation platform designed to enable the suppression of nonsense mutations and premature stop codons, which can edit a uridine (U) into a pseudouridine.Potential additional new pipeline target announcements in 2024.Continue to execute on partnership with Eli Lilly and Company (Lilly), with potential data updates to come in 2024 along with potential milestone income from existing partnership, and potential option to exercise for expansion of deal to 15 targets, which would result in a $50 million opt-in payment to ProQR.ProQR may selectively form new partnerships, which could include multi-target discovery alliances, or product alliances on specific programs. Year End 2023 Financial Highlights At December 31, 2023, ProQR held cash and cash equivalents of €118.9 million, compared to €94.8 million at December 31, 2022. Net cash generated by operating activities during the full year ended December 31, 2023 was €21.5 million, compared to €68.5 million net cash used in operating activities for the same period in 2022. The Company experienced a net positive cash flow from operating activities in 2023 primarily due to the receipt of the Lilly up-front payment of $60 million in February 2023. Research and development costs for the year ended December 31, 2023 were €25.1 million, compared to €50.9 million for the same period in 2022. Research and development costs for the year end December 31, 2022 included costs related to the winding down of ophthalmology programs, including the clinical trials. General and administrative costs for the year ended December 31, 2023 were €16.2 million, compared to €18.7 million for the same period in 2022. Net loss for the year ended December 31, 2023 was €27.7 million or €0.35 per diluted share, compared to €64.2 million, or €0.90 per diluted share for the same period ended December 31, 2022. For further financial information for the period ended December 31, 2023, please refer to our 2023 Annual Report on Form 20-F and our Statutory Annual Report which will be available on our website, www. proqr.com under Financials and Filings. About Axiomer™ ProQR is pioneering a next-generation RNA base editing technology called Axiomer™, which could potentially yield a new class of medicines for diverse types of diseases. Axiomer™ “Editing Oligonucleotides”, or EONs, mediate single nucleotide changes to RNA in a highly specific and targeted way using molecular machinery that is present in human cells called ADAR (Adenosine Deaminase Acting on RNA). Axiomer™ EONs are designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in the RNA – an Inosine is translated as a Guanosine (G) – correcting an RNA with a disease-causing mutation back to a normal (wild type) RNA, modulating protein expression, or altering a protein so that it will have a new function that helps prevent or treat disease. About Biliary Atresia (BA) and Primary Sclerosing Cholangitis (PSC) Cholestatic disorders refer to a group of diseases presenting excessive and toxic buildup of bile acids in the liver due to bile ducts dysfunction. This leads to liver damage and a range of debilitating symptoms. Without treatment, liver damage can progress through various stages, ultimately leading to liver failure and elevated risk of liver malignancy, affecting life expectancy. Cholestatic diseases remain leading causes of liver transplantation. There are no approved therapies for primary sclerosing cholangitis (PSC) for adults and biliary atresia (BA) for pediatrics It is estimated that 80,000 and 20,000 individuals have PSC and BA, respectively, in North America and in Europe. About AX-0810 targeting NTCP The majority of the bile acids present in the liver cells originate from the enterohepatic reuptake cycle. The key transporter responsible for hepatic uptake of bile acids from portal circulation is the sodium (Na+)-taurocholate cotransporting polypeptide (NTCP, SLC10A1 gene) expressed in the liver. AX-0810 is designed to introduce a loss of function variant in SLC10A1 RNA that has been found in human genetics to prevent re-uptake of bile acids in liver via NTCP. Based on its mechanism of action, AX-0810 has the potential to become a disease modifying treatment for PSC and BA primarily among other cholestatic diseases. About Cardiovascular Diseases Cardiovascular diseases (CVDs) are a group of health conditions that affect the heart and blood vessels, such as atherosclerosis which can lead to severe problems like heart attacks, heart failure, and stroke. CVDs represent the leading cause of disability and death in the world. Approximately 18 million people die every year from CVDs representing one third of all the global deaths. Despite available lipid lowering therapies and hypertension medications, the risk of CVDs is still projected to increase rapidly over the coming years. About AX-1412 targeting B4GALT1 Gene–based analysis of rare beta-1,4-galactosyltransferase 1 (B4GALT1) missense variant (p.Asn352Ser) is known to lead to B4GALT1 protein loss of function and showed an association with decreased coronary artery disease. These beneficial effects are mediated by hypo-galactosylation of the apolipoprotein B100 and fibrinogen, known – independent – drivers of increased risk of CVDs. AX-1412 introduces a protective variant into B4GALT1 RNA to address the remaining residual risk of developing cardiovascular diseases. ProQR intends to advance AX-1412 targeting B4GALT1 to early clinical proof of concept stage, then would seek to partner this program. About ProQR ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA therapies. ProQR is pioneering a next-generation RNA technology called Axiomer™, which uses a cell’s own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse a mutation or modulate protein expression and could potentially yield a new class of medicines for both rare and prevalent diseases with unmet need. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind. Learn more about ProQR at www.proqr.com. Forward Looking Statements This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “continue,” "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Such forward-looking statements include, but are not limited to, statements regarding our business, preclinical model data, our initial pipeline targets and the upcoming strategic priorities and milestones related thereto, our Axiomer™ platform, including the continued development and advancement of our Axiomer platform, the therapeutic potential of our Axiomer RNA editing oligonucleotides and our ability to expand preclinical in vivo and in vitro data, the timing, progress and results of our preclinical studies and other development activities, including the release of data related thereto, our patent estate, including our anticipated strength and our continued investment in it, as well as the timing of our clinical development, the potential of our technologies and product candidates, the collaboration with Lilly and the intended benefits thereof, and our financial position and cash-runway. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors in our filings made with the Securities and Exchange Commission, including certain sections of our annual report filed on Form 20-F. These risks and uncertainties include, among others, the cost, timing and results of preclinical studies and clinical trials and other development activities by us and our collaborative partners whose operations and activities may be slowed or halted shortage and pressure on supply and logistics on the global market; the likelihood of our preclinical and clinical programs being initiated and executed on timelines provided and reliance on our contract research organizations and predictability of timely enrollment of subjects and patients to advance our clinical trials and maintain their own operations; our reliance on contract manufacturers to supply materials for research and development and the risk of supply interruption from a contract manufacturer; the potential for future data to alter initial and preliminary results of early-stage clinical trials; the unpredictability of the duration and results of the regulatory review of applications or clearances that are necessary to initiate and continue to advance and progress our clinical programs; the ability to secure, maintain and realize the intended benefits of collaborations with partners, including the collaboration with Lilly; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated in research and development; general business, operational, financial and accounting risks, and risks related to litigation and disputes with third parties; and risks related to macroeconomic conditions and market volatility resulting from global economic developments, geopolitical instability and conflicts. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future, except as required by law. ProQR Therapeutics N.V. Investor contact:Sarah KielyProQR Therapeutics N.V.T: +1 617 599 6228skiely@proqr.comorPeter KelleherLifeSci AdvisorsT: +1 617 430 7579 pkelleher@lifesciadvisors.com Media contact:Robert StanislaroFTI ConsultingT: +1 212 850 5657robert.stanislaro@fticonsulting.com

— CASGEVY™ approved in the U.S., European Union, Great Britain, the Kingdom of Saudi Arabia and Bahrain — — Clinical trials ongoing for next generation CAR T product candidates, CTX112™ and CTX131™ targeting CD19 and CD70, respectively — — Clinical trials ongoing for in vivo gene editing product candidates, CTX310™ and CTX320™ targeting ANGPTL3 and Lp(a), respectively — — Clinical trial ongoing for CTX211™, an allogeneic, hypoimmune, gene-edited, stem cell derived product candidate for the treatment of Type 1 Diabetes (T1D) — — Strengthened balance sheet with $280 million registered direct offering, bringing current cash position to >$2.1 billion — ZUG, Switzerland and BOSTON, Feb. 21, 2024 (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, 2023. “2023 was a monumental year for CRISPR Therapeutics, with multiple milestones achieved across our pipeline, including the first-ever approval of a CRISPR-based gene-editing therapy in addition to entering the clinic with our first in vivo programs targeting cardiovascular diseases,” said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics. “We continue to advance our next generation CAR T cell programs, CTX112 and CTX131, which have the potential to be best-in-class cell therapies for the treatment of both liquid and solid tumors. Additionally, we plan to initiate a clinical trial of CTX112 in systemic lupus erythematosus (SLE) in the first half of 2024, with the potential to expand into additional autoimmune indications in the future. We are excited about our first two in vivo programs that are now in the clinic, and also expect to nominate additional in vivo programs targeting both rare and common diseases mid-year. I am incredibly excited about the year ahead as we continue to innovate across our platform and execute on our clinical trials across various therapeutic areas, including oncology, autoimmune, cardiovascular and diabetes, setting up a catalyst-rich 12-18 months for the company.” Recent Highlights and Outlook Hemoglobinopathies and CASGEVY™ (exagamglogene autotemcel [exa-cel]) CASGEVY has been approved in the U.S., E.U., Great Britain, Bahrain, and the Kingdom of Saudi Arabia (KSA) for the treatment of patients with either sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). Nearly 35,000 patients are living with severe SCD or TDT in the U.S. and Europe alone. CASGEVY is the first therapy to emerge from a strategic partnership between CRISPR Therapeutics and Vertex Pharmaceuticals established in 2015. As part of an amendment to the collaboration agreement in 2021, Vertex now leads global development, manufacturing, regulatory and commercialization of CASGEVY with support from CRISPR Therapeutics.The regulatory submission for CASGEVY for both SCD and TDT is currently under review in Switzerland, with submission in Canada planned for the first half of 2024.Vertex reported progress on CASGEVY launch in the U.S. with the activation of 12 authorized treatment centers (ATCs) in the U.S. and the signing of an agreement with Synergie Medication Collective, a contracting organization which supports payors covering approximately 100 million people in the U.S., to provide access to CASGEVY. Additionally, Vertex is actively engaging with state Medicaid organizations to secure immediate reimbursement and coverage for CASGEVY.Outside the U.S., Vertex reported progress on the launch with the activation of three authorized treatment centers in the E.U. and one in KSA. Additionally, the French National Authority for Health (HAS) approved a request for the implementation of an early access program (EAP) for the use of CASGEVY to treat eligible people with TDT. Vertex is also pursuing an EAP submission for SCD in France and expects to hear the outcome of this decision in the coming months.CRISPR Therapeutics has two next-generation approaches that each have the potential to expand the addressable population with SCD and TDT significantly. CRISPR Therapeutics continues to advance its internally developed targeted conditioning program, an anti-CD117 (c-Kit) antibody-drug conjugate (ADC), through preclinical studies. Additionally, CRISPR Therapeutics 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 (SLE) 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 by deeply depleting B cells. The Company’s first generation allogeneic CD19-directed CAR T program has demonstrated that allogeneic CAR T cells can effectively deplete B cells in clinical trials in oncology settings, which supports the potential of CTX112 in autoimmune diseases.CRISPR Therapeutics is on track to initiate a Phase 1 trial of CTX131 in hematologic malignancies, including T- and B-cell malignancies, in the first half of 2024. CTX131 is currently in an ongoing clinical trial in solid tumors. In Vivo CRISPR Therapeutics continues to advance a pipeline of in vivo gene editing programs using lipid nanoparticle (LNP) delivery of Cas9 mRNA and a guide RNA (gRNA) 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 (ANGPTL3). In humans, naturally occurring loss-of-function variants of the ANGPTL3 gene are associated with reduced levels of serum lipids and reduced risk of atherosclerotic cardiovascular disease. The Phase 1 trial is open to patients with mixed dyslipidemias, homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia, and severe hypertriglyceridemia.A Phase 1 clinical trial is ongoing for CTX320, targeting lipoprotein(a) (Lp(a)). 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 continues to advance a Phase 1 clinical trial for CTX211™ for the treatment of Type 1 Diabetes (T1D). CRISPR Therapeutics remains committed to its goal of developing a beta-cell replacement product that does not require chronic immunosuppression.Vertex has 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. Other Corporate Matters In February 2024, CRISPR Therapeutics announced that it has entered into an investment agreement for the sale of approximately $280 million of its common shares to a select group of institutional investors in a registered direct offering, at a price per share of $71.50, representing a premium of greater than 10% to CRISPR Therapeutics’ 30-day volume-weighted average price. The financing is expected to close on or about February 27, 2024, subject to customary closing conditions. Fourth Quarter and Full Year 2023 Financial Results Cash Position: Cash, cash equivalents, and marketable securities were $1,695.7 million as of December 31, 2023, compared to $1,868.4 million as of December 31, 2022. The decrease in cash of $172.7 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. Pro-forma cash, cash equivalents, and marketable securities were greater than $2.1 billion as of February 21, 2024, inclusive of a $200 million milestone received in January 2024 for the approval of CASGEVY and approximately $280 million in proceeds from the February 2024 registered direct offering.R&D Expenses: R&D expenses were $95.1 million for the fourth quarter of 2023, compared to $103.6 million for the fourth 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 $16.5 million for the fourth quarter of 2023, compared to $21.2 million for the fourth 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 $20.0 million for the fourth quarter of 2023, compared to $6.8 million for the fourth quarter of 2022. The increase of approximately $13.2 million in collaboration expense, net, was primarily driven by an additional $20 million licensing fee owed to Vertex in connection with the Amended and Restated Joint Development and Collaboration Agreement, offset by the fact that we reached the $110.3 million deferral limit on costs related to the CASGEVY program in the third quarter of 2023, whereas the limit was not reached until the fourth quarter of 2022.Net Income (Loss): Net income was $89.3 million for the fourth quarter of 2023, compared to a net loss of $110.6 million for the fourth quarter of 2022. 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 through a precise double-strand break. 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 VOCs for patients with SCD and transfusion requirements for patients with TDT. CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients. About the CRISPR Collaboration and VertexCRISPR 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. CASGEVY (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 CASGEVY and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics. Vertex is the manufacturer and exclusive license holder of CASGEVY™. About CTX112 CTX112 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting Cluster of Differentiation 19, or CD19, which incorporates additional edits designed to enhance CAR T potency and reduce CAR T exhaustion. CTX112 is being investigated in an ongoing clinical trial designed to assess safety and efficacy of the product candidate in adult patients with relapsed or refractory CD19-positive B-cell malignancies who have received at least two prior lines of therapy. About CTX131 CTX131 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting Cluster of Differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX131 incorporates additional edits designed to enhance CAR T potency and reduce CAR T exhaustion. 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. About in vivoOur lead investigational in vivo programs, CTX310 and CTX320, target angiopoietin-related protein 3 (ANGPTL3) and lipoprotein(a) (Lp(a)), respectively, two validated targets for cardiovascular disease, and we have initiated a Phase 1 clinical trial for both. About CTX211 CTX211 is an allogeneic, gene-edited, stem cell-derived investigational therapy for the treatment of T1D, which incorporates gene edits that aim to make cells hypoimmune and 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 TherapeuticsSince its inception over a decade ago, CRISPR Therapeutics has transformed from a research-stage company advancing programs in the field of gene editing, to a company with a diverse portfolio of product candidates across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine, cardiovascular and rare diseases. The Nobel Prize-winning CRISPR science has revolutionized biomedical research and represents a powerful, clinically validated approach with the potential to create a new class of potentially transformative medicines. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer and Vertex Pharmaceuticals. 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. To learn more, visit www.crisprtx.com. CRISPR THERAPEUTICS® standard character mark and design logo, CTX112™, CTX131™, CTX310™, CTX320™, CTX211™ and VCTX211™ are trademarks and registered trademarks of CRISPR Therapeutics AG. The CASGEVY™ word mark and design are trademarks of Vertex Pharmaceuticals Incorporated. 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 plans for and its preclinical studies, clinical trials and pipeline products and programs, including, without limitation, manufacturing capabilities, status of such studies and trials, potential expansion into new indications and expectations regarding data generally; (ii) 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; (iii) plans and expectations for the commercialization of, and anticipated benefits of, CASGEVY, including the anticipated patient populations eligible for CASGEVY in jurisdictions where it has been or may be approved; (iv) the sufficiency of its cash resources; (v) the expected benefits of its collaborations; and (vi) 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 will not continue or be repeated in ongoing or planned clinical trials or may not support regulatory submissions; 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; uncertainties inherent in the operation of a manufacturing facility; 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 AGCondensed Consolidated Statements of Operations(Unaudited, In thousands except share data and per share data) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 Revenue: Collaboration revenue $200,000 $6 $370,000 $436 Grant revenue 1,206 — 1,206 762 Total revenue 201,206 $6 $371,206 $1,198 Operating expenses: Research and development 95,144 103,555 387,332 461,645 General and administrative 16,479 21,169 76,162 102,464 Collaboration expense, net 20,000 6,823 130,250 110,250 Total operating expenses 131,623 131,547 593,744 674,359 Income (loss) from operations 69,583 (131,541) (222,538) (673,161)Total other income, net 19,997 11,490 71,816 22,661 Net income (loss) before income taxes 89,580 (120,051) (150,722) (650,500)(Provision) benefit for income taxes (233) 9,476 (2,888) 325 Net income (loss) 89,347 (110,575) (153,610) (650,175)Foreign currency translation adjustment 61 115 73 (80)Unrealized gain (loss) on marketable securities 8,649 6,501 17,487 (10,500)Comprehensive income (loss) $98,057 $(103,959) $(136,050) $(660,755)Net income (loss) per common share — basic $1.12 $(1.41) $(1.94) $(8.36)Basic weighted-average common shares outstanding 79,688,337 78,336,506 79,220,930 77,746,575 Net income (loss) per common share — diluted $1.10 $(1.41) $(1.94) $(8.36)Diluted weighted-average common shares outstanding 81,324,786 78,336,506 79,220,930 77,746,575 CRISPR Therapeutics AGCondensed Consolidated Balance Sheets Data(Unaudited, in thousands) As of December 31, 2023 December 31, 2022 Cash and cash equivalents $389,477 $211,885 Marketable securities 1,304,215 1,603,433 Marketable securities, non-current 1,973 53,130 Working capital 1,799,287 1,731,919 Total assets 2,229,571 2,243,057 Total shareholders' equity 1,882,803 1,875,479

Platform demonstrates robust in vivo editing capabilities reporting up to 70% editing of ACTB in the liver of non-human primates (NHPs) and miceFunctional effect demonstrated in mice in vivo via modulation of ANGPLT3 protein properties leading to favorable increase in LPL enzymatic activity and meaningful impact of biomarkersAdditional data to be presented throughout 2024, including in vitro and in vivo data for pipeline programs AX-0810 for Cholestatic diseases targeting NTCP and AX-1412 for Cardiovascular diseases targeting B4GALT1 LEIDEN, Netherlands & CAMBRIDGE, Mass., Jan. 19, 2024 (GLOBE NEWSWIRE) -- ProQR Therapeutics NV (Nasdaq: PRQR) (ProQR), a company dedicated to changing lives through transformative RNA therapies based on its proprietary Axiomer™ RNA editing technology platform, today highlighted key updates from its oral presentation at the 5th International Conference on Base Editing, Prime Editing & Related Enzymes (Deaminet 2024) in San Diego, California. “We were pleased to present new in vivo data for our proprietary Axiomer RNA editing technology platform at the Deaminet 2024 meeting, demonstrating robust editing of ACTB in the liver of NHP, as well as functional protein data with the liver target ANGPTL3 in mice,” said Gerard Platenburg, Chief Scientific Officer of ProQR. “To date, we have generated robust in vitro and in vivo preclinical platform data across a range of liver and CNS targets. These encouraging data and the progress of our science reinforce the potential of our Axiomer RNA editing oligonucleotides, and we look forward to presenting additional platform data, as well as the first preclinical data for our pipeline programs at upcoming scientific meetings, as we move our technology forward towards trials in humans.” Key updates from the presentation included: Axiomer Editing Oligonucleotides (EONs) demonstrated high intrinsic editing capability in the liver across models. Presentation of new data highlighting up to 70% editing efficiency of ACTB in liver of mice and NHPs at multiple timepoints.Editing levels confirmed through several reliable RNA analysis methods, including dPCR and RNAseq, showing consistent results.An EON editing ANGPTL3 in mice resulted in a 2-fold increase in lipoprotein lipase activity and a related decrease of LDL cholesterol in plasma of 40% in vivo.Preliminary nonclinical safety assessment showed a similar safety profile compared to other single-stranded RNA oligonucleotides.Ongoing platform advancements anticipated through increased knowledge of ADAR biology, selection of models for prediction of Axiomer potential in human tissue, EON sequence optimization, and investigation of delivery options. These new preclinical platform data further highlight the potential of Axiomer EONs in preparation for clinical development and supporting discovery of potential new therapeutic applications. The presentation “Axiomer™, an RNA editing technology to address liver-originated disorders and beyond” is available via ProQR’s website in the Presentations and Publications section. About Axiomer™ ProQR is pioneering a next-generation RNA base editing technology called Axiomer™, which could potentially yield a new class of medicines for diverse types of diseases. Axiomer “Editing Oligonucleotides”, or EONs, mediate single nucleotide changes to RNA in a highly specific and targeted way using molecular machinery that is present in human cells called ADAR (Adenosine Deaminase Acting on RNA). Axiomer EONs are designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in the RNA – an Inosine is translated as a Guanosine (G) – correcting an RNA with a disease-causing mutation back to a normal (wild type) RNA, modulating protein expression, or altering a protein so that it will have a new function that helps prevent or treat disease. About ProQR ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA therapies. ProQR is pioneering a next-generation RNA technology called Axiomer™, which uses a cell’s own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse a mutation or modulate protein expression and could potentially yield a new class of medicines for both rare and prevalent diseases with unmet need. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind. Learn more about ProQR at www.proqr.com. Forward Looking Statements for ProQR This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “continue,” "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Such forward-looking statements include, but are not limited to, statements regarding our Axiomer™ technology, including the continued development and advancement of our Axiomer platform, the therapeutic potential of our Axiomer RNA editing oligonucleotides and our ability to expand preclinical in vivo and in vitro data, the timing, progress and results of our preclinical studies and other development activities, including the release of data related thereto, and the potential of our technologies and product candidates . Forward-looking statements are based on management’s beliefs and assumptions and on information available to management only as of the date of this press release. Our actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors in our filings made with the Securities and Exchange Commission, including certain sections of our most recent annual report filed on Form 20-F. These risks and uncertainties include, among others, the cost, timing and results of preclinical studies and clinical trials and other development activities by us and our collaborative partners whose operations and activities may be slowed or halted shortage and pressure on supply and logistics on the global market; the likelihood of our preclinical and clinical programs being initiated and executed on timelines provided and reliance on our contract research organizations and predictability of timely enrollment of subjects and patients to advance our clinical trials and maintain their own operations; our reliance on contract manufacturers or suppliers to supply materials for research and development and the risk of supply interruption or delays from suppliers or contract manufacturers; the potential for future data to alter initial and preliminary results of early-stage clinical trials; the unpredictability of the duration and results of the regulatory review of applications or clearances that are necessary to initiate and continue to advance and progress our clinical programs; the ability to secure, maintain and realize the intended benefits of collaborations with partners, including the collaboration with Eli Lilly and Company; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated in research and development; general business, operational, financial and accounting risks, and risks related to litigation and disputes with third parties; and risks related to macroeconomic conditions and market volatility resulting from global economic developments, geopolitical instability and conflicts. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future, except as required by law. ProQR Therapeutics N.V. Investor contact:Sarah KielyProQR Therapeutics N.V.T: +1 617 599 6228skiely@proqr.comorPeter KelleherLifeSci AdvisorsT: +1 617 430 7579 pkelleher@lifesciadvisors.com Media contact:Robert StanislaroFTI ConsultingT: +1 212 850 5657robert.stanislaro@fticonsulting.com