Leber Congenital Amaurosis

- Preliminary LUNA data presented at the Annual Meeting of the Macula Society support potential best-in-class clinical activity and an encouraging safety profile in patients with wet AMD - - Completed $127.5 million private placement financing with new and existing institutional investors - - Cash runway expected into late 2025 – - 1-for-10 reverse stock split to be effective March 21, 2024 - REDWOOD CITY, Calif., March 18, 2024 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company pioneering the use of gene therapy as a new standard of care for highly prevalent ocular diseases, today reported financial results for the fourth quarter and full year 2023. The company also provided recent pipeline highlights and corporate updates. “We have made tremendous progress during 2023 and in 2024 to date in our development of Ixo-vec as a durable potential gene therapy treatment for the millions of patients suffering from wet AMD,” stated Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “We were pleased to present at Macula Society preliminary data from our ongoing LUNA Phase 2 trial of Ixo-vec, which demonstrated potentially best-in-class clinical activity at both the 2E11 and 6E10 doses of Ixo-vec, with the data trending similar to, or better than, the data in our first-in-human OPTIC trial. Importantly, the preliminary data demonstrated that Ixo-vec was generally well tolerated. We look forward to presenting the 26-week interim analysis of our LUNA Phase 2 program in mid-2024.” Dr. Fischer continued, “In the lead-up to the data presentation at Macula Society, Adverum completed a $127.5 million private placement financing with new and existing investors that we expect to meaningfully extend our cash runway into late 2025, well beyond the anticipated presentation of topline 52-week data from our ongoing LUNA Phase 2 trial. In parallel, we are continuing to interact with regulators in the U.S. and E.U. to inform Phase 3 development of Ixo-vec, which we plan to initiate in the first half of 2025.” Ixo-Vec Program Highlights: Preliminary Ixo-vec LUNA Trial Data at Macula Society 2024: In February 2024, we announced positive preliminary efficacy and safety data from the ongoing LUNA Phase 2 trial of Ixo-vec in patients with wet AMD at the 47th Annual Meeting of the Macula Society in Palm Springs, California.LUNA patients treated with either the 2E11 or 6E10 dose of Ixo-vec experienced potentially best-in-class reduction in annualized anti-vascular endothelial growth factor (VEGF) injections and the percentage of patients receiving no supplemental injections through 26 weeks. Patients at the 2E11 and 6E10 doses had mean 90% and 94% reductions, respectively, in annualized anti-VEGF injections.85% and 68% of patients at the 2E11 and 6E10 doses, respectively, received no supplemental injections through 26 weeks. Maintained or improved mean BCVA and mean CST at both dose levels.Ixo-vec continued to be generally well tolerated, with cases of intraocular inflammation responsive to local corticosteroids.No Ixo-vec related serious adverse events, episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion or hypotony were reported. Long-Term Ixo-vec OPTIC Trial Data at AAO 2023: In November 2023, the company announced 3-year data from the OPTIC extension study of patients with wet AMD during the Retina Subspecialty Day at the American Academy of Ophthalmology (AAO) 2023 Annual Meeting in San Francisco, California.Patients in the OPTIC extension trial continue to experience long-term benefit from Ixo-vec through 3 years of follow-up, including maintenance of vision, durability of anatomic improvements and sustained reduction in anti-VEGF treatment burden. Patients at the 2E11 dose had an 84% reduction in annualized anti-VEGF injections, with 53% of the participants at the 2E11 dose receiving zero supplemental injections through three years.Aflibercept protein levels have been sustained through follow-up, which is up to 4.5 years post-treatment.BCVA was maintained and CST was improved through 3 years. Ixo-vec was generally well tolerated, with the most common adverse event being dose-dependent inflammation that was responsive to topical corticosteroids. Corporate Updates: Approval of 1-for-10 reverse stock split: On March 8, the Board of Directors approved a 1-for-10 reverse stock split of the Company’s common stock. The Company's common stock will begin trading on a reverse stock split-adjusted basis on March 21, 2024. Following the reverse stock split, there will be approximately 20.8 million shares of the company’s common stock outstanding.$127.5 Million Private Placement Financing: In February 2024, the Company completed a private placement of 106.25 million shares of common stock (or pre-funded warrants in lieu thereof) to a select group of institutional and accredited healthcare specialist investors at a price of $1.20 per share, representing a premium of approximately 20% to Adverum’s 30-day volume-weighted average price. The financing was led by TCGX with participation from new and existing investors including 5AM Ventures, Commodore Capital, Frazier Life Sciences, Logos Capital, Samsara BioCapital, Venrock Healthcare Capital Partners and Vivo Capital, as well as two large investment management firms. The financing is expected to extend Adverum’s cash runway into late 2025.Appointment of Romuald Corbau, Ph.D. as Chief Scientific Officer: In January 2024, the company announced the appointment of Romuald “Romu” Corbau, Ph.D. as Chief Scientific Officer. Dr. Corbau brings over 25 years of experience in drug development, including leading Spark Therapeutics’ translational R&D for Luxturna®, a subretinal injection gene therapy product for Leber’s congenital amaurosis, an inherited vision loss disease that routinely results in blindness Anticipated Milestones 2024: Continued FDA and EMA formal and informal regulatory interactionsMid-2024: LUNA 26-week interim analysisH1 2025: Initiation of Phase 3 trial Financial Results for the Three Months Ended December 31, 2023 Cash, cash equivalents and short-term investments were $96.5 million as of December 31, 2023, compared to $117.1 million as of September 30, 2023, and $185.6 million as of December 31, 2022. Including proceeds from the February 2024 private placement financing, pro forma cash, cash equivalents and short-term investments was $223.8 million. Adverum expects its cash, cash equivalents and short-term investments to fund operations into late 2025.Research and development expenses were $15.3 million for the three months ended December 31, 2023, compared to $22.2 million for the same period in 2022. Research and development expenses decreased due to lower clinical trial related expense, lower material production and bioanalytics, lower stock-based compensation expense, lower license fees, and lower outside research and development services. Stock-based compensation expense included in research and development expenses was $1.0 million for the fourth quarter of 2023.General and administrative expenses were $10.9 million for the three months ended December 31, 2023, compared to $11.7 million for the same period in 2022. General and administrative expenses decreased due to lower facilities expense due to fewer premises leased in the current period and higher sublease income and lower depreciation expense. Stock-based compensation expense included in general and administrative expenses was $3.1 million for the fourth quarter of 2023.Net Loss was $23.7 million, or $0.23 per basic and diluted share, for the three months ended December 31, 2023, compared to $32.7 million, or $0.33 per basic and diluted share for the same period in 2022. About Wet Age-Related Macular DegenerationWet AMD, also known as neovascular AMD or nAMD, is a VEGF driven advanced form of AMD affecting approximately 10% of patients living with AMD associated with the build-up of fluid in the macula and the retina. Wet AMD is a leading cause of blindness in people over 65 years of age, with approximately 20 million individuals worldwide living with this condition. New cases of wet AMD are expected to grow significantly worldwide as populations age. AMD is expected to impact 288 million people worldwide by 2040, with wet AMD accounting for approximately 10% of those cases. Additionally, wet AMD is a bilateral disease, and incidence of nAMD in the second eye is up to 42% in the first two to three years. The current standard of care requires frequent life-long repeated bolus injections of anti-VEGF in the eye. IVT gene therapy has the promise to preserve vision and reduce most or all injections for the life of the patient by delivering stable therapeutic levels of anti-VEGF to control macular fluid. About Ixo-vec in Wet AMDAdverum is developing ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), its clinical-stage gene therapy product candidate, for the treatment of wet AMD. Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach), Ixo-vec is designed to be administered as a one-time IVT injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for Ixo-vec for the treatment of wet AMD. Ixo-vec has also received PRIME designation from the European Medicines Agency and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD. About Adverum BiotechnologiesAdverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases with the aspiration of developing functional cures to restore vision and prevent blindness. Leveraging the capabilities of its proprietary intravitreal (IVT) platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians’ offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. Additionally, by overcoming the challenges associated with current treatment paradigms for debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit www.adverum.com. Forward-looking StatementsStatements contained in this press release regarding events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements regarding the potential benefits of Ixo-vec as a one-time IVT injection for the treatment of wet AMD, including its potential to improve vision outcomes, the potential best-in-class clinical activity of Ixo-vec, and anticipated timing of preliminary and interim data from the Phase 2 LUNA trial and initiation of a Phase 3 trial, and statements associated with the Company’s cash sufficiency and runway, and other statements containing the words “anticipates,” “believes,” “expects,” “intends,” “plans,” “target,” “will” and similar expressions. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including risks inherent to, without limitation: risks associated with market conditions. Additional risks and uncertainties facing Adverum are set forth under the caption “Risk Factors” and elsewhere in Adverum’s Securities and Exchange Commission (SEC) filings and reports, including Adverum’s most recent Annual Report on Form 10-K filed with the SEC, as updated by any subsequent reports on Form 10-Q. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Corporate, Investor and Media InquiriesAdverum Biotechnologies, Inc.E: ir@adverum.com Adverum Biotechnologies, Inc.Selected Consolidated Balance Sheet Data(In thousands) December 31, December 31, 2023 2022 Cash and cash equivalents, and marketable securities$96,5261 $185,589Total assets 173,010 308,372Total current liabilities 24,914 32,246Total liabilities 89,541 126,854Total stockholders' equity 83,469 181,518 (1) Cash, cash equivalents, and marketable securities exclude approximately $127.8 million in net proceeds from Adverum's February 2024 private placement Adverum Biotechnologies, Inc.Consolidated Statements of Operations(In thousands except per share data) Three months ended December 31, Years ended December 31, 2023 2022 2023 2022 (Unaudited) (1) License revenue$— $— $3,600 $— Operating expenses: Research and development 15,278 22,199 77,676 99,277 General and administrative 10,880 11,741 49,915 57,858 Total operating expenses 26,158 33,940 127,591 157,135 Operating loss (26,158) (33,940) (123,991) (157,135)Other income, net 1,311 1,223 5,748 2,673 Net loss before income taxes (24,847) (32,717) (118,243) (154,462)Income tax benefit (provision) 1,133 (19) 1,078 (74)Net loss (23,714) (32,736) (117,165) (154,536)Net loss per share — basic and diluted$(0.23) $(0.33) $(1.16) $(1.56)Weighted-average common shares outstanding - basic and diluted 101,213 99,915 100,824 99,251 (1) Derived from Adverum's annual audited consolidated financial statements.

Subretinal injection of ATSN-201 was well tolerated in all patients in first cohort with no serious adverse events reported Enrollment is ongoing in first clinical trial utilizing AAV.SPR, the company’s novel spreading capsid March 13, 2024 -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced dosing has been initiated in the second cohort of the LIGHTHOUSE study, a Phase I/II clinical trial evaluating subretinal injection of ATSN-201 for the treatment of X-linked retinoschisis (XLRS). ATSN-201, a best-in-class gene therapy product candidate, leverages AAV.SPR, the company’s novel spreading capsid, to achieve therapeutic levels of gene expression in photoreceptors of the central retina while avoiding the surgical risks of foveal detachment. ATSN-201 was well tolerated in all three XLRS patients in the first cohort and no serious adverse events were reported. The Data and Safety Monitoring Board recommended proceeding with the second cohort, in which patients will receive the next dose level of ATSN-201. "We are encouraged by the excellent safety observed with the low dose of ATSN-201 in the LIGHTHOUSE study, which represents the first clinical utilization of AAV.SPR. Additionally, initial indications of structural and functional improvement observed within and beyond the injection areas suggest successful lateral spread of the vector,” said Kenji Fujita, MD, Chief Medical Officer of Atsena Therapeutics. “Advancing into the second cohort brings us one step closer to potentially bringing a much-needed one-time treatment to patients with XLRS, an inherited retinal disease that causes progressive vision loss and can lead to blindness.” The LIGHTHOUSE study is a Phase I/II, open-label, dose-escalation and dose-expansion clinical trial evaluating the safety and tolerability of ATSN-201 in male patients ages 6 and older with a clinical diagnosis of XLRS caused by pathogenic or likely pathogenic mutations in RS1. Enrollment in the LIGHTHOUSE study is ongoing. For more information, visit ClinicalTrials.gov (Identifier: NCT05878860). XLRS is a monogenic X-linked disease caused by mutations in the RS1 gene which encodes retinoschisin, a protein secreted primarily by photoreceptors. RS1 is localized to the extracellular surface of rods, cones, and bipolar cells. XLRS is characterized by schisis, or abnormal splitting of retinal layers, which causes impaired visual acuity that is not correctable with glasses and leads to progressive vision loss and ultimately blindness. XLRS primarily affects males and is typically diagnosed in early childhood. Approximately 30,000 males in the U.S. and EU have XLRS, for which there are currently no approved treatments. AAV.SPR, one of Atsena’s novel capsids, spreads laterally beyond the subretinal injection site to enable safe and efficient transduction of the central retina (where schisis cavities predominate in XLRS patient retinas) when injected into areas outside the macula. A preclinical study in non-human primates demonstrated that AAV.SPR promotes transgene expression well beyond subretinal injection bleb margins. This is in stark contrast to benchmark AAV vectors, which remain confined to the original bleb margins. At clinically relevant doses, AAV.SPR efficiently transduces foveal cones without the need for surgical detachment and does not cause inflammation. For more information about the preclinical study and how AAV.SPR works, visit https://atsenatx.com/our-approach/laterally-spreading-aav/. Atsena Therapeutics is a clinical-stage gene therapy company developing best-in-class treatments for the reversal or prevention of blindness from inherited retinal diseases. The company’s lead program is evaluating ATSN-201 in an ongoing Phase I/II clinical trial for X-linked retinoschisis (XLRS), a progressive genetic condition affecting boys and men that is typically diagnosed in childhood. Another ongoing Phase I/II clinical trial is evaluating ATSN-101 for Leber congenital amaurosis type 1 (LCA1), one of the most common causes of blindness in children. Atsena’s pipeline is powered by novel adeno-associated virus (AAV) technology tailored to overcome the hurdles presented by inherited retinal diseases. Founded by pioneers in ocular gene therapy, Atsena is led by an experienced team dedicated to addressing the needs of patients with vision loss. The content above comes from the network. if any infringement, please contact us to modify.

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