usherin

Agreement provides ProQR with initial payment of €12.5M and up to €135M in further payments, as well as potential additional earn outs based on commercial sales in the US and EU Divestment of sepofarsen and ultevursen supports ProQR’s strategic focus on the Axiomer® RNA editing technology platform and continued advancement of pipeline programs, AX-0810 and AX-1412, focused on genetic diseases originating in the liver LEIDEN, Netherlands, CAMBRIDGE, Mass., and CLERMONT FERRAND, France, Aug. 01, 2023 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq: PRQR) (ProQR), a company dedicated to changing lives through transformative RNA therapies, and Laboratoires Théa, the leading independent eye care group in Europe (“Théa”), today announced an agreement in which ProQR will divest its late stage ophthalmic assets, sepofarsen and ultevursen, to Théa. Under the terms of the agreement, ProQR will receive an initial payment of €12.5M and will also be eligible for up to €135M in further development, regulatory, and commercial payments, as well as additional earn outs up to high teens percentage based on commercial sales in the US and EU. “Théa’s proven expertise in the research, development, and commercialization of eye care products makes them the ideal company to continue the development of sepofarsen and ultevursen for patients with rare genetic eye diseases,” said Daniel A. de Boer, Founder and Chief Executive Officer of ProQR. “We look forward to continuing to advance our Axiomer RNA editing platform, with an initial focus on targets for cholestatic and cardiovascular diseases, as we seek to develop a new class of therapies for patients with high unmet need.” “For nearly 30 years, Théa has been committed to bringing the most modern and diverse range of innovative ophthalmic products to the market for the benefits of eye care practitioners and patients. We are very excited to continue the development of sepofarsen and ultevursen for patients,” said Jean-Frédéric Chibret, President of the Théa group. “These two programs can deliver hope for patients suffering from retinal diseases that lead to blindness. We look forward to returning these assets into the clinic.” Within Théa, a fully dedicated team specializing in inherited retinal disorders and a new organization are currently being set up to manage these two projects. More information on the next steps for these programs will be available in the coming weeks from Théa. ProQR’s financial advisor is Lazard, with Allen & Overy acting as legal advisor. Théa’s legal advisor is Dentons. The transaction is expected to close in the third quarter of 2023, subject to the satisfaction of certain closing conditions. 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. About Théa Théa is the leading independent European pharmaceutical company specialized in the research, development, and commercialization of eye care products. Based in Clermont-Ferrand, France, this family-owned and run company comprises more than 1700 collaborators and has expanded by opening more than 35 affiliates and offices in Europe, North Africa, North and South America, and the Middle East. Its products are available in 75 countries. In 2022, Théa’s turnover reached $941 million. Learn more about Théa at https://www.laboratoires-thea.com. About Sepofarsen Sepofarsen (QR-110) is an investigational RNA therapy designed to restore vision in Leber congenital amaurosis 10 due to the c.2991+1655A>G mutation (p.Cys998X) in the CEP290 gene. The mutation leads to aberrant splicing of the mRNA and non-functional CEP290 protein. Sepofarsen is designed to enable normal splicing, resulting in restoration of normal (wild type) CEP290 mRNA and subsequent production of functional CEP290 protein. Sepofarsen is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the United States and the European Union and received fast-track designation and rare pediatric disease designation from the FDA as well as access to the PRIME scheme by the EMA. About Ultevursen Ultevursen (formerly QR-421a) is a first-in-class investigational RNA therapy designed to address the underlying cause of vision loss in Usher syndrome type 2a and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. QR-421a is designed to restore functional usherin protein by using an exon skipping approach with the aim to stop or reverse vision loss in patients. Ultevursen is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the US and the European Union and received fast-track and rare pediatric disease designations from the FDA. 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. 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 "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 this divestment, the potential payments and earnouts arising out of the divestment, the expected timing for the closing of the divestment, the further development of sepofarsen and ultevursen, as well as 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 annual report filed on Form 20-F. These risks and uncertainties include, among others, the clinical development activities to be performed by Théa and the condition of successful market access for sepofarsen and ultevursen; the cost, timing and results of preclinical studies 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; 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 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; and general business, operational, financial and accounting risks, and risks related to litigation and disputes with third parties. 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. For ProQR Therapeutics N.V. Investor contact: Sarah Kiely ProQR Therapeutics N.V. T: +1 617 599 6228 skiely@proqr.com or Hans Vitzthum LifeSci Advisors T: +1 617 430 7578 hans@lifesciadvisors.com Media contact: Robert Stanislaro FTI Consulting T: +1 212 850 5657 robert.stanislaro@fticonsulting.com For Théa Julie Ahmed Communications Manager Julie.ahmed@theapharma.com

Uni-Rare Study will improve clinical understanding of more IRDs and boost development of potential therapies. COLUMBIA, Md., Nov. 10, 2022 /PRNewswire/ -- The Foundation Fighting Blindness, the world's leading organization committed to finding treatments and cures for blinding retinal diseases, is committing at least $8.6 million for its Uni-Rare Study, a new natural history study for approximately 1,500 people with one of more than 300 rare genes associated with inherited retinal diseases (IRDs) including: retinitis pigmentosa, Leber congenital amaurosis, Usher syndrome, and a broad range of other conditions. The study, due to begin recruitment in December, will help clinical researchers gain a better understanding of the course of retinal degeneration and vision loss for people with mutated genes that have not been well-characterized in the clinic. The study will also help the IRD research and therapeutic development community: 1) identify more people for clinical trials of therapies, 2) inform design of clinical trials, and 3) identify therapeutic targets for more people. "A majority of the 300 genes linked to inherited retinal diseases have not been well characterized in the clinic. That is, we do not have a good understanding of retinal degeneration and disease progression for those affected by these mutated genes," says Todd Durham, PhD, senior vice president, clinical development, at the Foundation Fighting Blindness. "We are excited to launch a highly inclusive study to benefit a large segment of the population affected by IRDs, which are so genetically diverse." "We are at a promising juncture in the clinical development of genetic therapies for inherited retinal diseases," says José-Alain Sahel, MD , distinguished professor and chairman of the department of ophthalmology at the University of Pittsburgh School of Medicine and Uni-Rare Study chair. "With dozens of emerging treatments in, or moving toward, clinical trials, the Uni-Rare Study will be invaluable in defining and validating outcome measures for clinical trials and establishing the infrastructure for multicenter studies. The Foundation Fighting Blindness, with its strong presence and relationships in the global IRD research community, is the ideal partner to lead the effort." The two-part Uni-Rare Study will be conducted by the Foundation's Clinical Consortium, a global, 40-site network of clinical research centers equipped with the experts and resources needed to launch IRD clinical trials and natural history studies. The Jaeb Center for Health Research will serve as the coordinating center. In the first part of the study, all participants will have an initial evaluation to collect their genetic data and clinical measures. When the study is initiated, study participants whose IRD is caused by variants in the RDH12 and MYO7A genes may qualify for the second part of the study, which involves collecting clinical measures for an additional four years. Additional gene cohorts for this part of the study are expected to be added in the future. The Foundation has received support for the study from families affected by Usher syndrome type 1B, Save Sight Now, Opus Genetics, Atsena Therapeutics, and Cove Therapeutics and is seeking additional support to add further gene cohorts to the second part of the study. "Opus is pleased to be an early supporter of this first-of-its-kind in ophthalmology initiative to understand natural histories around rare diseases of the retina in order to accelerate research and therapeutic development for these blinding conditions," said Jennifer Hunt, chief development officer at Opus Genetics. "Atsena Therapeutics is pleased to support the Uni-Rare natural history study and the inherited retinal disease community as we continue advancing the preclinical development of our dual AAV vector-based gene therapy to prevent blindness from USH1B," said Kenji Fujita, MD, chief medical officer at Atsena Therapeutics. "We are proud to sponsor such a robust interrogation of natural history that will be used to inform future clinical development plans and improve patient outcomes; these data will be fundamental for our understanding of several diseases and will serve to accelerate the development of Cove's non-viral gene therapies," said Niren Shah, PharmD, MBA, CEO and co-founder of Cove Therapeutics. IRD patients and physicians with IRD patients can get more information at clinicaltrials.gov. Patients with IRDs caused by mutations in the following genes are not eligible for the study: ABCA4, CEP290, CHM, CNGA3, CNGB3, EYS, GUCY2D, PCDH15, PROM1, RHO, RPE65, RPGR, USH2A. These genes are or have been part of other natural history studies or clinical trials. About the Foundation Fighting Blindness Established in 1971, the Foundation Fighting Blindness is the world's leading private funding source for retinal degenerative disease research. The Foundation has raised more than $891 million toward its mission of accelerating research for preventing, treating, and curing blindness caused by the entire spectrum of blinding retinal diseases including: retinitis pigmentosa, macular degeneration, and Usher syndrome. Visit FightingBlindness.org for more information. About Opus Genetics Opus Genetics is a groundbreaking gene therapy company for inherited retinal diseases with a unique model and purpose. Backed by Foundation Fighting Blindness's venture arm, the RD Fund, Opus combines unparalleled insight and commitment to patient need with wholly owned programs in numerous orphan retinal diseases. Its AAV-based gene therapy portfolio tackles some of the most neglected forms of inherited blindness while creating novel orphan manufacturing scale and efficiencies. Based in Research Triangle Park, N.C., the company leverages knowledge of the best science and the expertise of pioneers in ocular gene therapy to transparently drive transformative treatments to patients. For more information, visit opusgenetics.com. About Atsena Therapeutics Atsena Therapeutics is a clinical-stage gene therapy company developing novel treatments for inherited forms of blindness. The company's ongoing Phase I/II clinical trial is evaluating a potential therapy for a form of LCA, one of the most common causes of blindness in children. Its additional pipeline of leading preclinical assets is powered by an adeno-associated virus (AAV) technology platform tailored to overcome significant hurdles presented by inherited retinal disease, and its unique approach is guided by the specific needs of each patient condition to optimize treatment. Founded by ocular gene therapy pioneers Dr. Shannon Boye and Sanford Boye of the University of Florida, Atsena is based in North Carolina's Research Triangle, an environment rich in gene therapy expertise. For more information, please visit atsenatx.com. About Cove Therapeutics Cove Therapeutics is a privately held biotechnology company focused on developing non-viral, non-lipid, nanoparticle gene therapies for orphan and chronic prevalent indications. The Company utilizes a nanoparticle technology that overcomes limitations in gene therapy by enabling cell-specific tropism, scalable manufacturing, redosing, and packaging of large genes while maintaining a favorable safety profile. Together with these nanoparticles, Cove's lead franchise for ophthalmic conditions leverages a novel outpatient suprachoroidal device that enables broad distribution of therapeutics. Learn more about the Company through direct contact — Stephen Jasper, Gilmartin Group, [email protected], 858-525-2047. Media Contact: Chris Adams Vice President, Marketing & Communications [email protected] 410-423-0585 SOURCE Foundation Fighting Blindness

In line with corporate strategy update in April, ProQR to focus exclusively on the development of the Axiomer® RNA editing technology platform across multiple therapeutic areas; update on initial pipeline targets expected in late 2022/early 2023Additional pivotal trial recommended by EMA for sepofarsen prior to a regulatory submissionCompany will seek a strategic partner for ophthalmology assets Workforce reduction to be implemented within clinical stage ophthalmology programs Cash runway extended into 2026 Conference call today at 8:15am EDT LEIDEN, Netherlands & CAMBRIDGE, Mass., Aug. 11, 2022 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq: PRQR) (the “Company”), a company dedicated to changing lives through the creation of transformative RNA therapies, today provided an update on its ophthalmology programs following feedback from the European Medicines Agency (EMA) related to sepofarsen and will now focus exclusively on its Axiomer® RNA-editing technology platform. Following the results from the sepofarsen Illuminate trial, the EMA has recommended an additional clinical trial be conducted for sepofarsen prior to submitting a Marketing Authorisation Application (MAA). In light of this feedback and in order to continue advancement of the portfolio of ophthalmic product candidates, including sepofarsen for LCA10 and ultevursen (QR-421a) for USH2A-mediated Usher syndrome and retinitis pigmentosa, the Company will seek to identify a strategic partner to take the ophthalmology portfolio forward. To preserve operating capital, and until a partner is found that can fund the clinical programs moving forward, the current ongoing trials of sepofarsen and ultevursen – including Illuminate, Insight, and Brighten for sepofarsen, along with Sirius and Helia for ultevursen – will be wound down. For people currently participating in these trials, ProQR will offer continued access to currently available sepofarsen or ultevursen. Strategic Focus and Operational Update Further to the announcement in April 2022 on the Company’s strategy, going forward, ProQR will focus exclusively on accelerating the development of its Axiomer RNA-editing platform technology. Initial therapeutic areas include liver and CNS, which we believe have strong alignment with ProQR’s oligonucleotide delivery approaches. ProQR’s strategic growth initiatives related to the advancement of its Axiomer RNA editing platform include both in-house development of select pipeline programs using the technology and a partnering strategy for the platform. The Company continues to execute on its global licensing and research partnership with Eli Lilly, focused on the discovery, development, and commercialization of potential new medicines for genetic disorders in the liver and nervous system, and may selectively enter additional partnerships designed to advance and capture the full potential value of the platform. ProQR has established a leading IP estate in the ADAR-editing space related to its RNA-editing technology and the platform’s broad applicability has significant potential to treat a number of diseases. The Company will provide further updates on the Axiomer strategy, including announcing its internal development targets in late 2022/early 2023. Based on the wind down of sepofarsen and ultevursen clinical trials and associated workforce reduction, ProQR will realize cost savings in headcount, program, and related support activities, which are expected to extend ProQR’s cash runway into 2026. The cash runway into 2026 excludes any revenue generated from the Company’s existing partnership and any potential new partnering deals. “As we prioritize the development of our Axiomer RNA editing platform technology, we believe partnering our ophthalmology assets is the best strategy to drive these programs forward to patients,” said Daniel A. de Boer, Chief Executive Officer of ProQR Therapeutics. “The feedback we received from the EMA is helpful in designing an additional registration trial for sepofarsen based on the learnings from the Illuminate trial and we will seek a strategic partner for the further development of our ophthalmology programs, including sepofarsen and ultevursen. As a company dedicated to developing therapies to improve the lives of patients, we will offer clinical trial participants continued access to currently available sepofarsen or ultevursen. I want to thank the employees who will be separating from ProQR for their significant contributions in advancing sepofarsen and ultevursen to this stage, as well as the patients, providers, and supporters of these programs.” De Boer continued, “Going forward, we will focus our strategy and resources exclusively on advancing our Axiomer RNA-editing platform technology and the changes announced today will also enable us to extend our cash runway in 2026. We look forward to continued progress with the business, including sharing details of our development plans for Axiomer.” Conference call and webcast details Company management will host a call today, August 11, 2022, at 8:15am EDT to discuss this announcement. The live and archived webcast of the presentation will be accessible through this webcast link, or to access the live call by phone please register here. A dial-in and unique PIN will be provided to join the call. The archived webcast will be available for approximately 30 days following the presentation date. About Axiomer® technology ProQR is pioneering a next-generation RNA technology called Axiomer®, which could potentially yield a new class of medicines for genetic 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. The Axiomer® EONs are designed to recruit an endogenously expressed RNA editing system called ADAR, which can direct the change of an Adenosine (A) to an Inosine (I) in the RNA – an Inosine is translated as a Guanosine (G). About Leber Congenital Amaurosis 10 (LCA10) Leber congenital amaurosis (LCA) is the most common cause of blindness due to genetic disease in children. It consists of a group of diseases of which LCA10 is the most frequent and one of the most severe forms. LCA10 is caused by mutations in the CEP290 gene, of which the c.2991+1655A>G (p.Cys998X) mutation has the highest prevalence. LCA10 leads to early loss of vision causing most people to lose their sight in the first few years of life. To date, there are no treatments approved that treat the underlying cause of the disease. Approximately 2,000 people in the Western world have LCA10 because of this mutation. About sepofarsen Sepofarsen (QR-110) is an investigational RNA therapy designed to restore vision in Leber congenital amaurosis 10 due to the c.2991+1655A>G mutation (p.Cys998X) in the CEP290 gene. The mutation leads to aberrant splicing of the mRNA and non-functional CEP290 protein. Sepofarsen is designed to enable normal splicing, resulting in restoration of normal (wild type) CEP290 mRNA and subsequent production of functional CEP290 protein. Sepofarsen is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the United States and the European Union and received fast-track designation and rare pediatric disease designation from the FDA as well as access to the PRIME scheme by the EMA. About Usher syndrome type 2a and retinitis pigmentosa Usher syndrome is the leading cause of combined deafness and blindness. People with Usher syndrome type 2a are usually born with hearing loss and start to have progressive vision loss during adulthood. The vision loss can also occur without hearing loss in a disease called non-syndromic retinitis pigmentosa. Usher syndrome type 2a and non-syndromic retinitis pigmentosa can be caused by mutations in the USH2A gene. To date, there are no pharmaceutical treatments approved or in clinical development that treat the vision loss associated with mutations in USH2A. About ultevursen Ultevursen (formerly QR-421a) is a first-in-class investigational RNA therapy designed to address the underlying cause of vision loss in Usher syndrome type 2a and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. QR-421a is designed to restore functional usherin protein by using an exon skipping approach with the aim to stop or reverse vision loss in patients. Ultevursen is intended to be administered through intravitreal injections in the eye and has been granted orphan drug designation in the US and the European Union and received fast-track and rare pediatric disease designations from the FDA. 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 genetic diseases. 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 "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 strategy and future operations, statements regarding our product candidates, including sepofarsen (QR-110) and the clinical development and the therapeutic potential thereof, statements regarding ultevursen (QR-421a) and the clinical development and the therapeutic potential thereof, our regulatory strategy following feedback from the EMA, our plans to seek strategic partnerships for our ophthalmology assets, statements regarding the potential of and our plans with respect to our technologies and platforms (including Axiomer®), our other programs and business operations, our current and planned partnerships and collaborators and the intended benefits thereof, our planned interactions with regulatory authorities relating to our programs, our updated strategic plans 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 by the ongoing COVID-19 pandemic; the likelihood of our clinical programs being 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 later data to alter initial and preliminary results of early-stage clinical trials, including as a result of differences in the trial designs and protocols across different 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 outcomes of interactions with regulatory authorities; that any regulatory submissions that we may make may not yield marketing approval for any of our product candidates; the ability to secure, maintain and realize the intended benefits of collaborations with partners, including for our ophthalmology assets; 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; our ability to maintain and service our loan facility with Pontifax and Kreos; general business, operational, financial and accounting risks; and risks related to litigation and disputes with third parties. 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. Cautionary note on future updates The statements contained in this press release reflect our current views with respect to future events, which may change significantly as the global consequences of the ongoing COVID-19 pandemic rapidly develop. Accordingly, we do not undertake and specifically disclaim any obligation to update any forward-looking statements. ProQR Therapeutics N.V. Investor contact:Sarah KielyProQR Therapeutics N.V.T: +1 617 599 6228skiely@proqr.comorHans VitzthumLifeSci AdvisorsT: +1 617 430 7578hans@lifesciadvisors.com Media contact:Robert StanislaroFTI ConsultingT: +1 212 850 5657robert.stanislaro@fticonsulting.com