Amyotrophic Lateral Sclerosis 1

NANTONG, China and SUZHOU, China I September 10, 2024 I Ractigen Therapeutics, a clinical-stage pharmaceutical company dedicated to developing innovative therapies, today announced promising clinical data from an Investigator-Initiated Trial (IIT) of RAG-17, a small interfering RNA (siRNA) targeting the Superoxide Dismutase 1 (SOD1) gene. The study revealed encouraging results in the treatment of amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations (ALS-SOD1). The trial was led by Dr. Yilong Wang and conducted at Beijing Tiantan Hospital, one of China’s leading centers for neurological diseases. The trial enrolled six ALS-SOD1 patients and primarily focused on assessing the safety of RAG-17. Results demonstrated that RAG-17, administered intrathecally, was well-tolerated across all dose levels. All adverse events were mild. Comprehensive safety evaluations, including laboratory assessments, vital signs, and electrocardiograms, further supported the favorable safety profile. Encouragingly, early signs of clinical benefit were also evident. Notable changes in clinical outcomes and key biomarkers indicate the efficacy of RAG-17 within this patient population. These positive clinical findings align with Ractigen’s robust preclinical data, which demonstrated significant therapeutic effects of RAG-17 in SOD1-G93A ALS mouse and rat models, including delayed disease progression and improved survival. “These initial clinical results are truly encouraging and bring us one step closer to our goal of offering new hope to ALS patients,” stated Dr. Long-Cheng Li, Founder and CEO of Ractigen Therapeutics. “The positive outcomes from this trial underscore the potential of RAG-17 as a disease-modifying therapy for ALS-SOD1. We are fully committed to advancing its clinical development and ultimately delivering this much-needed treatment to patients.” This promising data will be presented at three upcoming conferences: the 27th National Conference of Neurology in China this September, followed by Neuroscience 2024 in Chicago, USA, in October, and the 35th International Symposium on ALS/MND in Montreal, Canada, in December—one of the largest annual gatherings dedicated to ALS and motor neuron disease research. RAG-17 received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) in March 2023 and Investigational New Drug (IND) was cleared for clinical trials in the U.S.. Additionally, in May 2024, the IND application was approved by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) for clinical trials in China. About RAG-17 RAG-17 is a siRNA specifically designed to suppress the SOD1 gene in ALS patients with pathogenic mutations. Utilizing Ractigen’s proprietary SCAD™ delivery platform, RAG-17 conjugated siRNA with an accessory oligonucleotide (ACO) for enhanced delivery into the central nervous system (CNS). Preclinical studies, including those using the hSOD1 G93A mouse model, have demonstrated remarkable therapeutic efficacy of RAG-17 in ameliorating motor function and prolonging survival. About ALS ALS, a severe neurodegenerative disease with no cure, significantly reduces life expectancy, with most patients succumbing to respiratory failure within 3-5 years of diagnosis. Initial symptoms typically include muscle cramps, twitching, and weakness. These symptoms progress to difficulties with movement and speech, the need for assisted breathing, paralysis, and ultimately death. Mutations in the SOD1 gene account for approximately 20% of the familial ALS and 5% of the sporadic ALS cases. About Ractigen Therapeutics Ractigen Therapeutics, a clinical-stage pharmaceutical company, is committed to developing innovative oligonucleotide drugs and therapeutic approaches. Ractigen has pioneered several globally leading oligonucleotide drug delivery platforms, including SCAD™ and LiCO™, and boasts a highly diverse pipeline of oligonucleotide drugs. These drugs are aimed to target a wide variety of indications, from neurodegenerative and neuromuscular diseases to cancer, metabolic disorders, and hematological diseases. The company is dedicated to delivering innovative therapeutic solutions for previously undruggable targets and addressing incurable diseases across various fields. For more information, please visit our website at www.ractigen.com . SOURCE: Ractigen Therapeutics

- Top-line safety and pharmacokinetic data expected in H1 2025 from recently initiated single ascending dose trial of anti-tau antibody for Alzheimer’s disease - - Three CNS gene therapy programs on track for INDs in 2025 following development candidate nominations for GBA1 and FA programs and pre-IND meeting for SOD1 ALS development candidate - - Appointed strategic financial leader Nathan Jorgensen, Ph.D., as Chief Financial Officer - - Strong cash position of $371 million as of June 30, 2024, expected to provide runway through multiple clinical data readouts into 2027 - LEXINGTON, Mass., Aug. 06, 2024 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (Nasdaq: VYGR), a biotechnology company dedicated to advancing neurogenetic medicines, today reported second quarter 2024 financial and operating results. “Voyager continued to progress our pipeline in the second quarter: we initiated the single ascending dose trial of our anti-tau antibody, which has been shown to substantially reduce the spread of tau in Alzheimer’s disease in vivo models, and enrollment is on track with top-line safety and pharmacokinetic data expected in H1 2025,” said Alfred W. Sandrock, Jr., M.D., Ph.D., Chief Executive Officer of Voyager. “In parallel, we continued to advance our gene therapy pipeline, and we and our partners are on track to achieve three IND filings in 2025. Our disciplined execution, backed by a strong cash position, should enable us to achieve multiple data readouts during 2025 and 2026.” Second Quarter 2024 and Recent Highlights Dosed first participants in Phase 1a single ascending dose (SAD) trial of anti-tau antibody VY7523 (formerly VY-TAU01) for Alzheimer’s disease: This randomized, double-blind, placebo-controlled, SAD trial is evaluating the safety and pharmacokinetics of VY7523 in healthy adult volunteers. Enrollment is on track, with a total of approximately 48 patients expected to enroll across multiple cohorts.Advanced VY9323 gene therapy program for SOD1 amyotrophic lateral sclerosis (ALS): Completed pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration (FDA) and initiated Good Laboratory Practice (GLP) toxicology studies to support IND filing.Selected development candidate in GBA1 gene therapy program: The joint steering committee with collaborator Neurocrine Biosciences selected a lead development candidate for the GBA1 gene therapy program for the treatment of Parkinson’s disease and other GBA1-mediated diseases, triggering a $3 million milestone payment to Voyager. This followed the selection of a lead development candidate for the Neurocrine-partnered Friedreich’s ataxia (FA) gene therapy program in the first quarter, which resulted in a $5 million milestone payment to Voyager.Appointed Nathan Jorgensen, Ph.D., as Chief Financial Officer: Dr. Jorgensen brings to Voyager a breadth of experience spanning investment banking, public and private healthcare investing, sell-side research, and operational roles in biotech, as well as expertise in neuroscience.Presented data at the American Society of Gene & Cell Therapy (ASGCT) 27th annual meeting: Presented a broad set of translational data, including new data on second-generation TRACER™-derived AAV capsids; translatability as evidenced by cross-species and receptor data; and activity against therapeutic targets in Alzheimer’s disease and ALS. Anticipated Upcoming Milestones VY7523 anti-tau antibody for Alzheimer’s disease: Voyager expects top-line safety and pharmacokinetic data from the ongoing SAD trial in H1 2025. Voyager expects to initiate a multiple ascending dose (MAD) trial in patients with early Alzheimer’s disease in 2025. The MAD study has the potential to generate initial tau PET imaging data in the second half of 2026 to demonstrate slowing the spread of pathological tau.VY9323 SOD1 silencing gene therapy program for SOD1 ALS: Voyager expects to file an IND in mid-2025 and initiate a clinical trial in SOD1 ALS patients. The clinical trial has the potential to generate proof-of-concept data for Voyager’s novel TRACER-derived capsids and for the treatment of SOD1 ALS based on biomarkers, including cerebrospinal fluid (CSF) SOD1 and plasma neurofilament.Partnered programs: Voyager and Neurocrine Biosciences expect to file INDs for the GBA1 and Friedreich’s Ataxia gene therapy programs in 2025, as previously disclosed. Second Quarter 2024 Financial Results Collaboration Revenues: Voyager had collaboration revenue of $29.6 million for the second quarter of 2024, compared to $4.9 million for the same period in 2023. The increase was primarily due to increased revenue recognized under our Neurocrine and Novartis agreements.Net Loss: Net loss was $10.1 million for the second quarter of 2024, compared to net loss of $22.2 million for the same period in 2023. The decrease is primarily due to increased collaboration revenue recognized during the second quarter of 2024, as discussed above.R&D Expenses: Research and development expenses were $34.5 million for the second quarter of 2024, compared to $22.0 million for the same period in 2023. The increase in R&D expenses was primarily a result of increased facilities costs, which includes a $2.5 million non-recurring lease impairment charge and $0.5 million in non-recurring relocation expenses, along with increased program-related spending and increased headcount.G&A Expenses: General and administrative expenses were $10.2 million for the second quarter of 2024, compared to $8.3 million for the same period in 2023. The increase in G&A expenses was primarily a result of $1.3 million in non-recurring items including lease impairment charge and personnel transition costs.Cash Position: Cash, cash equivalents and marketable securities as of June 30, 2024, were $371.0 million. Six Months Ended June 30, 2024, Financial Results Collaboration Revenues: Voyager had collaboration revenue of $49.1 million for the six months ended June 30, 2024, compared to $155.3 million for the same period in 2023. The decrease was primarily due to decreased revenue recognized under our Neurocrine and Novartis agreements.Net (Loss) Income: Net loss was $21.5 million for the six months ended June 30, 2024, compared to net income of $101.8 million for the same period in 2023. The change is primarily due to decreased collaboration revenue recognized during the 2024 period, as discussed above.R&D Expenses: Research and development expenses were $61.5 million for the six months ended June 30, 2024, compared to $40.6 million for the same period in 2023. The increase in R&D expenses was primarily a result of increased facilities costs, which includes a $2.5 million non-recurring lease impairment charge and $0.5 million in non-recurring relocation expenses, along with increased program-related spending and increased headcount.G&A Expenses: General and administrative expenses were $18.8 million for the six months ended June 30, 2024, compared to $17.3 million for the same period in 2023. The increase in G&A expenses was primarily a result of $1.3 million in non-recurring items including lease impairment charge and personnel transition costs. Financial Guidance Voyager is committed to maintaining a strong balance sheet that supports the advancement and growth of its platform and pipeline. Voyager continues to assess its planned cash needs both during the current period and in future periods. We expect our cash, cash equivalents, and marketable securities, along with amounts expected to be received as reimbursement for development costs under the Neurocrine and Novartis collaborations and interest income, to be sufficient to meet Voyager’s planned operating expenses and capital expenditure requirements into 2027. Conference Call Voyager will host a conference call and webcast today at 4:30 p.m. ET to discuss second quarter 2024 financial and operating results. To participate via telephone and join the call live, please register in advance here: https://register.vevent.com/register/BI796eccb31a2e48c9a71f6c41edd5c510. Upon registration, telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number and a unique passcode. A live webcast of the call will also be available on the Investors section of the Voyager website at ir.voyagertherapeutics.com, and a replay of the call will be available at the same link approximately two hours after its completion. The replay will be available for at least 30 days following the conclusion of the call. About Voyager Therapeutics Voyager Therapeutics, Inc. (Nasdaq: VYGR) is a biotechnology company dedicated to leveraging the power of human genetics to modify the course of – and ultimately cure – neurological diseases. Our pipeline includes programs for Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and multiple other diseases of the central nervous system. Many of our programs are derived from our TRACER™ AAV capsid discovery platform, which we have used to generate novel capsids and identify associated receptors to potentially enable high brain penetration with genetic medicines following intravenous dosing. Some of our programs are wholly owned, and some are advancing with partners including Alexion, AstraZeneca Rare Disease; Novartis Pharma AG; Neurocrine Biosciences, Inc.; and Sangamo Therapeutics, Inc. For more information, visit www.voyagertherapeutics.com. Voyager Therapeutics® is a registered trademark, and TRACER™ is a trademark, of Voyager Therapeutics, Inc. Forward-Looking Statements This press release contains forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as “expect,” “enable,” “will,” “believe,” “anticipate,” “potential,” “may,” or “continue,” and other similar expressions are intended to identify forward-looking statements. For example, all statements Voyager makes regarding Voyager’s ability to advance its AAV-based gene therapy programs and tau antibody program, including expectations for Voyager’s achievement of preclinical and clinical development milestones for its potential development candidates such as IND filings, the initiation of clinical trials, clinical trial enrollment, and generation of clinical data and proof-of-concept; Voyager’s ability to advance gene therapy product candidates under the Neurocrine collaboration; Voyager’s anticipated financial results, including the anticipated receipt by Voyager of revenues or reimbursement payments from collaboration partners; and Voyager’s cash runway and ability to generate sufficient cash resources to enable it to continue its business and operations are forward looking. All forward-looking statements are based on estimates and assumptions by Voyager’s management that, although Voyager believes such forward-looking statements to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Voyager expected. Such risks and uncertainties include, among others, the expectations and decisions of regulatory authorities; the timing, initiation, conduct and outcomes of Voyager’s preclinical and clinical studies; the availability of data from clinical trials; the availability or commercial potential of product candidates under collaborations; the willingness and ability of Voyager's collaboration partners to meet obligations under collaboration agreements with Voyager; the continued development of Voyager’s technology platforms, including Voyager’s TRACER platform and its antibody screening technology; Voyager’s scientific approach and program development progress, and the restricted supply of critical research components; the development by third parties of capsid identification platforms that may be competitive to Voyager’s TRACER capsid discovery platform; Voyager’s ability to create and protect intellectual property rights associated with the TRACER capsid discovery platform, the capsids identified by the platform, and development candidates for Voyager’s pipeline programs; the possibility or the timing of Voyager’s receipt of program reimbursement, development or commercialization milestones, option exercise, and other payments under Voyager’s existing licensing or collaboration agreements; the ability of Voyager to negotiate and complete licensing or collaboration agreements with other parties on terms acceptable to Voyager and the third parties; the success of programs controlled by third party collaboration partners in which Voyager retains a financial interest, and the success of Voyager’s product candidates; the ability to attract and retain talented directors, employees, and contractors; and the sufficiency of cash resources to fund its operations and pursue its corporate objectives. These statements are also subject to a number of material risks and uncertainties that are described in Voyager’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission. All information in the press release is as of the date of this press release, and any forward-looking statement speaks only as of the date on which it was made. Voyager undertakes no obligation to publicly update or revise this information or any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. Contacts Trista Morrison, NACD.DC, tmorrison@vygr.com Investors: Adam Bero, Ph.D., abero@kendallir.com Media: Brooke Shenkin, brooke@scientpr.com Selected Financial Information($ amounts in thousands, except per share data)(Unaudited) Three Months Ended Six Months Ended June 30, June 30, Statement of Operations Items: 2024 2023 2024 2023 Collaboration revenue $29,578 $4,853 $49,094 $155,333 Operating expenses: Research and development 34,452 21,985 61,544 40,553 General and administrative 10,151 8,294 18,758 17,322 Total operating expenses 44,603 30,279 80,302 57,875 Operating (loss) income (15,025) (25,426) (31,208) 97,458 Total other income 4,908 3,277 9,775 5,141 (Loss) income before income taxes (10,117) (22,149) (21,433) 102,599 Income tax provision 24 59 38 763 Net (loss) income $(10,141) $(22,208) $(21,471) $101,836 Net (loss) income per share, basic $(0.18) $(0.51) $(0.37) $2.42 Net (loss) income per share, diluted $(0.18) $(0.51) $(0.37) $2.33 Weighted-average common shares outstanding, basic 57,721,934 43,520,137 57,419,490 42,102,101 Weighted-average common shares outstanding, diluted 57,721,934 43,520,137 57,419,490 43,770,999 June 30, December 31, Selected Balance Sheet Items 2024 2023 Cash, cash equivalents, and marketable securities $371,021 $230,875 Total assets $436,225 $351,281 Accounts payable and accrued expenses $12,878 $18,427 Deferred revenue $39,989 $75,240 Total stockholders’ equity $335,417 $236,320 GAAP vs. Non-GAAP Financial MeasuresVoyager’s financial statements are prepared in accordance with generally accepted accounting principles in the United States, or GAAP, and represent revenue and expenses as reported to the Securities and Exchange Commission. Voyager has provided in this release certain financial information that has not been prepared in accordance with GAAP, including net collaboration revenue and net research and development expenses, which exclude the impact of reimbursement by Neurocrine Biosciences (Neurocrine) and Novartis Pharma AG (Novartis) for expenses we incur in conducting preclinical development activities under our collaboration agreements. Management uses these non-GAAP measures to evaluate the Company’s operating performance in a manner that allows for meaningful period-to-period comparison and analysis of trends in its business. Management believes that such non-GAAP measures are important in comparing current results with prior period results and are useful to investors and financial analysts in assessing the Company’s operating performance. Non-GAAP financial measures are not required to be uniformly applied, are not audited and should not be considered in isolation. The non-GAAP measures give investors and financial analysts a better understanding of our net revenue and net research and development expenses without the pass-through impact of Neurocrine costs. The non-GAAP financial information presented here should be considered in conjunction with, and not as a substitute for, the financial information presented in accordance with GAAP. Investors are encouraged to review the reconciliation of these non-GAAP measures to their most directly comparable GAAP financial measures set forth below. Reconciliation of GAAP to Non-GAAP Measures(in thousands) Three Months Ended Six Months Ended June 30, June 30, 2024 2023 2024 2023GAAP collaboration revenue $29,578 $4,853 $49,094 $155,333Revenue recognized for reimbursed research and development services (Note 1) $1,963 $3,050 $5,148 $3,378Net collaboration revenue $27,615 $1,803 $43,946 $151,955 GAAP total research and development expenses $34,452 $21,985 $61,544 $40,553Expenses incurred for reimbursed research and development services (Note 1) $1,963 $3,050 $5,148 $3,378Net research and development expenses $32,489 $18,935 $56,396 $37,175 Note 1: Under the Company's existing collaboration agreements with Neurocrine and Novartis, Neurocrine and Novartis have agreed to be responsible for all costs the Company incurs in conducting preclinical development activities for certain collaboration programs, in accordance with joint steering committee agreed upon workplans and budgets. Reimbursable research and development services performed during the period are captured within collaboration revenue and research and development expenses in the Company's consolidated statements of operations. During the three months ended June 30, 2024, we incurred $2.0 million of reimbursable research and development services recorded within collaboration revenue and research and development expenses. During the three months ended June 30, 2023, we incurred $3.1 million of reimbursable research and development services recorded within collaboration revenue and research and development expenses. During the six months ended June 30, 2024, we incurred $5.1 million of reimbursable research and development services recorded within collaboration revenue and research and development expenses. During the six months ended June 30, 2023, we incurred $3.4 million of reimbursable research and development services recorded within collaboration revenue and research and development expenses.

~ Announced RMAT designation for AMT-130 in Huntington’s disease and positive interim Phase I/II data demonstrating the slowing of disease progression and reductions in a key biomarker of neurodegeneration; Meeting with FDA expected in the second half of 2024 to discuss potential for expedited clinical development ~ ~ Initiated patient screening for three additional Phase I/II studies in mesial temporal lobe epilepsy, SOD1 ALS, and Fabry disease ~ ~ Today, announced an organizational restructuring intended to streamline operations; Together with the recent sale of the Lexington manufacturing facility, these changes are expected to reduce headcount by 65% and lower recurring cash burn by $75 million per year including savings from the retirement of $50 million of debt ~ ~ Strong cash position of approximately $524 million as of June 30, 2024, expected to fund operations through the end of 2027 and multiple value-generating inflection points ~ LEXINGTON, Mass. and AMSTERDAM, Aug. 01, 2024 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today reported its financial results for the second quarter of 2024 and highlighted recent progress across its business. “We have made significant progress over the past few months across several key business objectives, including advancing our clinical pipeline and taking important actions to considerably reduce our capital requirements,” stated Matt Kapusta, chief executive officer of uniQure. “With the recent Regenerative Medicine Advanced Therapy (RMAT) designation and the latest interim data supporting dose-dependent slowing of Huntington’s disease progression, we are eager to engage further with regulators to pursue an expedited clinical development pathway for AMT-130. We’ve also made meaningful progress across our three other clinical programs, with patient screenings underway and enrollment expected to begin shortly. At the same time, we’ve taken targeted measures to substantially reduce operating expenses, streamline operations, and extend cash runway. These actions are designed to ensure we have the funding required to achieve key milestones and drive shareholder value, as we endeavor to deliver transformative medicines to patients in need.” Recent Company Updates Advancing AMT-130 for the treatment of Huntington’s disease In June 2024, the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation for investigational gene therapy AMT-130, becoming the first therapeutic candidate to receive such a designation for Huntington’s disease. RMAT designation allows sponsor companies to have early, close and frequent interactions with the FDA. In July 2024, uniQure announced positive interim data from the ongoing U.S. and European Phase I/II studies of AMT-130 for the treatment of early-stage Huntington’s disease.1 A statistically significant, dose-dependent slowing in disease progression measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS) was observed through 24 months in patients receiving the high dose of AMT-130 compared to a propensity score-weighted external control (p=0.007). A statistically significant reduction of neurofilament light chain (NfL) in cerebrospinal fluid (CSF) was observed at 24 months in patients treated with AMT-130 compared to baseline (p=0.02). AMT-130 continued to be generally well-tolerated with a manageable safety profile across both doses. The Company expects to hold a Type B, multi-disciplinary RMAT meeting with the FDA in the second half of 2024 with the goal of defining the future clinical and regulatory pathway for AMT-130. Patient dosing is ongoing in a third cohort of up to 12 patients to further evaluate both doses of AMT-130 in combination with perioperative immunosuppression regimen, with a focus on evaluating near-term safety and tolerability. Enrollment in this third cohort is expected to be completed in the second half of 2024.The Company expects to provide an additional interim update from its ongoing Phase I/II clinical trials of AMT-130 in mid-2025. The update will include follow-up data on all patients treated with AMT-130 in the first two cohorts, including three years of follow-up on 21 treated patients. Initiating new Phase I/II clinical studies AMT-260 for the treatment of refractory mesial temporal lobe epilepsy (mTLE) – Patient screening in a Phase I/II clinical study has been initiated and enrollment is expected to begin in the third quarter of 2024. The first part of the U.S., multi-center, open-label trial Phase I/II is expected to include up to 12 patients across two dose cohorts. AMT-191 for the treatment of Fabry disease – Patient screening in a Phase I/II clinical study has been initiated and enrollment is expected to begin in the third quarter of 2024. The U.S., multi-center, open-label trial is expected to include up to 12 adult male patients across two dose cohorts. AMT-162 for the treatment of SOD1 amyotrophic lateral sclerosis (ALS) – Patient screening in a Phase I/II clinical study has been initiated and enrollment is expected to begin in the third quarter of 2024. The U.S., multi-center, open-label trial is expected to include up to 12 patients across three dose cohorts. Capital Preservation Initiatives uniQure conducted and recently concluded a detailed review of its operating expenses with the goals of conserving capital, streamlining operations, and ensuring sufficient cash resources to achieve multiple potentially meaningful value creating milestones. As a result of this review, uniQure has or will be taking the following steps: The sale of the Lexington, Massachusetts manufacturing facility to Genezen announced on July 1, 2024.Global workforce reductions aimed at organizational rightsizing, delayering and outsourcing sub- and non-critical activities. Inclusive of the sale of the manufacturing facility, the elimination of approximately 65% or 300 roles across the organization. Certain intended organizational changes are subject to review and advice from the Company’s Amsterdam-based works council, which is ongoing and expected to be completed in the third quarter of 2024. The Company expects to substantially complete the restructuring in the fourth quarter of 2024. A reduction in annual recurring cash burn of approximately 40% or $75 million, which includes savings in interest expense from the retirement of $50 million in outstanding debt.Current balance of cash, cash equivalents and investment securities of $524 million as of June 30, 2024 are expected to fund operations through the end 2027. As a result of the sale of the Lexington manufacturing facility, Pierre Caloz, chief operating officer of uniQure will depart the company. Amin Abujoub, Ph.D. who previously served as chief quality officer, has been appointed to the new role of chief technical operations officer in which he will be responsible for global oversight of contract manufacturers as well as internal operations, facilities, process and analytical development, and quality. “After a comprehensive review motivated by our patient-driven mission, we are making important changes to align uniQure with our objectives of delivering sustainable value creation and ensuring we are optimally positioned for the future,” added Matt Kapusta. “We have taken great care to ensure those impacted by these changes are supported, and greatly appreciate the contributions they have made to the company. I particularly want to thank Pierre for his leadership, dedication and compassion, all of which were critical in achieving multiple HEMGENIX® approvals and establishing world-class commercial manufacturing capabilities. Through our relationship with Genezen, we hope to leverage these capabilities for years to come.” “These decisions will enable us to prioritize investments in our Huntington’s disease, temporal lobe epilepsy and other gene therapy programs, as well as innovating and broadening the long-term applicability of AAV-delivered gene therapy.” Upcoming Investor Events Wells Fargo 2024 Healthcare Conference, September 5 – Boston, MA2024 Cantor Global Healthcare Conference, September 18 – New York, NY Financial Highlights Cash position: As of June 30, 2024, the Company held cash and cash equivalents and investment securities of $524.4 million, compared to $617.9 million as of December 31, 2023. Based on the Company’s current operating plan and pending successful completion of the capital preservation measures described above, the Company expects cash, cash equivalents and investment securities will be sufficient to fund operations through the end of 2027. Revenues: Revenue for the three months ended June 30, 2024, was $11.1 million, compared to $2.4 million in the same period in 2023. The increase of $8.7 million in revenue resulted from an increase of $6.8 million in collaboration revenue, an increase of $1.1 million in license revenue and an increase of $0.8 million in revenue from contract manufacturing of HEMGENIX® for CSL. Cost of license revenue: Costs of license revenues were $0.2 million for the three months ended June 30, 2024, compared to $0.0 million for the same period in 2023. The increase primarily relates to not incurring such costs in 2023. Cost of contract manufacturing revenues: Costs of contract manufacturing revenues were $7.2 million for the three months ended June 30, 2024, compared to $1.4 million for the same period in 2023. The increase primarily relates to expensing costs previously capitalized as inventory. R&D expenses: Research and development expenses were $33.7 million for the three months ended June 30, 2024, compared to $46.0 million during the same period in 2023. The $12.3 million decrease was primarily related to a decrease of $6.6 million in employee-related expenses partially offset by an increase of $1.1 million severance costs related to the sale of the Lexington facility, a $4.5 million decrease in costs incurred related to preclinical supplies, and a decrease of $2.0 million related to the changes in fair value of contingent consideration. SG&A expenses: Selling, general and administrative expenses were $15.8 million for the three months ended June 30, 2024, compared to $21.2 million during the same period in 2023. The $5.4 million decrease was primarily related to a $3.8 million decrease in financial advisory fees, a $1.6 million decrease in intellectual property fees and information technology expenses, and a $1.1 million decrease in employee-related expenses compared to the prior year period. These decreases were partially offset by a $1.6 million increase in professional fees primarily related to the sale of the Lexington facility. Other non-operating items, net: Other non-operating items, net was an expense of $11.3 million for the three months ended June 30, 2024, compared to $3.2 million for the same period in 2023. The $8.1 million increase in other non-operating items, net was primarily related to an increase in non-cash interest expense of $9.3 million related to the royalty agreement that the Company entered into in May 2023 and an increase in net foreign currency losses of $1.4 million, which were partially offset by an increase of $2.6 million in interest income earned on investment securities and cash on hand. Net loss: The net loss for the three months ended June 30, 2024, was $56.3 million, or $1.16 basic and diluted loss per ordinary share, compared to $68.5 million net loss for the same period in 2023, or $1.44 basic and diluted loss per ordinary share. About uniQure uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. The approvals of uniQure’s gene therapy for hemophilia B – an historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. uniQure is now advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases. www.uniQure.com uniQure 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," “establish,” "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," “seek,” "should," "will," "would" and similar expressions. 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. Examples of these forward-looking statements include, but are not limited to, statements concerning the Company’s cash runway and its ability to fund its operations through the end of 2027 and achieve multiple value-generating inflection points; the Company’s expectations regarding planned organizational changes, including reductions in headcount and lower annual cash burn resulting from such changes; the ability of such organizational changes to yield the funding required to achieve key clinical and regulatory milestones, maximize shareholder value, and deliver transformative medicines to patients; the Company’s planned workforce reductions, including the extent and timing thereof and the costs associated with such workforce reductions; the Company’s plans to announce additional interim updates from its ongoing U.S. and European Phase I/II clinical studies of AMT-130; the Company’s plans to meet the FDA regarding potential expedited clinical development pathways for AMT-130, the timing of such regulatory interactions and expectations regarding potential regulatory clarity from such interactions; the Company’s plans regarding the third cohort in its AMT-130 clinical trial and the timing of enrollment for such cohort; and the Company’s plans to initiate patient enrollment for AMT-191, AMT-260 and AMT-162 and the design of trials for the Company’s additional clinical programs. The Company’s actual results could differ materially from those anticipated in these forward-looking statements for many reasons. These risks and uncertainties include, among others: risks associated with the implementation of the Company’s restructuring plans; risks associated with the clinical results and the development and timing of the Company’s programs; the Company’s interactions with regulatory authorities, which may affect the initiation, timing and progress of clinical trials and pathways to approval; the Company’s ability to continue to build and maintain the company infrastructure and personnel needed to achieve its goals following planned workforce reductions; the Company’s effectiveness in managing current and future clinical trials and regulatory processes; the continued development and acceptance of gene therapies; the Company’s ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; the Company’s ability to obtain, maintain and protect intellectual property; the Company’s ability to fund its operations and to raise additional capital as needed; and the impact of global economic uncertainty, rising inflation, rising interest rates or market disruptions on its business. These risks and uncertainties are more fully described under the heading "Risk Factors" in the Company’s periodic filings with the U.S. Securities & Exchange Commission (“SEC”), including its Annual Report on Form 10-K filed February 28, 2024 and in other filings that the Company makes with the SEC from time to time. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and the Company assumes no obligation to update these forward-looking statements, even if new information becomes available in the future. uniQure Contacts: FOR INVESTORS:FOR MEDIA: Chiara RussoTom MaloneDirect: 617-306-9137Direct: 339-970-7558Mobile: 617-306-9137Mobile:339-223-8541c.russo@uniQure.com t.malone@uniQure.com uniQure N.V. UNAUDITED CONSOLIDATED BALANCE SHEETS June 30, December 31, 2024 2023 (in thousands, except share and per share amounts) Current assets Cash and cash equivalents $287,877 $241,360 Current investment securities 236,553 376,532 Inventories, net - 12,024 Accounts receivable 7,850 4,193 Prepaid expenses 18,278 15,089 Assets held for sale 37,964 - Other current assets 3,446 2,655 Total current assets 591,968 651,853 Non-current assets Property, plant and equipment, net $26,186 $46,548 Operating lease right-of-use assets 14,925 28,789 Intangible assets, net 58,659 60,481 Goodwill 23,112 26,379 Deferred tax assets, net 10,718 12,276 Other non-current assets 5,278 5,363 Total non-current assets 138,878 179,836 Total assets $730,846 $831,689 Current liabilities Accounts payable $4,407 $6,586 Accrued expenses and other current liabilities 26,491 30,534 Current portion of contingent consideration 28,060 28,211 Current portion of operating lease liabilities 3,625 8,344 Liabilities held for sale 17,885 - Total current liabilities 80,468 73,675 Non-current liabilities Long-term debt 102,507 101,749 Liability from royalty financing agreement 415,940 394,241 Operating lease liabilities, net of current portion 12,369 28,316 Contingent consideration, net of current portion 12,078 14,795 Deferred tax liability, net 7,323 7,543 Other non-current liabilities 3,054 3,700 Total non-current liabilities 553,271 550,344 Total liabilities 633,739 624,019 Shareholders' equity Total shareholders' equity 97,107 207,670 Total liabilities and shareholders' equity $730,846 $831,689 uniQure N.V. UNAUDITED CONSOLIDATED STATEMENTS OF OPERATIONS Three months ended June 30, 2024 2023 (in thousands, except share and per share amounts)Total revenues $11,126 $2,422 Operating expenses: Cost of license revenues (234) — Cost of contract manufacturing revenues (7,227) (1,352)Research and development expenses (33,655) (46,036)Selling, general and administrative expenses (15,767) (21,181)Total operating expenses (56,883) (68,569)Other income 1,983 1,302 Other expense (236) (229)Loss from operations (44,010) (65,074)Non-operating items, net (11,341) (3,237)Loss before income tax (expense) / benefit $(55,351) $(68,311)Income tax (expense) / benefit (948) (163)Net loss $(56,299) $(68,474) Basic and diluted net loss per ordinary share $(1.16) $(1.44)Weighted average shares used in computing basic and diluted net loss per ordinary share 48,622,440 47,649,520 ________________________________________1 All p-values are nominal and unadjusted. Statistical comparisons of patients treated with AMT-130 to the propensity score-weighted external control were conducted on a post-hoc basis.