C9orf72

UNC13A is an essential regulator of neurotransmitter release at synapses; mis-splicing is a critical RNA alteration occurring in up to 63 percent of all ALS patients and up to one-third of all FTD cases Preclinical data to be featured in a poster presentation at AD/PD™ 2024 CAMBRIDGE, Mass., March 4, 2024 /PRNewswire/ -- QurAlis Corporation, a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that will alter the trajectory of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases, today announced preclinical data that showed the company's UNC13A splice-switching antisense oligonucleotides (ASOs) modulate UNC13A splicing and restore normal synaptic activities in ALS and FTD. QurAlis' ASOs prevented cryptic exon inclusion in UNC13A transcripts, increased UNC13A protein levels, and normalized localization of UNC13A protein at the synapse. Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by the loss of neurons in the spinal cord, brainstem, and brain. A defining feature of both sporadic and familial disease is the cytoplasmic mis-localization of TAR DNA Binding Protein-43 (TDP-43). TDP-43 pathology is implicated in 95 percent of ALS cases and 50 percent of FTD cases. UNC13A is an essential regulator of neurotransmitter release at synapses and is one of a number of pre-mRNAs that becomes mis-spliced due to loss of nuclear TDP-43 in disease. Up to 63 percent of ALS patients and up to one-third of FTD patients carry a single nucleotide polymorphism in the UNC13A gene or show TDP-43 pathology which greatly exacerbates UNC13A mis-splicing leading to loss of function of the UNC13A protein. "There are currently no cures for ALS or FTD and limited therapeutic options are available for ALS and FTD patients who are in desperate need for effective therapies," said Dan Elbaum, Ph.D., chief scientific officer of QurAlis. "QurAlis has identified ASOs that modulate UNC13A splicing and restore normal synaptic activities. We believe that correction of UNC13A splicing can provide therapeutic benefit in relevant patient populations." These data will be featured in a poster presentation at the AD/PD™ 2024 International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders being held March 5-9, 2024 in Lisbon, Portugal. Details of the presentation are as follows: Title: UNC13A Targeting Splice Switching ASOs Ameliorate TDP-43 Dependent Mis-splicing Phenotypes in FTD and ALS Date(s)/Time: Thursday, March 7, 2024, and Friday, March 8, 2024 at 1:50-3:50PM CET Poster and Abstract Number: P1214 / 2851 Poster Topic: FTD, ALS: TDP43, C9orf72, and TMEM106B 1 Session: D02 Therapeutic Targets, Mechanisms for Treatment Location: Auditorium VIII Presenter: Marisa Kamelgarn, Ph.D., senior scientist, QurAlis Splice-switching oligonucleotides targeting UNC13A were screened via quantitative polymerase chain reaction (qPCR) and a small subset demonstrated correction of splicing and rescue of protein. From those rescue experiments, ASOs were used for functional assay testing. Using in-house models of induced pluripotent stem cell (iPSC) motor and cortical neurons, QurAlis established a phenotype to demonstrate the cellular consequences of UNC13A mis-splicing due to TDP-43 loss of function. TDP-43 mediated UNC13A loss partially disabled SNARE complex assembly and evoked synaptic vesicle release in human motor neurons. QurAlis' ASOs restored all or some aspects of SNARE complex assembly and synaptic vesicle fusion and release. About QurAlis' FlexASO™ Splice Modulator Platform Incorporating its proprietary FlexASO™ Splice Modulator Platform, QurAlis' ASOs correct UNC13A mis-splicing, restore UNC13A protein production, and reduce cryptic exons that may contribute to disease progression. The QurAlis FlexASO Splice Modulator Platform was developed to generate splice-switching ASOs with improved potency and an increased therapeutic index. In addition to UNC13A, QurAlis is currently exploring this ASO technology for multiple other disease targets. About QurAlis Corporation At QurAlis, we are neuro pioneers on a quest to cure. We work with a relentless pursuit of knowledge, a precise attention to craft, and an optimistic mindset to discover and develop effective precision medicines that will alter the trajectory of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases. Founded by an internationally recognized team of neurodegenerative biologists from Harvard Medical School and Harvard University, QurAlis is advancing a pipeline with therapeutic candidates that target specific components of ALS and FTD pathology and defined patient populations based on both disease-causing genetic mutation(s) and clinical biomarkers. For more information, please visit or follow us on Twitter @QurAlisCo. SOURCE QurAlis

Continued momentum in upliFT-D trial of PBFT02 for the treatment of patients with frontotemporal dementia (FTD) with granulin mutations (GRN) with clinical trial site expansion into Europe and seven global sites now activatedPursuing new indications for PBFT02, including adult neurodegenerative diseases FTD-C9orf72, amyotrophic lateral sclerosis (ALS) and Alzheimer’s diseaseEnded 2023 with robust balance sheet sufficient to deliver meaningful clinical data; with cash runway into Q4 2025 PHILADELPHIA, March 04, 2024 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on improving the lives of patients with neurodegenerative diseases, today reported financial results for the fourth quarter and year ended December 31, 2023 and provided recent business highlights. "In 2023, we achieved a significant milestone by announcing encouraging data from three patients in Cohort 1 of our FTD-GRN program. This data showcased the ability of PBFT02 to raise CSF progranulin to supraphysiologic levels, even at the lowest dose, Dose 1, and positions PBFT02 as a potential best-in-class treatment for FTD-GRN. Our global upliFT-D study continues to see strong momentum, and we're excited to announce the activation of our first clinical trial site in Europe to further bolster recruitment efforts. We are on track to complete dosing for Cohort 1 patients in the first half of this year and share 6-month additional safety and biomarker data from Cohort 1 in the second half of 2024," said Will Chou, M.D., president and chief executive officer of Passage Bio. "Buoyed by this promising data and additional evidence supporting progranulin's role in neurodegeneration, we are optimistic about expanding the application of PBFT02 beyond FTD-GRN and into new indications with significant unmet needs, including FTD-C9orf72, ALS, and Alzheimer's disease. We eagerly anticipate a catalyst-rich 2024, supported by our robust balance sheet, bringing us closer to improving patient outcomes across neurodegenerative diseases." Recent Highlights Sustained momentum in global Phase 1/2 upliFT-D clinical trial evaluating PBFT02 for frontotemporal dementia (FTD) with granulin mutations (GRN), marked by the activation of two new trial sites and expansion into Europe: Initial data from the first three patients in Cohort 1 demonstrated elevated CSF progranulin levels to supraphysiologic levels at the lowest tested dose, Dose 1, up to six months post-treatment (n=1). Additionally, Dose 1 of PBFT02 continued to be generally well-tolerated in patients who received an enhanced steroid regimen for immunosuppression. In the first half of 2024, the company expects to complete dosing for Cohort 1 patients and report 6-month safety and biomarker data in the second half of 2024. Following the positive data, multiple GRN+ patients have been identified and are being evaluated for eligibility across seven clinical trial sites in Brazil, Canada, the United States and Europe.Expansion of PBFT02 into additional adult neurodegenerative indications: In response to the promising initial data for PBFT02 in FTD-GRN and evidence supporting progranulin’s role in neurodegeneration, the company is currently evaluating the therapeutic potential of PBFT02 in additional indications, including FTD-C9orf72, ALS, and Alzheimer’s disease. The company is preparing for regulatory discussions and expects to obtain regulatory feedback on the clinical pathway to treating FTD-C9orf72 and ALS patients with PBFT02 in 2H 2024.Robust balance sheet to support operations: The company’s decision to focus resources on the exploration of PBFT02 in additional indications, while simultaneously pursuing potential out-licensing opportunities for clinical-stage pediatric programs in GM1 gangliosidosis, Krabbe disease and metachromatic leukodystrophy, provides sufficient cash runway into Q4 2025 to execute through critical value-inflecting milestones. Appointed Kathleen Borthwick as Chief Financial Officer, effective March 1, 2024: Ms. Borthwick previously served as the company’s Senior Vice President, Finance and Interim CFO and brings 25 years of pharmaceutical and biotech strategic financial leadership experience. Anticipated Upcoming Milestones: FTD-GRN Initiate dosing for Cohort 2 FTD-GRN patients in 1H 2024Report 6-month safety and biomarker data from Cohort 1 patients in 2H 2024Announce 12-month follow-up data from Cohort 1 patients in 1H 2025Report initial safety and biomarker data from Cohort 2 patients in 1H 2025 FTD-C9orf72 and ALS Obtain regulatory feedback on the pathway to treating FTD-C9orf72 and ALS patients with PBFT02 in 2H 2024 Fourth Quarter and Full-Year 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $114.3 million as of December 31, 2023, as compared to $189.6 million as of December 31, 2022. The company expects current cash, cash equivalents and marketable securities to fund operations into Q4 2025.Research and Development (R&D) Expenses: R&D expenses were $12.1 million for the quarter ended December 31, 2023, and $61.4 million for the year ended December 31, 2023, compared to $17.7 million and $86.1 million for the same quarter and year ended in 2022, respectively.General and Administrative (G&A) Expenses: G&A expenses were $6.3 million for the quarter ended December 31, 2023, and $41.6 million for the year ended December 31, 2023, compared to $10.6 million and $49.3 million for the same quarter and year ended in 2022, respectively.Net Loss: Net loss was $16.8 million, or $0.30 per basic and diluted share, for the quarter ended December 31, 2023 and $102.1 million, or $1.86 per basic and diluted share, for the year ended December 31, 2023, compared to a net loss of $27.1 million, or $0.50 per basic and diluted share, for the quarter ended December 31, 2022 and $136.1 million, or $2.50 per basic and diluted share, for the year ended December 31, 2022. About Passage Bio Passage Bio (Nasdaq: PASG) is a clinical stage genetic medicines company on a mission to improve the lives of patients with neurodegenerative diseases. Our primary focus is the development and advancement of cutting-edge, one-time therapies designed to target the underlying pathology of these conditions. Passage Bio’s lead product candidate, PBFT02, seeks to treat neurodegenerative conditions, including frontotemporal dementia, by elevating progranulin levels to restore lysosomal function and slow disease progression. To learn more about Passage Bio and our steadfast commitment to protecting patients and families against loss in neurodegenerative conditions, please visit: www.passagebio.com. Forward-Looking StatementsThis press release contains “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including the progress of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; our expectations about potential out-licensing opportunities related to PBGM01, PBKR03 and PBML04; and the ability of our product candidates to treat their respective target CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Passage Bio, Inc.Balance Sheets December 31,(in thousands, except share and per share data) 2023 2022Assets Current assets: Cash and cash equivalents $21,709 $34,601 Marketable securities 92,585 155,009 Prepaid expenses and other current assets 923 926 Prepaid research and development 2,742 6,508 Total current assets 117,959 197,044 Property and equipment, net 15,295 22,515 Right of use assets - operating leases 16,858 19,723 Other assets 433 4,267 Total assets $150,545 $243,549 Liabilities and stockholders’ equity Current liabilities: Accounts payable $1,298 $4,065 Accrued expenses and other current liabilities 11,670 11,011 Operating lease liabilities 3,373 3,275 Total current liabilities 16,341 18,351 Operating lease liabilities – noncurrent 22,921 23,832 Total liabilities 39,262 42,183 Stockholders’ equity: Preferred stock, $0.0001 par value: 10,000,000 shares authorized; no shares issued and outstanding at both December 31, 2023 and December 31, 2022 — — Common stock, $0.0001 par value: 300,000,000 shares authorized; 54,944,130 shares issued and outstanding at December 31, 2023 and 54,614,690 shares issued and outstanding at December 31, 2022 5 5 Additional paid‑in capital 705,789 694,733 Accumulated other comprehensive income (loss) (43) (966)Accumulated deficit (594,468) (492,406)Total stockholders’ equity 111,283 201,366 Total liabilities and stockholders’ equity $150,545 $243,549 Passage Bio, Inc.Statements of Operations and Comprehensive Loss Year Ended December 31,(in thousands, except share and per share data) 2023 2022Operating expenses: Research and development $61,419 $86,053 Acquired in‑process research and development — 3,000 General and administrative 41,580 49,341 Impairment of long-lived assets 5,390 — Loss from operations (108,389) (138,394)Other income (expense), net 6,327 2,269 Net loss $(102,062) $(136,125)Per share information: Net loss per share of common stock, basic and diluted $(1.86) $(2.50)Weighted average common shares outstanding, basic and diluted 54,743,490 54,429,023 Comprehensive loss: Net loss $(102,062) $(136,125)Unrealized gain (loss) on marketable securities 923 (553)Comprehensive loss $(101,139) $(136,678) For further information, please contact: Investors:Stuart HendersonPassage Bio267.866.0114shenderson@passagebio.com Media:Mike BeyerSam Brown Inc. Healthcare Communications312.961.2502MikeBeyer@sambrown.com

AC Immune Announces Upcoming Presentations at AD/PD™ 2024 Multiple presentations at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD™ 2024)Andrea Pfeifer, Ph.D., CEO to lead AC Immune-sponsored symposium on alpha-synuclein pathologies Lausanne, Switzerland, February 22, 2024 – AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, today announced upcoming presentations highlighting its precision medicine pipeline at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD™ 2024), taking place in Lisbon, Portugal March 5-9, 2024. In addition, Andrea Pfeifer, Ph.D., CEO of AC Immune SA will lead an industry symposium exploring the latest clinical advances in the diagnosis and treatment of alpha-synuclein pathologies. Industry Symposium: State-of-the-art of treatment and diagnosis of alpha-synuclein pathologiesSession Date/Time: March 6, 2024 at 8:40 – 10:40 am WET Opening and Closing Remarks: Andrea Pfeifer, Ph.D., CEO of AC Immune SA Recent developments in the diagnosis of synucleinopathies Presenter: Werner Poewe, M.D. (Medical University of Innsbruck, Austria)Time: 8:45 – 9:10 am WET Development of an a-syn-PET tracer for alpha-synucleinopathiesPresenter: Francesca Capotosti, Ph.D. (AC Immune)Time: 9:10 – 9:25 am WET New therapeutic approaches in Parkinson's diseasePresenter: Fabrizio Stocchi, M.D., Ph.D. (University San Raffaele Roma, Italy)Time: 9:25 – 9:45 am WET Morphomer a-syn: small molecules targeting a-syn for the treatment of PDPresenter: Elpida Tsika, Ph.D. (AC Immune)Time: 9:45 – 10:05 am WET Active immunotherapy ACI-7104.056 in early PD: update from the Phase 2 trial VacSYnPresenter: Nuno Mendonça, M.D. (AC Immune)Time: 10:05 – 10:20 am WET Oral PresentationsUtility of [18F]PI-2620 PET in clinical trials: insights into tau pathology deposition in Down SyndromePresenter: Marija Vukicevic, Ph.D. (AC Immune)Session: Therapeutic targets in AD: Tau proteinsDate/Time: March 8, 2024 at 8:55 – 9:10 am WET Targeting TDP-43 with a vectorized full-length antibody decreases neuropathology in a model of ALS/FTDPresenter: Damien Nevoltris, Ph.D. (AC Immune)Session: FTD, ALS: TDP-43, C9ORF72 and TMEM106B 02Date/Time: March 8, 2024 at 2:05 – 2:20 pm WET Discovery and preclinical development of [18F]ACI-19626, a first-in-class TDP-43 PET tracerPresenter: Tamara Seredenina, Ph.D. (AC Immune)Session: FTD, ALS: TDP-43, C9ORF72 and TMEM106B 02Date/Time: March 8, 2024 at 2:20 – 2:35 pm WET VacSYn study: An innovative biomarker-based phase 2 clinical trial to evaluate ACI-7104.056, a novel active immunotherapy for Parkinson’s diseasePresenter: Dymitr Kostrica, M.D. (AC Immune)Session: Advances in PD and LBD drug developmentDate/Time: March 9, 2024 at 5:25 – 5:40 pm WET Poster PresentationsAnti-Abeta liposomal vaccine, ACI-24.060, retains memory in aggressive mouse model of Alzheimer’s diseasePoster number: P0215 / #1422Presenter: Emma Fiorini, Ph.D. (AC Immune) Discovery and optimization of novel potent brain penetrant NLRP3 inhibitorsPoster number: P0114 / #1470Presenter: Tamara Seredenina, Ph.D. (AC Immune) ACI-7104.056, an active immunotherapy for synucleinopathies, induces a strong and sustained antibody response against alpha-synuclein in non-human primatesPoster number: P0996 / #1513Presenter: Guenther Staffler, Ph.D. (AC Immune) About AC Immune SAAC Immune SA is a clinical-stage biopharmaceutical company and a global leader in precision medicine for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and NeuroOrphan indications driven by misfolded proteins. The Company’s two clinically validated technology platforms, SupraAntigen® and Morphomer®, fuel its broad and diversified pipeline of first- and best-in-class assets, which currently features sixteen therapeutic and diagnostic programs, five of which are currently in Phase 2 clinical trials and one of which is in Phase 3. AC Immune has a strong track record of securing strategic partnerships with leading global pharmaceutical companies, resulting in substantial non-dilutive funding in potential milestone payments plus royalties. SupraAntigen® is a registered trademark of AC Immune SA in the following territories: AU, EU, CH, GB, JP, RU, SG and USA. Morphomer® is a registered trademark of AC Immune SA in CN, CH, GB, JP, KR, NO and RU. The information on our website and any other websites referenced herein is expressly not incorporated by reference into, and does not constitute a part of, this press release. For further information, please contact: SVP, Investor Relations & Corporate CommunicationsGary Waanders, Ph.D., MBAAC ImmunePhone: +41 21 345 91 91Email: gary.waanders@acimmune.comU.S. InvestorsCorey Davis, Ph.D.LifeSci AdvisorsPhone: +1 212 915 2577 Email: cdavis@lifesciadvisors.comInternational MediaChris MaggosCohesion BureauPhone: +41 79 367 6254Email: chris.maggos@cohesionbureau.com Forward looking statementsThis press release contains statements that constitute “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical fact and may include statements that address future operating, financial or business performance or AC Immune’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as “may,” “might,” “will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” “outlook” or “continue,” and other comparable terminology. Forward-looking statements are based on management’s current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments, and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include those described under the captions “Item 3. Key Information – Risk Factors” and “Item 5. Operating and Financial Review and Prospects” in AC Immune’s Annual Report on Form 20-F and other filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made, and AC Immune does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. All forward-looking statements are qualified in their entirety by this cautionary statement. Attachment 20240222_ACIU_ADPD Curtain Raiser updated FINAL