TMEM106B

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

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