Gait Ataxia

TAIPEI, March 26, 2025 /PRNewswire/ -- Yoda Therapeutics Inc. (YODA), an AI-driven company that focuses on Central Nervous System (CNS) drugs, today announced the dosing of the first patient in the Phase 2 trial of YA-101 for Multiple System Atrophy (MSA) in the United States. MSA is a rare and rapidly progressive neurodegenerative disorder that causes severe motor impairment (parkinsonism or cerebellar ataxia) accompanied by autonomic dysfunction, leading to a significant decline in patients' quality of life. Currently, no disease-modifying therapies exist to reverse or slow the progression of MSA, and symptomatic management offers limited relief and is not a practical long-term solution. YA-101, a novel chemical entity (NCE), is designed to treat neurodegenerative diseases by inhibiting neuroinflammation and enhancing neural plasticity. Following the successful completion of safety and tolerability assessments in Phase 1 clinical trial with healthy volunteers in Australia, YA-101 has entered Phase 2 trial, which aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of YA-101 in subjects with MSA at multiple sites in the United States and Taiwan. This Phase 2 trial is a randomized, double-blind, placebo-controlled investigation for MSA patients with walking ability, including those who need walking assistance. Measurement of clinical symptoms, biomarkers, and imaging will allow a comprehensive assessment. Further details are available at . "The dosing of our first patient in the Phase 2 clinical trial of YA-101 for Multiple System Atrophy represents a big step forward as we strive to bring a much-needed treatment option to individuals affected by this rare and debilitating neurodegenerative disorder." stated Yufeng Jane Tseng, PhD, Chief Executive Officer of YODA. About Multiple System Atrophy (MSA) MSA is a rare, rapidly progressive, and fatal neurodegenerative disorder characterized by motor impairment (parkinsonism or cerebellar ataxia) accompanied by autonomic dysfunction. Patients experience debilitating symptoms, including severe orthostatic hypotension, urinary dysfunction, ataxic gait, dysmetria, scanning speech, and cognitive decline, significantly impacting their quality of life. Current therapies focus on symptomatic management, such as dopamine therapy and medications for autonomic dysfunction, but often yield disappointing results. To date, no approved agents are available for MSA. About YA-101 YA-101 is an AI-pioneered NCE with a dual modulation mechanism specifically designed to treat neurodegenerative diseases. YA-101 not only demonstrated improvements in motor-related behavioral impairments in preclinical animal models of ataxia and MSA, but also exhibited a favorable safety profile and was well-tolerated in healthy adults during the Phase 1 trial. On July 1, 2022, it received Orphan Drug Designation (ODD) for MSA from the United States Food and Drug Administration (FDA). About Yoda Therapeutics Inc. (YODA) YODA is an AI-driven company advancing drug research and development targeting CNS disorders. YA-101 is the company's flagship drug, currently in Phase 2 clinical trial for the treatment of MSA. Guided by a mission to address critical unmet medical needs, we are dedicated to offering new treatment options that are innovative, effective, and safe. The company is based in Taipei, Taiwan. For more information, please visit the company's website at . SOURCE Yoda Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

LEIDEN, Netherlands & CAMBRIDGE, Mass., Dec. 11, 2024 (GLOBE NEWSWIRE) -- ProQR Therapeutics NV. (Nasdaq: PRQR) (ProQR), a company dedicated to changing lives through transformative RNA therapies based on its proprietary Axiomer™ RNA editing technology platform, today announced an expansion of its collaboration with the Rett Syndrome Research Trust (RSRT). Building on the initial $1 million research grant announced in January 2024, the expanded partnership includes an additional $8.1 million in funding from the RSRT, for a total of $9.1 million. The funding will support the advancement of AX-2402 into clinical trials. Rett Syndrome, a rare and devastating neurodevelopmental disorder, affects approximately 350,000 people worldwide, predominantly girls. With no current cures and limited treatment options, Rett Syndrome presents a significant unmet medical need. AX-2402 is being developed for individuals with Rett syndrome who have the R270X mutation in MECP2 gene, and is based on ProQR’s proprietary Axiomer RNA editing platform. Axiomer can target many mutations beyond R270X that collectively impact a large segment of the Rett population. Success with AX-2402 sets the foundation for developing RNA editing therapeutics to target the remaining mutations. “We are deeply committed to bring innovative solutions to patients with high unmet needs, such as those living with Rett Syndrome, and are grateful for the expanded partnership with the Rett Syndrome Research Trust,” said Gerard Platenburg, Chief Scientific Officer of ProQR. “The increased support from RSRT underscores the potential of our Axiomer RNA editing technology platform to address complex genetic CNS conditions. The expanded collaboration enables us to accelerate the development of AX-2402 for Rett syndrome and to advance this program into clinical trials.” Monica Coenraads, Founder and CEO of the Rett Syndrome Research Trust, commented: “Individuals with Rett Syndrome live with the profound effects of this condition every day, and they deserve transformative therapies. This partnership with ProQR is exciting and ambitious. We are encouraged by the progress we’ve seen so far and believe that together we are taking critical steps toward achieving our mission of eradicating Rett Syndrome.” The additional $8.1 million in funding will enable ProQR to accelerate work on RNA editing approaches tailored to the genetic mutations that cause Rett Syndrome. This next phase of the collaboration will focus on optimizing therapeutic candidates targeting the transcription factor Methyl CpG binding protein 2 (MECP2) and advancing them toward clinical development. About Axiomer™ ProQR is pioneering a next-generation RNA base editing technology called Axiomer™, which could potentially yield a new class of medicines for diverse types of diseases. Axiomer™ “Editing Oligonucleotides”, or EONs, mediate single nucleotide changes to RNA in a highly specific and targeted way using molecular machinery that is present in human cells called ADAR (Adenosine Deaminase Acting on RNA). Axiomer™ EONs are designed to recruit and direct endogenously expressed ADARs to change an Adenosine (A) to an Inosine (I) in the RNA – an Inosine is translated as a Guanosine (G) – correcting an RNA with a disease-causing mutation back to a normal (wild type) RNA, modulating protein expression, or altering a protein so that it will have a new function that helps prevent or treat disease. About Rett Syndrome Rett syndrome is a progressive neurodevelopmental disorder caused by genetic mutations in the Methyl CpG binding protein 2 (MECP2) and diagnosed primarily in females. It is characterized by apparently normal psychomotor development during the first six to 18 months after birth, followed by a period of developmental stagnation, then a regression in language and motor skills, followed by long-term relative stability. During the phase of regression, affected patients develop repetitive, stereotypic hand movements that replace purposeful hand use. Additional symptoms include gait ataxia and apraxia, seizures, tremors, episodic apnea and/or hyperpnea, gastrointestinal issues, scoliosis and musculoskeletal problems, anxiety and sleep issues and bruxism. About ProQR ProQR Therapeutics is dedicated to changing lives through the creation of transformative RNA therapies. ProQR is pioneering a next-generation RNA technology called Axiomer™, which uses a cell’s own editing machinery called ADAR to make specific single nucleotide edits in RNA to reverse a mutation or modulate protein expression and could potentially yield a new class of medicines for both rare and prevalent diseases with unmet need. Based on our unique proprietary RNA repair platform technologies we are growing our pipeline with patients and loved ones in mind. Learn more about ProQR at www.proqr.com. Forward Looking Statements This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “continue,” "anticipate," "believe," "could," "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," "should," "will," "would" and similar expressions. Such forward-looking statements include, but are not limited to, express and implied statements regarding our expanded collaboration with RSRT, including the plan of the collaboration and the intended benefits thereof, the further development and advancement of our Axiomer™ platform, including our anticipated strength and continued investment in it, as well as the potential of our technologies and product candidates, our ability to accelerate the development of AX-2402 for Rett syndrome and advance the program into clinical trials, the therapeutic potential of our Axiomer RNA editing oligonucleotides and our ability to optimize therapeutic candidates covered by the collaboration, and the timing, progress and results of our preclinical studies and other development activities, including the release of data related thereto, our business operations, as well as the timing of our clinical development. 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 expressed or implied by these forward-looking statements for many reasons, including, without limitation, the risks, uncertainties and other factors in our filings made with the Securities and Exchange Commission, including certain sections of our annual report filed on Form 20-F. These risks and uncertainties include, among others, the cost, timing and results of preclinical studies and clinical trials and other development activities by us and our collaborative partners whose operations and activities may be slowed or halted shortage and pressure on supply and logistics on the global market; the likelihood of our preclinical and clinical programs being initiated and executed on timelines provided and reliance on our contract research organizations and predictability of timely enrollment of subjects and patients to advance our clinical trials and maintain their own operations; our reliance on contract manufacturers to supply materials for research and development and the risk of supply interruption from a contract manufacturer; the potential for future data to alter initial and preliminary results of early-stage clinical trials; the unpredictability of the duration and results of the regulatory review of applications or clearances that are necessary to initiate and continue to advance and progress our clinical programs; the ability to secure, maintain and realize the intended benefits of collaborations with partners, including the collaboration with Eli Lilly and the 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; general business, operational, financial and accounting risks, and risks related to litigation and disputes with third parties; and risks related to macroeconomic conditions and market volatility resulting from global economic developments, geopolitical instability and conflicts. Given these risks, uncertainties, and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future, except as required by law. ProQR Therapeutics N.V. Investor contact:Sarah KielyProQR Therapeutics N.V.T: +1 617 599 6228skiely@proqr.comorPeter KelleherLifeSci AdvisorsT: +1 617 430 7579 pkelleher@lifesciadvisors.com Media contact:Robert StanislaroFTI ConsultingT: +1 212 850 5657robert.stanislaro@fticonsulting.com

Scientists have found our visual perception dips as our feet hit the ground. Further understanding this could help develop early diagnostics for neuromuscular or psychiatric illness; understand changes in mobility as we age; or help with sports science and athletic training. For the first time, neuroscientists have established a link between shifts in our visual perception and the cadence of our steps while walking. The research, published in Nature Communications, shows that the brain processes vision in a rhythmic manner, rising and falling in sensitivity in a cycle that corresponds to the rhythm of our steps. When swinging from one step to the next, human perception is good and reactions fast. During footfall, however, our vision is not as sharp and reactions are slowed. Lead author Dr Matthew Davidson from the School of Psychology at the University of Sydney said: "This work reveals a previously unknown relationship between perception and movement. It bridges a gap between experimental psychology and our natural, everyday behaviour." The study also confirms our understanding of the visual brain sensing the environment in a strobe-like way; our perception takes regular samples of the world before stitching them together to create our seamless experience. However, the new finding that reveals shifts in our visual perception has important implications for understanding human behaviour, how we interact with our environment and make decisions. The work was conducted by Dr Matthew Davidson with colleagues Professor David Alais and Professor Frans Verstraten in the School of Psychology, University of Sydney. Dr Davidson said: "We are consciously aware of a seamless stream of vision but this is deceptive. I use the analogy of a duck swimming on a pond. Beneath the smooth motion on the surface there is a lot cycling activity beneath." This study extends earlier work from the same lab showing that perception of vision and sound is cyclic, with our brain taking around eight samples per second. Professor Alais said: "The critical new finding in this study is that these oscillations in the brain's sampling of the world slow down when walking to match the step cycle. "Humans take about two steps per second when walking and generally keep to a consistent rhythm. The reported oscillations in visual sensitivity also occur at about two cycles per second and are locked to the step cycle. In some participants these rhythmic oscillations occur at four cycles per second but these were also locked to the step cycle." This work is the first time that visual perception has been finely and continuously sampled during walking. Without virtual reality headsets and motion tracking it would not be possible. Dr Davidson said: "Thanks to VR technology we have discovered that our vision moves through a good and a bad phase on every step." It is unclear why our brain's perceptual processes are so closely linked to walking. Professor Alais said: "One possible explanation is that vision becomes secondary to motor control while your foot is grounded and the next step is planned. Once you are in the swing phase between footfalls, the brain switches back to prioritising perceptual sampling of the world, creating an ongoing perceptual rhythm that harmonises with your step rate." The findings open questions that the research team will pursue in further studies. For example, does perception of sound and touch also modulate as we walk? And what about neural activity? The research team plans to follow up these questions to further understand the implications. Dr Davidson said: "An obvious question is whether these oscillations in perception are more pronounced in the elderly given difficulties with balance and coordination as we age. "It also raises the exciting possibility that we could develop cheap and easy diagnostic tests using VR headsets, or use this information to develop tests for early onset of neuro-muscular disorders or some psychiatric illnesses, which can manifest in abnormal gaits." He said it could also be applied to further research in sports science to see if the findings could be applied to optimise decision-making and reaction times in athletes. Underlying all this research remains a persistent mystery. If the world is sampled by our brains rhythmic pulses, why is our conscious perception so seamlessly smooth? Professor Verstraten said: "This was once a question for philosophers, but with access to technology neuroscientists have been able to shed light on how the gaps get filled in. The current view is that the brain is a predictive machine that actively constructs perception and predicts what ought to be there and fills in the blanks. But clearly, we need more research to deepen our understanding." Methods Researchers tracked the walking of 45 subjects walking back and forth along a 10-metre path in a virtual environment. During each walk (lasting about 9 seconds), subjects were required to respond to between zero and eight random visual stimuli. The same stimuli were also presented in stationary trials. Eye and head movement was tracked along with gait and walking information. Of the 45 subjects, insufficient data was collected for seven subjects. In the datasets for 38 subjects, reduced perception at footfall was recorded 83 percent of the time.