SMN2

New data from the RESPOND study show that neurofilament levels, an indicator of neurodegeneration, were reduced in nearly all study participants treated with SPINRAZAReductions in biomarker complement previously reported RESPOND efficacy results showing improved motor function in most participants treated with SPINRAZA after gene therapy CAMBRIDGE, Mass., March 06, 2024 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) announced interim 6-month biomarker data from the initial 29 participants in the open-label RESPOND study.* The Phase 4 study evaluates clinical outcomes and safety following treatment with SPINRAZA over a 2-year period in infants and toddlers with spinal muscular atrophy (SMA) who have unmet clinical needs after treatment with Zolgensma® (onasemnogene abeparvovec). The new data show that plasma neurofilament light chain (NfL) levels, an objective biomarker of axonal injury and neurodegeneration, were reduced in nearly all study participants treated with SPINRAZA. These data will be presented at the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference (March 3-6, 2024). “Our evolving understanding of gene therapy indicates there may be an opportunity for better outcomes,” said Crystal Proud, M.D., Pediatric Neurologist at Children’s Hospital of the King’s Daughters. “Improvements in motor function together with decreases in neurofilament levels seen after treatment with SPINRAZA in RESPOND show that we may be able to further maximize benefits for patients.” Today NfL data are being presented from study participants treated with SPINRAZA for 6 months showing: Among participants with 2 SMN2 copies: All participants had elevated baseline NfL levels relative to healthy children of similar ageIn infants (n=11) who were 9 months or younger at first SPINRAZA dose (mean baseline NfL: 148.3 pg/mL), NfL levels decreased by a mean of 70% from baseline.In children (n=11) over 9 months of age at first SPINRAZA dose (mean baseline NfL: 121.8 pg/mL), NfL levels decreased by a mean of 78% from baseline. Among participants with 3 SMN2 copies: Baseline NfL levels were elevated in 2 of 3 children (mean: 60.6 pg/mL).NfL reductions were observed in those with elevated levels at baseline and remained stable in the participant without an elevated level at baseline. “Biogen is at the forefront of pioneering research aimed at advancing biomarkers to accelerate development of drugs for people living with devastating neurodegenerative diseases like SMA and ALS,” said Priya Singhal, M.D., M.P.H., Head of Development and interim Chief Medical Officer at Biogen. “Prior to receiving SPINRAZA at the start of RESPOND, we saw that participants had elevated neurofilament levels, as compared to healthy children suggesting ongoing neuronal injury. The RESPOND findings underscore the value of neurofilament as an objective marker for assessing remaining unmet needs in SMA patients who have previously received gene therapy.” As reported at the SMA Research & Clinical Care Meeting in June 2023 from the same 29 participants, improvements in motor function were observed in most participants as measured by increased mean total Hammersmith Infant Neurological Examination Section 2 (HINE-2) score from baseline.1 No new emerging safety concerns have been identified in enrolled RESPOND participants who received SPINRAZA after Zolgensma. After a median of 230.5 days in the study, serious adverse events (AEs) were reported in 13/38 (34%) participants. Any AEs were reported in 31/38 (81.6%) participants. No serious AEs were considered related to SPINRAZA or led to study withdrawal, although some were related to administration. These data and additional data from the RESPOND study will be presented at subsequent conferences this year including the 4th International Congress on Spinal Muscular Atrophy hosted by SMA Europe. About SPINRAZA® (nusinersen)SPINRAZA is approved in more than 71 countries to treat infants, children and adults with spinal muscular atrophy (SMA). As a foundation of care in SMA, more than 14,000 individuals have been treated with SPINRAZA worldwide.2 SPINRAZA is an antisense oligonucleotide (ASO) that targets the root cause of SMA by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body.3 It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts.3 SPINRAZA has demonstrated sustained efficacy across ages and SMA types with a well-established safety profile based on data in patients treated up to 8 years,3 combined with unsurpassed real-world experience. The nusinersen clinical development program encompasses more than 10 clinical studies, which have included more than 460 individuals across a broad spectrum of patient populations, including two randomized controlled studies (ENDEAR and CHERISH). The SHINE and NURTURE open-label extension studies are evaluating the long-term impact of SPINRAZA. The most common adverse events observed in clinical studies were respiratory infection, fever, constipation, headache, vomiting and back pain. Laboratory tests can monitor for renal toxicity and coagulation abnormalities, including acute severe low platelet counts, which have been observed after administration of some ASOs. Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (Nasdaq: IONS). Please click here for Important Safety Information and full Prescribing Information for SPINRAZA in the U.S., or visit your respective country’s product website. About BiogenFounded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patient’s lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Facebook, LinkedIn, X, YouTube. Biogen Safe Harbor This news release contains forward-looking statements, the potential clinical effects of SPINRAZA; the potential benefits, safety and efficacy of SPINRAZA; the clinical development program for SPINRAZA; the identification and treatment of SMA; our research and development program for the treatment of SMA; the potential of our commercial business and pipeline programs, including SPINRAZA; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “potential,” “possible,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on our forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, uncertainty of success in the development and potential commercialization of SPINRAZA; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, including SPINRAZA; the occurrence of adverse safety events; the risks of unexpected hurdles, costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements. References: Proud C. Interim results from the ongoing RESPOND study evaluating nusinersen in children with spinal muscular atrophy previously treated with onasemnogene abeparvovec. June 2023. SMA Research & Clinical Care Meeting. Orlando, Fla.Based on commercial patients, early access patients, and clinical trial participants through December 31, 2022. SPINRAZA U.S. Prescribing Information. Available at: https://www.spinraza.com/content/dam/commercial/specialty/spinraza/caregiver/en_us/pdf/spinraza-prescribing-information.pdf. Accessed: February 2024.Core Data sheet, Version 13, October 2021. SPINRAZA. Biogen Inc, Cambridge, MA. * Clinical outcomes and NfL were analyzed in the 29 participants who had the opportunity for at least six months of treatment at the time of the interim analysis. Analysis of mean change in NfL includes participants with baseline and Day 183 assessments; a mean change from baseline was not reported in the 3 SMN2 copies group, due to the small number of participants. Safety data are reported in all participants (n=38) who received at least one dose of SPINRAZA in the trial. MEDIA CONTACT:BiogenJack Cox+ 1 781 464 3260public.affairs@biogen.comINVESTOR CONTACT:BiogenChuck Triano+1 781 464 2442IR@biogen.com

The SMART study supplements a growing body of evidence on the use of Zolgensma in a patient population older and heavier (1.5 – 9.1 years of age) than the children treated in previous clinical studies 1-6 Nearly all patients treated maintained or improved motor milestones after 52 weeks, with most switching to the one-time gene therapy from another chronically administered disease-modifying therapy 1-6 The SMART study is the first open-label clinical study of Zolgensma to include previously treated patients 1-6 March 4, 2024 – Novartis today presented new data that continue to support the clinical benefits of Zolgensma® (onasemnogene abeparvovec), the only one-time gene therapy for the treatment of spinal muscular atrophy (SMA). Final data from the SMART study highlight the safety and efficacy profile of Zolgensma in children with SMA weighing ≥ 8.5 kg to ≤ 21 kg, with a mean age of 4.69 years, most of whom (21/24, 87.5%) had discontinued use of another disease modifying therapy at the time of treatment. The new clinical results supplement emerging real-world experience and use of this innovative therapy in older and heavier children in countries where authorized use is not restricted by age. These data are among a Zolgensma data set being presented during the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference in Orlando, Florida, March 3 – 6. “The results from the SMART study provide evidence that Zolgensma is clinically beneficial for older and heavier patients with SMA, many of whom have had prior treatment with another disease-modifying therapy,” said Dr. Hugh McMillan, Pediatric Neurologist. “These data inform the use of Zolgensma in children up to 21 kg, supporting the use of a one-time gene replacement therapy as a therapeutic option for SMA in a broader population.” The primary study objective was to evaluate the safety and tolerability of Zolgensma in older and heavier patients than were treated in previous clinical studies. The majority of patients in the study experienced increases in transaminases and transient thrombocytopenia; all cases were asymptomatic and managed with appropriate monitoring and treatment, as described in the product labeling. No new safety signals were observed in the study. Most patients in the SMART study maintained motor milestones observed at baseline throughout the one-year study. The mean increase in total Revised Upper Limb Module (RULM) score was 2 points and a mean increase in total Hammersmith Functional Motor Scale – Expanded (HFMSE) score was 3.7 points. Four patients demonstrated new development milestones at week 52. "This data – the first Zolgensma open-label clinical study to include older and heavier, as well as previously treated, patients – should build confidence among caregivers and healthcare professionals as they make informed treatment decisions, consistent with their local product label, for the studied patient population,” said Dr. Sandra P. Reyna, Chief Scientific Advisor and Head of Global Medical Engagement for SMA at Novartis. “We remain committed to reimagining possibilities for the SMA community.” SMART was a Phase 3b, open-label, single-arm, multicenter study designed to evaluate the safety, tolerability and efficacy of a one-time IV infusion of Zolgensma in pediatric patients who have symptomatic SMA with bi-allelic mutations in the SMN1 gene, any copy number of the SMN2 gene, and weigh ≥ 8.5 kg and ≤ 21 kg. The study enrolled a total of 24 patients with heterogeneous phenotypes of SMA across three weight brackets (8.5 - 13 kg; >13 – 17 kg; >17 – 21 kg), ranging in age from ~18 months to 9 years (mean age of 4.69 years). Three patients were treatment-naïve to previous SMN-dependent therapies; 21 were treatment-experienced and discontinued risdiplam or nusinersen before enrollment in the study. The SMART study was the first open-label clinical study of Zolgensma to include previously treated patients. 1-6 Increases in transaminases (ALT or AST >3xULN) were observed in the majority of patients (21/24, 87.5%); transient thrombocytopenia were observed in 17/24 (70.8%) patients; all cases were asymptomatic and managed with appropriate treatment. There were no reported cases of acute liver failure or bilirubin elevations. Increases in RULM from baseline were demonstrated; mean (SD) increase from baseline at Week 52 was 2.0 (4.0) points. Increases in HFMSE from baseline were demonstrated; mean (SD) increase from baseline at Week 52 was 3.7 (4.3) points. Most patients maintained or improved motor milestones from baseline at the time of final analysis. Nearly all (23/24, 95.8%) patients who could sit with slight support still met this milestone at Week 52. Three patients achieved the milestone of newly standing with support and one achieved newly walking with support at Week 52. All patients (6/6, 100%) who could walk at baseline maintained this milestone until end of study. Zolgensma® (onasemnogene abeparvovec) is the only approved gene therapy for the treatment of spinal muscular atrophy (SMA) and the only SMA treatment designed to directly address the genetic root cause of the disease by replacing the function of the missing or non-working SMN1 gene to halt disease progression through sustained SMN protein expression with a single, one-time IV infusion. Zolgensma is now approved in more than 51 countries and more than 3,700 patients have been treated with Zolgensma globally across clinical trials, managed access programs, and in the commercial setting.7 Novartis is unwavering in its commitment to reimagine the possibilities for children living with SMA and continues to evaluate Zolgensma across a robust clinical development program, as well as the investigational intrathecal administration of OAV101 in patients with later-onset forms of SMA. Novartis AG has an exclusive, worldwide license with Nationwide Children's Hospital to both the intravenous and intrathecal delivery of AAV9 gene therapy for the treatment of all types of SMA; has an exclusive, worldwide license from REGENXBIO for any recombinant AAV vector in its intellectual property portfolio for the in vivo gene therapy treatment of SMA in humans; and an exclusive, worldwide licensing agreement with Généthon for in vivo delivery of AAV9 vector into the central nervous system for the treatment of SMA. Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disease and a leading genetic cause of infant death.8,9 Caused by the lack of a functional SMN1 gene, the most severe forms of SMA result in the rapid and irreversible loss of motor neurons, affecting muscle functions including breathing, swallowing and basic movement.10 Severity varies across a spectrum of types corresponding to the number of copies of the back-up SMN2 gene.11 The majority (>70%) of patients with two copies of SMN2 develop Type 1, the most common form, accounting for 60% of cases.12,13 Type 1 is severe and, left untreated, leads to death or the need for permanent ventilation by the age of two in more than 90% of cases.8,9 Most patients (>80%) with three copies of SMN2 develop Type 2, accounting for 30% of cases.12 Left untreated, patients with Type 2 are unable to walk and will require a wheelchair, and more than 30% will die by age 25.14 Loss of motor neurons cannot be reversed, so it is imperative to diagnose SMA and begin treatment, including proactive supportive care, as early as possible to halt motor neuron loss and disease progression.15,16 Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. References 1. Day JW, et al. Lancet Neurol. 2021; 20:284–93. 2. Mendell JR, et al. N Engl J Med. 2017; 377:1713–22. 3. Al-Zaidy SA, et al. J Neuromuscul Dis. 2019; 6:307–17. 4. Mercuri E, et al. Lancet Neurol. 2021; 20:832–41. 5. Strauss K, et al. Nat Med. 2022; 28:1381–9. 6. Strauss K, et al. Nat Med. 2022; 28:1390–7. 7. Data on File. Novartis AG, 2023. 8. Anderton RS and Mastaglia FL. Expert Rev Neurother. 2015;15(8):895–908. 9. Finkel RS, McDermott MP, Kaufmann P. et al. Neurology. 2014;83(9):810–7. 10. Sugarman EA, Nagan N, Zhu H, et al. Eur J Hum Genet. 2012;20(1):27–32. 11. Lorson CL, Rindt H, Shababi M. Hum Mol Genet. 2010;(15):111–8. 12. Verhaart IEC, Robertson A, Wilson IJ, et al. Orphanet J Rare Dis. 2017;4;12(1):124. 13. Feldkötter M, et al. Am J Hum Genet. 2002;70:358–68. 14. Darras BT, Finkel RS. “Natural history of spinal muscular atrophy.” In: Sumner CJ, Paushkin S, Ko CP, eds. Spinal Muscular Atrophy: Disease Mechanisms and Therapy. (2nd ed. London, UK: Academic Press/Elsevier; 2017. Pp. 399‒421. 15. Soler‐Botija C, et al. Brain. 2002;125(7):1624–1634. 16. Glascock J, et al. J Neuromuscul Dis. 2018;5:145–158. The content above comes from the network. if any infringement, please contact us to modify.

Kitted assays for clinical laboratories streamline the detection of challenging genes and variants to improve results for underrepresented populations MINNEAPOLIS , Nov. 2, 2023 /PRNewswire/ -- Bio-Techne Corporation (NASDAQ:TECH) today announced that Asuragen, a Bio-Techne brand, will present new data on clinical laboratory testing solutions related to cystic fibrosis variant detection, cancer monitoring, resolving conventionally inaccessible, disease-causing genes, and more at the upcoming meeting of the Association for Molecular Pathology (AMP), to be held November 14-18 in Salt Lake City, Utah. Attendees can learn about Asuragen's new products and innovations through a series of corporate workshops and poster presentations. "We are excited to connect with the innovative and dedicated AMP community as we all seek to improve clinical laboratory capabilities to deliver the best possible results for patients," said Bernard Andruss, PhD, Vice President and General Manager, Molecular Diagnostics Division, Bio-Techne. "We look forward to sharing new data that reinforces our commitment to more equitable healthcare, comprehensive genetic coverage, and novel approaches to cancer monitoring and management." In addition, Dr. Jordan Laser, Senior Director, Clinical and Medical Affairs for Bio-Techne's Diagnostics and Genomics Segment, will be recognized at the conference with the AMP Meritorious Service Award for his work to promote AMP as a member of the association. Poster Presentations Impact of Variants of Varying Clinical Consequence in Underrepresented Populations and Implications for a Minimum Variant Set for Pan-Ancestry Cystic Fibrosis Carrier Screening Presenter: Brian Haynes, PhD, CSO, Asuragen & Head of Bioinformatics Molecular Diagnostics Division Accurate Genotyping of Complex, Clinically-Relevant Variants in 11 Hard-to-Decipher Genes by Combining Novel PCR Chemistries with Any-Length Nanopore Sequencing for Carrier Screening Presenter: Brennan Greenlee, MS, Sr. Research Associate, Asuragen Development of a Novel Exosome-based, Multiplexed RT-qPCR Technology for Rapid and Accurate Detection of Circulating Tumor Acquired Resistance Variants in ESR1 at ≤ 0.1% Frequency Presenter: Julie Thibert, MS, Scientist, Asuragen Prototype RT-qPCR PML:RARA Reagents and a Commercial PML-RARA Kit Yield Highly Correlated Results Presenter: Ila Wolf, PhD, Scientist, Asuragen Corporate Workshops Simple, Sensitive, and Scalable: QuantideX® Suite of Assays for Targeted MRD Monitoring of Leukemic Fusions November 15, 11:00 am, Room 251F For highly sensitive detection of leukemic fusions using widely available qPCR equipment, Asuragen's QuantideX qPCR BCR-ABL kits offer IVD or RUO testing capabilities for molecular laboratories of any size. Learn about key features of these assays and see real-world performance data. Speaker: Holli M. Drendel, Ph. D., FACMGG Director, Molecular Pathology Laboratory Carolinas Pathology Group AmplideX® to the Rescue: One easy-to-implement test workflow enabling repeat expansion resolution, copy number assessment, and highly multiplexed variant detection. November 15, 12:00 pm, Room 251F Asuragen's simple and scalable AmplideX technology, the gold standard for FMR1 analysis, has been expanded to cover other repeat disorder genes, copy number assays, and highly multiplexed variant detection. This workshop will report the experience of a clinical lab that adopted the AmplideX SMN1/2 Plus Kit for detection of SMN1 and SMN2 copy numbers and genetic variants. Speaker: Sarah S. Murray, Ph.D., FACMG Clinical Professor, Department of Pathology Director, Medical Genetics and Genomics University of California San Diego About Bio-Techne Bio-Techne Corporation (NASDAQ: TECH) is a global life sciences company providing innovative tools and bioactive reagents for the research and clinical diagnostic communities. Bio-Techne products assist scientific investigations into biological processes and the nature and progress of specific diseases. They aid in drug discovery efforts and provide the means for accurate clinical tests and diagnoses. With thousands of products in its portfolio, Bio-Techne generated over $1.1 billion in net sales in fiscal 2023 and has approximately 3,200 employees worldwide. For more information on Bio-Techne and its brands, please visit or follow the Company on social media at: Facebook, LinkedIn, Twitter or YouTube. Bio-Techne Corporation (NASDAQ: TECH) Contact: David Clair, Vice President, Investor Relations & Corporate Development [email protected] 612-656-4416 Media Contact: Suzanne Howard [email protected] SOURCE Bio-Techne Corporation