HMN (Hereditary Motor Neuropathy) Proximal Type I

The cell and gene therapy market is forecasted to be worth $81bn by 2029, as per GlobalData’s sales and forecast database. Image Credit: JHVEPhoto / Shutterstock. Novartis has signed a collaboration and capsid license agreement with Voyager Therapeutics to develop gene therapies for Huntington’s disease and spinal muscular atrophy (SMA). Voyager will receive $100m in upfront payment, with $20m in equity. The US-based company will also be in line to receive up to $1.2bn in milestone-based payments and tiered royalties on global net sales, as per a 2 January press release. Following the news, Voyager stock was up by 24.8% when the market opened on 2 January, compared to the market close on 29 December 2023. The company’s market cap stands at $395.96m today (3 January), with the funds from the current deal expected to extend the company’s runway into mid-2026. The partnership leverages Voyager’s TRACER technology – tropism redirection of adeno-associated virus (AAV) by cell-type-specific expression of ribonucleic acid (RNA). The TRACER capsid discovery platform allows for the discovery of AAV capsids, which can cross the blood-brain barrier and target the central nervous system while de-targeting the liver and dorsal root ganglia. The companies have collaborated in the past, with Novartis signing a licensing option agreement with Voyager in March 2022. The agreement allowed Novartis access to Voyager’s technology to develop AAV capsids for use against diseases that affect the central nervous system and the option for two additional targets. Under the new deal, Novartis will have target-exclusive access to Voyager’s TRACER capsids related to SMA. It will also be responsible for the development and commercialisation of the SMA gene therapy. Novartis’ current portfolio contains an SMA gene therapy, Zolgensma (onasemnogene abeparvovec). The therapy was approved by the US Food and Drug Administration (FDA) for treating type 1 SMA in 2019. Following deal closure, Novartis will also gain global rights to Voyager’s AAV gene therapy for Huntington’s. Novartis will bear responsibility for the clinical development and commercialisation of the gene therapy whilst Voyager will be responsible for preclinical advancement. Novartis has invested in expanding its gene therapy portfolio. In May 2023, it acquired AVROBIO’s haematopoietic stem cell (HSC) gene therapy programme , designed to treat cystinosis. In July 2023, Novartis acquired San Diego-based preclinical stage biotech DTx Pharma for $1bn. DTx Pharma specialises in small interfering RNA (siRNA) therapies for central nervous system and neuromuscular indications. The cell and gene therapy market is forecasted to be worth $81bn by 2029, as per GlobalData’s sales and forecast database. GlobalData is the parent company of Pharmaceutical Technology . Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. By Cytiva Thematic By downloading this case study, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

RAINBOWFISH study met its primary endpoint with 80% of babies sitting without support for at least five seconds after 1 year of Evrysdi treatment – without treatment these babies would never be able to sit All babies were able to swallow and feed orally and none required permanent ventilation Evrysdi is the only non-invasive SMA therapy and is approved in over 100 countries with more than 11,000 patients treated globally Basel, 04 October 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today presented positive results from the primary analysis of the ongoing RAINBOWFISH study assessing the efficacy and safety of Evrysdi® (risdiplam) in babies with pre-symptomatic SMA (n=26), aged from birth to six weeks. The data were presented at the 28th World Muscle Society (WMS) Congress, 3-7 October 2023. “Evrysdi is the only non-invasive SMA treatment and can be used within hours of birth, potentially allowing these babies to sit, stand and walk, similar to healthy individuals,” said Levi Garraway, M.D., Ph. D., Roche’s Chief Medical Officer and Head of Global Product Development. “Evrysdi has now demonstrated its safety and efficacy in babies, children and adults and these compelling data continue to reinforce our confidence in this treatment.’’ Clinical studies show that the loss of motor neurons may begin before symptoms start so initiating treatment early is critical for better outcomes. The RAINBOWFISH study included babies with two or more copies of the SMN2 gene. Generally, the lower the number, the more severe the disease. The study met its primary endpoint with 80% of the primary efficacy population (n=5) sitting without support for at least five seconds after 1 year of Evrysdi treatment, assessed by Bayley Scales of Infant and Toddler Development, third edition (BSID-III). The primary efficacy population included babies with two SMN2 copies and a CMAP amplitude of ≥1.5 mV at baseline. CMAP amplitude measures the muscle response to a stimulus, and a low score correlates with symptom onset in SMA patients and worse functional outcomes. Of the 26 babies in the study, 81% could sit independently for 30 seconds, including all patients with low CMAP amplitude at baseline (<1.5 mV) and the majority were standing and walking. Without treatment, children with Type 1 SMA would never be expected to sit. RAINBOWFISH was the first trial to assess cognition with a standardised scale (BSID) as an exploratory endpoint and results showed cognitive skills typical of normal child development after 1 year of Evrysdi treatment, assessed by BSID-III. Adverse events (AEs) were more reflective of the age of the babies than underlying SMA. The majority of AEs were not considered treatment-related, and there were no deaths or AEs leading to withdrawal or treatment discontinuation. The most common AEs were teething, COVID-19, pyrexia, gastroenteritis, eczema and constipation. The AEs observed in the RAINBOWFISH primary analysis are generally consistent with those AEs seen in other Evrysdi trials in SMA. “These data reinforce the value of beginning treatment for SMA before symptoms appear, with the goal of preserving motor neurons while they are still abundant,” said Richard Finkel, M.D., RAINBOWFISH Principal Investigator and Director of the Experimental Neuroscience Program at St. Jude Children’s Research Hospital. “Coupled with widespread newborn screening programs, early treatment could counteract the effects of the disease to give babies with pre-symptomatic SMA the best possible start in life.” Roche is also investigating Evrysdi in combination with an anti-myostatin molecule, which is designed to promote muscle growth, among SMA patients 2-10 years of age in the Phase 2/3 MANATEE trial. About Evrysdi® (risdiplam)Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron (SMN) protein deficiency. Evrysdi is administered daily at home in liquid form and non-invasively by mouth or by feeding tube. Evrysdi is designed to treat SMA by increasing and sustaining the production of SMN protein in the central nervous system (CNS) and peripheral tissues. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and core motor functions such as swallowing, speaking, and breathing. Evrysdi was granted PRIME designation by the European Medicines Agency (EMA) in 2018 and Orphan Drug Designation by the U.S. Food and Drug Administration in 2017. In 2021, Evrysdi was awarded Drug Discovery of the Year by the British Pharmacological Society as well as the Society for Medicines Research Award for Drug Discovery. Evrysdi is currently approved in over 100 countries, and the dossier is under review in a further 15 countries. Evrysdi is currently being evaluated in five multicentre trials in people with SMA: FIREFISH (NCT02913482) – an open-label, two-part pivotal clinical trial in infants with Type 1 SMA. The study met its primary endpoint.SUNFISH (NCT02908685) – a two-part, double-blind, placebo-controlled pivotal study in people aged 2-25 years with Types 2 or 3 SMA. The study met its primary endpoint.JEWELFISH (NCT03032172) – an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in people with SMA aged 6 months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi. The study has completed recruitment (n=174).RAINBOWFISH (NCT03779334) – an open-label, single-arm, multicentre study, investigating the efficacy, safety, pharmacokinetics, and pharmacodynamics of Evrysdi in babies (n=26), from birth to six weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is fully enrolled.MANATEE (NCT05115110) – a global phase 2/3 clinical study to evaluate the safety and efficacy of GYM329 (RG6237), an anti-myostatin molecule targeting muscle growth, in combination with Evrysdi for the treatment of SMA in patients 2-10 years of age. The FDA Office of Orphan Products Development granted GYM329 Orphan Drug Designation for the treatment of patients with SMA in December 2021. The study is currently recruiting. In addition to bringing Evrysdi to people around the world, Roche also leads its clinical development as part of a collaboration with the SMA Foundation and PTC Therapeutics. About SMASMA is a severe, progressive neuromuscular disease that can be fatal. It affects approximately one in 10,000 babies and is the leading genetic cause of infant mortality. SMA is caused by a mutation of the survival motor neuron 1 (SMN1) gene, which leads to a deficiency of SMN protein. This protein is found throughout the body and is essential to the function of nerves that control muscles and movement. Without it, nerve cells cannot function correctly, leading to muscle weakness over time. Depending on the type of SMA, an individual’s physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.About Roche in NeuroscienceNeuroscience is a major focus of research and development at Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Roche is investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law. Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Nathalie AltermattPhone: +41 79 771 05 25 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262 Rebekka SchnellPhone: +41 79 205 27 03 Sileia UrechPhone: +41 79 935 81 48 Roche Investor Relations Dr. Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.com Dr. Sabine BorngräberPhone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.com Dr. Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Dr. Gerard Tobin Phone: +41 61 68-72942 e-mail: gerard.tobin@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 04102023_MR_RB WMS_en

RAINBOWFISH study met its primary endpoint with 80% of babies sitting without support for at least 5 seconds after 1 year of Evrysdi treatment — without treatment these babies would never be able to sit All babies were able to swallow and feed orally and none required permanent ventilation Evrysdi is the only non-invasive SMA therapy and is approved in over 100 countries with more than 11,000 patients treated globally SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today presented positive results from the primary analysis of the ongoing RAINBOWFISH study assessing the efficacy and safety of Evrysdi® (risdiplam) in babies with pre-symptomatic SMA (n=26), aged from birth to 6 weeks. These data were presented at the 28th World Muscle Society (WMS) Congress, October 3-7, 2023. “Evrysdi is the only non-invasive SMA treatment and can be used within hours of birth, potentially allowing these babies to sit, stand and walk, similar to healthy individuals,” said Levi Garraway, M.D., Ph. D., Genentech’s chief medical officer and head of Global Product Development. “Evrysdi has now demonstrated its safety and efficacy in babies, children and adults, and these compelling data continue to reinforce our confidence in this treatment.’’ Clinical studies show that the loss of motor neurons may begin before symptoms start, so initiating treatment early is critical for better outcomes. The RAINBOWFISH study included babies with 2 or more copies of the SMN2 gene. Generally, the lower the number, the more severe the disease. The study met its primary endpoint with 80% of the primary efficacy population (n=5) sitting without support for at least 5 seconds after 1 year of Evrysdi treatment, assessed by Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). The primary efficacy population included babies with 2 SMN2 copies and a CMAP amplitude of ≥1.5 mV at baseline. CMAP amplitude measures the muscle response to a stimulus, and a low score correlates with symptom onset in SMA patients and worse functional outcomes. Of the 26 babies in the study, 81% could sit independently for 30 seconds, including all patients with low CMAP amplitude at baseline (<1.5 mV), and the majority were standing and walking. Without treatment, children with Type 1 SMA would never be expected to sit. RAINBOWFISH was the first trial to assess cognition with a standardized scale (BSID) as an exploratory endpoint, and results showed cognitive skills typical of normal child development after 1 year of Evrysdi treatment, assessed by BSID-III. Adverse events (AEs) were more reflective of the age of the babies than underlying SMA. The majority of AEs were not considered treatment-related, and there were no deaths or AEs leading to withdrawal or treatment discontinuation. The most common AEs were teething, COVID-19, pyrexia, gastroenteritis, eczema and constipation. The AEs observed in the RAINBOWFISH primary analysis are generally consistent with those AEs seen in other Evrysdi trials in SMA. “These data reinforce the value of beginning treatment for SMA before symptoms appear, with the goal of preserving motor neurons while they are still abundant,” said Richard Finkel, M.D., RAINBOWFISH Principal Investigator and Director of the Experimental Neuroscience Program at St. Jude Children’s Research Hospital. “Coupled with widespread newborn screening programs, early treatment could counteract the effects of the disease to give babies with pre-symptomatic SMA the best possible start in life.” Genentech is also investigating Evrysdi in combination with an anti-myostatin molecule, which is designed to promote muscle growth, among SMA patients 2-10 years of age in the Phase II/III MANATEE trial. About Evrysdi® (risdiplam) Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron (SMN) protein deficiency. Evrysdi is administered daily at home in liquid form and non-invasively by mouth or by feeding tube. Evrysdi is designed to treat SMA by increasing and sustaining the production of SMN protein in the central nervous system (CNS) and peripheral tissues, as demonstrated in animal models. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and core motor functions such as swallowing, speaking, and breathing. Evrysdi was granted PRIME designation by the European Medicines Agency (EMA) in 2018 and Orphan Drug Designation by the U.S. Food and Drug Administration in 2017. In 2021, Evrysdi was awarded Drug Discovery of the Year by the British Pharmacological Society as well as the Society for Medicines Research Award for Drug Discovery. Evrysdi is currently approved in over 100 countries, and the dossier is under review in a further 15 countries. Evrysdi is currently being evaluated in five multicenter trials in people with SMA: FIREFISH (NCT02913482) – an open-label, two-part pivotal clinical trial in infants with Type 1 SMA. The study met its primary endpoint. SUNFISH (NCT02908685) – a two-part, double-blind, placebo-controlled pivotal study in people aged 2-25 years with Types 2 or 3 SMA. The study met its primary endpoint. JEWELFISH (NCT03032172) – an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics in people with SMA aged 6 months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi. The study has completed recruitment (n=174). RAINBOWFISH (NCT03779334) – an open-label, single-arm, multicenter study, investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of Evrysdi in babies (n=26), from birth to 6 weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is fully enrolled. MANATEE (NCT05115110) – a global Phase II/III clinical study to evaluate the safety and efficacy of GYM329 (RG6237), an anti-myostatin molecule targeting muscle growth, in combination with Evrysdi for the treatment of SMA in patients 2-10 years of age. The FDA Office of Orphan Products Development granted GYM329 Orphan Drug Designation for the treatment of patients with SMA in December 2021. The study is currently recruiting. Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics. About SMA SMA is a severe, progressive neuromuscular disease that can be fatal. It affects approximately 1 in 10,000 babies and is among the leading genetic causes of infant mortality. SMA is caused by a mutation of the survival motor neuron 1 (SMN1) gene, which leads to a deficiency of SMN protein. This protein is found throughout the body and is essential to the function of nerves that control muscles and movement. Without it, nerve cells cannot function correctly, leading to muscle weakness over time. Depending on the type of SMA, an individual’s physical strength and their ability to walk, eat or breathe can be significantly diminished or lost. What is Evrysdi? Evrysdi is a prescription medicine used to treat spinal muscular atrophy (SMA) in children and adults. Important Safety Information Before taking Evrysdi, tell your healthcare provider about all of your medical conditions, including if you: are pregnant or plan to become pregnant, as Evrysdi may harm your unborn baby. Ask your healthcare provider for advice before taking this medicine are a woman who can become pregnant: Before you start your treatment with Evrysdi, your healthcare provider may test you for pregnancy Talk to your healthcare provider about birth control methods that may be right for you. Use birth control while on treatment and for at least 1 month after stopping Evrysdi Pregnancy Registry. There is a pregnancy registry for women who take Evrysdi during pregnancy. The purpose of this registry is to collect information about the health of the pregnant woman and her baby. If you are pregnant or become pregnant while receiving Evrysdi, tell your healthcare provider right away. Talk to your healthcare provider about registering with the Evrysdi Pregnancy Registry. Your healthcare provider can enroll you in this registry or you can enroll by calling 1-833-760-1098 or visiting are an adult male. Evrysdi may affect a man’s ability to have children (fertility). Ask a healthcare provider for advice before taking this medicine are breastfeeding or plan to breastfeed. It is not known if Evrysdi passes into breast milk and may harm your baby Tell your healthcare provider about all the medicines you take You should receive Evrysdi from the pharmacy as a liquid. If the medicine in the bottle is a powder, do not use it. Contact your pharmacist for a replacement Avoid getting Evrysdi on your skin or in your eyes. If Evrysdi gets on your skin, wash the area with soap and water. If Evrysdi gets in your eyes, rinse your eyes with water The most common side effects of Evrysdi include: For later-onset SMA: fever diarrhea rash For infantile-onset SMA: fever diarrhea rash runny nose, sneezing, and sore throat (upper respiratory infection) lung infection (lower respiratory infection) constipation vomiting cough These are not all of the possible side effects of Evrysdi. For more information on the risk and benefits pro Evrysdi, ask your healthcare provider or pharmacist. You may report side effects to the FDA at 1-800-FDA-1088 or . You may also report side effects to Genentech at 1-888-835-2555. Please see full Prescribing Information for additional Important Safety Information. About Genentech in Neuroscience Neuroscience is a major focus of research and development at Genentech. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit . View source version on businesswire.com: Contacts Media Contact: Adam Pryor, (650) 467-6800 Advocacy Contact: Alana Paull, (925) 528-1014 Investor Contacts: Loren Kalm, (650) 225-3217 Bruno Eschli, +41 61 68 75284 Source: Genentech View this news release online at: