SOD1

SOD1- ALS is a devastating, uniformly fatal, and ultra-rare genetic form of ALS that represents approximately two percent of all ALS cases1 Health Canada regulatory decision on tofersen New Drug Submission expected in early 2025 TORONTO, March 19, 2024 /CNW/ - Biogen Canada Inc. announced today that Health Canada has accepted for review a New Drug Submission(NDS) for tofersen for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. If approved, tofersen will be the first treatment indicated in Canada to target a genetic cause of ALS. "The tofersen New Drug Submission represents a critical milestone for the Canadian ALS community and those suffering from this ultra-rare genetic form of the disease that robs them of time with loved ones," said Eric Tse, General Manager of Biogen Canada. "For over a decade, Biogen has been committed to advancing ALS research to provide a deeper understanding of this devastating disease. We are passionate about doing what we can to make a difference and are deeply committed to the rare disease community." According to the ALS Society of Canada, ALS currently impacts an estimated 4,000 Canadians, with approximately 1,000 new Canadians diagnosed each year.2 The NDS is based on results from the Phase 3 VALOR trial, a 28-week randomized, double-blind, placebo-controlled clinical study, which assessed the safety and efficacy of tofersen in patients with weakness attributable to ALS and a confirmed SOD1 mutation. A regulatory decision on the New Drug Submission is expected in early 2025. About tofersen Tofersen is an antisense oligonucleotide (ASO) designed to bind to SOD1 mRNA to reduce SOD1 protein production. The U.S. Food and Drug Administration granted accelerated approval for QALSODY™ (tofersen) to treat amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with tofersen. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).3 Tofersen also received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommending its marketing authorization under exceptional circumstances for the treatment of adults with ALS associated with a mutation in the SOD1 gene.4 A decision on a marketing authorization in the European Union is expected in the second quarter of 2024. Biogen licensed tofersen from Ionis Pharmaceuticals, Inc. under a collaborative development and license agreement. Tofersen was discovered by Ionis. In addition to an ongoing open label extension (OLE) of VALOR, tofersen is being studied in the Phase 3, randomized, placebo-controlled ATLAS study to evaluate whether tofersen can delay clinical onset when initiated in presymptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity (elevated plasma NfL). More details about ATLAS (NCT04856982) can be found at clinicaltrials.gov. About Amyotrophic Lateral Sclerosis and SOD1-ALS Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and the spinal cord that are responsible for controlling voluntary muscle movement. People with ALS experience muscle weakness and atrophy, causing them to lose independence as they steadily lose the ability to move, speak, eat, and eventually breathe. Average life expectancy for people with ALS is three to five years from time of symptom onset.5 Multiple genes have been implicated in ALS. Genetic testing helps determine if a person's ALS is associated with a genetic mutation, even in individuals without a known family history of the disease. More than 15 percent of people with ALS are thought to have a genetic form of the disease;6 however, they may not have a known family history of the disease.1 SOD1-ALS is diagnosed in approximately two percent of all ALS cases.1 In people with SOD1-ALS, mutations in their SOD1 gene cause their bodies to create a toxic misfolded form of SOD1 protein. This toxic protein causes motor neurons to degenerate, resulting in progressive muscle weakness, loss of function, and eventually, death.6 Biogen's Continuous Commitment to ALS For over a decade, Biogen has been committed to advancing ALS research to provide a deeper understanding of all forms of the disease. The company has continued to invest in and pioneer research despite making the difficult decision to discontinue a late-stage ALS asset in 2013. Biogen has applied important learnings to its portfolio of assets for genetic and other forms of ALS, with the goal of increasing the probability of bringing a potential therapy to patients in need. These applied learnings include evaluating genetically validated targets in defined patient populations, pursuing the most appropriate modality for each target and employing sensitive clinical endpoints. In addition to tofersen, the company has a pipeline of investigational drugs being evaluated in ALS, including BIIB105. About Biogen Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patient 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. Biogen has been proudly serving Canadian patients for more than 25 years. For information about Biogen Canada, please visit . SOURCE Biogen Canada

None  Welcome to this week's Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please send the good word—or the bad—from your shop to Max Bayer or Gabrielle Masson, and we will feature it here at the end of each week. Voyager returns to Biogen’s orbit, plucking another executive Voyager Therapeutics You can always count on Al Sandrock to have his finger on the pulse of Biogen. The 21-year vet of the neuroscience pharma has returned (metaphorically speaking) to his old haunting grounds, leaving with fresh talent. Voyager announced it was hiring Toby Ferguson, M.D., as its chief medical officer, effective March 25. Ferguson was most recently vice president and head of neuromuscular development at Biogen, where he joined in 2013. He started as a medical director and advanced to executive medical director, before taking his current position.  His claim to fame was leading the team that produced SOD1 ALS med Qalsody, which received FDA accelerated approval based on the reduction of a disease biomarker. In light of Amylyx’s recent late-stage failure, Qalsody is arguably the most significant ALS treatment advancement in recent years. Voyager is currently working on a SOD1 gene therapy that’s entering IND-enabling studies.  Before joining Biogen, Ferguson was an assistant professor of neurology at Temple University in Philadelphia. Release Pfizer names new CSO for anti-infectives research unit  Pfizer  Despite Pfizer making its oncology ambitions clear, the New York pharma does in fact have additional assets elsewhere, including anti-infectives. Much of that work centers on COVID treatment Paxlovid, with additional candidates aimed at RSV infection and complicated urinary tract infections.  Now, the company is bolstering that team, hiring Isabel Najera, Ph.D., as chief scientific officer of the anti-infective research unit. She previously was the head of research for infectious disease at Janssen, before the pharma dismantled and divested from the work altogether.  Najera cut her teeth at Roche, where she spent a total of 19 years across a number of different positions. She started in 1999 as a research scientist working on hepatitis C virology and spent the last four years there as the deputy head of discovery and head of clinical microbiology for inflammation, immunology and infectious diseases. Rigel hires ex-Sangamo CMO for the same role  Rigel Pharmaceuticals Lisa Rojkjaer, M.D., is joining Rigel as executive vice president and chief medical officer, the biotech announced this week. She joins from Sangamo where she held the same role. Rojkjaer at Sangamo for less than a year, from May 2023 to March 2024. She spent more than six-and-a-half years at two prior CMO gigs, with Viracta Therapeutics and Nordic Nanovector, respectively. She’s also spent more than six years across two stints at Novartis. Release > FibroGen has tapped Deyaa Adib, M.D., to serve as the oncology company’s SVP and chief medical officer. Before joining FibroGen, Adib was Triumvira Immunologics’ CMO and previously held roles at Rain Therapeutics, Blueprint Medicines, Baxalta, ARIAD Pharmaceuticals, Aventis, Sanofi and Astellas Pharma. Release > Jullian Jones, Ph.D., has joined MOMA Therapeutics to serve as the platform company’s chief business officer. Jones comes from Monte Rosa Therapeutics, where she also held the CBO title and oversaw the biotech’s recent partnership with Roche Pharmaceuticals. Release > Capsida Biotherapeutics has promoted Rob Murphy from his role as VP of technical operations to chief manufacturing and quality officer. Murphy joined the biotech in 2020 and helped design, build and staff Capsida’s state-of-the-art gene therapy manufacturing site. Release > Apellis Pharmaceuticals is appointing Philip Ferrone, M.D., to serve as the company’s chief medical retina adviser, effective March 18. Ferrone currently is, and will continue to be, the director of clinical research at Vitreoretinal Consultants in New York. Release > Tim Clackson, Ph.D., is taking the top spot at IDRx, replacing founding CEO and co-founder Ben Auspitz, while Brad Dahms will step on as chief financial officer and chief business officer. Clackson and Dahms both join IDRx from Theseus Pharmaceuticals, where they served as CEO and CFO, respectively. Release > GSK’s head of biologics and devices manufacturing Bill Dawson has been appointed the new chair of the Medicines Manufacturing Industry Partnership, an organization representing medicines manufacturers in the U.K. Dawson has been with GSK for nearly 8 years, and worked at Novartis before that, according to his LinkedIn. Release > Corinne Le Goff has resigned from her position as IMUNON’s president and CEO, exiting to pursue another business opportunity. Executive Chair Michael Tardugno, who served as CEO before Le Goff, will assume daily leadership responsibilities until a successor is selected. Release > VC 4BIO Capital has promoted Natalie Johnston, Ph.D., to principal, while appointing Abbas Hussain and Leszek Lisowski, Ph.D., to its advisory board. Previously, Johnston served as an investment associate for 4BIO, while Hussain most recently worked at Vifor Pharma and Lisowski helped establish two gene therapy companies: Exigen Biotherapeutics and Sendatu Therapeutics. Release > Y-mAbs Therapeutics EVP, Chief Financial Officer, Secretary and Treasurer Bo Kruse is resigning, effective as of the day a successor is appointed or July 31, 2024. Kruse has been with the company for nearly nine years, according to his LinkedIn profile. Release > Endeavor BioMedicines is bringing on two new leaders, appointing Enoch Kariuki as president and Vishaal Turakhia as chief financial officer. Kariuki most recently served as CEO of Lengo Therapeutics (acquired by Blueprint Medicines), while Turakhia was previously managing director at Piper Sandler’s healthcare investment banking group. Release > Joseph Bertelsen is joining U.K.-based biotech Nuclera as chief commercial officer. He previously worked at the Institute for Protein Innovation, a research site in Massachusetts, where he was the director of commercialization. Release

Natural products have unique chemical structures and biological activities and can play a pivotal role in advancing pharmaceutical science. In a pioneering study, researchers discovered Inaoside A, an antioxidant derived from Laetiporus cremeiporus mushrooms. This breakthrough sheds light on the potential of mushrooms as a source of therapeutic bioactive compounds. Natural products have unique chemical structures and biological activities and can play a pivotal role in advancing pharmaceutical science. In a pioneering study, researchers from Shinshu University discovered Inaoside A, an antioxidant derived from Laetiporus cremeiporus mushrooms. This breakthrough sheds light on the potential of mushrooms as a source of therapeutic bioactive compounds. The search for novel bioactive compounds from natural sources has gained considerable momentum in recent years due to the need for new therapeutic agents to combat various health challenges. Among a diverse array of natural products, mushrooms have emerged as a rich reservoir of bioactive molecules with potential pharmaceutical and nutraceutical applications. The genus Laetiporus has attracted attention for its extracts exhibiting antimicrobial, antioxidant, and antithrombin bioactivities. The species Laetiporus cremeiporus, spread across East Asia, has also been reported to show antioxidant properties. However, the identification and characterization of specific antioxidant compounds from this species have not been conducted. In a groundbreakng study, researchers led by Assistant Professor Atsushi Kawamura from the Department of Biomolecular Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, along with Hidefumi Makabe from the Department of Agriculture, Graduate School of Science and Technology, Shinshu University, and Akiyoshi Yamada from the Department of Mountain Ecosystem, Institute for Mountain Science, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, recently discovered the antioxidant compound derived from L. cremeiporus. The researchers collected fresh fruiting bodies of L. cremeiporus from the Ina campus of Shinshu University. The obtained extracts were concentrated and partitioned between water and ethyl acetate. After this, the extracts were subjected to advanced chromatographic techniques, which led to the successful isolation of Inaoside A, a new antioxidant phenolic compound, along with three other well-characterized bioactive compounds, i.e., 5'-S-methyl-5'-thioadenosine (MTA), nicotinamide, and adenosine. They reported their findings in an article that was made available online on 20 January 2024 and subsequently published in the journal Heliyon. "Our study marks the pioneering discovery of Inaoside A from an extract of the edible mushroom Laetiporus cremeiporus. To date, there has been only one prior report on the biological function of an extract of L. cremeiporus. We are the first to uncover the isolation of an antioxidant compound from L. cremeiporus," states Professor Kawamura, highlighting the breakthrough research. Next, the researchers wanted to determine the structure of the newly found antioxidant compound. For this, they utilized one and two- dimensional NMR and other spectroscopic analyses. The structure of Inaoside A revealed a planar configuration. With a molecular formula of C17H24O7, the compound was found to feature a distinctive ribose moiety, identified as α-ribofuranoside through stereochemical analysis. Subsequent investigation into the absolute stereochemistry confirmed the D-ribose configuration, thereby reinforcing the planar structure of this compound. The mushroom extracts were then isolated into fractions to determine the antioxidant activities of the four isolated bioactive compounds. These fractions were then examined by DPPH radical scavenging and superoxide dismutase assays. The findings were noteworthy as the DPPH radical scavenging activity exhibited by Inaoside A was significant, showing 80% inhibition at 100 μg/mL, indicative of its significant antioxidant properties. The IC50 value of Inaoside A was determined to be 79.9 μM, further highlighting its efficacy as an antioxidant agent. What are the objectives of the researchers following the discovery of Inaoside? Professor Kawamura reveals, "We are now focusing on investigating the chemical compositions and biological properties of natural compounds obtained from mushrooms. Our goal is to uncover the potential of edible mushrooms as functional foods through this discovery." The identification of Inaoside A as an antioxidant from Laetiporus cremeiporus marks a significant breakthrough in natural product research, highlighting the potential of mushrooms as a source of therapeutic bioactive compounds. These findings may lead to the development of novel antioxidant-based therapies for various health conditions. Further studies should focus on synthetic research and detailed investigations into the biological activity of Inaoside A, aiming to harness its potential as a pharmaceutical lead compound.