WVE-003

2024 was a challenging year for the biopharma industry, with companies like Bayer, Bristol Myers Squibb, and Johnson & Johnson cutting hundreds to thousands of jobs. Cassava Sciences announced layoffs of 10 employees, 33% of its workforce, following a failed Phase III trial for its Alzheimer's drug. CytomX Therapeutics cut 40% of its staff to focus on clinical programs. Velia, a San Diego biotech, is shutting down, affecting 47 employees. Regeneron's acquisition of Oxular led to layoffs, with no Oxular employees joining Regeneron. Javara, Ring Therapeutics, Outlook Therapeutics, Editas, Bavarian Nordic, BenevolentAI, Chroma Medicine and Nvelop Therapeutics, Cellectar Biosciences, Carisma Therapeutics, Belharra Therapeutics, National Resilience, AmplifyBio, Agenus, Alligator Bioscience, Idorsia Pharmaceuticals, Kronos Bio, Novartis, Recursion Therapeutics, Medigene, Alector, Bristol Myers Squibb, Sonata Therapeutics, 23andMe, Johnson & Johnson, Merck, Gilead Sciences, Adaptimmune, Sensei Biotherapeutics, Marinus Pharmaceuticals, Orna Therapeutics, Thermo Fisher Scientific, Charles River Laboratories, Aurinia Pharmaceuticals, Viracta Therapeutics, Astellas Gene Therapies, Sana Biotechnology, Sage Therapeutics, Compass Pathways, Spero Therapeutics, ICON, Pfizer, Takeda, SalioGen Therapeutics, Evonik, Medtronic, CareFusion Resources, Turnstone Biologics, Leo Pharma, Astellas Pharma, Prime Medicine, Kaléo, Stryker, Relay Therapeutics, ImmunityBio, Shattuck Labs, Inventprise, bluebird bio, Athira Pharma, AGC Biologics, Oncternal Therapeutics, Biosense Webster, Vesigen Therapeutics, Connect Biopharma, BioMarin, IN8bio, Edwards Lifesciences, DermTech, Repare Therapeutics, Genentech, Tome Biosciences, Aadi Bioscience, Lykos Therapeutics, Evotec, Galera Therapeutics, Grail, Ovid Therapeutics, Lexicon Pharmaceuticals, Acelyrin, Boundless Bio, FibroGen, Ajinomoto Bio-Pharma Services, AN2 Therapeutics, Entero Therapeutics, Precigen, Sumitomo Pharma America, uniQure, Vir Biotechnology, Arbutus Biopharma, HilleVax, and Bayer also announced significant layoffs, reflecting a tough year for the industry.

2024 marked significant progress in Huntington’s disease (HD) research, with breakthroughs in understanding somatic instability, advancements in drug development, and both challenges and triumphs in clinical trials. The HD community saw the power of collaboration and innovation, with new voices at HDBuzz and updates from global conferences. Despite setbacks, there's hope with ongoing trials and new drug approvals, moving closer to treatments that could slow or halt HD.

UniQure aligned with FDA on accelerated approval pathway for Huntington’s disease gene therapy AMT-130, using Phase I/II studies and composite Unified Huntington’s Disease Rating Scale as primary basis for Biologics License Application (BLA).

Vico Therapeutics' VO659, an antisense oligonucleotide targeting C-A-G repeats in Huntington's disease (HD), shows potential to reduce toxic HD protein levels and is being tested in a basket trial for HD, SCA1, and SCA3. Initial data suggest VO659's safety and efficacy, though radiculitis side effects were observed at higher doses, prompting future dosing adjustments.

Six companies—Ionis Pharmaceuticals, Isarna Therapeutics, Regulus Therapeutics, Sarepta Therapeutics, Secarna Pharmaceuticals, and Wave Life Sciences—are leading in the development of antisense oligonucleotides, a targeted treatment for various diseases. Ionis, a pioneer with over 40 drugs in its pipeline, recently priced a $500 million IPO. Isarna's ISTH0036 targets TGF-β for ophthalmic conditions. Regulus focuses on microRNA targeting with its lead candidate RGLS8429 for ADPKD. Sarepta has three approved PPMO therapies for DMD and a recent $1 billion deal with Arrowhead Pharmaceuticals. Secarna's SECN-15 targets NRP1 for oncology. Wave Life Sciences' WVE-003, for Huntington's disease, recently reported positive phase 1b/2a trial results. The antisense oligonucleotide market is projected to grow to $5,519 million by 2033.

Huntington's disease treatments face challenges due to rarity and trial failures, but recent milestones like Wave's WVE-003, Roche-Ionis' tominersen, uniQure's AMT-130, and PTC Therapeutics' PTC518 offer hope. Prilenia's pridopidine is under EMA review, while Annexon's ANX005 and Sage's dalzanemdor faced setbacks. Despite these, cautious optimism remains for effective treatments.

Day 2 of the 2024 Huntington Study Group Conference featured talks on palliative care, clinical trial challenges, and updates from various drug development companies, emphasizing the importance of early intervention and the use of biomarkers in HD treatment.

Wave Life Sciences announced financial results for Q3 2024, including first-ever RNA editing in humans with WVE-006 in AATD, and progress in three GalNAc-AIMer preclinical programs for cardiometabolic diseases. WVE-007 for obesity and WVE-N531 for DMD are advancing towards key milestones. FDA feedback on WVE-003 for HD supports potential accelerated approval. Cash and cash equivalents totaled $310.9 million as of September 30, 2024, with runway expected into 2027.

Despite decades of research, Huntington’s disease lacks a disease-modifying treatment. Clinical trials face challenges due to limited patient numbers and geographic barriers. Prilenia Therapeutics, Sage Therapeutics, uniQure, Wave Life Sciences, and Roche-Ionis are developing potential treatments, though some have faced setbacks. Prilenia’s pridopidine and Sage’s dalzanemdor showed mixed results, while uniQure’s AMT-130 and Wave’s WVE-003 demonstrated promising reductions in mutant huntingtin protein. Roche-Ionis’ tominersen faces ongoing development challenges.