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Investment in developers of cell and gene therapies has nosedived this year, a sharp drop-off that investors and analysts say reflect manufacturing and drug delivery challenges at a time when biotechnology companies with clear development paths are increasingly favored.So far this year, makers of cell and gene therapies have raised half of a billion dollars across 16 venture rounds, according to data from DealForma published by Nature. Even annualized, those numbers are well below the $8.2 billion in funding brought in by the 121 deals DealForma counted during the sectors peak in 2021. Last year, cell and gene therapy developers raised $3.5 billion across 65 deals.Were largely seeing investments shifting to things that are de-risked, said Jon Norris, a managing director at HSBC Innovation Banking. Cell and gene therapy is becoming an area we know better, because there are products that have advanced through development, but it still doesn't compare to the number of approvals and drugs commercially available in small molecules or biologics.Overall, biotech venture investment has ticked higher over the first half of 2024, according to a mid-year report from HSBC Innovation Banking. Yet, regardless of technology or research field, biotechs still face a challenging financing environment.Developers of cell and gene therapies face additional hurdles, however, given that the kind of capital required to advance these therapies is different from small molecule drugs or biologics, said Peter Sletteland, a managing director for Silicon Valley Banks life science and healthcare practice. You typically need to spend significant investment in manufacturing.Still, he added, cell and gene therapies garner a lot of attention because of the promise of what they could do.Six CAR-T cell therapies have been approved by U.S. regulators to treat cancer and, in some indications, their benefits can be dramatic. But hopes of replicating that success with so-called allogeneic therapies, which use donor cells rather than individual patients, has been harder to come by than initially envisioned by investors. And uptake of some of the approved CAR-T therapies has been slow, especially as companies work through manufacturing bottlenecks.In gene therapy, sickle cell treatments Casgevy and Lyfgenia secured milestone approvals from U.S. regulators late last year. But only a few dozen patients have begun the process to receive treatment, reflecting the long manufacturing and infusion times needed for each.Adoption has also been slow for the hemophilia gene therapies Hemgenix and Roctavian, while other gene therapy developers like Pfizer have hit clinical setbacks.Patient perception of gene therapy is a crucial barometer. “The therapy has to be worth it, but the question is, are there treatment alternatives?“ said Chris Bardon, co-managing partner at MPM BioImpact.For diseases that have limited treatment options, it may be easy for a patient to consider an intensive cell or gene therapy treatment, which can require arduous chemotherapy preconditioning. But such treatments may by less appealing to people with conditions that are manageable with approved medicines, such as is the case in hemophilia.“It has been a challenge for investors,“ Bardon said.The challenge of developing and selling cell and gene therapies, though, isnt enough to deter investors and drugmakers entirely.In cell therapy, for instance, theres buzz around the potential to target hard-to-treat autoimmune disorders, said Bruce Levine, a cell and gene therapy pioneer at the University of Pennsylvania who co-founded Tmunity Therapeutics and Capstan Therapeutics with colleague Carl June.That's the nature of a therapy that, currently, through the cost of goods and services, is expensive to manufacture, but delivers long-term, durable benefit in patients who have failed all other available therapies, Levine said. '

LEXINGTON, MA, USA and AMSTERDAM, The Netherlands I August 15, 2024 I uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that the first patient has been dosed in a Phase I/IIa clinical trial of AMT-191 for the treatment of Fabry disease, a rare, inherited genetic disease. The Phase I/IIa study is a multi-center, open-label trial being conducted in the United States with two dose-escalating cohorts assessing the safety, tolerability and early signs of efficacy of AMT-191 in individuals with Fabry disease. “We are very pleased to begin patient dosing for AMT-191 in Fabry disease, marking a significant milestone in this year’s goal to advance three new gene therapy candidates into clinical studies,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure . “AMT-191 utilizes the same AAV delivery technology incorporated in HEMGENIX ® , which has an extensive, long-term safety profile and demonstrated effectiveness in patients with preexisting neutralizing antibodies to the AAV capsid. Our trial is designed to capture well-established endpoints in Fabry disease and to rapidly generate clinical proof-of-concept data for AMT-191 with a differentiated product profile relative to other Fabry programs in clinical development.” AMT-191 is an investigational AAV5-based gene therapy that uses a proprietary, highly potent promoter to deliver a galactosidase alpha (GLA) transgene designed to target the liver to produce GLA protein. In patients with Fabry disease, a pathogenic variant in the GLA gene leads to α-galactosidase A (aGAL-A) enzyme deficiency, which in turn results in a progressive accumulation of lipids in multiple cell types, including kidney and heart cells, eventually resulting in a multi-system disorder. AMT-191 may offer a novel potential one-time intravenously administered approach to treating Fabry disease. The Phase I/IIa clinical trial of AMT-191 will be conducted in the United States. The multicenter, open-label trial consists of two cohorts with up to six adult male patients each: a low-dose cohort of 6×10 13 gc/kg and a high-dose cohort of 3×10 14 gc/kg delivered through a one-time intravenous infusion. Patients will continue to receive their regular enzyme replacement therapy until the criteria for withdrawal is met and will be followed for a period of 24 months. The trial will explore the safety, tolerability, and early signs of efficacy by measuring the expression of lysosomal enzyme aGLA-A. Additional details are available on www.clinicaltrials.gov (NCT06270316). “This achievement marks an exciting period for the company as we advance additional programs into clinical trials this year,” stated Matt Kapusta, chief executive officer of uniQure . “Building on our momentum, we are focused on multiple, exciting catalysts across our pipeline, including engaging with the FDA to pursue an expedited clinical pathway for AMT-130 in Huntington’s disease and the initiation of new clinical studies in temporal lobe epilepsy and SOD1-ALS. With a strong balance sheet and runway extended through the end of 2027 from multiple cost reduction initiatives, we believe we are in an excellent position to execute on key value-creating milestones.” About Fabry Disease Fabry disease is an Xlinked- genetic disorder resulting from a deficiency of GLA. Based on a 2020 study published in the Journal of Therapeutics and Clinical Risk Management, the prevalence is estimated to be between one in 40,000 and one in 117,000 individuals. The current standard of care for Fabry disease is bi-weekly infusions of enzyme replacement therapy, a treatment with limited effectiveness in many patients due to poor cross-correction, with inefficient clearance of substrates in the target organs, in particular the kidney and the heart. About uniQure uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. The approvals of uniQure’s gene therapy for hemophilia B – an historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. uniQure is now advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington’s disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases. www.uniQure.com SOURCE: uniQure