Cevaretigene ritoparvovec (MeiraGTx)

Dive Brief:French drugmaker Sanofi has invested $30 million into MeiraGTx Holdings, a London- and New York-based developer of gene therapies, through a purchase of 4 million shares at $7.50 apiece.The investment, announced by the gene therapy maker Monday, gives Sanofi the right of first negotiation to license certain MeiraGTx technology in immunology, neurology and metabolic disease settings.MeiraGTx is perhaps best known for its work on gene therapies for the eye, but Mondays deal shows its progress elsewhere. The company also signaled more transactions may be coming in the future, after being approached by multiple other companies interested in its work.Dive Insight:Sanofis investment comes after a disastrous end to last week, when its shares fell by almost 20% after the company adjusted its financial outlook alongside third quarter earnings. The pharmaceutical company also revealed plans to split off its consumer health business next year, a move similar to divestments done by other large drugmakers.Shares in Sanofi recovered slightly Monday, rising by more than 3%. News of the deal with MeiraGTx gave a much greater boost to that company, sending shares in the biotech higher by nearly half at one point Monday morning.The biotech previously secured a partnership with Johnson & Johnson on an experimental treatment for an inherited eye disorder known as retinitis pigmentosa. Early trial results showed some promise, and the therapy is now being studied in a larger Phase 3 trial.Sanofis interest in MeiraGTx is outside the eye, however. Specifically, the pharma is interested in MeiraGTxs Riboswitch technology for regulating targets related to immune and central nervous system conditions, as well as gut hormones like GLP-1. The latter has become the focus of a pharma industry arms race, boosted by the success of diabetes and weight loss drugs like Ozempic and Wegovy.Sanofi will also hold a right of first negotiation on MeiraGTxs program for radiation-induced xerostomia, a condition in which salivary glands are impaired or damaged.We look forward to working along side MeiraGTx as this innovative science moves forward to create a new generation of breakthrough medicines for immune-mediated and neurological diseases, said Sanofi CEO Paul Hudson in a statement. '

MeiraGTx’s gene therapy was able to rescue movement function or prevent motor neuron loss in several rodent models of amyotrophic lateral sclerosis. New data from mouse and rat studies show that MeiraGTx’s gene therapy for amyotrophic lateral sclerosis, or ALS, can repair a key cell-killing process that’s common in both genetic and sporadic forms of the disease. In a presentation Oct. 27 at the European Society of Cell and Gene Therapy conference in Brussels, the company showed that a single treatment with its gene therapy AAV-UPF1 prevented the loss of motor neurons in mouse and rat models with genetic and cellular defects seen in ALS, thereby improving clinical symptoms. The type of defect the treatment corrects is present in the vast majority of ALS patients, suggesting it could have wide-ranging benefit if validated in future studies. ALS is a progressive neurodegenerative disease where multiple aberrant cell processes destroy motor neurons. It’s more common in men than in women, though the gap closes with age, and comes in two forms: familial and sporadic. The familial form, or fALS, accounts for about 5% to 10% of cases, while the rest of patients have no obvious family history. Both types typically arise in people's late 40s through early 60s, with fALS starting slightly earlier. Though the timeline varies, patients usually progress from subtle muscle weakness to paralysis, respiratory failure and death within two to 10 years after the disease begins. There is currently no cure for ALS. Seven drugs have been approved by the FDA to treat the disease, including a new antisense oligonucleotide drug from Biogen and Ionis called tofersen, sold as Qalsody. The therapy targets a mutation in the gene SOD1, which affects about 10% to 20% of inherited or fALS patients. The SOD1 mutation leads to protein misfolding and aggregation within motor neurons, ultimately killing them. MeiraGTx’s new therapy also impacts the pathways that lead to protein misfolding and aggregation in motor neurons, but not the type that’s caused by SOD1. Instead, it targets a different cytotoxic, or cell damaging, process where a motor neuron protein called TAR DNA-binding protein 43, or TDP-43, incorrectly moves from the nucleus to the cytoplasm and builds up. While the TDP-43 pathology isn’t found in patients who have the SOD1 mutation, it is present in those who have the most common form of fALS, which is linked with the gene C9ORF72. It’s also found in nearly all patients with sporadic ALS, bringing its prevalence to more than 95% of ALS patients overall. To counteract TDP-43’s effects, MeiraGTx’s gene therapy increases the expression of the gene UPF1, which is important to RNA metabolism and several pathways that are dysregulated in ALS. Activating UPF1 seems to ameliorate the effects of TDP-43, along with other pathways leading to ALS pathology. The new data come from experiments in four models: one neonate and one adult model with reflex impairments induced by TDP-43 toxicity; a mouse model with a mutation in the C9ORF72 gene; and a mouse model with a mutation in the gene FUS, which is primarily associated with fALS but is also seen in some patients with sporadic disease. For the studies in the neonate rats with the induced TDP-43 dysfunction, the researchers measured whether AAV-UPF1 prevented them from developing forelimb impairment. Over the course of 12 weeks, forelimb function remained intact in all seven of the treated rats, while around 75% of the seven untreated rats showed impairments by Week 4. In the adult rats with induced TDP-43 dysfunction, the researchers looked at how well the treatment reduced the degree of impairments in hindlimb reflexes. While the untreated rats’ reflexes degraded to 25% of normal by Week 6 of the study—and fell further as the study progressed—the treated rats’ reflexes degraded to only about 75% of normal, even by Week 24. For the mice with genetic disease, the researchers measured whether the treatment could protect against motor neuron loss. In the FUS model, treated mice had nearly the same amount of motor neurons as controls, while the untreated mice exhibited motor neuron loss. The same was true for mice in the C9ORF72 model: The treated animals were protected from cell loss, while those that didn’t receive the treatment were not. In addition to the rodent studies, the MeiraGTx team presented data on AAV-hUPF1, a version of AAV-UPF1 that had been made smaller and more potent to optimize it for the clinic. They showed that it improved survival in human neurons derived from induced pluripotent stem cells with mutations in the TDP43 or C9ORF72 genes and rescued motor neuron loss in mice with the FUS gene mutation. Finally, the researchers also presented data on a new capsid, AAV2-retro, to deliver the ALS gene therapy as well as other neuronal indications. It was able to transduce the therapy in the brains and spinal cords of primates and also showed an effect in ALS patient-derived neurons harboring different disease-causing mutations.   MeiraGTx is continuing to optimize the vector for the clinic and plans to start studies for an investigational new drug application in 2024, presentation documents said.