AVB-101

In a sign of the times for gene therapy, Astellas did not take up its option on AviadoBio’s frontotemporal dementia treatment, the UK biotech company disclosed on Tuesday. Instead, a clinical trial of the therapy, AVB-101, will continue with funding by two nonprofits. It’s another instance in which industry funding for gene therapy has run cold and developers must seek out nonprofit and philanthropic funding. In some cases, patient groups are trying to push gene therapies forward on their own that were shelved by industry. Last year, the FDA granted its first approval to a gene therapy from a nonprofit. Astellas, however, is one of the few large companies that still has a focus on gene therapy. It currently has two clinical gene therapy programs listed in its pipeline, one for a rare genetic muscle disorder and another for Pompe disease. Astellas told Endpoints News its decision was a “strategic” one and was based on its “current near-term portfolio priorities, resource allocation, and internal timelines, which do not align with exercising our option related to AVB-101 at this time.” “We appreciate the collaboration with AviadoBio that has brought us to this point and remain open to exploring future collaborations in the gene therapy space,” Astellas said. AviadoBio said that it received investments from the Alzheimer’s Drug Discovery Foundation and the Association for Frontotemporal Degeneration to support the ongoing clinical trial, but declined to disclose details. In 2024, Astellas paid $30 million and invested another $20 million in AviadoBio for the chance to license the experimental gene therapy. The deal also included up to $2.18 billion in potential payments that AviadoBio will now no longer see. The Japanese pharma company remains a shareholder in AviadoBio, according to the press release . AviadoBio is studying its gene therapy in a form of familial frontotemporal dementia that’s caused by mutations to a single gene known as GRN, or FTD-GRN for short. The condition can lead to behavioral changes and progressive loss of speech, and eventually can affect people’s motor function and their ability to walk. AVB-101 delivers a functional version of the GRN gene that’s meant to restore levels of an important protein to the brain called progranulin. It’s a one-time infusion administered directly to the brain via surgery. AviadoBio said that it has treated 12 patients across three dose cohorts to date. The company said that early data showed “dose dependent elevations in the key biomarker of cerebrospinal fluid (CSF) progranulin,” but that it was saving the additional data for upcoming medical meetings. Next, it is treating a fourth dose cohort with up to six patients, the company told Endpoints News .

Novo cutting 400 jobs in IndianaAlltrna's first-in-human study of tRNA candidate will take place in AustraliaAstellas lets AviadoBio gene therapy option lapseSanofi's Rezurock bags conditional EU nod for chronic GvHD Novo cutting 400 jobs in IndianaNovo Nordisk confirmed to FirstWord Tuesday that it will reduce its workforce in Bloomington, Indiana by approximately 400 positions. Impacted staff will be notified in early May.The cuts primarily affect manufacturing roles, but extend across multiple functions, according to a company spokesperson. The layoffs will leave about 1400 employees at the site.The Bloomington site is "a critical part of our US manufacturing network" and the Danish drugmaker continues to invest there, the spokesperson said, adding the downsizing "reflects the business realities we face in today's competitive environment."The facility "requires a focused, right-sized team rather than the workforce size inherited when we acquired this site," the spokesperson explained. "We're aligning our staffing accordingly."In September, Novo said it would shrink its global workforce by 9000 positions, most in its home base of Denmark, as it looks to better respond to "a more dynamic and consumer-driven obesity market."-Anna BratulicAlltrna's first-in-human study of tRNA candidate will take place in AustraliaAlltrna said Tuesday that Australian regulators have cleared it to begin a Phase I trial of AP003 in healthy volunteers, marking the first therapeutic based on transfer RNA (tRNA) to enter the clinic. The trial, which will evaluate the safety and pharmacokinetics of single ascending doses of AP003 and inform future development, "begins to establish the clinical foundation to evaluate a single engineered tRNA across diseases that share the same premature termination codon," said Alltrna Chief Medical Officer Nerissa Kreher.In development for patients with liver Stop Codon Disease who carry an arginine-to-TGA (Arg-TGA) nonsense mutation, AP003 is a chemically modified, engineered tRNA therapy encapsulated within a liver-directed nanoparticle. The experimental treatment is designed to restore full length protein production by inserting the correct amino acid at an Arg-TGA premature termination codon.The study's impending launch comes nearly three years after the biotech raised $109 million in a series B to develop its tRNA-based machine learning platform (see – ViewPoints: How Alltrna is leveraging tRNA biology to address genetic diseases).-Elizabeth EatonAstellas lets AviadoBio gene therapy option lapseAstellas has stepped back from its deal with AviadoBio, allowing its option to license the AVB-101 gene therapy expire and returning full global rights to the biotech. The move unwinds a 2024 agreement that carried nearly $2.2 billion in potential milestones tied to the programme for frontotemporal dementia with progranulin mutations, though Astellas remains a shareholder in the UK company.AviadoBio said it continues to advance AVB-101 in the clinic, recently initiating a fourth dose-escalation cohort in the Phase I/II ASPIRE-FTD trial.The study has so far tested AVB-101 in 12 patients across the first three dose levels. Early data have shown dose-dependent increases in levels of cerebrospinal fluid progranulin alongside a clean safety profile, with no need for prophylactic or reactive immunosuppression, and no serious adverse events reported to date, according to the company.The move follows a similar retreat in October, when Astellas passed on licensing Taysha Gene Therapies' TSHA-102 for Rett syndrome before its pivotal trial. Meanwhile, an earlier gene therapy effort that stemmed from its purchase of Audentes Therapeutics was plagued with setbacks.-Anna BratulicSanofi's Rezurock bags conditional EU nod for chronic GvHDThe European Commission granted a conditional marketing authorisation for Sanofi's Rezurock (belumosudil) in chronic graft-versus-host disease (GvHD), clearing the selective ROCK2 inhibitor to treat adults and adolescents aged 12 and older when previous therapies have failed or are unsuitable.Having issued a negative opinion last October, the EMA's Committee for Medicinal Products for Human Use (CHMP) reached a positive conclusion in January after Sanofi requested a re-examination. At the time, Sanofi noted that it committed to conducting a new post-approval confirmatory study.Rezurock — gained through Sanofi's acquisition of Kadmon Pharmaceuticals — was first approved by the FDA in 2021. The drug is also being investigated in paediatric chronic GvHD and chronic lung allograft dysfunction.-Pavan Kamat