Posoleucel (AlloVir)

Looking to bounce back following clinical setbacks with its lead asset and a gutting of its workforce, cell therapy developer AlloVir announced that it is merging with Kalaris Therapeutics in an all-stock transaction. The key draw for AlloVir is Kalaris' retinal disease asset TH103, an anti-VEGF therapy currently in Phase I for patients with neovascular age-related macular degeneration (AMD).The planned merger comes less than a year after AlloVir was forced to discontinue late-stage trials of its lead asset posoleucel, a multi-virus-specific T-cell therapy that was being developed for off-the-shelf use to treat viral infections in transplant patients. The failures prompted AlloVir in January to slash its workforce by 95% in order to conserve cash."AlloVir ran a thorough and strategic process, and we believe that this transaction represents the company's commitment to delivering value to the AlloVir stockholders," said CEO Diana Brainard. TH103, she added, has "the potential to disrupt the large anti-VEGF market, with near-term, value-inflecting milestones and a well-credentialed management team to lead the combined company."Less frequent dosingDeveloped by VEGF pioneer, Napoleone Ferrara, TH103 is a fully humanised, recombinant fusion protein engineered to inhibit VEGF, the key driver of pathological angiogenesis and exudation in retinal diseases. Data from head-to-head preclinical studies indicated it has longer-acting and increased anti-VEGF activity compared to Bayer and Regeneron's Eylea (aflibercept)."This fusion protein was specifically engineered to utilise the natural configuration of important domains of VEGF receptor 1 and has demonstrated both potent anti-VEGF activity and sustained ocular residence time in preclinical studies. This could potentially lead to enhanced durability with less frequent dosing in the clinical setting," Ferrara said.Some major players already market longer-acting treatments. Roche's Vabysmo (faricimab-svoa), which blocks two causes of wet AMD, was approved in 2022 and allows patients to space out injections up to every four months, rather than every two months with the original version Eylea. A higher-dose formulation, known as Eylea HD, has since hit the market in the US and Europe, and also allows patients to go up to four months between treatments. See – KOL Views Q&A: Leading expert pegs odds-on favourite among long-acting TKIs – but Eylea, Vabysmo not key rival.Initial data from the Phase I trial of TH103 in treatment-naïve patients with neovascular AMD are due in the third quarter of 2025. The drug will also be explored in other diseases such as diabetic macular oedema and retinal vein occlusion.Under the terms of the merger deal, AlloVir will acquire 100% of Kalaris' equity in an all-stock transaction.  Upon completion, AlloVir and Kalaris stockholders are expected to own approximately 25% and 75% of the combined company, respectively. The merged entity, which will run under the Kalaris Therapeutics name, is expected to have about $100 million in cash to fund operations into the fourth quarter of 2026. The transaction is expected to close early next year.

The layoffs are an attempt to reduce costs and preserve capital, AlloVir said. Less than a month after AlloVir suffered a triple phase 3 failure, the allogeneic T cell immunotherapy biotech is cutting 95% of its workforce. The company is making the drastic move in light of the December 2023 discontinuation of the three unsuccessful studies of posoleucel, an off-the-shelf multi-virus-specific T cell therapy, which was being developed to prevent infections or diseases caused by multiple viruses. The board approved the layoffs on Jan. 1, according to a regulatory document (PDF) filed on Thursday. The cuts are expected to take place mostly in the first quarter of this year and finish up by Apr. 15. AlloVir will incur expenses of about $15 million tied to personnel-related restructuring charges from one-time employee termination cash expenditures, including severance payments and other benefits. This is expected to be mostly incurred in the first quarter, AlloVir said. The layoffs are an attempt to reduce costs and preserve capital, AlloVir said. After the phase 3 failures, the biotech’s shares plunged 64% to 83 cents. The stock was trading at 68 cents pre-market Friday. Posoleucel was being tested in three indications for allogeneic hematopoietic stem cell transplant patients: to prevent clinically significant infections or diseases from multiple viruses; virus-associated hemorrhagic cystitis (vHC); and for adenovirus. But three independent Data Safety Monitoring Boards recommended stopping the studies after determining that they were unlikely to meet their main goals. Afterward, AlloVir moved to discontinue the studies for its lead asset and moved forward with a review of strategic alternatives including a merger, company sale or divesting assets. Across the industry, 2024 has started off looking a lot like 2023, with a flurry of layoffs hitting companies such as Intellia Therapeutics, Pfizer and Aera Therapeutics in the opening days of the year.