Tacrolimus

Wednesday saw a spate of deals, headlined by Novartis' option agreement for Sironax's Brain Delivery Module (BDM) platform. The technology is designed to enable therapeutics — of varying modalities, including biologics — to cross the blood-brain barrier. Sironax retained the right to continue developing certain programmes with its platform. Following an option period during which Novartis will evaluate the BDM platform, the drugmaker can exercise its option to acquire full global rights to the technology. Sironax is eligible for up to $175 million in total between upfront and near-term payments. "Effectively delivering therapeutics across the blood-brain barrier remains one of the most important challenges in drug discovery," said Robert Baloh, global head of neuroscience, biomedical research at Novartis. "We're excited to enter into this agreement with Sironax to fully explore the promise of the BDM platform, leveraging our deep expertise and capabilities in neuroscience to bring forward next-generation therapies for patients in need."Customising AI for cancerRevolution Medicines has tapped Iambic Therapeutics and its AI platform to discover new oncology candidates.  Iambic will use Revolution's structures and molecular libraries to train custom-built versions of NeuralPLexer, the AI firm's protein-ligand structure prediction model. The cancer drug developer will also be able to access Iambic's PropANE platform: a pre-trained graph neural network used to evaluate drug properties for lead selection and optimisation.Both Revolution and Iambic will retain rights to a limited number of exclusive targets; they will each be able to designate additional exclusive targets to pursue on their own, and have access to the customised AI models.Iambic stands to receive up to $25 million between an upfront payment and expected near-term performance-based milestones, in addition to ongoing R&D reimbursements."The capabilities of Iambic’s AI-driven discovery platform, partnered with our unique collection of proprietary data, present an opportunity to rapidly explore oncology targets known to be challenging to address through conventional drug discovery approaches," commented Revolution CEO Mark Goldsmith.Improving immunosuppression for isletsHot on the heels of Sernova Biotherapeutics' teaser of positive data from a Phase I/II trial of its islet cell therapy for type 1 diabetes, the company has now broadened its clinical plans for the programme, thanks to a new partnership with Eledon Pharmaceuticals.Sernova is developing the Cell Pouch Bio-hybrid Organ, an implantable medical device with a highly vascularised tissue matrix that creates an organ-like environment for islet cell engraftment. However, an immunosuppressive regimen using tacrolimus — which can increase the risks of infection, cancer, and cardiovascular disease — must be given in conjunction with the experimental treatment.Now, Sernova will evaluate in its ongoing Phase I/II study whether replacing the current regimen with Eledon's anti-CD40L antibody, tegoprubart, can prevent transplant rejection and minimise toxicities, particularly toward insulin-producing beta cells. Per the deal terms, Eledon will supply tegoprubart for the trial. Results from an investigator-initiated study in patients with type 1 diabetes who received islet transplants found that tegoprubart better protects transplanted cells, improving graft survival and function. No unexpected adverse events or hypoglycaemic episodes were reported. "These data suggest that combining our Cell Pouch Bio-hybrid Organ technology with Eledon’s innovative immunosuppression could enable patients to achieve insulin independence more rapidly and with significantly less toxicity to islet cells," remarked Sernova CEO Jonathan Rigby.

Biogen has announced that it has initiated a phase 3 study of investigational felzartamab in adults with primary membranous nephropathy (PMN), a severe antibody-mediated kidney disease. The 104-week PROMINENT trial, expected to readout in 2029, will randomise approximately 180 patients with moderate- to -high-risk PMN to receive either felzartamab or tacrolimus. It will enrol both newly diagnosed and relapsed patients, and will compare the efficacy and safety of the two drugs in achieving complete remission of protein in the urine (proteinuria). Approximately 36,000 people in the US are affected by PMN, which carries a significant risk of kidney failure and currently has no specifically approved treatments. The condition is a leading cause of nephrotic syndrome, which often presents with very severe swelling and fatigue related to high-grade proteinuria. Despite treatments ranging from immunosuppressants to chemotherapy, approximately one third of patients do not achieve remission. Felzartamab has already been shown in clinical studies to selectively deplete CD38-positive plasma cells, which Biogen said “may allow applications that ultimately improve clinical outcomes in a broad range of diseases driven by pathogenic antibodies”. Travis Murdoch, head of the Biogen West Coast Hub, said the company is “encouraged by the opportunity to advance a phase 3 study for PMN, a condition that carries a significant risk of kidney failure”. Biogen gained access to felzartamab in July through its $1.8bn acquisition of Human Immunology Biosciences (HI-Bio), which had exclusively licensed the rights to develop and commercialise the asset across all indications in all countries and territories excluding China in 2022. The drug was originally developed by MorphoSys, which Novartis also acquired last year. Beyond PMN, Biogen has recently initiated two phase 3 studies of felzartamab in IgA nephropathy, and kidney transplant recipients who have been diagnosed with late antibody-mediated rejection. Principal investigator for the PROMINENT trial, Mohamed El-Shahawy, said: “Felzartamab’s mechanism of action designed to deplete the cells that produce the pathogenic antibodies is exciting news for patients that are waiting for potential meaningful new treatment options. “I’m grateful that Biogen is advancing research in this rare kidney disease and am eager to see the continued progress in the study’s enrolment.”