Apratastat

Flush with €63 million ($68 million) from an upsized series A funding, SciRhom is looking to challenge conventional wisdom in autoimmune disease treatment. The investment will support clinical development of the company's lead antibody candidate SR-878, which is directed against a protein many experts initially dismissed as an improbable therapeutic target.The oversubscribed round was co-led by Andera Partners, Kurma Partners, Hadean Ventures, MIG Capital, and Wellington Partners, with participation from new investor Bayern Kapital and existing backers including High-Tech Gründerfonds and PhiFund Ventures.Selective antibody approachSciRhom's approach focuses on iRhom2, a key regulator of TACE (also known as ADAM17), which plays a central role mediating major inflammatory signaling pathways like TNF-alpha, IL-6 and EGFR. For a long time, iRhom2 was thought to function exclusively inside cells and was therefore considered unsuitable for therapeutic antibodies. However, SciRhom co-founder Carl Blobel's work indicated it might actually be accessible on the cell surface, making it a potential antibody target after all.There have also been numerous attempts in the past to block TACE directly with small-molecule inhibitors – Pfizer/Wyeth's apratastat, Bristol Myers Squibb's DPC 333 and Incyte's INCB7839 were among the most studied, although all three ultimately failed. These drugs, chief operating officer Jens Ruhe told FirstWord, not only targeted TACE, but also interfered with closely related proteins."This sort of unspecificity was associated with additional side effects such as liver toxicity in one case or thrombosis…. One molecule was not effective at all," Ruhe said. "So this is being overcome with the fact that we have highly selective antibodies, which we tested in multiple preclinical screens, really only to interfere with iRhom2 itself and nothing else."The idea is to block only those aspects of TACE biology that are tied to disease-driving pathways, while at the same time preserving other vital functions that rely on TACE signaling.Dosing start in a few weeksSR-878 is poised to enter clinical testing in the coming weeks. "We actually have all the necessary regulatory approvals," said CEO Jan Poth. "It will be basically a standard single ascending dose trial in healthy volunteers. As usual, you want to see what the pharmacokinetics are of your drug in humans… and you certainly also want to get a first indication of the safety."If all goes well, the company is looking to move into Phase II "in the later second half of next year," he said.While the initial focus will be on rheumatoid arthritis and inflammatory bowel disease, based on positive preclinical data, the company sees room for eventual expansion. According to Poth, iRhom2 "is such a central mechanism in quite a number of autoimmune diseases that this is basically a pipeline in a molecule," along the lines of other immunological drugs like TNF inhibitors and AbbVie's anti-IL-23 antibody Skyrizi (risankizumab).SciRhom's early insight has also allowed the company, which was founded in 2016, to build up a solid patent portfolio around iRhom2-targeting therapies. Poth noted that with no existing patents on iRhom2, SciRhom had a "green field" to strategically secure patents, resulting in "a very strong patent portfolio covering that space."Looking ahead, the CEO acknowledged the significant funding required to fully develop SR-878 across multiple indications. "We can easily go up into the hundreds of millions, which you will need in order to bring it fully fledged to the market in all the possible indications. That is something which will definitely need more money than we have. So there will be different ways of how that can be approached by partnerships, by licensing, by an IPO. Nothing is fully decided yet,” he added.