RHBDF2

Transition into clinical-stage development marks a significant corporate and R&D milestone . MUNICH, Germany I October 17, 2024 I SciRhom GmbH, a biopharmaceutical company pioneering the development of first-in-class therapeutic iRhom2 antibodies, today announced that the dosing of participants has commenced in the first clinical study evaluating the company’s most advanced development program SR-878. The first-in-human, double-blind, placebo-controlled, single ascending dose study will assess the safety, tolerability, pharmacokinetic, and pharmacodynamic effects of SR-878 in up to 48 healthy volunteers. SciRhom is conducting the study in collaboration with the Department of Clinical Pharmacology at the Medical University of Vienna, Austria. The study is expected to read out in H2 2025. “ Initiating the first clinical study with our iRhom2-targeting approach represents a transformational milestone and value inflection point for the company. Our goal is to underpin the favorable safety profile of SR-878 observed in preclinical studies, and progress swiftly toward demonstrating the clinical benefits of our novel approach in patients in the subsequent Phase 2 trials, ” commented Dr. Jürgen Reess, CMO of SciRhom. Dr. Jan Poth, Managing Director & CEO of SciRhom added: “ Today’s exciting event brings us closer than ever before to demonstrating the breakthrough potential of targeting iRhom2 and thereby modulating the disease-relevant pathways controlled by TACE/ADAM17. We are very happy that we could engage the Department of Clinical Pharmacology at the Medical University of Vienna for this first study in humans, whose expertise will be very valuable in establishing a solid foundation for potentially multiple subsequent studies. ” With its SR-878 program, SciRhom aims to provide a new treatment paradigm for autoimmunediseases and potentially other indications by simultaneously blocking several pro-inflammatoryand disease-driving pathways. The highly selective engagement of iRhom2 is expectedto lead to superior efficacy compared to currently available treatments while preservingother vital functions of iRhom2’s interaction partner TACE/ADAM17, which should contributeto a favorable safety profile. About iRhom2 TACE (TNF-alpha converting enzyme, also known as ADAM17) controls several major signaling pathways, including TNF-alpha, IL-6R, and EGFR signaling. TACE is therefore widely accepted as a potential target to block pro-inflammatory pathways, but direct inhibition of TACE causes severe side effects. The more recent discovery that iRhom2 (inactive Rhomboid 2, RHBDF2) simultaneously and very specifically regulates the TACE-dependent release of TNF-alpha and other pro-inflammatory molecules from immune cells provides the exciting opportunity to target the disease-driving activities of TACE while preserving its other vital functions. Given the pivotal role of iRhom2, numerous new research studies have recently highlighted the therapeutic potential of targeting iRhom2 to treat immunological and inflammatory diseases and beyond, including oncological, infectious, and metabolic diseases. About SciRhom GmbH At SciRhom, we are translating world-leading expertise in the TACE/ADAM17 pathway and its central role in autoimmunity and other indications into breakthrough biopharmaceuticals. We are developing proprietary and first-in-class iRhom2-targeting therapies and are accelerating our lead antibody program SR-878 into and through clinical development. With strong support from international lead investors Andera Partners, Kurma Partners, Hadean Ventures, MIG Capital, Wellington Partners, as well as Bayern Kapital and current shareholders, SciRhom aims to push the boundaries in autoimmune medicine. For further information, please visit www.SciRhom.com SOURCE: SciRhom

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.

The investment will expedite the development of SciRhom’s therapeutic strategy, which focuses on autoimmune disorders. Credit: Pickadook / Shutterstock. German biopharmaceutical company SciRhom has secured €63m ($70m) in a Series A funding round to expedite the development of iRhom2-targeting therapeutics for autoimmune diseases. The significant financial boost was jointly led by a consortium of investors including Andera Partners, Hadean Ventures, Kurma Partners, MIG Capital and Wellington Partners. Bayern Kapital joined as a new investor, alongside existing stakeholders High-Tech Gründerfonds and PhiFund Ventures. The investment will expedite the development of SciRhom’s therapeutic strategy, which focuses on autoimmune disorders. Its lead candidate, SR-878, is a monoclonal antibody targeting iRhom2, with a clinical trial commencing in the second half of 2024. See Also: How will a Labour government support the UK clinical trials industry? TLC-2716 by OrsoBio for Familial Hypercholesterolemia (Type II Hyperlipoproteinemia): Likelihood of Approval SciRhom’s SR-878 is engineered to inhibit multiple inflammatory pathways such as TNF-alpha, IL-6R, and EGFR signalling. This multifaceted approach is aimed at preserving essential TACE/ADAM17-dependent functions. The therapy has the potential to modulate immune tolerance by enhancing TNFR2 signalling and regulatory T-cell expansion. In preclinical studies, the asset demonstrated efficacy in vitro and in animal models for rheumatoid arthritis and inflammatory bowel disease. SciRhom obtained CTA [clinical trial authorisation] in June 2024 with a trial anticipated to be launched in Austria to assess the safety of the asset in healthy volunteers. The board of directors of SciRhom will welcome five new members: Dr Olivier Litzka from Andera Partners, Dr Peter Neubeck from Kurma Partners, Dr Georgina Askeland from Hadean Ventures, Dr Fei Tian from MIG Capital and Dr Varun Gupta from Wellington Partners. SciRhom co-founder, managing director and chief operating officer Dr Jens Ruhe said: “Since its foundation, SciRhom has applied rigorous science to establish a leading position in iRhom2-targeting biopharmaceuticals including a comprehensive IND/CTA-enabling data and CMC [chemistry, manufacturing and controls] package and strong patent protection. “Now is the time to shift gears and accelerate our novel and potentially groundbreaking therapeutic strategy toward clinical proof-of-concept and beyond to reach patients in need of better autoimmune treatments.”