Targeting iRhom2 for better treatment of autoimmune diseases

Company

SciRhom GmbH is a pioneering biotech enterprise with the vision to translate advanced scientific findings into game-changing therapies for autoimmune diseases. Building on a detailed understanding of how a major cell-surface protease controls inflammation, SciRhom has worked closely with Prof. Carl Blobel of the Hospital for Special Surgery in New York City (USA) to develop first-in-class humanized antibodies against iRhom2. iRhom2 controls the enzyme TACE, a key node in several disease-causing signaling pathways. Tested in vitro and in mouse models of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), these antibodies potently and selectively inhibit TACE in immune cells, thereby protecting against RA and IBD. By targeting iRhom2/TACE, the SciRhom antibodies simultaneously block several established signaling pathways that are currently targeted individually by drugs approved for autoimmune disorders, including TNF-alpha and IL-6R signaling. Superior efficacy, as demonstrated in preclinical proof-of-principle studies, and an expected favorable safety profile make anti-iRhom2 antibodies prime candidates to outperform standard of care. Four patent families secure exclusivity for anti-iRhom2 inhibitors and provide broad protection against follow-on drugs. Current leading indications in the company’s development pipeline are RA, IBD, and lupus nephritis.

Anti-iRhom2 antibodies: a novel mode of action to tackle autoimmune diseases

  • Simultaneously blocks key pro-inflammatory pathways of TNF-alpha, IL-6, and HB-EGF
  • Potentially restores protective pathways by reactivating MerTK-mediated efferocytosis
  • Exhibits superior efficacy and an expected favorable safety profile

SciRhom GmbH: the expertise and vision
to change lives

  • Founded in 2016 to commercialize over 10 years of applied research
  • Strong financing through a consortium of knowledgeable life science investors
  • The experienced management team has initiated the path to market and secured first-in-kind IP

Management

Dr. Jens Ruhe
Managing Director, Chief Executive Officer
T +49 (0)89 614 2412-31
Ruhe@SciRhom.com

Jens co-founded SciRhom GmbH, formerly SciMab GmbH, in late 2016. He has a longtime experience in signal transduction biology and therapeutic antibody development. As co-founder of U3 Pharma GmbH, Jens was involved in new drug target identification, before he joined Prof. Dr. Axel Ullrich to establish a laboratory and cancer genome project at the Institute of Medical Biology (IMB), Agency of Science, Technology and Research (A*STAR) in Singapore. After the acquisition of U3 Pharma by Daiichi Sankyo, Jens served as Authorized Officer and Director Research & Development. In global teams, he was in charge of preclinical development of early to clinical stage antibody projects, including U3 Pharma’s Patritumab lead program. Jens was trained in genetics and immunology at the University of Konstanz, and obtained his PhD in Molecular Biology from Prof. Dr. Axel Ullrich at the Max Planck Institute of Biochemistry, Martinsried.

Dr. Matthias Schneider
Chief Scientific Officer
T +49 (0)89 614 2412-32
Schneider@SciRhom.com

Matthias co-founded SciRhom GmbH, formerly SciMab GmbH, in late 2016. He is a biologist with an extensive experience in biomarker identification and antibody development. Being with U3 Pharma/Daiichi Sankyo from 2008 to mid 2016, he advanced to the preclinical head of the Patritumab lead program. Matthias studied biology at the University Würzburg and earned his PhD in molecular biology in the lab of Prof. Dr. Axel Ullrich at the Max-Planck-Institute of Biochemistry, where he gained deep insights in GPCR/EGF-Receptor crosstalk in oncology.

Dr. Andreas Jenne
Managing Director, Chief Business Officer
T +49 (0)89 614 2412-36
Jenne@SciRhom.com

Andreas is a co-founder of SciRhom GmbH and served as Chairman of the Board before joining the company’s management team in 2020. Andreas has more than 20 years of executive management experience in the life sciences industry and co-founded six biotechnology companies. Prior to joining SciRhom GmbH he was the CEO of RSP Systems A/S, a Danish medical device company focusing on non-invasive diagnostics. Further professional stations include CEO positions at Kinaxo GmbH (a proteomics service provider sold to Evotec in 2011) and NEO New Oncology AG (a cancer diagnostics company sold to Siemens Healthcare in 2016). Andreas holds a Ph.D. in Chemistry from the Ludwig-Maximilians-University in Munich.

Dr. Jürgen Reeß, MD, PhD
Chief Medical Officer
T +49 (0)89 614 2412-30
Reess@SciRhom.com

Jürgen joined the management team of SciRhom GmbH in 2021. He brings over 20 years of experience in operative and strategic clinical development, most recently as Corporate Senior Vice President of International Project Management at Boehringer Ingelheim Human Pharma. A trained physician and expert leader in the pharmaceutical industry, Jürgen supervised the development, approval, and launch of numerous blockbuster therapies for autoimmune diseases, interstitial lung diseases, central nervous system disorders, and cancer. That success hinged upon Jürgen’s proficiency in fostering productivity and creativity in multidisciplinary teams to meet milestones in nearly 100 projects across several therapy areas. Jürgen holds a medical and doctorate degree from the University of Ulm (Germany), is a board-certified neurologist, and has a strong publication record.

Board of Directors

Prof. Carl Blobel
Scientific Founder

Carl is Professor of Medicine (Rheumatology Division) and of Physiology, Biophysics and Systems Biology at Weill Cornell Medicine, and Chairman of the Arthritis and Tissue Degeneration Program at the Hospital for Special Surgery in New York City. He received his medical degree from the Justus-Liebig University, Giessen (Germany) and his Ph.D. in Biochemistry and Biophysics from the University of California, San Francisco (USA). Carl’s groundbreaking research on iRhom2 revealed its potential as a therapeutic target for autoimmune diseases. His membership on the Board of Directors provides unrivaled knowledge to lay out and steer the technological roadmap of the company and to strengthen the scientific evolution of the product.

 

 

Dr. Wolfgang Baiker
Venture Partner at Wellington Partners

After more than 30 years at Boehringer Ingelheim, Wolfgang is an internationally respected advisor and partner for multiple life science business projects. He holds several positions on boards and committees across academia and industry and, as such, has also taken up interim leadership positions at startups. Having served on the Board of Managing Directors and as President and CEO of Boehringer Ingelheim USA, Wolfgang is a veteran in global pharmaceutical production, development, and project management. He fulfills a key role on the SciRhom Board of Directors in advising the expansion of the company organization and infrastructure with sights on the international market. Wolfgang holds a Doctorate in Medicine from the University of Ulm (Germany) and an MBA from Pace University (USA).

Hans-Ulrich Rabe
Strategic Finance Consultant

Deeply embedded in advising direct investments into high-potential German biotech companies, Hans-Ulrich is a well-established and networked consultant for strategic asset allocation and finance management. He serves on several advisory boards in the biotech industry, having developed strong business acumen from work in the banking and nationwide food wholesale sectors as well as from extensive experience evaluating business opportunities and investment candidates. He rounds off the SciRhom Board of Directors with a wealth of expertise in logistics, risk assessment, and driving improved financial performance.

SciRhom – from meticulous research
to novel antibody therapies

Founded in 2016 at the Innovation and Startup Center (IZB) in Martinsried, Germany, SciRhom builds on the cutting-edge research of Professors Carl Blobel and Axel Ullrich.

Prof. Blobel’s pioneering work on membrane-anchored metalloproteases (ADAMs) revealed iRhoms 1 and 2 as key upstream regulators of ADAM17 (also referred to as TACE), an enzyme that mediates pro-inflammatory signaling via TNF-alpha, IL6-R, and EGFR. That crucial piece to the complex puzzle of immune responses is the Achilles heel that SciRhom leverages to suppress autoimmune disease mechanisms. His research and vision advance the company’s development efforts at the forefront of this novel therapeutic opportunity. Prof. Blobel continues to play an essential role at SciRhom both as a collaborating partner and member of the Board of Directors.

Prof. Ullrich is a world-renowned innovator and catalyst of groundbreaking medications. His extraordinary research track record includes meticulous insights into human signal transduction that underscore the translation of iRhom2 into a novel strategy to tackle autoimmunity and cancer. He contributed to the development of genetically engineered human insulin and the first targeted antibody-based cancer therapy, Herceptin. A lifetime dedicated to science produced one of the most cited bodies of scientific literature in the past 25 years, the establishment of six biotech companies, and numerous awards.

Today, SciRhom has demonstrated the therapeutic potential of iRhom2 inhibitors, expanding the scientific foundation laid by Professors Blobel and Ullrich into a rapidly advancing drug development pipeline on track to bring a promising new therapy to market.

About iRhom2

TACE (TNF-alpha-converting enzyme), also called ADAM17, is an essential regulator of major pathophysiological processes of inflammatory disease, including the TNF-alpha (tumor necrosis factor alpha) and EGFR (epidermal growth factor receptor) signaling pathways (1). The pharmaceutical industry has pursued TACE as a drug target for over a decade. Inhibiting that single enzyme blocks several pro-inflammatory pathways at the same time. However, small molecule TACE inhibitors failed at the clinical stage because blocking TACE directly caused severe side effects (2). The issue is that globally deactivating TACE also shuts down the protective action of the EGFR, as TACE no longer processes the EGFR-ligand TGF-alpha, which is crucial for protecting the skin and intestinal barriers (3,4). In fact, patients lacking TACE activity suffer from severe skin infections and intestinal lesions (5).

iRhom2 (inactive Rhomboid 2 or RHBDF2) offers a promising alternative strategy. The TACE-dependent release of TNF-alpha and other pro-inflammatory mediators from immune cells is regulated by iRhom2 (6-8). As such, inhibiting iRhom2 targets the pro-inflammatory activities of TACE without impacting its protective functions in epithelia, which can be maintained by the related iRhom1 (6-8). iRhom2 knock-out mice are protected against rheumatoid arthritis (7,10), inflammatory arthritis caused by hemophilia (11), and glomerulonephritis caused by systemic lupus erythematosus (12). The mice are normal, healthy, and do not develop the skin or intestinal defects seen in mice and patients deficient in TACE (6-8).

A growing collection of research studies point to iRhom2 as an attractive emerging target across several medical areas, including immunology, inflammation, oncology, infectious and metabolic disease. Thus, inhibiting iRhom2 is a therapeutic opportunity to not only selectively target the pro-inflammatory functions of TACE without causing severe side effects, but also to explore novel mechanisms of action urgently needed for other indications.

  1. Blobel CP. Nature Rev Mol Cell Bio. 2005;6:32-43.
  2. Calligaris M et al. Molecules. 2021;26:944.
  3. Chalaris A et al., J Exp Med. 2010;207(8):1617-1624.
  4. Franzke CW et al., J Exp Med. 2012;209(6):1105-1119.
  5. Blaydon DC et al., N Engl J Med. 2011;365(16):1502-1508.
  6. McIlwain DR et al., Science. 2012;335(6065):229-232.
  7. Issuree PD et al., J Clin Invest. 2013;123(2):928-932.
  8. Adrain C et al., Science. 2012;335(6065):225-228.
  9. Li X et al., Proc Natl Acad Sci U S A. 2015;112(19):6080-6085.
  10. Buckland J., Nature Rev Rheumatol. 2013;9(3):136.
  11. Haxaire C et al., Blood. 2018;132(10):1064-1074
  12. Qing X et al., J Clin Invest. 2018;128(4):1397-1412.

Press Release

Contact

Jens Ruhe
CEO
T +49 (0)89 614 2412-31

SciRhom GmbH
Am Klopferspitz 19
82152 Martinsried
Germany