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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. Jan Poth
Managing Director, Chief Executive Officer
T +49 (0)89 614 2412-36
Poth@SciRhom.com

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Jan is a key member of the management team of SciRhom GmbH since 2022. In over
20 years working for the pharmaceutical industry, Jan has held senior roles in
both the development and the commercial side of the pharma value chain. He has
experience across several therapeutic areas, including immunology, where he
served for several years as Therapeutic Area Head at Boehringer Ingelheim. With
scientific curiosity and extensive know-how, he led teams in bringing to market
several compounds to help patients suffering from cardiovascular, central
nervous system, or autoimmune diseases. Jan is a licensed pharmacist and holds a
PhD in pharmaceutical sciences from the Christian-Albrechts-University of Kiel
(Germany).

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

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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

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

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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.

Dr. Andreas Jenne
CEO at Ventura BioMed Investors

Andreas co-founded SciRhom GmbH and served as Managing Director from 2020 to
2021 before joining the company’s Board of Directors. He is also an active Board
Member in various other biotechnology companies and CEO of Ventura BioMed
Investors GmbH, a venture capital investor in early-stage biotechnology
companies developing pioneering technologies and innovative therapies. Andreas
has more than 20 years of executive management experience in the life sciences
industry and launched six biotechnology companies, which he led as Managing
Director or CEO. Prior to joining SciRhom’s management, he was 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.

Clinical Advisory Board

Decades of cutting-edge research and clinical leadership in rheumatology and
inflammation distinguish the members of SciRhom’s Clinical Advisory Board. In
concert with our Management Team, the Board guides the continued development of
SciRhom’s therapeutic concept, steering its path from bench to bedside.

Prof. Carl Blobel, Chairman of the Arthritis and Tissue Degeneration Program at
the Hospital for Special Surgery and Professor of Medicine and Physiology,
Biophysics, and Systems Biology at Weill Cornell Medicine. An authority on the
enzyme TACE and its signaling pathways, Dr. Blobel was a driving force in
establishing the knowledge foundation for SciRhom’s anti-iRhom2 antibodies and
continues to guide the company’s scientific evolution.

Prof. Iain McInnes, Professor of Medicine and Vice Principal and Head of the
College of Medical, Veterinary, and Life Sciences at the University of Glasgow.
Dr. McInnes leads a research program investigating inflammatory synovitis in
rheumatoid arthritis and is involved in multi-center clinical trials evaluating
novel biologic agents in inflammatory arthritis. He is also actively engaged in
several international rheumatology consortia.

Prof. Jane Salmon, Collette Kean Research Chair and Director of the Lupus and
Antiphospholipid Syndrome Center of Excellence at the Hospital for Special
Surgery and Professor of Medicine and Obstetrics and Gynecology at Weill Cornell
Medicine. Dr. Salmon’s decades of clinical research have led to key insights
into the causative role of inflammation in lupus-associated tissue damage and
defined new treatment targets.

Prof. Georg Schett, Chair of the Department of Medicine III Rheumatology &
Clinical Immunology and Vice President of Research at the Friedrich-Alexander
University, Erlangen-Nuremberg. Dr. Schett is a globally renowned expert in
rheumatology and serves as principal investigator on several research projects
examining the molecular basis of immune-inflammatory diseases with rapid
translation into clinical practice.

Prof. Michael Weinblatt, Co-Director of Clinical Rheumatology at Brigham and
Women’s Hospital and John R. Riedman Professor of Medicine at Harvard Medical
School. Dr. Weinblatt has worked on the development of treatments for rheumatoid
arthritis for over 40 years. He has evaluated numerous biologics used to treat
rheumatoid arthritis and helped establish methotrexate as a standard of care.

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


SCIRHOM SECURES EUR 63 MILLION SERIES A FINANCING ROUND TO ACCELERATE
IRHOM2-TARGETING THERAPIES IN AUTOIMMUNE DISEASES

Jul 9, 2024

The upsized and oversubscribed Series A financing round will be used to drive
the lead development program toward clinical...

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SCIRHOM FILES CLINICAL TRIAL APPLICATION FOR FIRST-IN-HUMAN TRIALS OF NOVEL
ANTIBODY AGAINST AUTOIMMUNE DISEASES

Nov 15, 2023

SciRhom GmbH, a pioneering biotech enterprise specialized in developing
first-in-class therapeutic antibodies, announced...

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SCIRHOM ANNOUNCES APPROVAL OF FIRST CLINICAL TRIAL APPLICATION FOR A NOVEL
IRHOM2-TARGETING ANTIBODY AGAINST AUTOIMMUNE DISEASES.

Jun 12, 2024

Munich, Germany, June 12, 2024 – SciRhom GmbH, a biopharmaceutical company
pioneering the development of first-in-class...

read more


SCIRHOM ANNOUNCES ADDITION TO THE MANAGEMENT TEAM

May 12, 2022

To optimize management expertise for the next phase of development, Dr. Jan Poth
will assume the role of Chief Executive...

read more


Contact

Jan Poth
CEO
T +49 (0)89 614 2412-36

SciRhom GmbH
Am Klopferspitz 19
82152 Martinsried
Germany

email to
info@SciRhom.com



SciRhom GmbH
Am Klopferspitz 19
82152 Planegg/Martinsried
Germany

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