Antibody Diversity and Precision Signaling matters

We are developing canonical signaling monoclonal antibodies to significantly improve therapeutic treatments
in Oncology, Immune-modulation, Immunology and most urgently for Covid-19

Our Goal

We are addressing the urgent need for particular effective treatments for Covid-19 and its potentially fatal outcome driven by Acute Respiratory Distress Syndrome (ARDS) and Cytokine Release Syndrome (CRS). Also, significant improvement in clinical outcomes is required for treatment of disorders in acute inflammatory conditions including several severe rare diseases like Macrophage-Activation Syndrome, SJIA / Still’s Disease or IBD and Gout where sometimes even specific treatments are missing, with the goal of addressing underlying causes. The same holds true for clinical outcome in cancer therapy, whether it is through neoadjuvant treatment of women with early Breast Cancer, or via novel immuno-oncology treatments across multiple solid cancers.

Science

We are exploiting the unlimited potential of rabbit monoclonal antibody diversity achieving the most precise and potent canonical inhibitory or agonistic signaling without the need of extensive in vitro maturation or engineering, achieving optimized biological activity and eliminating liabilities

Science

While monoclonal antibody discovery has progressed significantly in the last decades, precise canonical antibodies have not been well exploited to address clinically validated and/or clinical targets in a physiological manner.

IcanoMAB has secured three advanced clinical candidates in IND-enabling stage from MAB Discovery.


The technology of MAB Discovery was developed to generate large numbers of antibody-producing B-cells (>10,000) providing monoclonal antibodies with high diversity and potency without the need of additional in vitro maturation or engineering to optimize therapeutically relevant paratopes. Resulting antibodies have been applied to Pharma derived high throughput screening in functional assays to identify lead candidates that fulfill a predefined list of biological activities and provide optimal potency essential for differential therapeutic application. Potential leads have gone through a focused, sophisticated sequence optimization: Humanization, elimination of T-cell epitopes & potential CMC liabilities.

Addressing validated targets generated proprietary molecules with novel modes of intervention and the knowledge of first-generation molecules enabled a well guided in vitro differentiation. This approach allows focused activities for in-vivo PoC in animal models and in the clinic with limited remaining CMC risks.

Overall 50 projects were prosecuted in the last ten years, of which 96% were successful generating functional monoclonal antibodies of which several have reached the clinic. No changes had to be applied to those antibodies demonstrating the solidity of the approach.

Then after 10 years of successful monoclonal antibody discovery projects with large Pharma companies and mid- and large-size Biotech companies, MAB Discovery sold its antibody production platform and laboratory to BioNTech (NASDAQ: BNTX) in 2019.

Reference:

  • Weber J et al, From rabbit antibody repertoires to rabbit monoclonal antibodies, Experimental & Molecular Medicine (2017) 49, e305 doi:10.1038/emm.2017.23

Our Portfolio

We have a differentiated monoclonal antibody portfolio with potential to enter clinical development for indications of high unmet medical need soon, including neoadjuvant eBC, immuno-oncology for solid cancers and acute inflammatory conditions incl severe infectious diseases

Portfolio

While collaboration projects were performed, MAD Discovery also developed a pipeline of proprietary molecules. At the end of 2019, a pre-clinical project in the field of Immuno-oncology was licensed to a Top Pharma company. Three advanced clinical candidates in IND-enabling stage have now been secured by IcanoMAB: a HER2newC apoptosis inducer, a CD-40 agonist and an IL-1R7 antagonist.


HER2newC apoptosis inducer – Early Breast Cancer

Clinical unmet need

Antibody based cancer therapies have achieved convincing success rates combining enhanced tumor specificity and reduced side effects in patients. Trastuzumab targets the human epidermal growth factor related receptor 2 (HER2) and is one of the greatest success stories in this field. For decades, trastuzumab based treatment regimens have significantly improved the prognosis of HER2-positive breast cancer patients both in the metastatic and the (neo-) adjuvant setting. Nevertheless, ~50% of trastuzumab treated patients experience disease progression within one year, with a variety of molecular mechanisms having been described.


Scientific basis

In-vitro, trastuzumab demonstrably reduces tumor cell multiplication per time interval mainly driving HER2 positive cells into quiescence (i.e., non-proliferating state, G1-phase). This might cause a reduced sensitivity to the combined cytotoxic treatments in vivo because chemotherapy predominantly affects proliferating cells (in S-phase). Furthermore, the same mechanism might be increasing the amount of dormant disseminated cells, potentially contributing to metastases formation at a later time point.

Conversely, an antibody not generating a significant number of quiescent cells (only slowing down the proliferation speed, e.g., by G1 prolongation) and inducing apoptotic cell death could be more efficient than a treatment with trastuzumab (or other treatments that cause tumor cell dormancy).

Status to date

Our developed antibody demonstrates a favorable profile in proven relevant tumor models with superior efficacy and apoptosis induction even in tumor cells that are resistant to current standard of care, plus therapeutic efficacy in vivo against primary tumors and metastases (including brain metastases) superior to current standard of care supporting IND-enabling steps.

Clinical development will aim at proof of concept and initial indication as neoadjuvant treatment for early Breast Cancer.

References:

  • Nahta R, Yu D, Hung M-C, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer.
    Nat Clin Pract Oncol. 2006;
    3:269–80
  • Brockhoff G, Heckel B, Schmidt-Bruecken E, Plander M, Hofstaedter F, Vollmann A, Diermeier S. Differential impact of Cetuximab, Pertuzumab and Trastuzumab
    on BT474 and SK-BR-3 breast cancer cell proliferation. Cell Prolif. 2007 Aug;40(4):488-507
  • Wege et al., A novel rabbit derived anti‑HER2 antibody with pronounced therapeutic effectiveness on HER2‑positive breast cancer cells in vitro and in
    humanized tumor mice (HTM), J Transl Med (2020) 18:316 https://doi.org/10.1186/s12967-020-02484-9


CD40 agonist – Immuno-Oncology/Severe Infectious Diseases

Clinical unmet need

Response to immuno-oncology treatments is yet to be improved. Along the cancer immunity cycle, the activation of CD40 is a cornerstone, providing a powerful tool to specifically induce neo-antigen-specific T cell immunity against tumor cells. But so far, all CD40 agonists with effective response in patients are associated with severe side effects (e.g. grade 3-4 liver tox, thromboembolic events) or reduced therapeutic window, strongly limiting the potential therapeutic use.


Scientific basis

First described in 1996 (Basel Institute of Immunology), in vivo studies of a murine IgG2a antibody (corresponding functionally to a human IgG1) hitting the CD40L binding site demonstrated inducing a canonical signal. In addition, the murine lgG2a antibody cross-linked with its Fc-domain to several Fc receptors. In 2002, CD40 stimulation was demonstrated to lead to effective therapy of CD40 negative tumors through induction of strong systemic cytotoxic T lymphocyte immunity – without the need of directly killing CD40 positive tumors as has been generally been hypothesized.

Almost all profiles of human specific CD40 agonists to date have been geared towards cell killing of CD40 positive tumors. In 2016 the hypothesis was confirmed that FcRγIIb binders can cause serious toxicity in vivo. IgG4 and IgG2 antibodies have shown not to be FcR-silenced antibodies potentially causing serious (liver) toxicity.

An antibody that activates CD40, and that competes with the CD40 ligand, and does not induce large receptor complexes (CD40 – CD40 ligand – integrins), and with a silenced Fc domain preventing additional Fc-receptor cross-linking (neither CDC, ADCC nor platelet activation), could lead to significantly reduced toxicity while maintaining strong antitumor/anti-infective activity through direct activation of dendritic cells and subsequent triggering of antigen-specific T cells.

Status to date

Our data to date demonstrate a favorable pharmacology profile vs existing CD40 agonists supporting IND-enabling studies in NHP models.

Clinical studies will be performed in solid tumors.

References:

  • Rolink et al., 1996, Immunity, Vol. 5, 319–330, October, 1996
  • Van Mierlo et al., PNAS April 16, 2002 vol. 99, no. 8, 5561-5566
  • Byrne et al., J Immunol 2016; 197:179-187
  • Stopforth et al., 2016 Regulation of Monoclonal Antibody Immunotherapy by FcγRIIB, J Clin Immunol 2016, 36, Suppl 1: 88 – 94


IL-1R7 antagonist – Acute inflammatory diseases

Clinical unmet need

Effective treatments are particularly urgent for Covid-19 and its potentially fatal outcome driven by Acute Respiratory Distress Syndrome (ARDS) and subsequent Cytokine Release Syndrome (CRS). While Vaccine development is progressing and sufficient broad population protection is yet to be demonstrated, risks of detrimental effects via Antibody Dependent Enhancement (ADE) will require specific therapeutic intervention. In any case, an effective treatment is urgently needed as an option for clinicians to treat severely affected late-stage Covid-19 patients. Significant improvement of clinical outcome is also required for the treatment of disorders in immunology and inflammation including several severe rare diseases like macrophage-activation syndrome, SJIA / Still’s Disease or IBD and Gout where sometimes even specific treatments are missing, that address the underlying cause.


Scientific basis

In Covid-19, SARS-CoV-2 infects cells expressing ACE2 and TMPRSS2. Active virus replication and release cause host cell pyroptosis and release damage-associated molecular patterns, incl. ATP, nucleic acids and ASC oligomers, recognized by neighboring epithelial cells, endothelial cells and alveolar macrophages, triggering the generation of pro- inflammatory cytokines and chemokines (incl IL-6, IP-10, MIP1α, MIP1β and MCP1). These attract monocytes, macrophages and T-cells to the infection site, promoting further inflammation (together with IFN-γ produced by T-cells) and establishing a pro-inflammatory feedback loop.

Defective immune response may lead to further accumulation of immune cells in the lungs, causing overproduction of pro-inflammatory cytokines, eventually damaging lung infrastructure. The resulting cytokine storm circulates to other organs, leading to multi-organ damage and subsequent failure. In addition, non-neutralizing antibodies produced by B-cells may enhance SARS-CoV-2 infection through ADE, further exacerbating organ damage.

The production of IFN-γ has been shown to be essential in the early avalanche of cytokines produced in MAS. The cytokine storm is induced by fast acting, residual IL-18 which is released by damaged lung tissue (macrophage activation).

The antibody targets IL-1R7, the signaling domain of the IL-18 receptor. IL-18 has originally been identified as the main inducing factor of IFN-y. In contrast to the IL-18 binding protein (IL-18BP), our IL-1R7 antibody blocks the release of IFN-γ but does not affect the protective/ regenerative activities of IL-18 and IL-37. IL-37 is an anti-inflammatory cytokine that binds to IL-1R5 and IL-18BP and induces signaling via a different co-receptor, IL-1R8.

Additionally, inflammasome inhibitors reduce protease activation of IL-18 precursor protein and would be ineffective in the acute IL-18 release situation.

Status

Our data to date support an effective blockade of IL-18 signaling with subsequent blockade of  IFN-y release in primary human cells and the initiation of IND-enabling activities.

Initial clinical studies will target acute treatment for severely ill Covid-19 patients and / or patients with Macrophage Activation Syndrome.

References:

  • Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;1–12
  • Shimabukuro-Vornhagen et al. Journal for ImmunoTherapy of Cancer (2018) 6:56 https://doi.org/10.1186/s40425-018-0343-9
  • Morris KV. Molecular Therapy Vol. 28 No 7 July 2020
  • De Benedetti F et al. Interferongamma (IFN-γ) Neutralization with Emapalumab and Time to Response in Patients with Macrophage Activation Syndrome (MAS) Complicating Systemic Juvenile Idiopathic Arthritis (s-JIA) who failed High-Dose Glucocorticoids [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10)
  • Dinarello etal 2013, Interleukin 18 and IL-18 binding protein
  • Kaplanski 2017, Interleukin-18: Biological properties and role in disease pathogenesise:

Our Company

We are a private German Biotech company founded by highly experienced entrepreneurs and senior Pharma industry alumni with a successful track record in drug development collaborating with leading experts and renowned organizations across the world

Company

IcanoMAB is a private Biotech company headquartered in Polling, Germany focusing on the pre-clinical and development of precision canonical antibodies for the treatment of cancer, immune-system- and inflammation-related-diseases and Covid-19. The company is developing its proprietary clinical candidates to exploit novel approaches for improving clinical outcomes in immuno-oncology, solid tumors and immunology and inflammation.

IcanoMAB has secured three clinical candidates in IND-enabling stage and funding from MAB Discovery GmbH, originally generating the licensed antibodies from a novel antibody discovery platform. IcanoMAB will use its proceeds to advance the clinical candidates to allow IND-enabling activities and respective partnering activities with selected third parties.

IcanoMAB was founded by highly experienced entrepreneurs and scientists with a track record of successful drug development in multiple companies including Boehringer Mannheim, Roche, MAB Discovery, Xantos Biomedicine, JSB Partners, Novartis and TVM Capital Life Science. The company was founded by MAB Discovery, represented by Dr. Stephan Fischer, its CEO, Dr. Ulrich Pessara and Daniel Parera, M.D..

By addressing validated targets, proprietary molecules with novel modes of intervention were generated. Knowledge of first-generation molecules enabled a well guided in vitro differentiation. This approach allows focused activities for in-vivo PoC in animal models and in the clinic with limited remaining CMC risks.

Overall 50 projects were prosecuted in the last ten years, of which 96% were successful at generating functional monoclonal antibodies of which several have reached the clinic. No changes had to be applied to those antibodies, which demonstrates the solidity of the approach.

After 10 years of successful monoclonal antibody discovery projects, with large Pharma companies and mid- and large-size Biotech companies, MAB Discovery sold its antibody production platform and laboratory to BioNTech (NASDAQ: BNTX) in 2019.

Our Team

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Dr. Stephan Fischer
co-CEO and CSO
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Daniel Parera
MD, co-CEO and CMO
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Dr. Ulrich Pessara
CBO

Our Team

Dr. Stephan Fischer – Co-CEO and CSO

Stephan has more than 30 years Life Science industry experience with Boehringer Mannheim and Roche AG.  

He is CEO and Founder of MAB Discovery GmBH, which utilized a unique and proprietary rabbit-based antibody discovery platform to generate various mAbs for several pharma partners and proprietary mAbs prior to the trade sale of its production technology and lab operations to BioNTech (NASDAQ: BNTX) in 2019. He also was Partner of Bioscope Associates LLC from 2009 to 2017. Prior to that, Stephan was SVP, Head Biologics Research and Strategy at Roche until 2009. Previous roles at Roche included the Global Project Lead for Retavase® and NeoRecormon® from Discovery through Commercialisation.

Stephan received a PhD from TU Munich and worked as a PostDoc at EMBL Heidelberg (D)

Daniel Parera, M.D. – Co-CEO and CMO

Daniel is an entrepreneur, investor and advisor in the Life Science and Food industry.

He co-founded three companies and previously was an Executive-in-Residence at TVM Capital Life Science in Munich for almost 4 years – amongst reviewing several hundred opportunities a year worldwide, closing a large pre-IPO investment with subsequent IPO, serving on the Board of Directors of three portfolio companies, and as part of new fund raising was instrumental for the first closing with a key European strategic investor.

He had joined TVM from Novartis, where he spent 12 years in various line function roles across three Divisions including Global Franchise Head Strategic Marketing for Immunology & Infectious Diseases, Pharma in Basel, Switzerland, Global Head of Development, Diagnostics for Vaccines & Diagnostics in Emeryville, CA, USA and Global Head New Product & Portfolio Strategy Biopharmaceuticals for Sandoz in Holzkirchen / Munich, Germany. During his tenure, he oversaw and was a team member for multiple collaborations, licensing deals and acquisitions from academic to multi-billion-dollar transactions, world-wide commercial launches and FDA / EMA / CFDA / ANVISA registrations with respective global clinical trials.

Prior to Novartis he was at McKinsey & Company, Inc. in Germany, trained as an MD at Johannes-Gutenberg-University Mainz, Germany with clinical training in Germany, Switzerland and the USA (UC Davis Medical Center, Sacramento, CA) and was a scientific co-worker at the Institute for Occupational, Social and Environmental Medicine in Mainz for several years

Dr. Ulrich Pessara – CBO

Ulrich has broad experience in business and financial transactions in the pharmaceutical and biotech environment and a solid scientific career in immunology/oncology for more than ten years.

He is currently serving as senior consultant with Staatz Business Development & Strategy. Since 2013, he serves as CEO of UP Biotech Management AG based in central Switzerland. From 2004 to 2013, Ulrich was General Partner of JSB Partners LP/USA and was serving as managing director of the subsidiary in Germany and Switzerland being responsible for international partnering- and financing activities for Financial, Pharma and Biotech industries. As member of the Investment Board of the Corporate Finance Holding of the Sächsische Landesbank, Leipzig/Germany, Ulrich was serving in several boards of Germany biotech companies. From 2000 to 2004, he was co-founder and Chief Development Officer of Xantos Biomedicine AG, a Munich based Biotech company, where he was responsible for business development, intellectual property and strategic development.

From 1997-2000, he served as director of program management for international biotech alliances at Hofmann-La Roche. During that time, he was managing director and board member in international joint venture biotech companies in San Diego/USA, Milan/Italy and Hanover/Germany. From 1991-1997, he worked for Boehringer Mannheim where he was responsible for biopharmaceutical drug development with international academic and industrial partners.

He received his MS at the University of Cologne/Germany, his PhD at the German Cancer Research Center in Heidelberg/Germany and held postdoctoral positions at the Universities of Heidelberg/Germany and Strasbourg/France

Scientific collaborations

The IcanoMAB portfolio has been developed to date and is in collaborations
with leading experts and renowned organizations across the world like

  • The Dinarello Lab, Department of Medicine, University of Colorado Denver, Aurora, Colorado/USA and Department of Medicine, Radboud University Medical Center, Nijmegen/The Netherlands
  • Division of Immunology and Allergy, Karolinska Institutet, Stockholm/Sweden
  • Department of Infectious Disease and Institute of Clinical Medicine Aarhus University Hospital, Aarhus/Denmark
  • Department of Gynecology and Obstetrics, Medical Center University Regensburg/Germany
  • Division of Genetics, University of Erlangen/Germany
  • Division of Asthma Exacerbation & Regulation, Research Center Borstel, Leibniz Lung Center, Borstel/Germany
  • Vall d’Hebron Institute of Oncology, Barcelona/Spain (VHIO)

News

We will keep you updated on our progress

News

Polling, Germany – September 7, 2020
IcanoMAB GmbH founded with private funding to develop precision canonical monoclonal antibodies in Oncology, Immune-modulation, Acute Inflammation and most urgently for Covid-19

Press Release (PDF)

Contact

Get In Touch​

Contact Info

Our Location

IcanoMAB GmbH
Tassilostr. 2
82398 Polling

Call Us

+49 881 399 08940

Our Email

info@IcanoMAB.com