NatiMab Therapeutics is an Italian SME located in the premises of the Bioindustry Park Canavese scientific and technological park, at Colleretto Giacosa (Torino). Registered on 02/01/2008 in Torino, NatiMab was founded by Gianni Garotta, Maurizio Denaro, Marianne Murphy and Gerritt Hagens. On 10/12/2014, two previously key collaborators, Francesco Novelli and Guido Forni joined the company as shareholders.

Goal and Clinical Application

The overall goal of NatiMab Therapeutics srl is the identification and development of human antibodies (Abs) for the therapy and diagnosis of infectious diseases and cancer.

Initially, NatiMab has concentrated on identifying Tumor Associated Antigens (TAAs) that are recognized by Abs in the serum from patients with Pancreatic Ductal Adenocarcinoma (PDAC) using the method of Serological Proteome Analysis (SERPA) (shown in figure 1).

Figure 1. SERPA method to identify TAAs recognized by Abs present in PDAC patient sera

PDAC accounts for the vast majority (85-100%) of all exocrine pancreatic tumors [Kloppel G and Luttges, J Curr Gastroenterol Rep 2004, 6:111]. It is the fourth leading cause of cancer-related deaths in western countries with an overall 5-year survival rate of less than 5% [Hidalgo M, N Engl J Med 2010, 362:1605; Jemal A, CA Cancer J Clin 2010, 60:277]. This very low rate of survival is mainly attributed to the fact that most patients are not diagnosed until the disease has already metastasized and therapeutic resection is not possible. The development of new tools for early diagnosis of PDAC is a clear unmet medical need and NatiMab plans to exploit the findings of PDAC TAAs recognized by Abs in patient serum to develop novel diagnostic kits for this critical medical need.


Novel Findings

NatiMab Therapeutics has used Serological Proteome Analysis (SERPA, figure 1) to identify tumor-associated antigens (TAAs) that are recognized by specific autoantibodies (Abs) present in the serum of patients with PDAC. NatiMab will exploit these novel TAAs for use in the diagnosis of PDAC, as targets for monoclonal antibodies or tumor vaccines. Patent applications were filed by NatiMab, claiming the detection of Abs to two of these TAAs [Ezrin (EZR) and a phosphorylated isoform of α-Enolase (ENOA)] for use in the diagnosis of PDAC.

Intellectual Property


Patent TO2012A000523 was filed June 15, 2012 and is still pending. A novelty search was made in 03/2012 and no novelty destroying prior art was found. The PCT extension WO2013186748 was filed June 14, 2013 and entered the regional phases in 12/2014.
The patent describes the plasma membrane cytoskeleton linker molecule EZR whose over-expression and membrane translocation correlates with metastatic potential and poor prognosis and which has been identified as an early TAA. Abs to EZR are present in a subpopulation of PDAC patients with resectable tumors and, in a retrospective study, could be found in some patients up to 5 years before PDAC diagnosis. EZR is also an early marker of disease in a mouse model of spontaneous pancreatic cancer.

Alpha-Enolase (ENOA)

Patent TO2009A0697 was filed September 11, 2009 and granted November 2013.
The PCT extension WO2011/030302 was filed Sept 9, 2010 and published March 17, 2011.
The US patent 2012/0164146 A1 was published June 18, 2012 (priority publication date) and granted as US8895697 B2 in Nov 2014 with validity from Sept 9, 2010 to Jan 25, 2031.
The patent describes an intracellular protein that may be expressed on the cell surface and acts as a plasminogen receptor. Specific isoforms of ENOA are identified in PDAC cells by serum from 62% of patients with PDAC and the presence of these Abs is correlated with specific stages of disease.

Development plans

To summarize NatiMab’s novel findings, the presence of EZR-Abs is a marker associated with the initial stage of PDAC. The simultaneous presence of Abs to both EZR and the ENOA identifies a more advanced stage of PDAC. Further, the simultaneous presence in the blood of EZR-Abs and ENOA-Abs detects PDAC with even greater sensitivity and specificity, when used together with the measurement of CA19.9, the only serum marker that is currently used in clinical practice for PDAC and which, on its own, can only detect advanced stages of the disease.

To exploit these exciting findings, NatiMab is developing sensitive and specific diagnostic kits for the detection of EZR-Abs and ENOA-Abs in patient sera. When the EZR-Abs and ENOA-Abs kits are used in combination with the CA19.9 assay, a rapid, reliable and non-invasive procedure for the diagnosis of PDAC will be possible (Figure 2).

Figure 2. Use of EZR-Abs, ENOA-Abs and CA19.9 kits for the diagnosis of Pancreatic Cancer

The EZR-Abs kit is also of particular interest for detecting those patients who are at risk of PDAC development, including patients with newly diagnosed Type II diabetes, chronic pancreatitis, PDAC family history, stomach ulcer, IBD, tooth or gum disease and obese individuals. The proposed use of the EZR-Abs kit for screening newly diagnosed Type II diabetes patients is shown in figure 3.

Figure 3. Blood test for EZR-Abs as PDAC screen of patients with a new diagnosis of Type II diabetes

There are currently no blood tests to detect PDAC at an early stage, while there are large populations at risk of developing the disease. Thus, the reliable and easy to perform diagnostic tools being developed by NatiMab will meet a clear unmet medical need and have a profound impact on PDAC diagnosis and treatment, resulting in an overall increase in survival rate for these patients.


Management team

NatiMab exploits the experience of the management team to lead and coordinate outsourced R&D activity. The NatiMab Management Team has extensive experience in the discovery and development of biologics for drugs and diagnostics, with a unique know-how in monoclonal antibody technologies and tumor biology.

  • Gianni Garotta

    PhD, General Manager and NatiMab Founder, academic experience at General Pathology Institute of Milano University, Istituto Tumori of Milano (Italy), Wistar Institute of Philadelphia (PA, USA) and Basel Institute for Immunology (Basel, Switzerland) and more than 30 years Biotech and Pharma experience at Roche (Basel, Switzerland), Human Genome Sciences (Rockville, MD, USA) Serono and RiboVax Biotechnologies (Geneva, Switzerland). At Roche he was responsible for preclinical research on Interferons, Cytokines and monoclonal antibodies, at Human Genome Sciences he was responsible for the Biology Department, at Serono he was the VP for Extramural Research and at RiboVax he was the CEO. In his career, Gianni Garotta pioneered the diagnostic application of monoclonal antibodies, discovered several molecules and characterized them as potential drugs. Seven of these drugs entered clinical trials and one has been approved for therapy. Gianni Garotta served as scientific advisor for Index Venture (Geneva, Switzerland) and Eporgen Venture (Ivrea, Italy).
  • Marianne Murphy

    PhD, Head of Discovery and NatiMab Founder, academic experience at Wistar Institute, University of Pennsylvania (Philadelphia, PA, USA) and University of California, San Francisco (CA, USA). She has 18 years Biotech experience at Human Genome Sciences (Rockville, MD, USA), Celltech (Slough, UK) and RiboVax Biotechnologies (Geneva, Switzerland). Marianne Murphy has extensive experience in T cell and cytokine biology, monoclonal antibody technologies and project management. She played a key role in the discovery and validation of numerous clinical targets and was one of the first to produce neutralizing monoclonal antibodies and an immunoassay to human TNF, the target for Remicade and Enbrel.
  • Francesco Novelli

    PhD, Project Coordinator and NatiMab shareholder, academic experience at University of Turin, Wistar Institute, Philadelphia (PA, USA) and Necker-Enfants-Malades Medical School (Paris France) and was a Visiting Researcher in the Molecular Biology Department, Central Research Units, Roche, Basel (Switzerland). Francesco Novelli has 25 years experience in tumor immunology and is an expert in the identification and characterization of novel tumor associated antigens in PDAC using a proteomic approach, in the development of preclinical models of pancreatic cancer and the design of novel immunotherapeutic strategies based on DNA vaccination.
  • Maurizio Denaro

    MD, Head of Development and NatiMab Founder, academic and clinical experience at University of Bologna (Italy), Uppsala University (Sweden), Stanford University (CA, USA) and Oncology Center of Aviano (Italy), 30 years Biotech and Pharma experience at Lepetit (Milano, Italy), Hoechst Marion Roussel (Cincinnati, OH, USA and Gerenzano, Italy), Amylin Pharmaceutical (San Diego, CA, USA), OSI Pharmaceutical (New, York, NY, USA), Bracco (Milan, Italy) and Aptuit (Verona, Italy). At Bracco he was accountable for a Business unit in the area of ultrasound research, managing R&D, commercial and manufacturing operations while at Aptuit he was the CEO and Senior Vice President for all the world wide operations. Maurizio Denaro has extensive experience in drug development for infectious disease, inflammation, cancer and diabetes and in management of multi-center program and strategic alliances. In his career he has been involved in more than 10 products being brought to IND status. Of these, 4 have become commercial products, in the field of antibacterials, diabetes and in vivo imaging.
  • Gerrit Hagens

    PhD, MBA, Head of Operations and NatiMab Founder, academic experience at University of Berne, University of Lausanne and University of Geneva (Switzerland). He has 18 years Biotech and Pharma experience at Serono (Geneva, Switzerland), ExcellGene (Monthey, Switzerland), RiboVax Biotechnologies (Geneva) and BioXpress Therapeutics (Plan-les-Ouates, Switzerland). Gerrit Hagens has extensive experience in molecular biology, developing manufacturing processes for biologics, monoclonal antibody technologies and project management. He was responsible for the development of a new Rebif`clone to satisfy worldwide Rebif demand, as well as the clinical trial in the US which resulted in marketing authorization from the FDA. In his managerial capacity, Gerrit Hagens served as COO in ExcellGene and RiboVax Biotechnologies. Beside his activities at BioXpress, Gerrit is acting as Corporate Advisor for several biotech companies and lecturer at the University of Applied Sciences, Sion, Switzerland, where he teaches Master and PhD students in manufacturing of biologics.
  • Guido Forni

    MD, Scientific Expert and NatiMab shareholder, academic experience at University of Turin. He spent several years as Visiting Scientist at the Laboratory of Immunology, NIAID, NIH, Bethesda (MD, USA), and at the Immunology Unit, University College (London UK). Guido Forni has 45 years experience in tumor immunology. He is an expert in the bioinformatic identification of new onco-antigens and in the establishment of innovative DNA vaccines against onco-antigens to prevent tumor occurrence. He serves as a consultant for pharmaceutical companies involved in clinical trials on anti-cancer vaccines.

Collaborators and consultants

In the framework of the EZR-Abs and ENOA-Abs kit development, NatiMab works with academic institutions, consultants and expert scientists.

  • Department of Molecular Biotechnology and Health Sciences (DMBHS) of University of Turin (UNITO)

    Thanks to the collaboration with DMBHS, NatiMab can access the infrastructure, technical equipment and expertise required to accomplish its tasks.
  • Department of Medical Sciences (DSM) of University of Turin (UNITO)

    The agreement with DSM gives NatiMab access to the infrastructure, technical equipment and expertise of Prof. Malavasi’s Laboratory of Immunogenetics.
  • EPIC Foundation, Verona University, Torino University and Regina Elena National Cancer Institute, Rome, Italy

    NatiMab has obtained prediagnostic serum samples of PDAC patients from the European Prospective Investigation into Cancer and Nutrition (EPIC). The Turin cohort, used by NatiMab includes samples from 10,604 healthy subjects at the moment of enrollment (6,047 males and 4,557 females, aged 35–65 years). Recruitment took place from 1993 to 1998 and involved blood donors and other healthy volunteers. Subjects were monitored longitudinally for cancer or other disease development. Co-operation with the local cancer registry and the local health authority enabled access to hospital discharge information and all newly diagnosed cancer cases. Study design, population and baseline data collection have previously been described in detail [Riboli E et al, European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 2002, 5:1113; Chuang SC et al, Eur J Cancer 2011, 47:1808]. Forty PDAC patients identified from the Turin EPIC cohort are included in the studies described in Novel Findings. An additional 50-60 prediagnostic PDAC samples from the Turin center of the EPIC study area are available from the Human Genetic Foundation, Turin Italy and availability to NatiMab is currently under review with the Ethics Committee.
  • ARC-NET Applied Research Centre, University of Verona, Italy and Regina Elena Cancer Institute Rome, Italy

    ARC-NET has two additional independent cohorts of PDAC patients, including serum from many patients with early-stage resectable PDAC.
  • Consultants and Clinical Experts

    The following consultants will provide expert clinical and technical advice to NatiMab.

    Luca Gianni

    Head of the Medical Oncology Department, San Raffaele Hospital, Milano.

    Lorenzo Piemonti

    Head of the β-Cell Unit of the Diabetes Research Institute of San Raffaele Hospital, Milano.

    Aldo Scarpa

    Head of Department of Pathology of the Verona University.

    Michele MiIella

    Clinician, Regina Elena Cancer Institute, Rome.

    Roberto Ringhini

    Immunoassay Expert, RP Consulting Srl, Cassina de Pecchi, Milano.

    Giuseppe Caputo

    Coaching for EU grant application, MeTech Srl, Torino.


  • Previous Funding and Projects

    To date, NatiMab has worked with private funds (mainly founders) and with funds from the Piedmont regional government and EU programs.

    Previous projects in which NatiMab has been involved include:

    European Pancreatic Cancer - Tumor Microenvironment Network (EPC-TM) funded by 7FP (2011-2013) - In the frame of the project: “Targeting the tumour microenvironment to improve pancreatic cancer prognosis”, NatiMab was involved in the identification of pancreatic cancer associated antigens suitable for diagnostic and immunotherapeutical purposes.

    Consortium BIOTHER funded by the Regione Piemonte. In the frame of the “Converging Technology Program”. Title of the project: Modeling Oncogenic Pathways: from Bioinformatics to Diagnosis and Therapy (2009-2012). NatiMab was involved in the identification of tumor associated antigens and development of monoclonal antibodies to them to be used for therapeutic purposes. Consortium IMMONC funded by the Regione Piemonte, in the frame of the program “Piattaforme Innovative nel settore delle Biotecnologie per le scienze della vita”. Title of the project: Innovative approaches to activate anti-tumor activity (2010-2013). NatiMab was involved in the identification of tumor associated antigens and development of monoclonal antibodies to these antigens, to be used for therapeutic, diagnostic and prognostic purposes.

  • Horizon 2020 Research and Innovation Framework Program

    In collaboration with other small European companies (see Partner companies) NatiMab was accepted for a SME Instrument Phase 1 Feasibility Study for the European Union Horizon 2020 Research and Innovation Framework Program. Following this initial Feasibility study, NatiMab and its partners are applying for a Horizon 2020 Fast Track to Innovation Pilot 1 project to fund the development of the EZR-Abs and ENOA-Abs kits. For this project, NatiMab will continue our academic collaborations and will work with partner companies.

  • Partner Companies

    GeNeuro Innovation SAS - GeNeuro Innovation is a French biotech based in Lyon and Archamps. It was created in 2009 as a subsidiary of GeNeuro SA, Switzerland and has the status of small medium enterprise (SME) granted by the European Medicine Agency. In collaboration with NatiMab, GeNeuro will express and purify the human recombinant EZR to be used as capture antigen for the EZR-Abs kits.

    Iris Biotech GmbH - Iris is a German SME based in Marktredwitz. It was created in 2001 as a spin-off of Cfm Oskar Tropitzsch GmbH, the first chemical factory in Germany. Iris will produce and purify the phosphorylated ENOA peptide to be used as capture antigen for the ENOA-Abs kits.

    Dia.Pro Diagnostic BioProbes S.r.l. - Dia.Pro is an Italian company that operates in the field of In-vitro Diagnostics (IVD). In particular the company develops, produces and distributes IVD kits based on the Enzyme-Linked-Immuno-Sorbent-Assay (ELISA) and Chemi-Luminescent-Immuno-Assay (CLIA) technologies. Dia.Pro will focus on the development and industrialization of ELISA and CLIA immunoassays to EZR-Abs and ENOA-Abs, starting from the raw materials developed by NatiMab and our partners at GeNeuro and Iris. In addtion, Dia.Pro will work with NatiMab to obtain the CE Certification for the EZR-Abs and ENOA-Abs kits.


NatiMab Therapeutics S.r.l.

Via Ribes, 5 - 10010 Colleretto Giacosa (TO), Italy

Gianni Garotta