Masked Antibodies & Cytokines As Prodrugs:

a landscape analysis of stakeholders, technologies, pipelines, business and financing from an industry perspective

This report provides you with a landscape description and analysis of prodrug antibodies and cytokines employing conventional and novel masking technology platforms from an industry perspective as of October 2021.

The prodrug concept of masking technologies is an elegant approach to address the selectivity ?limitations of conventional therapeutic antibodies and cytokines.

The report brings you up-to-date with information about and analysis of


  • Stakeholders in the field: technology and major pharmaceutical companies and investors;
  • Masking technologies: conventional (kinetically controlled); pH dependent and protease cleavage in the tumor microenvironment
  • Targets of masked antibodies and type of masked cytokine selected for development of masked biologics;
  • Business strategy: pure play (foundational or converted) masking technology company, diversified technology company, exit options, preferred antibody modality or type of cytokine, investment case;
  • Financing situation of technology companies and key investors in the field;
  • Partnering deals with financial terms;
  • Major pharmaceutical companies: preferences for masking technologies, collaboration and licensing agreements.

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Background
Therapeutic antibodies have become a clinically and commercially successful treatment modality with more than 100 antibodies approved for therapy and commercial sales of more than US$ 184 bln in the year 2020. However, systemic administration of monoclonal antibodies or cytokines may induce severe adverse events with mechanism-of-action effects, meaning off-tumor on-target toxicity in healthy tissue. In order to increase the selectivity of antibodies and cytokines at the disease site, antibodies should ignore the target antigen and cytokines the receptor in normal healthy tissue and be preferentially active in the disease region.

The use of antibody prodrugs is one new strategy for more specific tumor targeting of biological therapies. Conventional prodrugs are pharmacologically inactive compounds that are converted into active forms in the body after administration. They can be designed to be activated at the intended site of action, thereby lowering exposure of normal tissues to active drug and minimizing toxicity. The most common novel approach to creating antibody prodrugs are protease-activated antibodies that use antigen binding site ‘masks’.

The mask is typically a recombinant protein extension of the light and/or heavy chain of the antibody that has been designed to block access to the antigen binding site and physically prevent binding of the antibody to the cognate antigen. A protease substrate sequence is also inserted between the mask and the antibody. When the prodrug antibody enters the tumor microenvironment, upregulated proteases that are common in cancer tissues cleave the substrate sequence, the mask separates from the antibody, and the antibody becomes competent to bind to its target in the tumor. This doesn’t happen efficiently in normal tissues because there is insufficient extracellular protease activity to remove the mask. The same principle does apply to prodrug cytokines.

Methodology
This report evaluates the industry landscape of masked antibodies and cytokines in research and development. The report is based on the identification and description of 40 stakeholder, 24 of which are companies with masking technologies and 16 are pharma/biotech companies partnered with masking technology companies.

For each masking technology company, a profile has been elaborated providing information about the company background/history, the financial situation, relevant technology, partnering deals and target & pipeline overview. Short profiles are provided for pharma & biotech companies with a stake in masking technologies. The company profiles are preceded by a chapter of stakeholder analysis.

Profiles of 20 different masking technologies were also elaborated and presented separately for masking technology onloy applied to antibodies, only applied to cytokines and applied to both, antibodies and cytokines. The masking technologies are analyzed with special focus on origin of technology, inactivation domain, linkers and substrates for protease cleavage. Conventional and universal masking technologies are also discussed.

Eventually, profiles of 25 masked antibody R&D programs and of 10 masked cytokine programs. Each masked antibody profile was assigned to one of three groups: immuno-oncology antibodies; antibody-drug conjugates (ADC) and T-cell engaging (TCE) bi- or trispecific antibodies. Masked cytokine profiles are presented separately for interleukin-2 (IL-2); IL-12 & IL-15; and interferon alpha. Discussion of the masked antibody programs includes applied masking technology, targets or type of cytokine, stage of development, preclinical and clinical experience.

In a separate chapter, aspects of business models, financing and partnering are presented and discussed. Further stakeholders of masking technologies include investment firms which are presented by company and investment round. Financial terms of partnering deals are also described and discussed.

All information in the three chapters of Company Profiles, Technology Profiles and Drug Candidate Profiles are fully referenced with 79 scientific references, in many cases with hyperlinks leading to the source of information (abstracts, Posters, papers). Non-scientific references, such as press releases, annual reports or company presentations, are disclosed within the text with an embedded hyperlink leading to the online source of information. Details about R&D strategy, collaboration and licensing agreements, financing rounds & sources are described in the company profiles.

The report further includes 35 tables to summarize and directly compare information and uses illustrations to explain principles of masking technologies.

What will you find in the report?

  • Profiles of antibody & cytokine masking technology companies active in the field;
  • Description of major pharma’s/biotech’s role in the field (in-house R&D, partnering and investing);
  • Comprehensive description and analysis of emerging masked antibodies and cytokines;
  • Pharmacologic profiles of selected masked antibodies and cytokines;
  • Characterization, profiling and state of antibody & cytokine masking technologies;
  • Target selection for each antibody masking technology;
  • Selection of type of cytokine for each cytokine masking technology;
  • Description and analysis of financing rounds (capital raised, investors);
  • Economic terms of collaboration and licensing deals;
  • Sources of financing.

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Who will benefit from the report?


  • Venture capital, private equity and investment managers;
  • Managers of Big Pharma venture capital firms;
  • Financial analysts;
  • Business development and licensing (BDL) specialists;
  • CEO, COO and managing directors;
  • Corporate strategy analysts and managers;
  • Chief Technology Officer;
  • R&D Portfolio, Technology and Strategy Management;
  • Clinical and preclinical development specialists.