Masked Antibodies & Cytokines As Prodrugs: a landscape analysis of stakeholders, technologies, pipelines, business and financing from an industry perspective

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Publisher: La Merie Publishing
Pages: 433
Format: PDF
Product Line: Full Report
Product Code: LMFR0034
Release Date: October of 2021

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.


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.


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.

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.

Table of Contents



1Executive Summary


2Introduction, Overview & Methodology


3Stakeholder Analysis


3.2Masking Technology Companies
3.3Pharma/Biotech Companies Partnered with Masking Technology Companies


4Profiles of Stakeholders in Masking Technologies


4.1Profiles of Masking Technology Companies
4.1.1Accurus Bioscience
4.1.3Amunix Pharmaceuticals
4.1.4Ascendis Pharma
4.1.5AskGene Pharma
4.1.7Bright Peak Therapeutics
4.1.8CytomX Therapeutics
4.1.10Harpoon Therapeutics
4.1.11Janux Therapeutics
4.1.12Maverick Therapeutics
4.1.13Meditope Biosciences
4.1.14Molecular Partners
4.1.15Nektar Therapeutics
4.1.16Revitope Oncology
4.1.18Shanghai Affinity Biopharmaceutical
4.1.19Tansoar Biotech
4.1.20Trutino Biosciences
4.1.21Werewolf Therapeutics
4.1.22Xilio Therapeutics


4.2Profiles of Pharma & Biotech Companies with a Stake in Masking Technologies
4.2.2ADC Therapeutics
4.2.4Astellas Pharma
4.2.6Boehringer Ingelheim
4.2.7Bristol Myers Squibb
4.2.9I-Mab Biopharma
4.2.12Junshi Biosciences
4.2.14Mitsubishi Tanabe Pharma
4.2.17Takeda Pharmaceutical Co


5Analysis of Masking Technologies


5.1Origin of Masking Technologies
5.2Prodrug Antibody Technologies
5.3Prodrug Cytokine Technologies
5.4Prodrug Antibody & Cytokine Technologies


6Profiles of Masking Technologies


6.1Masking Technologies Appied Only To Antibodies
6.1.1Adagene: SAFEbody Technology
6.1.2BioAtla: Conditionally Active Biologics (CAB)
6.1.3Harpoon Therapeutics: ProTriTAC Technology
6.1.4Janux Therapeutics: Tumor Activated T Cell Engager (TRACTr) Technology
6.1.5Maverick Therapeutics: COBRA Technology
6.1.6Molecular Partners: Anti-CD3 ProDrug DARPin (CD3-PDD) Technology
6.1.7Revitope Oncology: PrecisionGATE Technology Platform
6.1.8Roche: Protease-Activated T-Cell Bispecific (TCB) Antibodies
6.1.9SeaGen: Coiled-Coil Masking Domain Technology
6.1.10Tansoar Biotech: Universal Antibody Lock Technology


6.2Masking Technologies Applied Only To Cytokines
6.2.1Ascendis Pharma: TransCon Technology
6.2.2AskGene Pharma: Smartkine Prodrug Technology
6.2.3Meditope Biosciences: SnAP Technology
6.2.4Nektar Therapeutics: Kinetically Controlled Prodrug Technology
6-2.5Trutino Biosciences: On-Demand-Cytokine (ODC) Platform
6.2.6Werewolf Therapeutics: PREDATOR Technology Platform


6.3Masking Technologies Applied to Antibodies & Cytokines
6.3.1Amunix Pharmaceuticals: Pro-XTEN Technology
6.3.2CytomX Therapeutics: Probody Technology
6.3.3Xilio Therapeutics: Geographically Precise Solutions (GPS) platform


Zymeworks: PROTECT Technology Platform
7Analysis of Pipeline and Masked Antibody & Cytokine Prodrug Candidates




7.2Analysis of the Pipeline of Masked Antibodies
7.2.1Overview of the Masked Antibody Pipeline
7.2.2Pipeline of EGFR-Targeted Masked Antibodies
7.2.3Pipeline of CTLA4-Targeted Masked Antibodies
7.2.4Pipeline of EpCAM-Targeted Masked Antibodies
7.2.5Pipeline of Her2-Targeted Masked Antibodies
7.2.6Pipeline of Masked Antibodies Targeting TROP2, PSMA or B7-H3
7.2.7Pipeline of Other Masked Antibodies with Designated Targets
7.2.8Clinical Proof of Mechanism and Concept
7.3Analysis of the Pipeline of Masked Cytokines
7.3.1Pipeline of Masked Interleukin-2 Molecules
7.3.2Pipeline of Masked Interleukin-12 and -15 Molecules
7.3.3Pipeline of Masked Interferon alpha Molecules


8Profiles of Masked Antibody & Cytokine Product Candidates


8.1Masked Immuno-Oncology Antibodies
8.1.2Anti-CD47 Prodrug Antibody
8.1.8PD-L1 x CD28 Costimulatory Bispecific


8.2Masked Antibody-Drug Conjugates
8.2.3Mecbotamab vedotin
8.2.4Ozuriftamab vedotin
8.2.5Praluzatamab ravtansine


8.3Masked T-Cell Engaging (TCE) Antibodies


8.4Masked Interleukin-2 (IL-2) Cytokines
8.4.3TransCon IL-2 β/γ (beta/gamma)


8.5Masked Interleukin-12 (IL-12) and -15 (IL-15) Cytokines
8.5.1ASKG215β (beta) and ASKG215γ (gamma)
8.5.2ProTECT IL-12 Fc


8.6Masked Interferon (IFN) Cytokines
8.6.1Dual Masked Interferon α2b (alpha2b)


9Business, Financing & Partnering






Tables in the Text


Figures & Tables

Table 1Corporate Stakeholders in Masking Technologies
Table 2Focus of Masking Technology Companies
Table 3Profiles of Companies with Masking Technologies
Table 4Interests of Pharma/Biotech Companies in Applications of Masking Technologies
Table 5Partnerships between Masking Technology Companies and Pharma/Biotech Companies
Table 6Levels of Interest and Participation of Major Pharma/Biotech Companies in Masking Technologies
Table 7Adagene’s Partnered SAFEbody Discovery Programs
Table 8Adagene’s SAFEbody Pipeline
Table 9Amunix Pharmaceuticals’ Unpartnered Pipeline of XPATs and XPACs
Table 10BioAtla’s Pipeline of Conditionally Active Biologics (CABs)
Table 11Pipeline of Proprietary and Partnered Probody Therapeutics from CytomX Therapeutics
Table 12TRACTr & TRACIr Pipeline of Janux Therapeutics
Table 13Maverick Therapeutics’ Pipeline of COBRA Molecules
Table 14Werewolf Therapeutics’ Pipeline of Indukine Molecules
Table 15Xilio Therapeutics’ Pipeline of Masked Antibodies and Cytokines
Table 16Source of Technology and Pharma Partners of Foundational Masking Technology Companies
Tables 17Foundational & Main Technology Platforms of Companies with Evolution to Masking Technologies
Table 18Overview of Applications of Masking Technologies to Different Antibody Constructs
Table 19Characteristics of the Masking Moiety Used for Generation of Prodrug Antibodies
Table 20Characteristics of the Linker Moiety Used for Generation of Prodrug Antibodies
Table 21Overview of Applications of Masking Technologies to Different Cytokines
Table 22Characteristics of the Masking Moiety Used for Generation of Prodrug Cytokines
Table 23Characteristics of the Linker Moiety Used for Generation of Prodrug Cytokines
Table 24Overview of Applications of Masking Technologies to Different Cytokines & Antibody Constructs
Table 25Characteristics of the Masking Moiety Used for Generation of Prodrug Antibodies & Cytokines
Table 26Characteristics of the Linker Moiety Used for Generation of Prodrug Antibodies & Cytokines
Table 27Overview of Masked Antibody R&D Programs
Table 28Overview of Antibody Modality and R&D Stage of Masked Antibodies
Table 29Overview of Antibody Modality and Targets of Masked Antibodies
Table 30EGFR-Targeted Masked Antibody Programs in R&D
Table 31CTLA4-Targeted Masked Antibody Programs in R&D
Table 32EpCAM-Targeted Masked Antibody Programs in R&D
Table 33Her2-Targeted Masked Antibody Programs in R&D
Table 34Masked Antibody Programs Targeting TROP2, PSMA or B7-H3
Table 35Pipeline of Other Masked Antibodies with Designated Targets
Table 36Synopsis of Clinical Results of Masked Antibodies
Table 37Overview of Masked Cytokine Programs in R&D
Table 38Overview of Type of Cytokine and R&D Stage for Masked Cytokines
Table 39Overview of Masked Interleukin-2 Programs in R&D
Table 40Overview of Masked Interleukin-12 & -15 Programs in R&D
Table 41Overview of Masked Cytokine Programs in R&D
Table 42Financing of Converted Pure Play Masking Technology Companies
Table 43Financing of Foundational Pure Play Masking Technology Companies
Table 44Financial Terms of Partnering Deals Based on Masking Technology



Accurus Bioscience


ADC Therapeutics



Ascendis Pharma

AskGene Pharma

Astellas Pharma



Boehringer Ingelheim

Bright Peak Therapeutics

Bristol Myers Squibb

CytomX Therapeutics



Harpoon Therapeutics

Himalaya Therapeutics

I-Mab Biopharma



Janux Therapeutics

Junshi Biosciences

Maverick Therapeutics (Takeda Pharmaceutical Co)

Meditope Biosciences


Mitsubishi Tanabe Pharma

Molecular Partners

Nektar Therapeutics


Revitope Oncology



Shanghai Affinity Biopharmaceutical


Trutino Biosciences

Werewolf Therapeutics

Xilio Therapeutics


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