Technologies

Emergent's ADAPTIR platform is a novel antibody platform technology capable of building unique monospecific and bispecific protein therapeutics that are at the forefront of scientific development and new product discovery.

ADAPTIR Immunotherapeutics

The ADAPTIR™ (modular protein technology) platform is Emergent BioSolutions’ novel platform technology for generating immunotherapies that have the potential to address unmet treatment needs in multiple clinical areas, including autoimmune and inflammatory diseases and oncology.

Modular Protein Design

Emergent BioSolutions' custom ADAPTIR platform is designed to expand the utility and effectiveness of antibodies in new arenas.

The ADAPTIR platform technology can produce monospecific and multispecific (eg, bispecific) therapeutic molecules.

Because of their structural differences from monoclonal antibodies (mAbs), ADAPTIR immunotherapeutics engage the disease target in a unique manner and produce a unique signaling response.

The Emergent BioSolutions Capability

Emergent BioSolutions has experienced scientific, antibody engineering, manufacturing, and commercial leadership.

Emergent BioSolutions has a successful history of product candidate generation, validation, and clinical development. Emergent BioSolutions has the ability to drive ADAPTIR molecules from concept to marketed product:

Emergent's ADAPTIR platform is a novel antibody platform technology capable of building unique monospecific and bispecific protein therapeutics that are at the forefront of scientific development and new product discovery.

ADAPTIR Monospecific Platform

ADAPTIR monospecific molecules may have potential application in the treatment of

  • Autoimmune and inflammatory diseases1,2
  • Cancer3-5
  • Transplant rejection
  • Infectious diseases
  • Other areas of unmet medical need

Structural Characteristics

ADAPTIR monospecific molecules are single-chain polypeptides comprising three components: a binding domain (VL and VH), a hinge domain, and an effector domain (huFc).

ADAPTIR monospecific molecules bind to a single antigen target and have the potential to bind to cell surface antigens, as well as neutralize soluble antigens.

The binding domains in the ADAPTIR monospecific molecules are closer together (60-80 Aº) than the binding domains in conventional monoclonal antibodies (mAbs) (95-140 Aº).

In addition, the molecular weight of ADAPTIR monospecific molecules is approximately one-third less than that of mAbs (105 kDa vs 150 kDa).

The modular design of ADAPTIR monospecific molecules enables customized balancing of various biological activities such as1-4,6-8

  • Target signal induction
  • Complement-dependent cytotoxicity (CDC) and
  • Antibody-dependent cellular cytotoxicity (ADCC)

Reliable Manufacturing

ADAPTIR monospecific molecules can be produced in large scale, using standard mammalian cell lines and conventional processes, similar to that of mAbs.

ADAPTIR monospecific molecules have been and are currently being manufactured for use in multiple clinical trials in oncology and autoimmune and inflammatory diseases.1-4

Characteristics

ADAPTIR monospecific molecules have potential advantages over mAbs:

References

  1. Fleischmann R, Cohen S, Pardo P, Dessouki E, Clowse M, Korth-Bradley J, Bhattacharya I, Diehl A, Gourley I. Subcutaneous administration of SBI-087 provides potent B cell depletion in subjects with controlled RA. The European League Against Rheumatism Congress, June 16-19, 2010, Rome, Italy (slide presentation).
  2. Fleischmann R, Cohen S, Pardo P, Shaw M, Bhattacharya I, Sridharan S, Diehl A, Gourley I. B cell depletion in subjects with controlled systemic lupus erythematosus (SLE) after intravenous or subcutaneous administration of SBI-087. The European League Against Rheumatism Congress, June 16-19, 2010, Rome, Italy (poster).
  3. Furman RR, Andritsos L, Flinn IW, Forero-Torres A, Foon KA, Pagel JM, Singhal A, Stromatt SC, Byrd JC. Phase 1, dose escalation study of TRU-016, an anti-CD37 SMIP™ protein in relapsed and refractory CL. American Society of Hematology (ASH) 52nd Annual Meeting, December 4-7, 2010, Orlando, FL, USA (slide presentation).
  4. Andritsos L, Furman R, Flinn IW, Foreno-Torres A, Foon K, Flynn JM, Stromatt SC, Byrd JC. A Phase 1 trial of TRU-016, an anti-CD37 small modular immunopharmaceutical (SM IP™) protein in relapsed and refractory CL: Early promising clinical activity. American Society of Hematology (ASH) 52nd Annual Meeting, December 4-7, 2010, Orlando, FL, USA (poster).
  5. Abou-Nassar K, Brown JR. Novel agents for the treatment of chronic lymphocytic leukemia. Clin Adv Hematol Oncol. 2010;8(12):886-95.
  6. Wang C, Beckett T, Odegard V, Hussell S, Mohler K, McMahan CJ. Small modular immunopharmaceutical (SMIP™) molecules directed at the TCR complex (CD3) block T cell activation and cause minimal cytokine release in vitro. The American Association of Immunologists 97th Annual Meeting, May 7-11, 2010, Baltimore, MD, USA (poster).
  7. Mohler KM. SMIP™ and SCORPION™ proteins: novel, mono or multi-specific therapeutic proteins for autoimmune diseases and oncology. Next Generation Protein Therapeutics Summit, June 21-23, 2010, Burlingame, CA, USA (slide presentation).
  8. Rafiq S, Cheney C, Thompson PA, Siadak T, Algate P, Cerveny C, Byrd JC, Muthusamy N. Glycovariant CD37 small modular immunopharmaceutical (TruADhanCe™ SM IP) promotes enhanced natural killer cell mediated cytotoxicity against primary chronic lymphocytic leukemia cells. American Society of Hematology (ASH) 51st Annual Meeting, December 5-8, 2009, New Orleans, LA, USA (poster).
  9. Beckman RA, Weiner LM, Davis HM. Antibody constructs in cancer therapy: protein engineering strategies to improve exposure in solid tumors. Cancer. 2007;109(2):170-9.

Emergent's ADAPTIR platform is a novel antibody platform technology capable of building unique monospecific and bispecific protein therapeutics that are at the forefront of scientific development and new product discovery.

ADAPTIR Bispecific Platform

The ADAPTIR bispecific platform is a promising platform technology within the rapidly growing field of immuno-oncology therapeutics.

Structural Characteristics

ADAPTIR bispecific molecules are designed as single-chain polypeptides that are capable of engaging two targets. The structure is comprised of two N- and C-terminal binding domains and an effector domain based on immunoglobulin Fc regions.

The ADAPTIR bispecific platform is compatible with IgG1, IgG2, and IgG4 formats. The size of ADAPTIR bispecific molecules is comparable with mAbs (150-160 kDa).

Proprietary Technology

ADAPTIR bispecific molecules mediate Redirected T-Cell Cytotoxicity (RTCC) to eliminate tumor cells.  The ADAPTIR bispecific platform has been shown in preclinical models to redirect T cell killing against multiple tumor targets. In addition, it has the potential to treat solid and hematologic malignancies. Safety of our lead ADAPTIR candidate MOR209/ES414 is under evaluation in a Phase I clinical trial.

Reliable Manufacturing

ADAPTIR bispecific molecules are produced using antibody-like manufacturing methods. They are made in standard eukaryotic manufacturing cell lines as disulfide-linked proteins. GMP manufacturing up to 2000 L has been demonstrated.

Platform Characteristics

The ADAPTIR bispecific for RTCC has shown multiple competitive advantages in preclinical studies:

In addition, preclinical studies have shown the benefits of

  • Orientation of binding domain (less steric hindrance)
  • Customized distance between binding domains
  • Two to four targets in one molecule
  • Multiple constructs produced

Other Multispecific ADAPTIR Molecules

Besides bispecific molecules, the ADAPTIR platform can also be configured to produce other types of multispecifics.

MVAtor™ (modified vaccinia virus Ankara vector) is a viral vector platform used to construct recombinant vaccine and therapeutic candidates.

MVAtor™ (modified vaccinia virus Ankara vector)

MVAtor™ is a flexible, proprietary, viral vector platform based on modified vaccinia virus Ankara (MVA) for delivery of protective or therapeutic antigens. MVA was administered to more than 100,000 subjects as a “prevaccine” prior to use of unattenuated vaccinia. We are using MVAtor to develop novel prophylactic and therapeutic vaccines. MVAtor is derived from an MVA strain isolated before bovine spongiform encephalopathy (BSE) was identified.

MVA can infect mammalian cells and goes through early and late stage protein production, but is unable to complete final stages of replication. It can be used to induce an immune response to genes inserted in the virus (recombinant antigens).

MVA in Clinical Trials

MVA-based constructs containing recombinant genes for antigen delivery are being evaluated in prevention and treatment of a wide range of infectious diseases and cancers. Human trials have been conducted against infectious diseases including tuberculosis, malaria, and HIV. MVA expressing tumor antigens such as 5T4 and melanoma antigens are being studied in human trials for treatment of cancer.

MVA in Manufacturing

Recombinant MVA products have previously been produced in primary chick embryo fibroblasts. In order to standardize production, we have developed a manufacturing process based on the use of a continuous avian cell line, which has the following potential advantages:

  • Readily scales up to commercial levels,
  • Amenable to single-use disposable equipment making transfer of the technology to new manufacturing sites relatively simple as identical equipment can be rapidly installed reducing time and capital cost requirements.