Technology Approach

WHAT ARE IMUNEXINS^TM?

Imunexins^TM are engineered from a naturally occurring, non-antibody, human protein sequence with physical properties similar to those of the binding regions of antibody V-domains (imunexins^TM are referred to as V-like domains).Imunexins^TM have 3 binding loops akin to the binding loops of antibodies which can be engineered to bind to any target of interest. The unique physical properties of imunexins^TM allows attachment to other protein sequences including antibodies without perturbation of either the parent antibody sequence or the imunexin^TM maintaining the parent antibody’s properties and manufacturability.Imunexins^TM are easily genetically fused to an existing antibody via simple standard cloning protocols.

Diagrammatic representation of an imunexin^TM relative to the VH binding domain of antibodies.

WHAT ARE THE ADVANTAGES OF THE IMUNEXIN APPROACH?

Key advantages the Imunexin^TM multispecific antibody generation platform include:

Imunexin properties:

• Imunexins^TM are human in origin and are potentially less immunogenic.
• No reformatting or engineering is required post discovery stage.
• Can be genetically fused to any protein sequence without affecting the folding or expression of either the recipient protein or the imunexin^TM.
• Discovery is via high throughput screening of our 10+10 randomised library via the Company’s proprietary HTP screening technology.

Simple and highly efficient multispecific antibody generation:

• Applicable to any antibody sequence.
• No antibody- imunexin^TM matching needed.
• Antibody retains original binding sites and specificity.
• Proper pairing of antibody heavy and light chains.
• Imunexins^TM are simply cloned into exiting IgG vectors to generate a multispecific with no additional protein engineering required.

The parent antibody retains its original structure and function:

• The antibody’s original sequence, specificity and functions fully retained.
• Antibody retains its binding avidity.
• Imunexins^TM fused to antibodies also show binding avidity.
• Antibody-mediated effector functions are retained or can be modulated for select applications.
• Antibody pharmacokinetics including serum half-life are retained.

Integrates seamlessly into existing production processes:

• The manufacturability of the antibody-imunexin^TM fusion mirror those of the parent antibody.
• Manufacturing, purification, formulation and all other processes are based on standard IgG processes and remain the same.

GENERATING MULTISPECIFC MOLECULES

Imunexus converts parent antibodies from single binding antibodies into dual or tri binding antibodies by linking imunexin^TM “modules” directly to the parent antibody. In essence, Imunexus takes well validated or commercial monoclonal antibodies that have one therapeutic binding region and converts them into multispecific antibodies that have two or three therapeutic binding regions. One key advantage of this approach is that imunexin^TM modules can be added to existing antibodies without modifying the sequence or any of the properties of the parent antibody while seamlessly adding additional therapeutic functionality to the original antibody.

One strength of Imunexus’ multispecific approach for generating therapeutics is predicated on the fact that there are an abundant number of parent antibodies available to Imunexus. Parent antibodies based on commercial antibodies that are approaching or are already off patent are readily available as well as numerous failed or poorly performing clinical and preclinical antibodies.

The imunexin^TM approach to drug development has a number of clear advantages:

1. The fusion of imunexins^TM to antibodies is a simple process that does not appear to affect the physical or binding properties or manufacturability of either the parent antibody or the attached imunexin^TM. This gives Imunexus the potential to quickly develop unique drug candidates from almost any antibody or protein sequence, with flexibility and through-put that is not possible with most other bispecific antibody approaches.
2. Imunexus believes that this approach has reduced clinical development risk as commercial, clinical or advanced preclinical parent antibodies have a strong scientific rationale supported by extensive preclinical or human clinical data.
3. A clear advantage is speed, cost, and productivity. Unlike most other antibody therapeutic programmes, once we identify and optimise an appropriate imunexin, we can fuse the same imunexin^TM to a number of parent antibodies and quickly generate extensive pipelines. We can develop these bispecifics from concept to investigational new drug candidate ready for pre-clinical studies comparatively quickly and for significantly less cost per multispecific relative to traditional drug discovery approaches.

Diagram Illustrating the potential for rapid pipeline expansion via the same imunexin modules readily added to a number of different exixsting antibody drugs to quickly createmultiple products.