Technology platform

AIDD’s approach includes: pharmacological approaches (biosensor design, antibody- and peptide-enabled small molecule drug discovery), computational methods, protein preparation techniques, chemical methodologies (fragment- and structure-based drug design), and biophysical techniques (e.g. X-ray crystallography and NMR).

Specifically, AIDD leverages five highly sophisticated and mutually reinforcing technologies:

  1. Aura Assays: ultra sensitive cellular assays for high throughput screening
  2. Systems for antibody- or peptide-enabled drug discovery (AEDD)
  3. Fragment-based drug discovery (FBDD)
  4. Structure-based drug design (SBDD)
  5. Native membrane protein purification (NMPE)

tech platform

 

 

 

 

 

 

 

 

 

 

 

Under AIDD’s aegis, it will be the first time that such a unique set of competencies and synergistic technologies have been brought together to rationalize and accelerate drug discovery. 

Combining these approaches allows AIDD to isolate targets in their native form and identify (and validate) hits using approaches that generate synergistic structural and functional data. We expect that this will increase discovery efficiency to generate exciting highly differentiated clinical candidates and related molecular probes that can elucidate mechanisms of action in vitro and in vivo, including preclinical proof of concept studies.

We believe the AIDD’s Aura Assays and allostery know-how combined with AEDD, FBDD, SBDD, and NMPE is unmatched throughout the industry. This combination will allow AIDD to make data-driven decisions faster and earlier in project progression, leading to decreased attrition rates during lead generation, higher quality leads and better overall discovery efficiency than industry averages to date.

One of the challenges of modern drug discovery lies in defining and orchestrating optimal combinations of available technologies to “drug” each individual therapeutic target. Picking the appropriate set of tools for each target can significantly increase the chances of success and substantially expand the number of druggable targets. With its broad network and deep understanding of both the quality of academic output and the pharmaceutical industry’s needs, AIDD can successfully bridge both worlds, fostering commercialization of a steady flow of highly desirable projects. Indeed, the team already has a track record of identifying successful leads against previously intractable targets.

Our approach for the identification of quality leads will especially rely on the following approaches:

1) Aura assays: We will perform HTS-enabling conversion of our in-house target-proximal, dynamic, ultra-sensitive Aura Assays to a relevant plate format (e.g. 384-well plate format) and subsequently screen one or more chemical libraries that cover a wide swathe of chemical diversity. Chemical libraries are readily available through academic collaborations, industrial partners, fee-for-service providers, and several non-for-profit enterprises.

2) AEDD: For target classes for which there is no formal evidence of druggability, camelid nanobody binders will be selected by panning with the target of interest. Binders will then be assessed for their pharmacological properties using Aura Assays. Nanobodies with desirable properties will be used to guide structure-based or ligand-based drug discovery. In some cases, nanobodies may be selected for optimization and development as drug-candidates. The combination of antibody-enabled drug discovery (AEDD) screening with NMPE and complementary Aura Assays is unique and differentiates AIDD from other groups performing drug discovery.

3) FBDD: In parallel, we will apply a fragment screening approach to membrane protein targets and soluble protein targets. Again, the choice of which approach to use will be made on a case-by-case basis dependent on the nature of the target protein. Our proximal, highly sensitive cellular Aura Assays are highly complementary to a fragment based approach, and resolve one of the critical issues of fragment discovery, namely the difficulty of validating functional activity of the identified binding fragment. Once fragment binders have been identified, we will use our Aura Assays to triage the fragments for priority investigation based on functional information that would not otherwise be available to those pursuing this avenue of hit identification. The combination of FBDD with NMPE and complementary Aura Assays is unique and differentiates AIDD from other groups performing drug discovery.

4) SBDD: In addition, as early as possible, AIDD will obtain precise structural information on the binding site of small molecule, fragments or nanobody antibodies through X-ray crystallographic methods (i.e. co-crystals) and pursue SBDD. As mentioned above, access to structural data will be facilitated using unique NMPE and extraction techniques and/or with the use of nanobody chaperones.The combination of structural data streams from FBDD and/or AEDD with SBDD and complementary Aura Assays is unique and differentiates AIDD from other groups performing drug discovery.

Using these synergistic technologies for preliminary hit identification, hit validation and demonstration of structure-activity relationship (SAR), AIDD will be highly differentiated from and complementary to potential industrial partners and its peers. We will be well placed to tackle the most interesting and attractive novel targets, many of which are currently beyond the reach of other, less synergistic discovery engines.