Scientific community

AIDD will contribute to maturing and marketing the universities’ intellectual property (IP) portfolio around a given project and, as a result, the project will have a better chance of attracting industrial partnership.  Therefore, academic discoveries will reach society more rapidly; and, universities will receive additional financial returns from their IP, providing funding for future research and other academic pursuits.

This is possible because AIDD aims to discover novel molecular entities (NME), which can be effectively protected by IP and will be supported by solid data to establish that they are potential drugs. By helping to create data packages that can stand the test of pharmaceutical companies’ scrutiny, these potential drugs are more likely to attract pharmaceutical partners than related precursor IP or other knowledge generated at universities. In short, AIDD will work with its academic partners to take the crucial step to ensure the translation of their R&D efforts into industrial projects that can be marketed for out‐licensing.

In addition to identifying patentable NME drug-candidates AIDD also identifies non drug-like molecular probes, which are useful for academic research - for example, characterization of biological pathways. In this way, AIDD collaborations will facilitate academic research and publication of important data describing biological pathways in greater detail than was previously possible.

In summary, universities will, on the one hand, have increased deal flow, while, on the other hand, they will be serviced by AIDD in the undertaking of industrial activities that may not be aligned with academic goals (e.g. standard medicinal chemistry), and that might expose them to the liabilities associated with drug development. This model enables a virtuous cycle, allowing for better quality, more competitive  research, richer more rounded educational opportunities for students, faster development of medicines for society and more profits for universities to fund future academic pursuits.

AIDD aims to be open source – enabling collaborators at all levels – and work according to ideals of open innovation. Therefore, AIDD’s  goal will be to share non‐proprietary methodologies and know‐how available to us with university collaborators in order to create drug discovery projects (e.g. drug-­candidates in lead optimization) and establish out-­licensing  and drug discovery partnerships with pharmaceutical partners. AIDD will federate its resources and competencies with complementary technologies and manpower from universities and industrial partners in order to facilitate drug discovery and target characterization. On selected therapeutic targets of interest to university researchers, AIDD will collaborate to adapt its proven methodologies for discovery of allosteric modulators. This highly  sensitive  approach  also  works  for  finding  conventional  “orthosteric”  agonists  and antagonists. In addition, AIDD’s approach can be used to identify small molecule, protein and/or peptide ligands for a broad variety of targets (GPCRs, non-­GPCR receptors, enzymes…etc).

AIDD will collaborate with academic groups on discovery projects by partnering with them and their university (e.g. via a CTI grant) on drug discovery projects. Under these partnering agreements, a Principal Investigator (PI) from the university would be paired with a Discovery Expert (DE) from AIDD. Depending on the collaboration agreement between AIDD and the university laboratory (via the relevant tech transfer department), either the PI or the DE would be named the project leader (PL) and be empowered with primary responsibility (and accountability) for advancing the project, according to timelines mutually agreed between the university and AIDD. While the PL would provide project leadership, the other individual (PI/DE) also would have responsibility for their activities under the relevant project plan and also an important role on the project team as the primary backup to the PL and with joint responsibility for the development of the project plan.

Together the PI and DE will develop project-­specific strategies to access relevant expertise including: design and construction of  biological screening tools, chemical library selection,  bioinformatics, biophysics, medicinal chemistry, in vivo pharmacology studies, toxicology and any other capabilities deemed relevant for a given project.

Allosteric modulators are commercially validated small molecule drugs that have broad potential for treatment of unmet medical needs and offer important  pharmacological  advantages  over  available  treatment  modalities. Although marketed allosteric modulators were identified by serendipity, while working for Addex Pharmaceuticals we have learned robust methods to identify allosteric drug candidates that have been validated by pharmaceutical partnerships. 

Although there is a growing number of allosteric modulators in pharmaceutical pipelines, historically, the vast majority of drugs – both small molecule and biological – have been “orthosteric” agonists or antagonists. Allosteric modulators have three important differences compared to orthosteric drugs: 

1) Orthosteric molecules act on therapeutic targets to switch them on or off via a binary mechanism.  In contrast, allosteric modulators offer gradable influence because they bind to a different (“allo”) site on their target, thereby increasing or decreasing its activity. This more refined influence over therapeutic targets can offer differentiated efficacy, tolerability and safety compared to orthosteric drugs. 
 
2) Since most allosteric sites have no known endogenous ligand they generally demonstrate greater heterogeneity and, thus, molecules that bind them can achieve greater selectivity than orthosteric drugs between closely related receptors. Achieving selectivity can result in superior safety and tolerability and is a common challenge for orthosteric drugs. 
 
3) Since allosteric modulators do not bind to the target’s “active site”, where orthosteric molecules bind, small molecule allosteric modulators can successfully modulate targets without competing against (high affinity) natural orthosteric ligands. Thus, allosterism is expanding the druggable space. Of particular interest are targets already validated using biologicals but which have been intractable to orthosteric small molecules. 

In summary, allosteric drugs offer greater selectivity and gradable control over therapeutic targets as well as an opportunity to revisit validated targets that have been intractable to small molecules.