ENABLE-2 Hit to Lead programme

WHAT WE OFFER

ENABLE-2 funding is non-dilutive. Accepted programmes will receive (free-of-charge) expert advice on development strategies (including TPPs); access to experimental platforms (chemistry, microbiology, ADMET, in vivo pharmacology, formulation, etc.) who will perform assays in collaboration with programme owners; funding to carry out approved assays, not available within the platform, at CROs; retain ownership of all data generated and retain IP rights to all new compounds developed.

ENABLE-2 is set up with a strong focus on developing small molecule programmes in the Hit to Lead stage and offers development up to a level of advancement (Lead optimization) with the aim to graduate to later stage initiatives or to out-licensing. ENABLE-2 currently has the capacity to develop 4-7 Hit to Lead programmes in parallel. Applications outside of this description (e.g., complex natural products, and more advanced programmes, etc.) may be accepted subject to capacity.

ELIGIBILITY

Researchers at publicly funded universities and research institutes in Europe (including non-EU countries such as UK, Norway, Switzerland, etc.) are eligible to submit a non-confidential Expression of Interest (EoI) Word, 59 kB. to ENABLE-2 at opencall.enable2@ilk.uu.se.

Compounds should be direct-acting against one or more of the following priority pathogens: ESBL-producing/carbapenem-resistant Enterobacteriaceae (E. coli, K. pneumoniae), carbapenem-resistant P. aeruginosa, carbapenem-resistant A. baumannii; methicillin-resistant S. aureus; vancomycin-resistant E. faecium.

To be accepted within the ENABLE-2 portfolio, compounds should have a novel mode of action which can include a novel target, a novel mechanism of inhibition against a known target, or a known mechanism of inhibition against a known target so long as there is demonstrated activity against a broad range of drug-resistant strains and management of any identified liabilities is feasible.

PROGRAMME ENTRY THRESHOLDS

Molecules with direct mode of action targeting in-scope pathogens

direct acting small molecules, or natural products, with potential for systemic antibiotic activity (anti-virulence, anti-biofilm compounds are not in scope)
potentiator molecules may be in scope (e.g. beta-lactamase inhibitors)
activity against drug-resistant clinical strains
single pathogen spectrum possible

Minimum inhibitory concentration (MIC) ≤ 16 μg/mL vs. at least one of the key ENABLE-2 pathogens

E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus, E. faecium
evidence that antibacterial activities are specific (activity not due to broad cytotoxicity, e.g., detergents)

Potential for optimization

novel chemical structure and preliminary Structure–Activity Relationship
reasonable route of synthesis (or demonstrated availability if a natural product)
favorable physical/chemical properties

IP situation/Freedom to operate (essential for entry)

clear legal/IP situation (applicant must have ownership of compound and freedom to operate)

Interesting programmes but lacking some key data

programmes that meet many of the entry requirements but lack some key data may still be able to present to the ENABLE-2 PMC following a Material Transfer Agreement (MTA) route.
the MTA route allows engagement of ENABLE-2 to generate missing data on the novel compound or series (e.g., MIC against resistant isolates of different species, haemolysis and cytotoxicity against human cell lines) towards submitting a full data package to the PMC at a later date.

APPLICATION PROCESS

Applicants submit a non-confidential Expression of Interest (EoI Word, 59 kB.)
Evaluation by panel of external experts to check for eligibility
Zoom call with the ENABLE-2 management team
Sign a confidentiality agreement
Applicants prepare a full application
Presentation to the Portfolio Management Committee (PMC)
Applicants notified of outcome
Successful applicants sign a user agreement including work plan

The Call is Open Continuously but to be considered for entry at the Portfolio Management Committee (PMC) meeting in October 2024, applications should reach us before 3 September 2024. Applications received after this date will be evaluated at the following PMC meeting in March 2025.