The novel Pept-inTM mode of action makes the platform applicable in any type of organism or cell that relies on protein synthesis. By functionally inhibiting disease-driving proteins, a therapeutic effect can be achieved. Proofs of concept have already been demonstrated in the functional knock-down of mammalian, bacterial, viral, and fungal protein targets for treatment of human diseases.
Currently, Aelin is advancing programs to candidate selection and early-stage clinical research to demonstrate safety and early indications of efficacy in patients. The initial strategic focus lies on:
A new class of anti-bacterials
Increasing numbers of bacteria are becoming resistant to antibiotics, escalating the number of patients dying from untreatable infections. Without access to medicines that rely on a new mode of action, healthcare will start to regress to a pre-antibiotic state. In particular, Gram-negative bacteria, which include the well-known species E. coli, are causing major problems around the world.
Pept-insTM represent a promising novel class of antibiotics. While most APRs are unique, a small minority occur in multiple proteins. By selecting such cross-reactive APRs, a selective proteostatic collapse can be achieved. This clears even multi-drug resistant (MDR) infections quickly and efficiently.
Two proofs-of-concept have been published targeting the Gram-negative E. coli and the Gram-positive S. epidermis. In vitro efficacy data showed that:
- Pept-insTM kill bacteria rather than suppressing growth
- They have a broad activity spectrum, targeting multiple bacterial species with one Pept-inTM
- Activity is not influenced by the MDR genotype or phenotype
- Resistance develops very slow, if not at all, thanks to the fast kinetics of killing and its effect on multiple proteins creating a larger hurdle for corrective mutations
The positive effects were confirmed in in vivo sepsis, thigh abscess and urinary tract infection models, showing:
- Impressive reductions in tissue bacterial load
- Similar potency to Standard of Care existing antibiotics
- The ability to reach distant sites of infection
- No cytotoxicity or adverse effects
Read the full case in our papers
High-value, undruggable targets
Pept-insTM also represent first-in-class therapeutics against high-value undruggable targets. Despite huge advances in molecular medicine, many disease-associated proteins remain undruggable. For example, they lack an obvious active site to which small molecules can bind or are out of reach of biologics inside the cell.
The unique characteristics of the Pept-inTM technology can overcome these challenges. This potential was demonstrated by targeting VEGFR2, an important signaling protein involved in the formation and growth of blood vessels. VEGFR inhibition is a known strategy for treating various cancers.
In vitro and in vivo testing of the Pept-inTM revealed that:
- It reaches the tumor site after IV administration
- It reduced VEGFR2 dependent tumor growth in mice to the same extent as a standard-of-care tyrosine kinase inhibitor.
- The effect was highly specific and it did not impact VEGFR negative cells
- No systemic or organ-specific toxicity was observed