Isomerase has a curated library of compounds which contains a selection of isolated or partially isolated compounds collected from projects over the last 20 years at Isomerase Therapeutics, Biotica Technology Ltd., and the University of Cambridge. It contains many novel and proprietary compounds. Details are stored in Isomerase’s relational databases including the structure of the compounds plus activity data generated when using these compounds. This database has been maintained and it has continued to grow since 2003.
Whilst serving our partners is the core strategic focus of Isomerase, over the last couple of decades the Isomerase team has built up a collection of compounds, strains, and processes. In most cases, these consist of novel microbial strains (usually engineered) capable of directly producing novel or known compounds, often characterised by screening and development data.
Isomerase has built partnerships underpinned by our technical knowledge, and access to proprietary compounds or strains equity linked to the service provision by Isomerase or other forms of license agreement.
The following lists a few examples of proprietary compounds available for partnering, licensing or are accessible for screening.
Rapamycin and rapalogs are potent mTOR inhibitors and are approved treatments for prophylaxis of organ rejection, in oncology and in drug-eluting stents. They are also being trialled in several other therapeutic areas, including several diseases of ageing.
The team at Isomerase have a long history stretching back over 20 years of working on the rapamycin biosynthetic cluster and discovering and developing novel rapamycin analogues for use in a wide variety of therapeutic areas. Isomerase acquired materials and all unfiled IP from historical collaborations with Wyeth, Pfizer and work carried out at the University of Cambridge and Biotica Technology.
FKBPs are a family of peptidyl-prolyl isomerases, present in many tissues, e.g., brain tissue. Their inhibition has been shown to have potential in neuroprotection and neuroregeneration, leading to work by Wyeth to generate and develop a non-immunosuppressive analogue of rapamycin (ILS-920) for the treatment of ND diseases (Ruan et al., 2008).
We have generated non-immunosuppressive, potentially brain penetrant potent FKBP inhibitors, based on FK506 (tacrolimus), rapamycin and FK520 (ascomycin) scaffolds with improved properties for the treatment of neurodegenerative diseases. It is also a novel scaffold to enable the discovery of other FKBP inhibitors, generated by our proprietary recombineering technology.
Inhibition of virulence factors has long been suggested as a potential antimicrobial strategy that is non-destructive to the bacteria and therefore has much less chance of selecting for resistance. This could open up new ways of treating bacterial infections, such as prophylactic dosing, new combination regimes and broader applicability of new treatments. However, most virulence factors are specific to one bacterial genus or even species, meaning that the treatment, once developed, would only be applicable to a fraction of infections.
Macrophage infectivity potentiators (MIPs) are peptidyl-prolyl isomerases which are conserved across a wide range of key human Gram-negative pathogens, including Klebsiella, Acetinobacter, Legionella, Pseudomonas, Burkholderia, Coxiella and Neisseria. Previous work has shown that their inhibition or knockout leads to a large reduction in virulence, with significant extension in mouse survival, reduction in bacterial survival in macrophage assays and visual effects, such as loss of flagella. It would therefore seem that this protein could be a central regulator of virulence in these bacteria – many of which make up the ESKAPE pathogens, where resistance in hospital-acquired infections is a serious concern.
Isomerase has several bioengineered lead molecules, based on the rapamycin scaffold, but with mTOR inhibition abrogated or removed, which have been confirmed as natural product inhibitors of MIPs. They can be produced by direct fermentation and therefore have the potential for eventual low cost of goods. We are collaborating with Prof Barrie Wilkinson at the John Innes Centre to generate data to support their further development.
Generated using a proprietary natural product glycosylation technology, Isomerase scientists have generated strains and processes to produce a variety of analogues of erythromycin, building upon historical Biotica projects, now owned by Isomerase.
Many cytotoxic Antibody Drug Conjugates (ADCs) utilise natural product-based payloads also known as High Potency Active Pharmaceutical Ingredients (HPAPIs). Clinically approved examples include taxol, maytansinoids, calicheamicin and PDBs.
Isomerase has built up a collection of ADC payloads, strains, and processes for producing the products both for the sale of small quantities of R&D product sales companies and also for potential start points for partners. Examples include pladienolide B, bafilomycins, leptomycins, rhizoxins and PDB analogs.
Get in touch if you would like to discuss access to any of our proprietary compound collections or unpartnered projects.