Innovative macrocycle drugs for challenging targets

Discovery collaborations with Polyphor

Our unique technologies and capabilities support partners in research & development for a broad range of target classes and diseases, providing effective solutions that address yet unmet medical needs.

Collaborations in macrocycle-based drug discovery

We aim for collaborative drug discovery partnerships. Flexible business models maximise the contributions of both partners.

Polyphor is a recognized leader in macrocycle drug discovery. We have delivered several clinical candidates for novel and challenging targets, discovered promising leads for previously non-druggable targets, and achieved several milestones in research collaborations with small, medium and global pharmaceutical companies.

Speed up drug discovery process

In strong partnerships we focus on targets selected by our research partner. In a joint effort we typically deliver leads and preclinical candidates for challenging, novel, non-druggable targets and macrocycle solutions for targets that have previously yielded results with only suboptimal chemical matter. Due to our design-based targeted and automated macrocycle medchem operations, progress from hit identification through HtL and LO is greatly accelerated. In addition, macrocycles offer the opportunity for new IP, in particular for projects in a crowded chemical IP space.

Macrocycle specific know-how brought to the table in collaborations
  • A detailed and sophisticated understanding of the properties of our macrocycles on a structural, chemical and physical properties level
  • Structure-based (ligand- or receptor-based) macrocycle design to complement and enrich screening with focused libraries
  • Understanding of how macrocycles interact with protein targets
  • Apply our successful design principles to allow macrocycles to cross membranes (intracellular activity, oral bioavailability)
  • Medicinal chemistry expertise to address and optimize hits and leads to fulfill the desired TPPs
Operational contributions by Polyphor in collaborations
  • Biological testing (assay development, screening of libraries, etc.)
  • ADMET testing
  • Biostructural research (protein expression, crystallization, X-ray in-house)
  • Rapid array synthesis of macrocycles
  • Biophysical characterization
  • Design and modeling
  • Logistics and assay-ready plating
  • Bioanalytics

We aim for collaborative drug discovery partnerships that maximise the contributions of both partners

Capabilities

From hit identification to PCC

Hit identification, HtL, LO up to PCC rationally designed, shape-diverse collection of semi-rigid macrocyles complemented by target-based focused libraries of macrocycles for hit identification.

Array assembly and purification

Established robust, rapid and flexible high-throughput array synthesis and high-throughput HPLC purification of macrocycles guarantee short optimization cycles and rapid project progress.

Modeling

Structure-based design (receptor- or ligand-based), scaffold docking and matching of key pharmacophores.

Macrocycle conformational analysis

Macrocycle conformations are analyzed extensively using high field NMR and X-ray data sets, and specialized CADD and SBDD tools support precise medchem optimization.

Binding interface know-how

Understanding of prerequisites for macrocycles to cross membranes and to bind to a target (interface know-how) from a chemical, conformational, biophysical and structural/3D point-of-view.

Structural biology

Gene to structure in-house incl. protein expression, crystallization and in-house protein X-ray.

Transfer of a cyclopeptide hit to a non-peptidic macrocycle

Proven to achieve cell permeability and/or oral bioavailability. Also useful to probe oral step-down for biopharmaceuticals.

PEMphage®

PEMphage®, a phage-display-based hit identification platform (107 to 109 molecules), which is structurally linked to Polyphor’s optimizable macrocycles – including structure-based transfer of cyclopeptide to non-peptidic macrocycles for oral and intracellular TPPs.

Critical mass

We have critical mass in all relevant disciplines (chemistry, biology, ADMET, biostructural research, modeling, project management) to move the projects forward in close collaboration with our partners.

Alternative starting points

SAR expansion, HtL, LO for a macrocycle hit originating from alternative macrocycle platforms. Optimize with us and tap into Polyphor’s vast medchem experience with macrocycles (peptidic & non-peptidic).

ADMET optimization

Detailed understanding of ADMET optimization of macrocycles, in particular for cell permeation and oral bioavailability.

New IP space solutions

New IP space solutions even for very crowded targets.

Design-assisted medchem

The use of privileged building blocks (natural product-like) in our macrocycles constrains conformational degrees of freedom in a predictable manner, enabling directed, precise medchem optimization.

Discovery collaborations with Polyphor

If you are interested to discuss our discovery collaboration opportunities please contact us.

Discovery collaborations contact

Jonathan J. Butcher, Ph.D.
Head Business Development Discovery

T: +41 61 567 16 32