Receptor.AI and Sethera Therapeutics Form Integrated Discovery Alliance for AI-Guided Polymacrocyclic Peptide Medicines
Collaboration combines Sethera’s proprietary enzymatic polymacrocyclisation and trillion-scale encoded screening with Receptor.AI’s physics-based modelling and multiparameter peptide optimisation
SALT LAKE CITY and CAMBRIDGE, Massachusetts, 3 August 2026. Receptor.AI Inc. (“Receptor.AI”), a TechBio drug discovery company developing integrated AI- and physics-based platforms for molecular design and preclinical discovery, and Sethera Therapeutics (“Sethera”), a biotechnology company developing a proprietary enzymatic platform for polymacrocyclic peptide medicines, today announced a strategic research collaboration to establish a closed-loop discovery and optimisation workflow for difficult therapeutic targets.
Under the collaboration, Sethera will generate and experimentally screen architecture-diverse polymacrocyclic peptide libraries. Receptor.AI will apply physics-based modelling, artificial intelligence, and multiparameter optimisation to interpret sequence, architecture, enrichment, and activity data; develop binding hypotheses; prioritise candidate series; and guide focused optimisation cycles. The companies will then design, synthesise, and experimentally test new candidates, using the resulting data to inform each subsequent cycle.
Sethera’s platform installs one to six stable cross-links to generate polymacrocyclic, nested, in-line, and interpeptide structures across large, encoded libraries. Unlike constrained-peptide approaches centred on a predetermined structural motif, Sethera’s platform explores multiple experimentally accessible topologies, allowing target biology and screening data to identify the most productive molecular architecture. By combining this chemical space with Receptor.AI’s computational capabilities, the companies intend to advance screening-derived hits toward validated lead series with improved potency, selectivity, stability, permeability, and other developability characteristics.
The initial programme will focus on a mutually selected hard-to-drug target. The companies will prospectively assess whether the integrated workflow improves hit confirmation, target selectivity, and lead optimisation compared with conventional enrichment- and assay-led prioritisation. Following validation of the initial workflow, Receptor.AI and Sethera intend to pursue additional internal programmes and jointly structured discovery collaborations with pharmaceutical and biotechnology partners across selected target classes and therapeutic areas. Additional terms of the collaboration were not disclosed.
“Sethera’s platform creates experimentally accessible peptide architectures that conventional design approaches do not readily reach,” said Dr Alan Nafiiev, Founder and CEO of Receptor.AI. “Our objective is to use physics and AI not as a substitute for experimentation, but to learn from each experimental cycle and direct the next one. That closed feedback loop is where we believe the collaboration can create distinctive value.”
“Sethera can search enormous physical libraries and identify target-binding sequence and architecture families that cannot be generated through conventional peptide design alone,” said Dr Karsten Eastman, CEO and Co-Founder of Sethera Therapeutics. “Receptor.AI adds a powerful layer for understanding why those hits work and how they can be improved. Together, we intend to create a coordinated design-make-test-learn process that moves more efficiently from experimental discovery to validated lead series.”
The collaboration is specifically focused on applying Receptor.AI’s computational platform to Sethera’s proprietary polymacrocyclic peptide chemistry, encoded screening data, and resulting therapeutic candidates. Each company will retain its background platform technologies, and joint programmes will be conducted under coordinated research plans with defined experimental, computational, data, and programme management responsibilities.
Through the alliance, Receptor.AI and Sethera aim to establish a repeatable discovery system that continuously learns from sequence, architecture, counterselection, binding, functional, and developability data generated across experimental campaigns. The resulting workflow is intended to reduce the number of design cycles required to progress from initial screening hits to differentiated peptide lead series.
About Receptor.AI
Receptor.AI is a US-based TechBio drug discovery company developing integrated AI- and physics-based platforms for preclinical discovery. Its technology combines generative AI, structure- and physics-based modelling, multiparameter optimisation, and adaptive decision systems to help pharmaceutical and biotechnology partners define discovery strategies and design, prioritise, and optimise candidates for complex target biology. Receptor.AI supports programmes across small molecules, peptides, and induced-proximity therapeutics.
More information: https://www.receptor.ai
About Sethera Therapeutics
Sethera Therapeutics is developing a proprietary enzymatic platform for the discovery and development of polymacrocyclic peptide therapeutics. Sethera’s technology installs defined, stable thioether cross-links to create single-macrocyclic, nested, in-line, and interpeptide architectures. The platform integrates enzymatic macrocyclisation, large-scale encoded-library screening, next-generation sequencing, peptide synthesis, and biological validation to discover differentiated candidates for difficult therapeutic targets. Sethera is advancing internal and partnered programmes in oncology, inflammation and immunology, metabolic disease, and other therapeutic areas.
More information: https://setheratx.com
