Posters

Pyroglutamate (Pgl) formation is a temperature-driven side reaction that compromises the efficiency of lactam-bridged peptide synthesis under MW-assisted SPPS. Here, IRBM systematically evaluates both process parameters and sequence determinants governing intramolecular Pgl formation. Integration of protocol optimization with CD spectroscopy and residue-scanning identifies the key conformational states enabling N-terminal cyclization. These findings establish a defined structure–reactivity framework and deliver a validated synthetic protocol for constrained peptides and macrocyclic therapeutics.

Reliable preclinical models represent one of the biggest limits in brain tumor drug discovery: classical 2D cell cultures rarely reproduce the cellular architecture and spatial organization of glioblastoma, so encouraging readouts often fail to translate. This poster outlines Complex 3D Patient Organoids (C3POs), engineered ex vivo spheroids that assemble patient-derived glioma stem-like cells with astrocytes and microglia in defined proportions, each population followed by fluorescent labeling and high-content imaging across a panel of molecular subtypes. Rebuilding this cellular context reshapes measured drug sensitivity and brings potency closer to tumor in vivo behavior, strengthening lead optimization, combination work, and subtype-specific testing. Download the poster to explore the model design and comparative drug-response data.

A variant of this poster was presented at AACR 2026 and can be found further down this page.

De-risking CNS drug discovery depends on translational models that can reliably predict whether a compound will cross the blood-brain barrier (BBB), a structure that both protects the brain and blocks most therapeutics from reaching it. This poster describes IRBM’s validated human BBB model, generated from iPSC-derived brain-like microvascular endothelial cells in a 2.5-dimensional, non-contact culture and benchmarked against key features of the in vivo barrier. It outlines how the system characterizes barrier integrity, polarized transporter activity, and receptor-mediated transcytosis, then links in vitro permeability readouts to unbound drug exposure measured in rodent brain and cerebrospinal fluid. The approach improves selection of CNS-penetrant candidates and strengthens translational relevance beyond animal models. Download the poster to explore the model characterization, functional assays, and in vitro/in vivo correlation data in detail.

Drug metabolism and pharmacokinetics (DMPK) often enter drug discovery too late, allowing potent compounds with poor exposure to advance and fail in later stages. This poster presents IRBM’s exposure-driven DMPK framework, which integrates early in vitro profiling and in vivo pharmacokinetics into a structured, multiparametric decision process that weighs unbound exposure and developability criteria alongside potency. Applied to a small-molecule SHP2 inhibitor program, the approach supported the assessment of CNS potential and guided optimization toward a CNS-active candidate with efficacy in an orthotopic glioblastoma model. Download the poster to explore the decision framework and in vivo characterization in detail.

Helicases are essential enzymes in coronavirus replication but have historically proven difficult to drug. The SARS-CoV-2 NSP13 helicase, conserved across coronaviruses and central to viral RNA synthesis, represents a compelling antiviral target that remains largely unexploited. This poster describes a multi-assay screening campaign conducted by IRBM, combining ATPase and unwinding assays to screen the IRBM small molecule library, followed by dose-response profiling and counter-screens to triage hits. Confirmed inhibitors display a time-dependent, irreversible inhibition profile, supported by jump dilution experiments and HRMS intact mass analysis, with selectivity over human helicases and key SARS-CoV-2 enzymes. Download the poster to explore the screening funnel, mechanistic characterization data, and structure-activity findings in detail.

SHP2 is a validated regulator of the RAS-MAPK pathway in oncology, yet no SHP2 inhibitor is approved and no active clinical trial currently addresses brain cancers, where poor CNS exposure continues to constrain therapeutic outcomes. This poster presents IRBM’s focused multiparameter optimization (MPO) strategy, integrating structure-based design, in silico property prediction, and iterative in vitro/in vivo ADME profiling, which converted potent, peripherally restricted inhibitors into the brain-penetrant candidate I-1000233 while preserving cellular activity. The work provides a practical framework for enabling CNS exposure in small molecules, with relevance for primary brain tumors and metastatic disease. Download the poster to explore the SAR, design strategy, and full in vivo characterization in detail.

Bicyclic peptides enhance receptor binding and proteolytic stability through conformational constraint, but their synthesis typically requires multistep assembly, orthogonal protection strategies, and repeated purification. This poster presents IRBM’s one-pot solution-phase route via bis-lactam cyclization, pairing head-to-tail macrolactamization with in situ Allyl/Alloc deprotection and spontaneous cross-link formation in a single vessel. A screen of coupling reagents and solvents reduces resin handling, reaction time, and solvent use while supporting reproducible scale-up. Download the poster to explore the reagent-solvent screen and cyclization workflow in detail.

Zika virus (ZIKV) continues to pose public health concerns due to its association with congenital and neurological complications, and currently, there are no approved antiviral therapies. This poster outlines an integrated drug discovery campaign at IRBM: it begins with a stable ZIKV sub-genomic replicon assay optimized for high-throughput phenotypic screening and traces target identification through resistance mapping and reverse genetics, pinpointing the NS2B–NS3 protease as the molecular target. Using X-ray crystallography, kinetic analysis, and medicinal chemistry, the team characterized a novel allosteric binding site and optimized an initial hit into IRBM-Z-2, a nanomolar inhibitor with broad-spectrum activity, a favorable off-target profile, and oral efficacy in mouse infection models. Download the poster to explore the complete screening process, structural data, and detailed in vivo efficacy results.

All Coronaviruses, including the highly pathogenic SARS-CoV and SARS-CoV-2, exploit a conserved discontinuous transcription mechanism to produce the subgenomic RNAs required for viral assembly, making this process an attractive target for broad-spectrum antiviral development. This poster presents a comprehensive screening strategy that includes both a phenotypic approach — using a SARS-CoV stable replicon cell line and a >400K compound collection — and an RNA-targeted approach employing biophysical methods against conserved 5′UTR stem-loop elements. Together, these workflows have led to the identification of two structurally distinct small-molecule inhibitors with nanomolar potency that selectively disrupt subgenomic RNA synthesis, as well as validated RNA-binding hits with confirmed direct interaction through NMR analyses. Download the poster to explore the complete screening cascade, mechanistic data, and findings related to structure–activity relationship in detail.

Glioblastoma remains one of the most aggressive brain tumors, with dismal clinical outcomes. A challenge made all the more daunting by the inadequacy of conventional 2D and animal models to recapitulate the structural and cellular complexity of the human tumor microenvironment. IRBM’s C3PO (Complex 3D Patient Organoids) platform addresses this gap by integrating patient-derived glioma stem-like cells with astrocytes and microglia into self-assembled, multicellular spheroids that reproduce key TME features — including nutrient and oxygen gradients, cell-ECM interactions, and subtype-specific genomic profiles. Tested across multiple GBM subtypes and compounds, C3POs reveal resistance mechanisms hidden in 2D assays and yield potency values that correlate more closely with in vivo efficacy data, supporting stronger translational confidence in compound prioritization. Download the poster to explore the full model characterization, drug-response data, and in vitro–in vivo comparisons in detail.

Werner helicase (WRN) has emerged as a compelling synthetic lethal target in microsatellite instability-high (MSI-H) cancers, yet its dynamic helicase domain presents significant challenges for traditional drug discovery. This poster presents IRBM’s electrophile-first drug discovery platform — a covalent fragment library of over 1,600 compounds paired with a multi-assay kinetic toolbox (enzymatic unwinding assays, intact mass LC-HRMS, peptide mapping, and covalent docking) — applied to rapidly identify ATP-competitive covalent inhibitors selectively engaging Cysteine 727 of WRN. Screening, hit expansion, and X-ray crystallography together confirmed the covalent binding mode and provided a structural rationale for further structure-based optimization. Download the poster to explore the full screening cascade, SAR findings, and crystallographic data in detail.

DNA mismatch repair (MMR) helps preserve genome integrity, but it also drives somatic triplet-repeat expansion in Huntington’s disease, making the MutSβ (MSH2–MSH3) complex a relevant target to modulate somatic instability. This poster presents an integrated workflow combining NMR with LC-SEC and LC-HRMS to assess full-length human MutSβ stability in solution, characterize ligand interactions, and confirm both non-covalent and covalent hit engagement while providing early binding-site contact insights to support SAR-driven optimization. It also outlines an NMR-enabled strategy to triage compounds for their ability to block or disrupt MutSβ–DNA complex formation, establishing assay benchmarks even when initial tool compounds do not inhibit this high-affinity interaction. Download the poster to explore the assay cascade and validation/triage logic in detail.

Coronaviruses can drive epidemics and pandemics, highlighting the need for pan-coronavirus antiviral strategies that go beyond single-strain solutions. This poster focuses on discontinuous transcription, an essential process shared across coronaviruses, and describes a phenotypic cellular approach built to interrogate this process in a screening-compatible format. The work reports establishing a stable model of coronavirus replication and shows that a high-throughput campaign can surface compounds with promising potency and selectivity profiles. An expanded set of follow-up assays is now being validated to deepen hit characterization and clarify mode of action. Download the poster to see how the model and assay workflow support discovery efforts targeting coronavirus transcription biology.

This poster describes an integrated hit-to-lead workflow to discover covalent inhibitors of the SARS-CoV-2 helicase NSP13, a conserved enzyme required for viral RNA synthesis, replication, and transcription. It outlines an HTS campaign using ATPase and helicase unwinding assays, followed by a selection funnel that combines intact-mass confirmation of covalent adduct formation, intrinsic thiol-reactivity profiling, peptide mapping by LC–MS/MS to localize modified cysteines, and chemoproteomics in cellular lysates to assess specificity and site selectivity. By integrating biochemical and proteomics readouts, the workflow identifies covalent NSP13 binders with demonstrated activity and supports structure–activity studies to optimize potency and selectivity. Download the poster to explore the screening funnel and assay cascade in detail.

This poster presents an automated, high-throughput workflow for peptide bioanalysis and plasma protein binding assessment, crucial for advancing peptide drug candidates. By combining mass spectrometry–based detection with different binding approaches (Transil PPB and Rapid Equilibrium Dialysis), the workflow enables sensitive and reproducible measurements, including for peptides with very high protein binding. The optimized workflow increases throughput and robustness, allowing accurate estimation of the unbound fraction and supporting efficient ADME characterization of peptide drug candidates.

Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is a powerful, non-radioactive tool used in radioligand drug discovery for quantifying metal-conjugated peptides with high accuracy in radioligand drug discovery. This poster outlines IRBM’s systematically validated ICP-MS workflow, applied to Lutetium-labeled candidates to support targeted radiotherapy research. The established platform enables sensitive measurement of cellular uptake, distribution, and pharmacokinetics across a range of biological samples—accelerating early-stage evaluation without the complexity of radioactive assays. Discover how integrating ICP-MS facilitates robust analysis for oncology-focused radiotheranostic programs and streamlines the path to clinical translation.

Coronaviruses rely on a unique process called discontinuous transcription to generate subgenomic RNAs essential for viral replication. This poster introduces a stable cell-based model of coronavirus replication, designed with a SARS-CoV replicon and NanoLuciferase reporter, enabling high-throughput screening for inhibitors of this process. Learn how phenotypic screening, supported by extensive follow-up assays, provides a framework for discovering potential pan-coronavirus antivirals.

Targeting NSP13 helicase, an enzyme critical for coronavirus replication and highly conserved across coronaviridae, presents both an opportunity and a challenge in antiviral discovery. This poster outlines a multidisciplinary strategy combining biochemical, biophysical, and fragment-based approaches to identify and characterize NSP13 inhibitors. The established assays, from NMR, ASMS and SPR to ATPase and unwinding assays, now support ongoing hit-to-lead optimization efforts.

Innovative strategies are reshaping small-molecule drug discovery, enabling access to previously “undruggable” targets. This poster presents IRBM’s integrated platforms for rapid hit identification, such as the Proteolysis Targeting Chimera (PROTAC) screening platform and the covalent fragment platform. The PROTAC platform leverages a “Direct to Biology” approach, pairing protein-of-interest ligands with a tailored ProtoDegron library for fast degrader evaluation, while the covalent fragment platform applies diverse electrophilic warhead-containing fragments to uncover starting points for covalent inhibitor design.

R2R01 is a novel long-acting peptide agonist of RXFP1, developed as a potential therapy for cardiovascular and renal disorders. Building on the therapeutic promise of the natural hormone Relaxin-2, over 800 analogues were explored to overcome metabolic and safety limitations, resulting in potent single-chain agonists with enhanced stability and prolonged half-life. This poster outlines the discovery journey leading to R2R01, its distinctive pharmacological profile, and its advancement into Phase 2 clinical development.

PROTACs represent a transformative strategy for degrading disease-relevant proteins, but their development is often resource-intensive and slow. This poster introduces an automated platform designed to accelerate the discovery of novel degraders by integrating direct-to-biology evaluation. With a dedicated ProtoDegron library and optimized workflows for rapid assembly and profiling, the approach offers a more efficient path toward expanding PROTAC discovery.

NSP13 helicase is a critical component of coronavirus replication, yet notoriously difficult to target due to its conformational dynamics. In this second part, we share how IRBM’s covalent fragment platform was applied to this enzyme. This approach led to the identification and characterization of hits using a functional assay to monitor the enzymatic activity of the target protein, binding specificity was conducted by LC/MS analysis and peptide mapping allowed the identification of the cysteine residues binding sites. A preliminary SAR of one of the hit compounds enabled the optimization of activity and binding, open prospectives for future developability.

This is Part 2 of the study—if interested, do not forget to download Part 1 for the full context.

The search for broad-spectrum coronavirus antivirals remains urgent, as no drugs with cross-activity have yet been approved despite multiple outbreaks. In this first part of our work, we present the results of a high-throughput screening campaign against the viral helicase NSP13. Among the hit compounds identified, two series inhibit NSP13 by forming a covalent adduct with the protein. Although the series explored showed limited tractability, the findings demonstrate the feasibility of covalent approaches to this essential viral enzyme.

This is Part 1 of the study—if you find it relevant, you may also be interested in downloading Part 2 for further insights.

Macrolactam peptides are an emerging therapeutic modality suited to complex, traditionally undruggable targets, yet their synthesis remains difficult and often constrains their potential in drug discovery. This poster presents IRBM’s streamlined strategy for bicyclic peptide production, developed to overcome the recurring obstacles of multistep synthesis while improving efficiency, reproducibility, and scalability. By simplifying a traditionally demanding route, the approach broadens practical access to conformationally constrained peptides for therapeutic development. Download the poster to explore how this strategy eases the main constraints of bicyclic peptide synthesis.

This poster presents the generation and biophysical characterization of novel rabbit-derived monoclonal antibodies against the SARS-CoV-2 NSP13 helicase, a highly conserved and essential component of the viral replication complex. These antibodies show high affinity and specificity, and have been validated in Western Blot and immunoassay formats. Their development addresses a critical gap in tools for studying helicase-targeting antivirals, enabling more precise investigation of NSP13 function and mechanism of action in cellular models.

This poster presents the development of C3PO—complex 3D patient-derived glioblastoma organoids designed to replicate the cellular and structural heterogeneity of the tumor microenvironment. Integrating glioma stem-like cells with stromal and neural components, these models enable pharmacological evaluation of therapeutic candidates under conditions that more closely reflect the in vivo tumor setting than classical monolayer and monoculture systems. Examples include compound testing with SHP2 and EGFR inhibitors across stratified GBM models, supporting both efficacy profiling and responder identification.

This poster illustrates the capabilities of IRBM’s CRISPR/Cas9 genome editing platform, designed to generate tailored cellular models for translational research. Applications span from gene knock-outs to targeted insertions and point mutations, across both immortalized and stem cell systems. The platform supports target validation, mechanistic studies, and therapeutic evaluation in areas including neurodegeneration, oncology, and rare diseases.

This poster presents the development and characterization of AM E3-SG3249, a first-in-class antibody-drug conjugate targeting CRLF2 for the treatment of CRLF2-rearranged Ph-like B-ALL. It highlights the biophysical properties of the ADC and evaluates its efficacy and tolerability in relevant xenograft models.

This poster illustrates how peptide pharmacokinetics can be improved through a rational, data-driven approach that links sequence design to physicochemical and biological performance. Through two case studies, we show how strategies like formulation adjustment, backbone lipidation, and cyclization were employed to overcome solubility and stability issues, ultimately enabling better in vivo exposure and progression in drug development.

This poster presents the preclinical development of AM E3-SG3249, a first-in-class antibody-drug conjugate targeting CRLF2 for the treatment of CRLF2-rearranged Ph-like B-ALL. The compound demonstrates potent cytotoxicity in vitro and significant antitumor activity in xenograft models, with efficacy linked to CRLF2 receptor density. A surrogate ADC enabled further validation and therapeutic window assessment.

This poster outlines the discovery and characterization of I-1000233, a brain-penetrant, orally available SHP2 allosteric inhibitor. The compound demonstrates activity in preclinical models of primary brain tumors and CNS metastases driven by RTK/RAS/ERK pathway dysregulation. Data on in vitro potency, in vivo efficacy, and initial insights into potential responder populations are presented.

In this poster, we outline the development of a novel inducible cellular model to support SARS-CoV-2 replication in a safe and controlled manner. Given the virus’s cytopathic nature and BSL-3 classification, we implemented a Tet-Off system to enable conditional expression of viral components, thereby avoiding cytotoxicity and allowing for stable replicon expression. Additionally, we employed an EBV-based episomal vector to address challenges posed by the large size of the SARS-CoV-2 genome, enabling stable maintenance of the replicon without genomic integration. This system lays the foundation for high-throughput antiviral screening in a BSL-2 setting, facilitating the identification of candidate molecules targeting SARS-CoV-2 replication.

In this poster, we present a high-throughput screening (HTS) campaign aimed at discovering novel pan-coronavirus antivirals targeting the discontinuous transcription process. Using a stable SARS-CoV replication cell model expressing a NanoLuciferase-tagged RNA replicon, we screened approximately 413K compounds from the IRBM collection, leading to the selection of 2319 hits with >45% inhibition. Reconfirmation and follow-up studies are assessing potency, cytotoxicity, and mechanism of action, and these evaluations are ongoing. Our work underscores the strength of phenotypic screening in identifying antiviral candidates with potential for broad coronavirus coverage.

In this poster, we present IRBM’s small-molecule discovery platforms designed to address previously “undruggable” targets through novel mechanisms of action. We describe how our expanded internal libraries (~420K compounds) and technologies support rapid hit identification, leading to the selection of promising degraders and covalent inhibitors. The PROTAC screening platform enables a “Direct to Biology” (D2B) approach by pairing POI ligands with a tailored ProtoDegron library, while the covalent fragment platform identifies starting points for target-specific covalent inhibitors. Follow-up studies will assess potency, selectivity, and developability, and these evaluations are ongoing.

In this poster, we present a high-throughput screening (HTS) campaign aimed at discovering novel pan-coronavirus antivirals targeting the discontinuous transcription process. Using a stable SARS-CoV replication cell model with a NanoLuciferase-expressing RNA replicon, we screened approximately 413K compounds from the IRBM collection, leading to the selection of 2319 initial hits. Reconfirmation and follow-up studies will assess potency, cytotoxicity, and mechanism of action, and these evaluations are ongoing. Our findings highlight the potential of phenotypic screening for discovering effective antiviral compounds against coronaviruses.

In this poster, we present IRBM’s multidisciplinary approach to developing covalent inhibitors targeting cysteine 727 of Werner helicase (WRN), a synthetic lethality target in mismatch repair-deficient (dMMR)/microsatellite instability (MSI-H) colorectal cancers. We describe the assay cascade established to identify and characterize novel covalent pharmacophores, leveraging biochemical, LC/MS, and cell-based assays. Our findings highlight two series of ATP-competitive inhibitors with limited cellular activity and ATP-cooperative inhibitors demonstrating robust biochemical and cellular potency. Ongoing optimization focuses on enhancing the biochemical and cellular profiles of these covalent WRN inhibitors.

In this poster, we present the identification and development of I-0436650 and the brain-permeable I-1000233, potent and selective SHP2 allosteric inhibitors with oral bioavailability. Using high-throughput biological, biochemical, and pharmacodynamic assays to guide Structure-Activity Relationship (SAR) studies, we optimized physicochemical and pharmacological properties to target tumors with dysregulated RTK/RAS/ERK signaling pathways.

In this poster, we showcase an advanced peptide program designed to inhibit the MLH1-MSH3 interaction, a key target in the DNA Mismatch Repair pathway implicated in Huntington’s disease. We detail the development of biochemical and biophysical assays used to guide Structure-Activity Relationship (SAR) studies, resulting in increasingly potent peptide inhibitors.