Day One

• Profiling regulome activity in live human cells enables real-time, proteome-wide responses to compound treatment
• Discovery and optimization of small molecules that actively displace transcription factors from DNA, shutting down disease-driving gene expression
• Predicting safety liabilities by leveraging transcription factor signatures to identify offtarget effects, including early signals of liver toxicity

• Exploring deubiquitinases as a tractable covalent target class, demonstrating how structural diversity enables surprising selectivity versus traditional enzyme families like kinases
• Leveraging novel and underexplored warheads (e.g., SNAr electrophiles, propargylamines, cyanamides) to access cysteine proteases beyond classical acrylamide chemistries
• De-risking emerging covalent chemotypes through integrated chemoproteomics and in vivo validation to achieve selective, exposure-ready compounds across oncology and antiviral programs

• Targeting glycolytic vulnerabilities in cancer through site-specific covalent activation of PFKL to induce metabolic imbalance
• Stabilizing enzyme conformational states via selective covalent modification to disrupt tumor cell metabolism and growth
• Delivering cytotoxic payloads through electrophile-drug conjugates as a novel intracellular alternative to antibody-drug conjugates

Join our speed networking session tailored for covalent professionals, like yourselves, to connect with fellow industry peers to facilitate rapid yet meaningful exchanges of insights and expertise. Elevate your networking experience during this session designed for impactful connections within the space.

• Leveraging chemoproteomic screening platforms to identify covalent hits with high selectivity, incorporating orthogonal assays and kinetic profiling (kinact/KI) to distinguish tractable opportunities from liabilities
• Accelerating optimization into brain-penetrant proof-of-concept molecules through integrated assessment of selectivity, reactivity, and exposure
• Exploiting prolonged target residence time in the brain to enhance efficacy, enabling reduced dosing strategies while minimizing safety risks through deeper understanding of protein turnover and covalent engagement

• How does shifting from traditional occupancy-driven covalent inhibition to induced proximity strategies redefine pharmacology and target selection?
• How can distal or previously non-functional nucleophilic residues be effectively leveraged through covalent induced proximity to expand the utility of covalent fragments?
• What are the key opportunities and challenges in designing covalent induced proximity systems (e.g., PROTACs, molecular glues) to unlock new therapeutic mechanisms beyond inhibition?

• Case-study–driven insights from FAAH, JAK3, and BTK programs highlighting key learnings in covalent inhibitor discovery
• Defining when covalent targeting adds value across enzyme and kinase classes
• Linking hepatic selectivity to safety, with a focus on DILI risk and mechanistic understanding

• Exploring a “warhead-first” approach to covalent inhibitor design beyond traditional binder optimization strategies
• Leveraging novel reactive chemistries and molecular trajectories to uniquely engage on-form KRAS G12C selectivity
• Linker geometry, electrophilicity and heterocycle basicity jointly govern covalent potency against on-form KRAS G12C

• Profiling proteome-wide amino acid selectivity of electrophiles using unbiased mass spectrometry-based approaches
• Exploring electrophiles targeting amino acids other than cysteine as a novel strategy for expanding covalent drug discovery applications
• Developing diverse electrophile libraries and direct-to-biology workflows to identify covalent binders

• Targeting a non-traditional nucleophilic residues such as histidine to expand the scope of covalent drug discovery beyond cysteine-centric approaches
• Inducing covalent-driven conformational changes that remodel E3 ligase surfaces and enable recruitment of entirely new substrate
• Reprogramming degradation profiles by engagement of a non-classical degron

Take this opportunity to showcase your latest research and innovations with your peers and understand the strategies of your fellow covalent experts.

• How are different organizations assessing covalent safety risk prior to first in human studies, and how are these assessments informing starting dose and escalation strategy?
• How reliably do preclinical toxicity and target engagement signals translate across species for covalent drugs, and where do current models consistently fail to predict clinical outcomes?
• What practical criteria are teams using today to progress covalent candidates into the clinic in the absence of definitive, predictive safety models?