Pathi Pandarinathan

Leading the extra hepatic delivery platform technology development and discovery/development chemistry of nucleic acid therapeutics. Managing a small team of chemists (in house and CRO) Advancing multiple portfolio projects of GalNAc-siRNA for various CVMD indications Collaborating with CDMO for CMC and GMP activities of DS and DP for clinical trial materials

Designed and executed novel technology platforms for hepatic and extra hepatic siRNA therapeutics program. Helped launch one clinical candidate and currently in Phase II.

Providing value addition to aspiring biotechs and pharma industries working on bringing oligonucleotide therapeutics from early discovery to market. Full service provided to start your oligonucleotide chemistry capabilities from the scratch (upstream-downstream and analytical) and complete solutions offered to all your problems. Advice rendered to most of your discovery and development chemistry projects in xRNA therapeutics.

Design and synthesis of chemically modified and conjugated oligonucleotides (1-300mg) to support various discovery projects covering multiple therapeutic areas (antiviral, oncology and neuroscience) Procurement, installation, maintenance, SOP, training and trubleshooting of instruments (Akta- synthesis, chromatography, CFF, Mermade- synthesis, GeneVac- evaporation, Virtis-lyophilization) Vendor selection, price negotiation, inventory control and management of solvents and reagents Mentorring, idea sharing and onboarding of new hires Competitive intelligence and literature update

Medicinal chemistry of siRNA molecules for RNAi therapeutics. Design, outsourcing, management and procurement of modified nucleoside phosphoramidites. Synthesis, purification and desalting of chemically modified and conjugated siRNA molecules on mg to gram (umole to mmole) scale. Managing CRO and CMO; non-GMP and GMP manufacturing of lipid conjugated duplex oligonucleotide drug substance and drug product. CMC and IND document preparation, stability and forced degradation study of peptide and nucleotide drug substances and products.

Team member of antibacterial drug discovery chemistry; Hit Evaluation, Hit-Lead, Lead optimization and Process routing. Delivered one MS2 and one pre MS4 candidate. Design and synthesis of libraries using robotic synthesis and purification techniques. Effective analoging with privileged physicochemical properties and druggability. Team member of chemistry outsourcing and logistics management (procured more than 4000 compounds). Synthesized over 150 compounds on milligram to multigram quantities using diversity oriented and multistep approach.

Lead chemist and team member supporting medical chemistry efforts to design and synthesize enzyme inhibitors and receptor modulators for cannabinoid pharmacology in multiple therapeutic areas; Pain, Obesity, Addiction, Multiple Sclerosis, Emesis, Glaucoma. Design and syntheses of molecular probes for the structural biology (proteomic) study of endocannabinoid targets Synthesized 70 tetrazole analogs and discovered a new class of anandamide transport inhibitor. Developed fluorescence based low background and robust assays for discovering enzyme inhibitors using in-house synthesized fluorogenic substrate. Synthesized 100 heteroaryl ureas using microwave accelerator and identified a highly selective endocannabinoid deactivating enzyme inhibitors. Designed and synthesized labeled and unlabeled endocannabinoids (proven/putative) as Lipid Signaling molecules. Evaluate, procure, install and train chemists on validated throughput synthesis/purification instruments.

Team member providing medicinal chemistry support to discover drug to treat Tuberculosis. Analyzed HTS results, filtered, clustered, NN pulled, and prioritized actives for resynthesis and confirmation. Analoged to identify emerging SAR from Hits (10-50 compounds per series).

Lead chemist and team member of anti-malarial drug discovery efforts. Synthesized novel benzimidazole, indazole, and pyrazole derivatives (60 analogues) as antimalarial agents acting against chloroquine resistant Plasmodium falciparum. Achieved sub micromolar MIC within a library of forty compounds.

SAR analysis and synthesized pyrazole analogs to obtain a drug like highly potent CB1 inverse agonist with three log reduction in clogP within a library of 35 compounds

Synthesized functionalized styrene monomers with fluorine at strategic positions and polymerized to obtain non cross-linked and cross-linked polystyrenes. Application of these novel polymers in organic synthesis on support was investigated with due reference to facile reaction monitoring using 19F NMR technique. Study of DAST-mediated ring expansion of cyclic epoxy alcohols (C-C bond cleavage in presence of C-O-C bond) to yield stable fluoro vinyl ethers