Preclinical Programme Leader, Cardiovascular & Metabolic Diseases Full-time

Preclinical Programme Leader, Cardiovascular & Metabolic Diseases

The Nucleic Acid Therapeutics Initiative (NATi), hosted by A*STAR, is Singapore's national platform dedicated to advancing RNA-based medicines and revolutionizing drug and vaccine development. NATi's mission is to establish Singapore as a globally recognized hub of excellence in nucleic acid therapeutics research, clinical translation, and commercialization. NATi focuses on key RNA modalities such as antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA). To drive this vision, NATi is building a biotech-like translational engine focused on asset and technology development spanning discovery to clinical development. We are actively seeking passionate and committed individuals with deep translational expertise to join us in advancing the next generation of RNA-based therapeutics.

Position Overview: We are seeking a scientific Preclinical Programme Leader, Cardiovascular & Metabolic Diseases for discovery toward clinical development of oligonucleotide (siRNA / ASO) programmes targeting MASH, obesity, and cardiometabolic diseases. This role will own programmes from target validation to selection of a Preclinical Candidate ready for IND-enabling studies. The successful candidate will rely on hands-on laboratory experience to establish discovery and preclinical development capabilities (e.g. in vitro models, animal models, PK/PD workflows) through a combination of internal build-up and oversight of external CROs. The successful candidate will combine deep oligonucleotide modality expertise with programme management experience, and strategic oversight of programme execution plan within budget and on time. Successful candidate will progressively transition from hands-on execution to building and mentoring a team to support multiple pipeline programmes.

Key Responsibilities:

• Own end-to-end scientific and project strategy for one or more siRNA / ASO discovery programs from target validation to selection of a Preclinical Candidate in MASH, obesity and/or musculoskeletal diseases
• Establish and execute integrated in vitro and in vivo workflows to support pipeline projects and generate robust high-quality data to support decision-making process
• Drive clear, go / no-go recommendations based on integrated assessment of biology, PK/PD, and disease-relevant efficacy endpoints
• Ensure scientific rigour, reproducibility, documentation, and transparency across internal and CRO-executed activities
• Actively contribute hands-on laboratory operations as needed to establish platforms, assays, and workflows

Oligonucleotide Discovery & Screening:

• Design, execute, and optimize in vitro screening cascades for siRNA / ASO programmes across key metabolic tissues (liver, muscle, adipose), incorporating potency, durability, concentration response curve, and delivery-dependent activity
• Develop and deploy mechanistic and functional cell-based assays to link target knockdown with metabolic pathway modulation and disease-relevant phenotypes
• Support discovery and optimization of novel siRNA/ASO delivery platforms, with emphasis on enabling effective extrahepatic cellular uptake and functional knockdown
• Lead hit identification, prioritization, and lead generation by integrating in vitro potency, functional relevance, delivery compatibility, and translational hypotheses
• Establish assay transferability and performance standards for internal execution and CRO deployment
• Enable rapid identification of lead siRNA/ASO candidates with validated tissue-specific potency, functional relevance, delivery feasibility, and clear translational readiness for in vivo progression

Pharmacology & Translation:

• Design, oversee, and interpret in vivo PK/PD, biodistribution, and knockdown efficacy studies
• Establish exposure response and knockdown response relationships to guide lead optimization and selection
• Select, justify, and govern disease-relevant in vivo models for:
• MASH: histology, non-invasive fibrosis and inflammation biomarkers
• Obesity: metabolic, cardiometabolic, and weight-related outcomes
• Skeletal muscle: functional, metabolic, and mitochondrial readouts
• Deliver robust in vivo PK/PD and efficacy datasets linking exposure, knockdown, and disease-relevant outcomes across MASH, obesity, and skeletal muscle models

Disease Biology Expertise:

• Deep expertise in liver biology, including:
• MASH pathophysiology
• Hepatic lipid metabolism, inflammation, and fibrogenesis
• Translational biomarkers relevant to clinical development
• Strong understanding of obesity biology, including:
• Energy balance and metabolic regulation
• Adipose tissue inflammation, remodeling, and endocrine signaling
• Working knowledge of skeletal muscle metabolism, insulin sensitivity, and glucose utilization
• Systems-level understanding of liver-adipose-muscle crosstalk driving metabolic disease
• Apply deep, systems-level disease biology expertise to guide target selection, target validation, in vitro and in vivo model selection to drive the pharmacology and biomarker strategy across liver, adipose, and skeletal muscle in metabolic disease

Scientific Governance, Project Leadership & Collaboration:

• Establish, author, and maintain SOPs for:
• In vitro screening
• In vivo PK/PD and efficacy models
• Tissue distribution and early tolerability workflows
• Lead or support IACUC / local animal ethics submissions, umbrella protocols, and regulatory compliance
• Build, mentor, and manage junior scientists as programs and internal capabilities scale
• Act as primary scientific and operational interface with CROs, ensuring experimental quality, timelines, data integrity, and budget alignment
• Serve as the biology/pharmacology point-of-contact with chemistry, bioinformatics, pathology, analytical, and external partners
• Partner closely with senior management to align program execution with portfolio strategy, resourcing, and milestone delivery
• Standardized, compliant biology-pharmacology execution delivering high-quality, reproducible data on time and within budget. Aligned teams and partners advancing programs efficiently against portfolio milestones

Qualifications & Professional Attributes:

• PhD in Molecular Biology, Pharmacology, Biochemistry, or related discipline
• A minimum of 4+ (Scientist), 8+ (Senior Scientist), 12+ (Principal Scientist) years of industry experience leading siRNA / ASO discovery programs, ideally in CVMD
• Strong hands-on expertise in:
• Cell-based screening and mechanistic assays
• In vivo PK/PD and knockdown biology
• Obesity and MASH disease models
• Demonstrated success in early drug discovery, from target validation through hit identification and lead generation
• Experience establishing new capabilities or platforms and scaling programs through CRO partnerships
• Strong program management skills with the ability to drive decision-grade outcomes
• Scientifically rigorous, data-driven leader with excellent written and verbal communication skills
• Collaborative mentor capable of balancing hands-on execution, team building, and strategic ownership

Global Recruitment & Competitive Compensation: NATi is conducting a global search for top-tier talent in RNA therapeutics. We welcome applications from leading pharmaceutical scientists and biotech innovators worldwide. This role provides a highly competitive compensation package aligned with global industry standards, including attractive benefits and long-term career growth opportunities within Singapore's thriving biomedical innovation ecosystem. Join us in shaping the future of RNA-based medicines and establishing Singapore as a world-class hub for nucleic acid therapeutics.