Preclinical Programme Leader, Cardiovascular & Metabolic Diseases

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.

• Own end-to-end scientific and project strategy for one or more siRNA / ASO discovery programnes 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

• Design, execute, and optimise 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 optimisation of novel siRNA/ASO delivery platforms, with emphasis on enabling effective extrahepatic cellular uptake and functional knockdown
• Lead hit identification, prioritisation, 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
• Target Output:
  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

• Design, oversee, and interpret in vivo PK/PD, biodistribution, and knockdown efficacy studies
• Establish exposure response and knockdown response relationships to guide lead optimisation 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
• Target Output:
  Deliver robust in vivo PK/PD and efficacy datasets linking exposure, knockdown, and disease-relevant outcomes across MASH, obesity, and skeletal muscle models

• 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, remodelling, and endocrine signalling
• Working knowledge of skeletal muscle metabolism, insulin sensitivity, and glucose utilisation
• Systems-level understanding of liver-adipose-muscle crosstalk driving metabolic disease
• Target Output:
  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…