Principal Scientist - Computational Chemistry

POSITION SUMMARY
Amphista Therapeutics is a fast-growing Cambridge-based biotech and the leading European Targeted Protein Degradation (TPD) company. Our unique scientific approach to TPD, one of the hottest areas in modern drug discovery, gives us a range of advantages over other therapeutic strategies.

We have completed an oversubscribed $53M funding round to allow us to progress our portfolio of projects and greatly strengthen the development of our underlying scientific platform. We were delighted to recently announce two separate collaboration deals with Bristol Myers Squibb and Merck Healthcare which will allow us to grow and advance our therapeutic portfolio even faster, utilising our unique technology. In addition, we were recently named as one of the Fierce Biotech Fierce15 winners for 2022.

Initially founded from the laboratory of Professor Alessio Ciulli (University of Dundee) our team comprises both academic and drug discovery pioneers of the TPD field and a growing R&D team focused on advancing a portfolio of medicines to the clinic using our proprietary next generation TPD technologies. We’re now growing the team further and have an opportunity for an biologist to join us to help advance our platform technologies and therapeutics.

As Head of Computational Chemistry at Amphista you’ll be a key member of the R&D leadership team with significant opportunity to drive R&D and company success through your leadership of key activities supporting projects within our therapeutic portfolio as well as continued platform development. You’ll also have responsibility for continuing to shape the strategy and development of the computational function within Amphista.

You’ll use your extensive experience of applying a range of computational & data analysis tools across projects ranging from hit ID, lead optimisation and preclinical development. You’ll work closely with other chemistry, cell biology, pharmacology and development teams to deliver projects to milestones as well as also introducing new capabilities. To expand Amphista’s srud discovery capabilities. This is an exciting opportunity to join a fast growing and dynamic company operating at the cutting edge of one of the most transformational recent developments in drug discovery strategies to develop first in class and best in class medicines.

Roles & Responsibilities include:
Providing computational chemistry input to Amphista projects to allow chemistry programmes to proceed quickly to agreed milestones across hit to lead entry, lead optimisation start and clinical candidate nomination. Also support the continued growth of the proprietary Amphista protein degrading platform.

• Providing computational chemistry input to specific Amphista drug discovery projects including molecular modelling & docking through to cheminformatic analyses and predictive model building. Specific areas include:
o Identification, design and optimisation of ligands and subsequent bifunctional degraders from literature analyses or virtual screening
o Collation and analysis of complex, multi-parametric datasets to rationalise SAR and build predictive models in areas such as biological activity, selectivity, in vivo properties and others
• Providing computational analyses and solutions to projects via your own personal contributions as well as by working with external vendors or collaborators where appropriate
• Working closely with medicinal chemists and wider project teams to critically analyse project data and contribute ideas that will drive projects forward.
• Maintaining an up to date literature knowledge of computational chemistry strategies and protein degradation chemistry
• Creating data summaries and visualisations able to communicate and display complex datasets and conclusions in intuitive and interactive ways
• Present to project teams with the potential to also present to R&D leadership & external audiences.
• Maintaining electronic lab notebook records and contributing to drafting of patent applications when appropriate.

Essential requirements:
• PhD in a computational chemistry-related discipline or equivalent experience with at least 3 years experience of hands-on delivery of computational chemistry support of one or more drug discovery projects in pharma, biotech or an academic drug discovery unit
• Experience of structure-based and ligand-based design using one or more of shape, fingerprint and pharmacophore-based methods including library design & enumeration and lead-hopping
• Experience of SAR analysis of project data sets, calculation of ADME/Tox properties and building of models to allow property prediction.
• Good working knowledge and hands on experience of using a wide range of computational tools across molecular modelling and cheminformatics
o These may include one or more of MOE, Cresset, Schrodinger or other tools
• Good working knowledge of usage of data analysis, visualisation & pipeline tools which may include Vortex, Spotfire, Data Warrior, Pipeline Pilot, Knime
• Track record of successfully working in multidisciplinary settings and in a collaborative manner where your work has directly impacted project decisions and success
• Good interpersonal & communication skills able to explain complex concepts to medicinal chemists and other project team members
• Proven track record of delivery from your own personal project contributions
• Willingness to travel to and spend significant time onsite at Amphista’s UK R&D hub near to Cambridge, UK to work closely with project team members.

Experience in the following areas would be preferred but not essential:
• A working knowledge of the Dotmatics suite of tools and other languages/ environments including Python, R, Linux & HPC

What’s on offer
Competitive salary and benefits package including share options and discretionary bonus.
Hybrid working

More about Amphista
Amphista’s approaches use completely novel mechanisms to build on all the advantages of TPD while directly addressing the emerging limitations of existing TPD strategies to expand the utility of the field. In particular, we have shown our approach has the potential to be superior to all other TPD approaches (PROTACs, molecular glues etc) improved druglike properties and reduced tumour resistance potential. We have a range of projects in the discovery phase, initially focused on oncology with potential to expand into other therapy areas including CNS disease & immunology.

The Amphista team contains a wide range of experienced drug discovery experts across both biology and chemistry disciplines, creating the ideal learning environment to advance your scientific career development quickly. This is an exciting opportunity to join a fast growing and dynamic company operating at the cutting edge of protein degradation-based drug discovery to develop first-in-class medicines to treat cancer and other areas of high unmet medical need.

Application Instructions: 

Please visit www.amphista.com/careers to apply via our website

Application Closing Date: 
17 February 2023