Not for profit — Q&A with Lhasa’s product manager, Nik Marchetti

We talk to Dr Nik Marchetti, product manager of Lhasa Limited, a not-for-profit organisation and educational charity, about products, developments and innovations driving the company forwards. 

Q. Could you give a brief overview of Lhasa?

Established in 1983, Lhasa is a not-for-profit organisation and educational charity, which creates in silico prediction and database systems for use in metabolism, toxicology and related sciences.

Today, the company has 140 employees across sites in the UK, USA and Poland. There are more than 350 consortium members from global companies, covering pharmaceutical, consumer products, universities and academics, regulatory bodies, government organisations and charities.

From the outset, Lhasa has been owned and controlled by members. Founder members were interested in LHASA (Logic and Heuristics Applied to Synthetic Analysis), a computer system originating from and further developed in conjunction with Harvard University, to assist chemists in the design of complex organic molecule syntheses. The aim of the founding members was to fund and support the development and refinement of the transformations (generalised retrosynthetic reactions) in the LHASA knowledge base.

Q. The lead product, Derek Nexus, has recently won an award, could you tell us more?

We’re thrilled with the success of Derek Nexus, which contributed to the company receiving its first Queen’s Award for Enterprise in Innovation in 2016, and more recently, the Yorkshire Business Masters Innovation Award.

Derek Nexus is a knowledge-based software that provides accurate toxicity predictions. Using this tool to conduct in silico toxicity tests, enables the potential identification of toxic chemicals. Ultimately, aiding experts in rejecting any unsuitable drug candidates.

Whether you’re in academia, or involved in the cosmetic, pharmaceutical or chemical industries, Derek Nexus can be used to evaluate the potential toxicity of existing or prospective chemicals. The software allows users to make decisions about which chemicals are likely to have ‘more favourable’ toxic profiles when not all of the experimental information is readily available.

Q. How can Lhasa help pharma manufacturers ensure drug formulation is optimised?

We’re involved in many pre-competitive data-sharing initiatives, which often result in the development of databases. These include Vitic Excipients, which allows the anonymous sharing of excipient vehicle toxicity data, and Vitic Elemental Impurities, which is designed to share analytical data on the levels of trace metals within batches of excipients used in the formulation of pharmaceutical drug products.

Our role in these projects is to facilitate data-sharing, develop the database schema using the Vitic Nexus platform, and curate and input the data.

Users of these databases have the opportunity to access existing information that has not previously been in the public domain, and by sharing the information, we can reduce duplication across different companies. This can lower the need to repeat costly experiments.

As well as ensuring thorough cross-referencing, information that is found in the database can be used to inform testing strategies, meaning efficient use of laboratory resources.

Q. Do you comply with regulatory guidance?

The data within the Vitic Excipients database lends itself to the REACH initiative, allowing members to retrieve relevant information quickly, while potentially avoiding the need for costly experiments.

However, the changing regulatory guidance has led to the need to build knowledge of elemental impurities in excipients. ICH Q3D establishes permitted daily exposures (PDEs) for elemental impurities of toxicological concern in drug products. The Vitic Elemental Impurities database can be used as part of the overall ICH Q3D risk assessment process as a support tool.

Q. What other products does Lhasa offer?

We’ve also got Zeneth, which is an actively maintained system for the prediction of degradation. As an expert-rule based system, the software is comprised of a knowledge base of transformations implemented by Lhasa’s scientific experts. Zeneth is a solution for scientists who need to understand the forced degradation pathways of organic compounds.

It provides information for decision-making when there is little or no experimental data available, supporting regulatory submissions and informing early stages of development. The software shows predicted transformation and degradant information graphically, while assisting in the selection of appropriate excipients and highlighting the potentially problematic ones.

It is also able to act as a training or learning tool, as it helps the user develop more in-depth knowledge about forced degradation.

In addition, sitting alongside Derek as a Queen’s Award winner, is Sarah Nexus — a statistical-based system for the prediction of mutagenicity. The software allows identification of potentially toxic chemicals. The predictions are represented by positive and negative results, including confidence figures for the overall prediction and the fragments on which it is based.

The predictions also facilitate a thorough review by experts, giving a simple understanding on why your chemical is or isn’t predicted to be mutagenic. Sarah Nexus not only provides a confidence score, but a structural explanation for each prediction as well.

Q. Is it possible to integrate Lhasa products with other Lhasa products and/or with external products?

Vitic, Derek, Sarah and Meteor all sit within the Nexus platform. After a prediction, the Nexus results window provides all the information that you need as part of your decision support system for your overall risk strategy.

Predicted structures from one Lhasa programme can also be submitted for processing in another within the same interface. Within Nexus, both Derek and Sarah are integrated in an ICH M7 workflow to allow fully compliant two-system predictions for use within ICH M7 submission portfolios.

The products can also be outsourced to help other pieces of software achieve results. For example, StarDrop by Optibrium has a Derek Nexus module, which helps to guide in hit-to-lead and lead optimisation.