DISRUPTIVE GPCR LEAD DISCOVERY PLATFORM DELIVERING NEW AND SAFER THERAPEUTICS

Project Information

PICARD

Grant agreement ID: 880322

DOI

10.3030/880322

Project closed

EC signature date 20 September 2019

Start date 1 October 2019

End date 31 May 2021

Funded under

• INDUSTRIAL LEADERSHIP - Innovation In SMEs

Total cost

€ 2 493 167,50

EU contribution

€ 1 745 217,25

Coordinated by

INTERAX BIOTECH AG
Switzerland

Periodic Reporting for period 2 - PICARD (DISRUPTIVE GPCR LEAD DISCOVERY PLATFORM DELIVERING NEW AND SAFER THERAPEUTICS)

Reporting period: 2020-10-01 to 2021-05-31

Summary of the context and overall objectives of the project

InterAx is pioneering a new scientific discipline at the intersection of biology, mathematical modelling, and machine learning with the aim to be on the forefront of the digital transformation of drug discovery and ultimately improve human health.
We are a Swiss biotech company, spinoff of ETH Zurich incorporated in 2016, reinventing drug discovery to significantly reduce the time and costs needed to discover and develop new drugs for a wide array of human diseases.
There is a strong need for novel methods improving the prediction of drug effect in humans and reducing clinical failure rates. New drug development and clinical trials take about 15 years and cost about € 2.3 B with a success rate of 12%. Long timeline and high financial cost are the result of an inefficient drug discovery and selection process. The most challenging aspect is the prediction of how the drug candidates will behave in humans based on data from in vitro experiments.
Our solution developed and validated with PICARD lies in the combination of in-house experimental assays, mathematical modelling and artificial intelligence to analyze and predict the response of cells to drugs. InterAx platform can describe, analyze, and simulate the complex action of drug molecules in their cellular context and guide the optimization of drug candidates to achieve a specific cellular response. This allows to maximize drug efficacy and reduce side effects in humans, thus significantly accelerating drug discovery and de-risking clinical trials.
The application of PICARD platform to the InterAx in-house drug discovery program is now contributing to the development of effective drug candidates targeting a member of chemokine receptor family. Mis-regulation of this receptor is linked with numerous cancer conditions, as well as many inflammatory and neurological disorders. InterAx drug candidates show good efficacy in vitro on cancer cell lines, aiming initially on the unmet need for triple negative breast cancer treatment.
Our Mission
- Fulfill unmet medical needs 
- Explain why drugs fail and reduce trial-and-error cycles in discovery / pre-clinics
- Reduce costs and number of failed animal studies
- Shorten development timelines

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During PICARD, InterAx has proven and extended its technology, and shaped its business environment to enable the next phase of the company growth to achieve its vision.
All milestones and deliverables were met or overreached. InterAx expanded its systems biology platform (PIC-Sys) and experimental assays (PIC-Say) to several additional GPCR targets – showing the technology is applicable to different GPCRs and drug modalities. In parallel, a unique AI platform (PIC-VisAI) driven by systems biology was developed and applied on real drug discovery programs. InterAx discovery platform now only allows to find good binders and characterize their effect on cells, but also to predict in silico which drug candidates will have desired signaling properties and efficacy. InterAx launched own in-house drug discovery in the field of oncology and conducted several revenue-generating commercial projects, including Lundbeck, Boehringer Ingelheim, and GPCR Therapeutics. An array of relations with potential customers, partners and investors was established to launch the next phase of growth of the company. The potential impact of our platform on drug discovery was confirmed by very positive feedbacks from key opinion leaders at scientific conferences and from major GPCR industry players, as well as from venture capital firms.
Main achievements during the second reporting period:
Milestone 3 (WP2): the capacity of PIC-VisAI algorithm to predict GCPR signaling parameters was verified – with not just one, but five signaling parameters of beta-2-adrenergic receptor shown amenable for prediction. The PIC-VisAI was tested close to real-world scenario – predicting properties of a test set of novel chemical entities, before their synthesis and characterization. The algorithm showed an average 69% and maximum 85% prediction accuracy, thus opening a way to generate in vivo-mimicking systems biology information at the early stages of drug development.
Milestone 4 (WP4): the customer portfolio pipeline was grown with more than 60 presentations at 7 partnering conferences, 25+ dedicated follow-up presentations to scientific teams in respective companies, 10+ initiated negotiations for pilot projects, 3 pilot project launches and 5 more currently in negotiation phase. Moreover, InterAx continuously engaged with stakeholders and key opinion leaders in pharmaceutical industry and academia. This disseminates the knowledge about InterAx vision and technology, maintains existing connections, and builds new ones with potential customers and business partners.
Milestone 5 (WP3): three external customer projects were successfully launched, and additional fourth internal drug-discovery project at InterAx. All projects demonstrated strong value of PIC-Say / PIC-Sys / PIC-VisAI technology to measure and explain drug pharmacological action at the cellular level. Several important technology advancements were made along the way, in particular the formulation and use of “signaling fingerprint” data representation, which summarizes the outputs of InterAx mathematical models into a human- and machine-readable form.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The current screening process for a new drug begins with target and hit identification, resulting in a collection of 5,000 to 20,000 molecules that must be ranked according to the probability that they possess the desired biological activity. Ranking the candidates to select a suitable biologically active compound (lead compound) can leverage assay-based, structure-based or computational approaches. Each of these, however, has little to non-existent in vivo predictability, which results in high trial-and-error rate when testing selected candidates in animals. Affinity and assay-based efficacy of the drug are known at this point, but the crucial information is often missing on the mechanistic effects of the drug action at the cellular level.
PICARD is a technology platform that combines mathematical modeling of biological networks with machine learning algorithms to design drug candidates with desired mechanistic and in vivo properties for pharmaceutical and biotech companies. PICARD remarkably increases the efficiency of the drug discovery process, offering economic savings of at least €150.7 million per developed drug and a reduction of time to market to 10 years.
PICARD focuses on G-Protein Coupled Receptors (GPCRs), which are the target of 40% of the developed drugs. However, >70% of the pharmacologically relevant GPCRs are yet to be exploited, which creates an untapped global market opportunity of €71.2 billion. We intend to acquire, in seven years, 1-2% of the European and US available markets (€940 million). To achieve this goal, we designed a business model in which PICARD is offered at increasing levels of support, investment and risks for our customers: service projects, pilot projects and long-term partnerships. This strategy was devised to lower market entry barriers, allowing InterAx to start commercialization of the PICARD technology platform as early as year 2 of this project. In fact, InterAx outperformed own goals by already entering the market in year 1 with currently three pilot projects commissioned by pharma and biotech companies.

Picard Platform