INVENesis
Drug Discovery For Everyone

When it comes to the complex world of multidisciplinary pharmaceutical research, INVENesis, a Swiss biotech company, has assumed the duty to enable organisations—of all sizes—excel in the arena of drug discovery. Be it a large pharmaceutical company, a startup, or a two-person operation wanting to test the potency of a compound, INVENesis has established a suitable business model to tackle every possible request.

Interestingly, the founding members of INVENesis arrived at this all-inclusive modus operandi soon after their former employer, Novartis Animal Health, was acquired by American pharma giant Eli Lilly. “After splitting from Novartis, we realised that the American Way of doing business requires a clearly-defined ‘why’ and ‘drug discovery for everyone’ was our choice,” says Dr. Jean-Luc Perret, one of the managing directors of INVENesis.

At the time of its inception, in March 2017, INVENesis was admittedly sceptical about its “drug discovery for everyone” motto and felt such an ambitious plan sounded “demagogic.” Nearly three years later, INVENesis has overcome its apprehensions, becoming an integral part of an ecosystem of biotechs that search for drugs, pheromones, bio-control tools, natural products, and technological solutions with applications in parasitology, agriculture, and human medicine. Simply put, if an organisation has molecules they wish to evaluate for any kind of application on ion channels or parasitological applications, INVENesis is a suitable ally.

Like any other blossoming organisation, INVENesis banks on its collegial leadership team of managing directors Jean-Luc Perret, Elodie Valazza Rufener (CFO), and Lucien Rufener to lead the charge.

The three associates base their expertise through 15 years of experience in industrial R&D and a track record of successful drug discovery, especially during their stint at Novartis. Although the trio has, over the years, developed several innovative approaches to look at the efficacy of chemical compounds using whole organisms, it hasn’t stopped in its pursuit of unearthing newer methods. Every week, the trio expresses more and more ion channels so it can record effects on single targets in the form of ion channels, as well as the full organisms.

This dedicated approach has propelled INVENesis to emerge as a trusted ally in molecular biology, electrophysiology, and parasitology for target validation, hit-finding, lead-optimisation, due diligence, mode of action elucidation, and resistance studies.

Serving as a One-Stop-Shop

To better aid its clients to measure and assess phenotypes on whole organisms, or find compounds against parasites, INVENesis provides a number of technologies and services. The technology platforms include electrophysiology (on oocytes), model organism and parasite assays (C. elegans, D. melanogaster, ecto- and endoparasites), and customised R&D (protocols, molecular biology, machine and software development).

INVENesis stands out through its ability to serve as a one-stop-shop to clients, with regard to in-vitro work in electrophysiology and organism-based screening. INVENesis enables its clients to truly study the effect of active ingredients on individual targets (e.g. a ligand-gated ion channel), organs (e.g. an antenna), and whole organisms (e.g. a tick or flea). In other words, INVENesis’ customers—both manufacturers (pharmaceutical, animal health, and plant protection companies) and academic institutes—do not need to work with different partners to elucidate all those different aspects. INVENesis’ assays can also be used to identify modes of action and side effects of compounds.

By incorporating cutting-edge technology, miniaturisation, and automation into every step of its assays, INVENesis can use tiny amounts of compounds (typically 10 microliter of a 20 mM solution for an ecto and endoparasite profile) and apply these high-added-value tests on compound libraries that contain several million samples.

We showed that even with a common plant such as tobacco, a lot can be discovered for pharmacopoeia

INVENesis uses only high-precision Mettler Toledo weighing machines and Tecan pipetting robots to handle its clients’ compounds. It also utilises an automated tube store system to store libraries and perform hit-picking tasks; the identity of customers and compounds is anonymised and tracked using barcodes.

Furthermore, INVENesis’ automated screening technologies can measure phenotypes, such as motility, migration, development, repellency, and deterrency. Many of its assays use machine vision algorithms, removing human bias from the phenotype analysis.

Offering a Catalogue of Validated Assays

Over the years, INVENesis has assembled a catalogue of phenotypic assays—both organism-based and electrophysiology— for testing small molecules and natural extracts. One of the latest additions to the catalogue is the new nematode Migration Trap Assay (MTA). INVENesis has collaborated with CSEM (the applied research institute dedicated to microtechnologies in Switzerland) to develop a microplate compatible labware allowing the measurement of the worms migration speed. “This new assay is a game-changer in the quest for the next generation prophylactic treatment for heartworm in dogs,” says Dr. Perret. Innovation is urgently needed in that area of veterinary medicine as existing treatments face resistance from the parasites in parts of the U.S.A.

While organism-based assays allow the measurement of phenotypes independently of molecular target assumptions, the Xenopus oocyte expression system (electrophysiology) enables the expression of functional ligand-gated ion channels, voltage-gated ion channels, GPCRs, and transporters in the membrane of individual oocytes and the due measurement of their physiological function. INVENesis also leverages an automated injection platform (Roboinject) to inject oocytes—with cDNA or mRNA— encoding for the receptor of interest. Thereafter, the effect of compounds on the heterologously-expressed channels are recorded using an automated two electrodes voltage-clamp automate (HiClamp, Multichannel system).

This unique system of electrophysiology profiling leads to faster expression of ion channels (just a few days), a catalogue of over 100 ready-to-use ion channels from vertebrates and invertebrates. Furthermore, unlike its competitors, who use a patch clamping technique, INVENesis does not require to maintain a culture of cell lines. “If a customer wishes to test a compound, we can inject the target on Friday and start testing/measurements on Monday itself,” says Dr. Rufener.

To illustrate the benefits of its Xenopus oocyte expression system, INVENesis cites the example of a nicotinic acetylcholine receptor (nAChR) that has anywhere between 12-16 different subunits that can be co-assembled to form different channels. Since each of the channels has unique pharmacology, they react differently to different drugs. However, to assess the given compounds on nAChR, one must test the compound on all the different subtypes, which subsequently requires the maintenance of up to 20 different cell lines with patch clamp systems. The process is expensive and time-consuming.

Now, compare that to INVENesis’ technology. “We can simply mix the different subunits within the injection pipette, and inject a row of cells—off all sides—with the mix. This means we don’t have to maintain each single cell line to access all the different subtypes and perform the full characterisation of new compounds,” explains Dr. Rufener.

Similarly, if one injects two different subunits—alpha and beta—they can co-assemble in a different stoichiometry, and those two separate channels, although made out of the same subunits, react differently to drugs. Again, INVENesis can inject ten times more of the alpha subunits (than the beta), to force a specific stoichiometry to assemble above the other one. Surely, manipulating cell lines is a complicated process that INVENesis can simplify.

As part of its electrophysiology profiling, INVENesis also records signals from arthropods to measure the effect of chemical compounds on neurological function and sensory perception by ectoparasites.

Protecting Mother Nature in the Process

Besides offering proven technology to conduct multidisciplinary pharmaceutical research, INVENesis provides another advantage that warrants attention.

In recent years, neonicotinoid, a class of compounds, has been frequently leveraged by plant protection and animal health companies to control different pests present on crops or animals. However, while the compounds kill insects, they unnecessarily eliminate bees and threaten biodiversity.

By comparison, INVENesis technology can express the receptor from the various species of insects it wishes to destroy, by selecting the compounds with the highest selectivity toward a parasite that needs to be controlled. This way, the bees can be protected!

To further elucidate on INVENesis’ competent drug discovery methods, Dr. Perret narrates a published use case involving Philip Morris International (PMI), a large tobacco company with its R&D in Switzerland. As part of the engagement, INVENesis looked at extracts from tobacco and attempted to discover “something interesting” not named nicotine. To dig deeper into the tobacco plant, INVENesis miniaturised assays to discover the effect of minor components in natural extracts. The biggest surprise that INVENesis has discovered thus far is that nicotine has a drastic effect when it comes to fighting off ticks compared to its natural role as insecticide in the tobacco plant. “We showed that even with a common plant such as tobacco, a lot could be discovered for pharmacopoeia. Since natural products are interesting and complex, our miniaturized and automated assays always work their magic in such projects,” adds Dr. Perret.

Allowing Clients to Generate IPs

In scripting such customer success stories, INVENesis offers a business model that enables clients to keep their intellectual property (IP) rights on the active ingredients. While its standard assays are charged per data point, plus a test set fee, INVENesis does not charge an FTE or fixed costs. So flexible is INVENesis’ service model that clients are charged only based on results delivered. This is a far cry when compared to other CROs and biotechs, who typically charge based on “time spent” on a project and not the deliverables. “Customers pay only for what they get. If the controls are not good, we go back to the drawing board and do not stop until we deliver results. We incur all the costs of experiments,” says Dr. Rufener.

These are exciting times for INVENesis, which is presently nearing the end of its incubation period. Besides receiving strong financial backing from Innosuisse, and working on confidential projects with high-profile partners, INVENesis has a well-laid-out plan for the next 18 months. The financial stability will lead to the opening of a new laboratory in Q2 of 2020. The 370 sq. metre premises will include BSL 2 and all safety measures to work with toxic compounds. Meanwhile, INVENesis France, a newly-registered firm, will open another lab in France.

As part of its expansion, INVENesis has hired a new PhD to join its team of 4 biologists and three senior lab technicians. With its proven technology and team of passionate experts with a combined experience of over 50 years in multidisciplinary pharmaceutical research, INVENesis is ready to take the next step in its evolution.

On a closing note, it’s important to highlight that besides helping its clients build their own drug discovery flowchart and drug portfolio, INVENesis conducts extensive research of its own, and constantly expresses new channels to unearth new subunits in its catalogue. However, its focus remains on the customers. “We develop our own technologies for drug discovery, but we only progress drug candidates for our customers,” concludes Dr. Perret.