BioTrinity 2017: Gut Potential, Drug Delivery Innovations And Partnering Opps

Industry experts, investors and start-ups from across the pharma, biotech and medtech sectors gathered at the annual BioTrinity conference held in London this week (May 9-10) to explore partnering and investment opportunities, as well as future trends in the health care industry. Medtech Insight spoke to VC firm Seventure on the growing buzz around microbiome and how life sciences companies can capitalize on opportunities in this field, and took a closer look at two companies with very different drug delivery approaches. This article also includes a round-up of the early-stage medtech companies showcasing their technologies at the meeting.

Industry experts, investors and start-ups from across the pharma, biotech and medtech sectors gathered at the annual BioTrinity conference held in London this week (May 9-10) to explore partnering opportunities and future trends in the health care industry.

The two-day event opened with a discussion on the growing microbiome field which panelists explained held "huge potential" for life sciences companies. Tim Spector, CEO of Map My Gut, a consumer gut microbiome analysis service, said the technologies emerging from this field could be "bigger than genetics," and "more useful than DNA" when looking at health outcomes but big pharma were yet to realize its possibilities.

Denise Kelly, an investment advisor for Paris-based venture capital firm Seventure echoed Spector, saying the field is growing rapidly, particularly in France, which has become a major "hub of excellence." Seventure currently manages the Health for Life Capital fund which focuses primarily on microbiome-based tech innovations in Europe, North America and Asia. "In the period I've been with Seventure I've seen how the field is growing exponentially," Kelly told Medtech Insight. "There are new start-ups emerging regularly and the ones that currently exist are doing extremely well."

Kelly said the Health For Life Capital Fund has raised in excess of €160m and is keen to expand its microbiome portfolio. "Before making investments we look at the credibility of the science, the team, the academics and the work they’ve got. It has to really hold together," she said. "Sometimes we find that companies are coming to us far too early and their preclinical data is just not strong enough – that's a risk we aren't willing to take so it's really looking at a package that has done as much as it can in preclinical phase to really show efficacy. We also like to see they have a pipeline of opportunities and are not just one-product companies."

Kelly highlighted Enterome and Vedanta as two key companies in Seventure's portfolio that have massive promise. French company Enterome has developed two metagenomics platforms, one that characterizes the metagenome linked to a particular disease phenotype and another that screens genomic and metagenomics libraries to discover novel drugs and targets. The company has already inked partnerships with major businesses including AbbVie, Bristol-Myers Squibb and Takeda.

"There is a clear evidence that you have dysbiosis in disease and what we're seeing now is incredible sequencing ability but also incredible computational ability to really do a deep dive and look at bacteria at strain level," said Kelly. "If you use a particular technology you can look at the bacteria on a genus level but if you use metagenomics, you can look right down to strain level. You can have a single species where you have multiple strains and the function is very distinct so really you're looking at high level resolution and high quality but basically being able to identify the bugs involved in causality driving disease, so the technology is moving that way.

"Enterome is one of the first companies to finish Phase I on their lead product, EB8018, a molecule that blocks attachment of the pathogenic stream involved in the pathology of Crohn's disease," said Kelly.

Kelly added French biotech Eligo Biosciences was an exciting company on the rise. The start-up raised €2m in a Series A round led by Seventure for its platform gene-editing technology that delivers CRISPR via phages to target bacterial strains. She explained the immune-oncology field was also catching on to the potential of the microbiome field, as research shows certain immunotherapies are reliant on the gut's microflora. "Enterome are now working in this area with BMS and looking at how microbiota influences the efficacy of immune modulators such as checkpoint inhibitors which are big in immunotherapeutics," she said.

But despite the hype, Kelly said the field still faced a series of challenges. "The main challenges with this type of technology are that it's not straightforward to make a live bacteria therapeutic. You have all the challenges of manufacturing, safety and the regulatory framework. But there's companies now leading the way and starting to produce products that are being tested in human so in all, it's an extremely exciting time."

Drug Delivery Differentiation

Drug delivery innovations have always been a strong theme among the companies attending BioTrinity, with the event presenting fertile ground for partnerships between drug delivery specialists and pharma firms.

One of the companies presenting at BioTrinity's medtech showcase was Medherant Ltd, a University of Warwick spin-out that has developed the TEPI Patch, a transdermal drug delivery platform. Speaking to Medtech Insight, CEO Nigel Davis said that the young company, founded only two years ago, is planning a Series A financing round at the end of this year. It is aiming to raise up to £10m ($12m) in this round to fund pivotal clinical studies of the first couple of TEPI Patch products for pain relief, notably a patch for delivering ibuprofen (Medherant's lead product) and another for lidocaine.

What differentiates the TEPI Patch from other currently available drug delivery skin patches is its adhesive, which Medherant had originally licensed from Bostik, the multinational adhesive and sealant technologies specialist. The adhesive has been designed to be compatible for high drug loadings, while offering steady delivery of drug and good adhesion over a prolonged period. "Because we can achieve a higher loading of drugs, this means we can make a smaller patch that delivers the same dose of drugs than other patches," explained Davis. "Other patches are big, not very comfortable and some don't stick very well. But the TEPI Patch sticks well, is very comfortable too wear and does not leave any residue on the skin."

Additionally, the TEPI Patch has shown to have very low levels of residual drug at the end of the delivery period, continued Davis. "There is very little drug left on the patch; so, if it is a hormone that the patch is delivering, there will be less of an environmental impact after the patch is disposed. And if it is a controlled drug, there would be less potential for drug abuse."

While ibuprofen is widely available in pill form and as a topical gel or cream, there is an absence of ibuprofen-delivery patches on the market. "There are patches that provide pain relief but these are heat patches, and do not deliver any drugs," said Davis. Medherant's ibuprofen TEPI Patch will be designed as a 24-hour patch, to be sold directly to consumers. The firm does not intend to do the commercialization itself, but to license it to a larger pharmaceutical partner to sell.

Davis told Medtech Insight that there are two strands to Medherant's business model: the first, is to develop TEPI Patches for well-established drugs, like it is doing with ibuprofen and lidocaine. "We know of at least 30 different drugs that can be used with our patch," he said. The second strand of the company's business model is to partner with pharma companies that are clinically investigating a new molecule that could be delivered using the TEPI Patch.

To date, Medherant has received around £2.2m in seed funding from UK investment group Mercia Holdings, business angels and a number of high net worth individuals. This will help the company build out its management team as it preps for its Series A fundraising and safety and efficacy studies which are expected to start at the end of 2017. Davis estimated that it will take a year for the clinical studies to complete, before submitting its regulatory approval application for the ibuprofen patch at the end of 2018.

Medtech Insight also met up with another company at BioTrinity who has also developed a novel drug delivery approach – very different from Medherant's in terms of the delivery technique and the type of drug –and has just embarked on the clinical trial path.

French biotech firm Eyevensys is targeting the ophthalmic disease sector with its EyeCET platform technology, from which the lead product, EYS606 for non-infectious uveitis (NIU), has been used to treat the first patient of a Phase I/II trial.

EyeCET comprises two components. The first are the plasmids, non-viral nucleic acid-based drugs which, when inserted into a cell, act like "a computer program" for the cell to express particular therapeutic proteins; EYS606 uses a plasmid encoding for the production of an anti-TNFα therapeutic protein (TNFα is a cytokine that has been shown to play a pivotal role in mediating intraocular inflammation in NIU patients). Eyevensys uses plasmids licenced from US biopharma company, Nature Technology Corporation (NTC). "These particular plasmids have already been used in clinical studies in oncology but we have an exclusive licence from NTC to use their plasmids in the ophthalmic field," said Eyevensys CEO Raffy Kazandijian.

The second, and what Kazandijian believes to be the critical, component of the EyeCET platform is the company's proprietary electro-transfection injection device for delivering the plasmids into the cells of the eye's ciliary muscle. The device is designed to facilitate the placement of the electrodes in the ciliary muscle of the eye; once the electrodes are in position, the plasmid drug is injected into the ciliary muscle and short electrical pulses are delivered to create temporary pores in the cell membranes, allowing the plasmid drug to enter the cells.

Eyevensys EyeCET plasmid-delivery system

Source: Eyevensys

The electro-transfection procedure using Eyevensys' device takes less than five minutes. Kazandijian told Medtech Insight that the EyeCET offers not only a less invasive approach than the intravitreal injections currently used for delivering anti-VEGF medications for back-of-the-eye macular disease, but also a more cost-efficient solution as the ciliary muscle would express the therapeutic protein over a prolonged period, obviating the need for monthly injections. Kazandijian said that up to six months of protein expression have been observed in animal models following treatment with EYS606. "We are hoping to replicate the results we have achieved with EYS606 in animal models, treating NIU patients once- or twice-yearly."

The Phase I/II trial for EYS606 aims to demonstrate the safety and tolerability of treatment. It will recruit initially nine patients with severe NIU from France and the UK, and extend this to 15 patients with slightly less severe NIU, to confirm safety and detect early clinical signs of efficacy, said Kazandijian.

Eyevensys has to date raised €10m in equity financing and received around €2.5m in non-dilutive funds. It has a further €1.3m in committed venture capital which will help support the Phase I/II study. Early results from this trial are expected around the end of this year and by the second half of 2018, the plans are to start a Phase II study in the EU And US To establish clinical feasibilty, safety and efficacy of EYS606 in NIU patients and demonstrate sustained release of the therapeutic drug.

Pending positive Phase II data, the company hopes to file for conditional approval of EYS606 at the end of 2020.

Kazandijian said Eyevensys has successfully expressed around 20 proteins with the EyeCET technology and some of these can target eye diseases with large unmet needs. Hence, the company is building a portfolio of products addressing major eye diseases and may potentially partner with other companies to develop solutions in other major ophthalmic indications.

BioTrinity also featured a showcase of early-stage medtech companies, which are listed in the table below.

Medtech Early Stage Showcase Round-Up

Company	Technology	Sector
Oxford Endovascular	Brain aneurysm treatment device. The stent-like device, made from a shape memory alloy, is posted into a catheter during surgery, inserted into the brain and opened up into a tiny mesh tube that fits into the natural shape of the blood vessel, diverting the blood away from the aneurysm and allowing it to heal. Seeking at least £3m for CE mark trial, approval and early commercialization.	Neurology
SelfDiagnostics	Disposable home-based/POC molecular diagnostic tests for infectious and genetic diseases using urine/saliva/blood samples. Results turnaround time is within 30 minutes. First application is chlamydia trachomatis (CT) and Neisseria gonorrhea (NG) from urine sample.	IVD
Palpation Diagnostics	Sensor-based prostate cancer diagnostic device ProstaPalp. Device measures dynamic stiffness of prostate gland, during a 15-minute examination.	Oncology/Diagnostics
Intelligent RespiLabs	InspiWave is a non-invasive continuous monitoring device that uses breath technology to measure lung function and cardiac output. Patients are given a small amount of oxygen and nitric oxide and the device measures response within certain parameters.	Respiratory/Diagnostics
Oxford Cardiomox	Non-invasive magnetocardiography (MCG) diagnostic device capable of detecting local current signals emitted by heart muscle cells.	Cardiology/Diagnostics
Stent Tek	A minimally-invasive catheter system for patients receiving hemodialysis. To create a vascular access site, guide wires are inserted into vein and artery and catheters are then inserted and aligned. A crossing needle is ejected and punctured into the vein. The guide wire is then delivered through the needle and into the vein, and a new guide wire deploys a stent graft that makes connection between artery and vein. Single-use device, for use outside of the operating room.	Hemodialysis management/Vascular care
Momentum Bioscience	Rapid diagnostic tests for use with blood cultures to detect sepsis and bloodstream infection. The tests are being developed to run on automated platforms on the market. Detects micro-organisms using Enzymatic Template Generation and Amplification (ETGA) technology which uses a combination of phenotypic markers and molecular PCR.	IVD
MyCartis	Developing multiplex biomarker analysis platform Evaluation, designed to analyze a protein and nucleic-based biomarkers in real-time.	IVD
SIME Diagnostics	Digital screening for neonatal respiratory care. Cloud-based digital health SaaS and big data analytics.	Digital health/Neonatal monitoring
Unguis	Medical device for treating fungal nail infections using Cold Atmospheric Plasma gas. Cold Atmospheric Plasma is an ionized mix of gases with antimicrobial properties. The plasma is delivered from a small device that targets the fungal nail infection. Device aims to reduce the need for antibiotics.	Infection control
BioSignatures	Developing a portfolio of blood diagnostic tests using proteomics technology to identify disease. First product BiopSave is already in the clinic. Patient blood samples are processed using a multiple protein patient monitoring system which uses Tiger analytical software to identify proteins that can predict disease state. Looking to raise £2.5m.	IVD