shelley margetson, Author at V-Bio

First Closing of V-Bio Fund 2 is announced at EUR 78 million. V-Bio Fund 2 will ensure seamless continuation of investment activities in early-stage European life sciences companies. V-Bio Ventures announces expansion of executive team, with Shelley Margetson joining as Managing Partner

Ghent, Belgium, 4 February 2021 – V-Bio Ventures (V-Bio) announces today the first closing of V-Bio Fund 2 with capital commitments of EUR 78 million (USD 95 million).

V-Bio Ventures will continue its prosperous relationship as a preferred partner of VIB, a Belgium-based life sciences institute ranking among the world’s premier research organizations. VIB has a strong reputation in basic and translational life sciences research and an impressive track record in creating successful start-up companies.

The new fund will build on the successful investment strategy of V-Bio Fund 1, launched in 2015. Investments of V-Bio Fund 1 have resulted in:

– The creation of new start-up companies turning scientific discoveries into innovations that benefit society, including Aphea.Bio, Augustine Therapeutics and AgomAb.
– The growth and internationalization of companies such as Orionis Biosciences, Confo Therapeutics and Precirix.
– New experimental treatments reaching patients, developed by companies like Oxular, Syndesi Therapeutics and ExeVir.

The aim of V-Bio Fund 2 is to create new companies which contribute to society either through effective healthcare or sustainable agriculture. The fund supports companies which either have an asset-centric focus or are based on differentiated technology platforms. V-Bio will continue to be active throughout Europe with a focus on company creation in Belgium.

Most of the investors in V-Bio Fund 1 have re-joined for Fund 2, which has already exceeded the size of the first fund. Fund 2 includes a range of investor types, with the European Investment Fund (EIF) as cornerstone investor, joined by institutional investors, academic endowment funds and family offices.

Shelley Margetson is joining V-Bio as Managing Partner, complementing the existing team members’ solid scientific backgrounds and expertise in investing and company building. Margetson is an experienced Senior Executive who has worked for multiple European biotechnology companies since 2001, including Merus (MRUS) which listed on the Nasdaq in 2016 with her as CFO. Her financial and deal-making expertise will contribute to the further growth of the fund and V-Bio’s respective portfolio companies.

Christina Takke and Willem Broekaert, Founding Managing Partners of V-Bio, stated: “We are extremely pleased with the successful first closing of our second fund. This would not have been possible without the trust and support of our investors. Fund 2 is a testament to the successful combination of proprietary access to top-notch science with our team’s collective and complementary expertise, which has proven to be a key differentiator for V-Bio.”

Shelley Margetson, Managing Partner of V-Bio, added: “I am excited to have joined such an experienced organisation. V-Bio’s track record over the years has been impressive, and I look forward to making a valuable contribution to the fund by enhancing both the development of the start-ups and the investment portfolio.”

Jérôme Van Biervliet, Managing Director at VIB, commented: “VIB congratulates the V-Bio team on the exciting first close of the second fund and looks forward to extending it. As a co-founder of V-Bio Ventures, and through their many investments in VIB’s start-ups, we have formed a privileged relationship. We have witnessed V-Bio Ventures become a powerful force in our biotech ecosystem, creating significant value beyond the deal. Their scientific expertise, market feedback and extensive network is of crucial value to VIB, alongside their investment capacity.”

Alain Godard, EIF Chief Executive: “We are very pleased to see the first closing of V-Bio Fund 2, a testament to the hard work and success of the first V-Bio Fund. Supporting groundbreaking research, particularly in the life-sciences field, and its transition into a viable business venture is a key element in realizing Europe’s innovation potential and safeguarding the competitiveness of our economy. This is something to which the EIF attaches great importance and we are therefore very glad to be contributing to this initiative.”

Koenraad van Loo, Managing Director FPIM: “The Federal Holding and Investment Company is delighted to be participating in V-Bio’s second initiative which perfectly fits within FPIM’s investment framework. The team has already proven in the past that it possesses the necessary expertise and competences to get the right parties around the table and to lead the start-up companies to a next level. We are convinced that V-Bio Fund 2 will contribute to the stimulation of innovative entrepreneurship as well as the creation of highly skilled jobs, which are indispensable to the biotech eco-system and the prosperity of the Belgian economy.”

Michel Casselman, CEO of the Flemish investment company PMV: “We are very pleased to continue our journey together with the enlarged V-Bio Ventures team. We consider the life sciences sector of the utmost importance for the economic development in Flanders, which has grown to become the leading European life sciences hub. We recognize the importance of innovation and value creation by companies seeking new solutions to unmet medical needs or making agriculture more sustainable. Access to finance is paramount to company creation in healthcare or sustainable agriculture. We are therefore excited to participate again in the new fund, after our successful investment in V-Bio Fund 1.”

About V-Bio Ventures

V-Bio Ventures (www.v-bio.ventures) is an independent venture capital firm specialized in building and financing young, innovative life science companies. V-Bio Ventures was established in 2015 and works closely with Belgium-based VIB, one of the world’s premier life science institutes. The fund invests throughout Europe in start-up and early-stage companies with high growth potential focusing on technologies that provide transformational improvements in the biotech, pharmaceutical and agricultural sectors.

V-Bio Ventures’ cornerstone investor is the European Investment Fund (EIF). EIF’s contribution is supported by InnovFin Equity, with the financial backing of the European Union under Horizon 2020 Financial Instruments and the European Fund for Strategic Investments (EFSI) set up under the Investment Plan for Europe. The purpose of EFSI is to help support financing and implementing productive investments in the European Union and to ensure increased access to financing.

One of the key ingredients to start-up success is a stellar management team. Attracting (and retaining) the right kind of talent is a challenge though, especially when trying to balance the skills and personalities of different individuals. Getting this balance right is key to a well-rounded and cohesive team that will let a company grow into its full potential. Here is our advice on some important factors to bear in mind when building a life sciences management team.

This article was authored by Willem Broekaert from V-Bio Ventures.

Three golden rules (according to us)

Unfortunately, no rules are set in stone when it comes to life sciences start-ups. Each case is unique: the needs of a venture starting off with a €1 million seed round, versus one propelled by a €100 million mega-round (as seems fashionable these days in the US), are not exactly the same. However, in our experience, there are there are some universal snippets of wisdom when building a management team.

It takes a village

Our first piece of advice is that a team is always better than a single manager. However talented a person may be, running a start-up is akin to a treacherous mountain climb: not really recommended for solo adventurers. A single founding CEO can manage the helm for a short period of time, but as the venture picks up steam, additional team members need to be brought on board quickly in order to broaden the collective skill set. A founding CEO who lacks awareness of his/her own weaknesses and obstructs or delays in hiring others to compensate for the gaps, sets the course for failure

Diversity is best…

A second vital element for start-up success is team diversity. In the narrowest sense, diversity is about building a team with a broad spectrum of past professional experiences. The team needs to include members who each have complementary experience in the roles required for a life sciences company, such as general management, R&D, finance, admin, etc.

However, diversity should go beyond just picking the right suite of experiences and former functions. Research from a growing body of literature shows that companies with diverse management teams perform better in the long run. Building a team with a range of personal identities, with variation in factors like gender, age, social background and even education, is beneficial to a company. The archetypical all-white-male team with a background in pharma is often at risk of sharing the same blind spots. For the same reasons that genetic variation increases resilience in nature, diverse management teams are more likely to find creative and efficient solutions to the challenges that invariably crop up in a start-up environment.

… but don’t sacrifice cohesion

Having just extolled the virtues of diversity, you also need to ensure that your different team members work well together. Given the stresses and uncertainties in a start-up’s path to success, it is critically important that everyone in management is aligned on the same goals. This team cohesion means fostering a feeling of shared passion and solidarity, not unlike team sports. Always think twice before adding a new employee if there is a risk of stirring up serious personal frictions with existing team members. When hiring, considering team dynamics and how an individual’s disposition might blend with other personalities is equally important as assembling complementary skills and experiences. Constant fights over miniscule matters can sink a start-up, so make sure to keep your team diverse but harmonious.

Adding soft skills to the mix

In Europe, start-up investors usually like to kick off with a relatively limited budget. Once they become more comfortable with the progression of the technology and the team’s performance, they’ll gradually increase their investments in line with their rising confidence. With more money, companies can expand their teams, but this resulting growth requires constant balancing and adjustment to take into account the evolving needs of a maturing company. Although team members may come and go, at any given moment an effective management team should strive to cover each of the following six soft skills categories:

– Vision and imagination
– Drive and audacity
– Patience and prudence
– Organization and structure
– Focus and resourcefulness
– Outward orientation and communicativeness

It’s clear from this list that finding all these attributes combined in a single person is nearly impossible; some of the skills are even outright opposites of each other. An excellent team is one that collectively encapsulates all of these skill areas. Taking careful consideration when adding team members to make sure you have all bases covered is key to fielding an all-star team.

It’s worth noting that some playbooks say the CEO should be the person that radiates vision and imagination. However, we believe that it is more important that the CEO shows leadership by orchestrating and motivating the team, than that the CEO conforms to any particular archetypical profile. Although it certainly helps if the CEO is a bit of an all-rounder, we’ve seen highly effective teams where these soft skills are embodied by various combinations of different team members, not just the CEO.

As a VC fund focused on building companies from the ground up, we have witnessed the evolution of many management teams over the years. The companies that do best tend to have well-rounded teams where members with diverse experiences, skills and identities work together to tackle challenges. This cohesiveness increases resilience, with teams able to make the best of the ups and downs invariably faced by life sciences start-ups.

Complete paradigm shifts in medicine are rare, but there have nevertheless been several major examples in the past hundred years. Treatments and approaches that seemed set in stone one decade can easily seem silly the next, as new information about the disease or underlying biology comes to light. Hindsight grants us clarity, but sometimes the factors that lead us down a particular treatment path can be as arbitrary as a feud between colleagues. Might there be paradigm shifts looming in oncology, neurology and more, triggered by a return to previous treatments?

This article was authored by Ward Capoen from V-Bio Ventures.

Ask anybody about the standard treatment for diabetes and they will tell you it is insulin. Certainly, since the discovery and purification of this miraculous substance a century ago, that has been the case. Dr Frederick G. Banting first isolated insulin in a series of experiments in 1921-23 and demonstrated that it was able to reduce blood sugar and ketoacidosis in a 14-year-old boy. The rest is history: initially obtained from animal cadavers and then famously produced at Eli Lilly and Genentech in 1982, insulin took over as the number-one treatment for diabetes.

However, diabetes has been recognized as a disease for millennia, well before insulin was first isolated. The first know references to the condition even date back to as early as 1500 BC. For all these years, the disease didn’t go completely untreated: the standard treatment recommended by doctors was essentially a low carb diet. In the 19th century medical bible, “The principles and practice of medicine”, Sir William Osler even prescribes a diet that would likely be identified today as an Atkins or ketogenic diet (depending on if you’re asking a baby boomer or a millennial).

A number of companies have been founded in the last few years, using ketogenic diets as an added treatment for diabetes. They have so far been very successful at treating the disease with significantly less need for medications. One hundred years after insulin was discovered, we are returning to a combination therapy using the original effective treatment for diabetes.

The feud that (nearly) killed cancer immunotherapy

Have there been other similar paradigm shifts in medicine recently? As with the diabetes diets, the rise in immuno-oncology could also be described as a return to earlier treatment methods. Until the early 2000s, a combination of surgery with chemotherapy or radiation therapy was overwhelmingly the standard in cancer treatments. This domination of chemo can partially be traced back to the work of a single pediatric pathologist: Dr Sidney Farber of the Children’s Hospital in Boston. Experimenting with different folate analogues in the 1940s, he was able to treat children with acute lymphoblastic leukemia (ALL), making this childhood leukemia the first cancer type to be successfully treated with chemotherapy. To this day, Dr Farber is acknowledged as the father of modern chemotherapy, but the standard treatment for cancer may have taken a different path if it hadn’t been for some coincidences and personal feuds half a century earlier.

These stories show us how treatment paradigms can take a particular route based on luck, timing, and even the (inter)personal relations of the scientists involved.

In 1891, New York oncologist Dr William Coley became intrigued by a patient case where a bacterial infection seemed to eliminate an untreatable neck tumor. Delving into the medical records for similar cases, Coley found more evidence of cancer regression linked to bacterial infections. He decided to explore the phenomenon to see if an immune response triggered by bacteria could purposefully be used as a cancer treatment.

In his early attempts, Coley injected ten patients with live streptococcus bacteria. Though the treatments seemed to work for the cancer, the unpredictable nature of the bacterial infection led to the deaths of two patients. Coley switched to using a formula of dead bacteria, later dubbed Coley’s toxins, which he used to treat hundreds of patients through his career with reasonable efficacy. However, the controversy of the initial deaths hounded his work, and another therapy had arisen that many doctors viewed as a safer alternative: radiation therapy.

One of Coley’s most outspoken detractors was his own boss, Dr James Ewing (who later would lend his name to Ewing’s sarcoma). As evidenced by their memos to one another, there was a strong interpersonal animosity between Coley and Ewing, with the latter being a passionate proponent of radiation therapy. Ewing eventually outlawed the use of the Coley’s bacteria-based method at the hospital altogether. If not for this personal feud and the coincidental concurrent rise in radiation therapy, cancer immunotherapies may have had an added 100 years of research and development.

Breakthroughs in the brain domain

We can find more modern examples of paradigm shifts in the fields of neurology. When pharmaceutical companies discovered the effect of selective serotonin reuptake inhibitors (SSRIs) on depression, it quickly led to the launch of the blockbuster drug Prozac in 1987. Since then, very little progress has been made in the treatment of depression; companies have developed marginally safer SSRIs, which have boosted sales but had little impact on patient outcomes.

Interestingly, around the time that the first SSRIs were being marketed, researchers were also starting to see the correlation between depression and inflammation. By the early nineties, the Macrophage Theory of Depression had formed, postulating that inflammatory cytokines released by macrophages can drive depression. The implication was that underlying, subchronic inflammation may be contributing to the mental illness. This theory has since been supported by the correlation between depression and certain auto-immune diseases, and the fact that using cytokines like interferon alfa or TNF to treat other diseases has led to depressive symptoms in patients.

The potential of anti-inflammatory drugs in the treatment of depression has now started gaining traction as a potential alternative for classic antidepressants. That the genericization of SSRIs has caused other treatment avenues to become more financially interesting has no doubt contributed to this renewed interest, but the discovery of novel pathways and druggable targets has doubtlessly contributed as well.

Medical standards can easily shift, causing controversy and disruption in the field but ultimately bringing value to the patients.

Other recent neuro-immunology approaches (with success in preclinical studies) include the use of inflammasome inhibitors in neurodegenerative diseases such as Alzheimer’s, and the discovery of innate immune cell involvement in the initiation and chronification of pain. Though still in early phases, these new methods may lead to treatment shifts of their own in the future.

These stories show us how treatment paradigms can take a particular route based on luck, timing, and even the (inter)personal relations of the scientists involved. Sometimes historical rejects can provide inspiration for new therapeutic pathways forward. For us at V-Bio Ventures, it is clear that medical standards can easily shift, causing controversy and disruption in the field but ultimately bringing value to the patients. These examples of new approaches seem to be particularly rich at the interface between different disciplines, like nutrition and endocrinology, or immunology and oncology/neurology. The exchange of expertise between disciplines can be a valuable source of innovation, and lateral thinking will bring better treatments to patients in the years to come.

Developing new therapies is sometimes not enough: for retinal indications, accurate delivery is key to making a drug work. Lowering the patient burden by minimizing injections is also an important factor to consider. Oxular, an Oxford-based biotech and V-Bio Ventures portfolio company, has developed a technology platform to address the unmet need for less frequent dosing and better drug delivery in retinal diseases.

By Amy LeBlanc

Around the world, an increasing number of people are struggling with vision loss. With an aging world population, and diabetes sharply on the rise, millions of patients are struggling with retinal diseases that cause vision loss. As new products are being developed to try and help these people, the global retinal therapeutics market is set to surpass $14 billion by 2024.

However, several unmet needs remain, including improved formulation technology and drug delivery. Current treatments are still administered to the eye via an injection straight into the jelly-like interior of the eye, not directly to the structures that require intervention (like the macula at the back of the eye). Injections are also frequent, burdening patients with regular, costly and uncomfortable visits to the doctor’s office. Formulations need to be upgraded to enable long acting treatments and reduced dosing schedules.

Seeing this unmet need, an Oxford-based team decided to tackle the challenge. They founded Oxular: a company dedicated to safe and effective retinal drug delivery solutions and transformational treatments with a profound impact on patients’ quality of life.

Setting their sights on a painful problem

Oxular was founded in 2014 by CEO Tom Cavanagh and CSO Ronald Yamamoto and since 2016 supported by V-Bio Ventures. The company has created a technology platform for unparalleled drug delivery to back-of-the-eye structures like the macula, with a pipeline of treatments for several prevalent retinal diseases, including diabetic macular edema (DME), ocular cancers and other rare and orphan conditions. Tom Cavanagh explains the inspiration for Oxular’s genesis:

If we could design a product that could reduce the number of times someone has an injection in their eye, we could increase that patient’s quality of life dramatically. – Tom Cavanagh

“Both Ron and I were looking at unmet needs in ocular diseases, particularly for retinal diseases. At the time, the world was in the middle of a therapeutic revolution, where new types of drugs were transforming how retinal diseases are treated. Previously, options had been limited to laser eye surgery and other drug classes that weren’t as effective or had severe side effects. These new drugs, like anti-VEGFs, really changed the game.

However, the dosing regimen was very burdensome for patients. We felt that there was an opportunity to deliver retinal therapies prepared in longer lasting formulations in a more targeted way, to make it so that so patients would have to have fewer injections. For current anti-VEGF treatments, for example, treatments often start with around seven injections in the first year. And although the number of injections is typically lower in subsequent years, you’re still looking at about fifteen injections in a five-year period.

Nobody enjoys a needle to the eye, and the burden of the regular appointments, coupled with the cost of so many injections, has led to attrition rates as high as 40% where patients give up on their treatment altogether. We felt there was clearly an unmet medical need not being addressed. If we could design a product that could reduce the number of times someone has an injection in their eye, we could increase that patient’s quality of life dramatically.”

Eye-catching technology

Spurred on by this patient need, the Oxular team set out to develop a safer and longer lasting drug delivery system. Oxular’s technology platform is based on the combination of their slow-release drug product formulations, called Oxuspheres, combined with their unique drug delivery devices such as the OxuLumis.

The Oxuspheres are biodegradable drug-containing microspheres. They can be adjusted, depending on the drug, to release precise dosages per day over a long period of time. Because they are slow to degrade, they extend the duration of the drug release, with the aim of reducing treatment injections to only be required every twelve months.

Our long-acting drug formulation prolongs the effects of a single administration, so that there is less burden of frequent injections for the patients. This is particularly important for diabetic or elderly patients, who already have a large burden of care. – Tom Cavanagh

The medical device OxuLumis, about the size and shape of a pen, is a unique injection tool: it is semi-automated and is able to accurately access the back of the eye using the world’s smallest, illuminated microcatheter. The precision of the injection is unparalleled and allows for the pin-point delivery of drugs via the posterior suprachoroidal space in close proximity to macula itself, via the side of the eye rather than straight through it. Cavanagh confirms:

“The combination of long-acting drug product formulations with the accurate drug delivery is what makes Oxular’s technology platform unique in the ocular field. The devices allow us to deliver drugs to specific back-of-eye structures, increasing both the safety and efficacy of treatments. Other ocular injection devices simply inject drugs into the fluid space of the middle of the eye, letting the drug diffuse through the whole eye structure. This leads to less concentrated doses in the structures that actually require the drug, and potentially more side effects as the drug can affect off target structures.

Our long-acting drug formulation using the microspheres then prolongs the effects of a single administration, so that there is less burden of frequent injections for the patients. This is particularly important for diabetic or elderly patients, who already have a large burden of care. There are convergent technologies: together they help us address the unmet needs of patients with a wide variety of eye diseases.”

Easing the burden on children

The Oxular team are working on applications for their technology in a range of different applications. The lead program is for ocular steroids in Diabetic Macular Edema (DME) as well as Retinal Vein Occlusion (RVO) and Uveitis. They are also tackling several types of eye cancers using chemotherapy, including Retinoblastoma and Uveal Melanoma, as well as supporting the delivery of gene and cell therapies. Cavanagh elaborates:

“In addition to developing our own drug assets, we also work together with partners. Often these are companies that have a potent asset, but it has a short half-life. Even if you have a great drug, if it requires an injection once a month to work, that’s not going to be feasible for patients. By combining their drugs with our technology, we can extend the duration of the drug release, thereby making the assets practicable.”

When asked about his hopes for the future, Cavanagh spoke of one of the company’s secondary pipeline programs, chemotherapy delivery for retinoblastoma in children:

“We have a passion for the retinoblastoma program because it is an ocular cancer that affects very young children. The standard of care carries both significant procedural risks and/or drugs side effects. It may not be the company’s biggest program, but it is nevertheless our favorite. We want to help these kids, reduce the invasiveness of current procedures, and reduce the side effect profile of current treatments while preserving vision.”

Gent, Belgium, 27 October 2020 – Today V-Bio Ventures announces its investment in Animab, a new venture spin-off from VIB, in a EUR 3.4 million Seed financing round. The company develops monoclonal antibodies for oral administration to ensure intestinal health of livestock. The initial focus is on improving the resilience of piglets during the fragile post-weaning period. The start-up will use the seed capital to develop its first oral antibody product for protection against ETEC and initiate a product portfolio for the livestock industry.

Animab builds on a proprietary platform technology enabling efficient generation of monoclonal antibodies to prevent intestinal infections in animal production. This new class of orally administered antibodies is designed to improve the health and performance of animals by targeting specific disease-causing pathogens.

The monoclonal antibody platform is based on the cross-disciplinary research and expertise within VIB, the leading life sciences research institute based in Flanders, Ghent University and Vrije Universiteit Brussel (VUB). Animab’s proprietary antibodies mimic secretory IgA, a type of natural antibodies passed on via the colostrum and milk. In a collaborative effort by VIB and the Ghent University Faculty of Veterinary Medicine, these antibodies were further improved and tailored to target specific intestinal pathogens in livestock with speed and precision, without altering the healthy microbiome. Animab will continue to collaborate with these top academic research groups to expand the high precision biologic toolbox for protection of young animals.

The first monoclonal antibody lead product is designed specifically for pig production. Post-weaning diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is an economically important disease in pig production worldwide. Young piglets are very susceptible to this infection, resulting in a morbidity ranging between 25 to 50% in Europe. Animab’s lead product will provide the swine producers with an alternative to antibiotics for the control of gastrointestinal pathogens and contribute to a more sustainable animal production.

Although the company will initially focus on ETEC protection in piglets, it will rapidly expand its pipeline with new product opportunities that target bacteria, viruses and host factors in livestock animals, spanning a range of gastrointestinal indications.

The firm is led by seasoned business strategist Alain Wille, leveraging more than 25 years of animal health experience, including leadership positions at Boehringer Ingelheim and Merial. He is joined by Scientific Director Vikram Virdi, whose PhD laid the groundwork for 11 years of research on edible antibodies that form the solid scientific framework of Animab. Nesya Goris completes the management team as Animab’s Technical and Regulatory Director and brings more than 10 years of cutting-edge technology development experience to the firm. She combines her role at Animab with the chief development officer function at ViroVet. Chairman of the Board is former CEO and co-owner of the Nuscience group Patrick Keereman. Under his wings, the Belgian animal nutrition company Nuscience has transformed into a multi-product global player. Animab’s chairman brings decades of industry knowledge and executive experience that will help guide and grow the new venture. Together, the team has a wealth of knowledge and proven track records in the animal science field.

Animab is backed by a solid European investor consortium who invested EUR 3.4 million in a Seed round led by Seventure Partners and PMV, and with the participation of Agri Investment Fund, V-Bio Ventures and VIB. The ambition of the investor consortium is to further support the growth of the company through future financing rounds, allowing it to bring this innovative concept to the market as a commercial product.

Commenting on the announcement, CEO Alain Wille says: “The mission of Animab is to design and bring to the market cost-effective solutions that ultimately benefit animals, producers and consumers. Clearly, our first product embodies that goal as it targets widespread pathogenic intestinal bacteria in pigs. Additionally, reducing the need to use antibiotics in animal production is also good for people and society.”

Nico Callewaert (VIB-Ghent University), one of scientific founders, explains: “Together with the labs of Profs. Ann Depicker (VIB-Ghent University), Henri De Greve (VIB-VUB) and Eric Cox (Ghent University), our cross-disciplinary science teams collaborated intensely to develop a new antibody technology designed for oral ingestion, set up a scalable, cost-effective microbial production process, and demonstrate that they can protect piglets against ETEC infection. It is very rewarding to see that our scientific discoveries will now be translated by Animab into market-ready products.”

Laëtitia Gerbe (Seventure Partners) and Kenneth Wils (PMV) also mention: “It is clear that the technology has potential to bring about a disruptive change in the animal production. E. coli is a highly prevalent pathogen causing disease in swine production without effective non-antibiotic control options. We are proud to support Animab whose management has the necessary expertise and vision to provide the industry with a totally new range of solutions.”

Willem Broekaert (Managing Director at V-Bio Ventures) adds: “We are excited about the opportunity to invest in Animab, in particular because it is a true platform company capable of launching several products thereby leveraging synergies in development, manufacturing and commercialization.”

Jérôme Van Biervliet, Managing Director of VIB, adds: “We are thrilled to announce our newest spin-off Animab, adding a new player to the growing animal health start-up ecosystem. By moving VIB innovations beyond human health, we recognize the importance of the One Health approach, as the health of people, animals and the environment are all interconnected.”

More Info

About Animab
Animab is a new venture designed to address the changing needs of animal production. Using proprietary research discoveries, Animab targets the emerging science and new possibilities in the gut. The interdisciplinary team integrates cutting-edge research, animal science, and biotechnology for product breakthroughs in animal health, cost-efficiencies and sustainability. Led by an experienced group of experts with expertise in a range of relevant domains from vaccines, biotechnology, business management and international marketing, Animab is dedicated to offering a safe and sustainable way to ensure animal performance. More information: www.animab.com.

About VIB
VIB is an excellence-based entrepreneurial research institute in life sciences located in Flanders, Belgium. VIB’s basic research leads to new and innovative insights into normal and pathological life processes. It unites the expertise of all its collaborators and research groups in a single institute, firmly based on its close partnership with 5 Flemish universities (Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel and Hasselt University) and supported by a solid funding programme from the Flemish government. VIB has an excellent track record on translating basic scientific results into pharmaceutical, agricultural and industrial applications. Since its foundation in 1996, VIB has created 25 start-up companies, now employing over 900 people. More information: www.vib.be.

About Seventure Partners
With €750m net commitments under management as of the end of 2018, Seventure Partners is a leading venture capital firm in Europe. Since 1997, Seventure Partners has been investing in innovative businesses with high growth potential in two fields: Life sciences across Europe, Israel, Asia and North America, and Digital technologies mainly in France and Germany.
In Life sciences, the main areas of focus include “classic” approaches such as biotechnology and pharmaceuticals, diagnostic and medtech, industrial biotechnology, as well as “beyond the pill” approaches such as MICROBIOME-linked innovations, nutrition, foodtech, digital/connected health and personalized medicine. Investments can range between €500k and €10m per round, and up to €20m per company, from early to late stage. In March 2018, Seventure Partners launched AVF, a new fund dedicated to animal nutrition, feed and health with Adisseo as strategic partner. For more details: www.seventure.fr/en Twitter: @seventurep

About PMV
PMV is an investment company that shapes the economic future of Flanders by financing promising companies from the very start to growth and internationalization. With over 1 billion euros in assets under management and led by experienced professionals, PMV offers tailor-made financial solutions for entrepreneurs with a solid business plan and a strong management team, including venture capital, loans and guarantees. More info about PMV can be found on www.pmv.eu.

About V-Bio Ventures
V-Bio Ventures is an independent venture capital firm specialized in building and financing young, innovative life science companies. V-Bio Ventures was established in 2015 and works closely with Belgium-based VIB, one of the world’s premier life science institutes. The fund invests throughout Europe in start-up and early-stage companies with high growth potential focusing on technologies that provide transformational improvements in the biopharmaceutical, pharmaceutical, diagnostics and agricultural sectors. More info: www.v-bio.ventures.

About Agri Investment Fund
Agri Investment Fund (AIF) is an investment company, part of MRBB, the financial holding of Boerenbond (Farmer’s Union). AIF invests in innovative companies that contribute to strengthen the competitiveness of the agricultural production in the regions where Boerenbond is active. AIF is located in Leuven, Belgium. www.aifund.be

About Ghent University
After more than twenty years of uninterrupted growth, Ghent University is now one of the most important institutions of higher education and research in the Low Countries. Ghent University yearly attracts over 41,000 students, with a foreign student population of over 2,200 EU and non-EU citizens. Ghent University offers a broad range of study programs in all academic and scientific fields. With a view to cooperation in research and community service, numerous research groups, centers and institutes have been founded over the years. For more information www.UGent.be.

About Vrije Universiteit Brussel
The Vrije Universiteit Brussel (VUB) is a thriving university in the heart of Belgium and Europe, which in 1969-1970 split off from the Université Libre de Bruxelles (ULB), founded in 1834. VUB combines excellence in teaching with excellence in research. Several of its 150 research groups are topranked worldwide. The principle of independent research is central at VUB, but the quality of its undergraduate and graduate programs is no less important, as the university provides an environment where students are treated as individuals and supported in their personal development. Currently, VUB has some 9,000 students and 2,700 staff, divided over eight faculties and two Brussels campuses (in Etterbeek/Elsene and Jette). The VUB University Hospital is adjacent to the Medical Sciences campus in Jette and employs 3,000 people. More info: www.vub.ac.be/.

While physicians care for their individual patients and are interested in the factors contributing to the individual’s condition, evolutionary biologists investigate the cause of the biological phenomenon, trying to understand for example why a certain disease has developed in a particular species such as our own Homo sapiens. By combining the view of physicians with the view of evolutionary biologists, the field of evolutionary medicine has the potential to improve our understanding of certain diseases and how to prevent them.

This article was authored by Christina Takke from V-Bio Ventures.

Lessons from history

What can history teach us about identifying new treatments for current and future diseases? Since Charles Darwin published his ideas on evolution in On the Origin of Species (1859), our understanding of biological processes has increased dramatically. The basic principles of evolution by natural selection, as described by Darwin, are still actively used by biologists today in trying to understand the world in which we live.

As a refresher, evolution by natural selection occurs when there is an disequilibrium between the reproductive potential of a population (i.e. the number of offspring a certain organism can generate) and the environmental resources available (e.g. food, space, mating partners, etc.). In these circumstances, individual organisms in a population must compete for survival and reproduction. Evolution occurs when differing individuals leave behind a different number of offspring that are able to go on to reproduce. Traits which predispose individuals to survive to reproductive age are transmitted more frequently to the next generation through their offspring and are therefore positively selected for.

People often confound the term “survival of the fittest” with “survival of the healthiest”, where this is not necessarily the case. The only parameter on which evolution by selection takes place is the number of fertile offspring an individual organism can produce. In humans, for example, the heritable disorder Huntington’s disease is not usually selected against, despite being a deadly disease. This is because the onset of symptoms typically doesn’t occur until a person is in their 30s or 40s, often after they have already had children. Therefore, the condition persists in the population despite the lethality of it.

Although one might think that historical selective pressures should have caused us to evolve defences to most weaknesses and conditions, evolution’s prioritization of reproduction over health and wellbeing has actually left humanity vulnerable to a range of conditions and diseases. By incorporating aspects of evolution into medical research, this perspective can provide us with new insights into the development of specific diseases and therefore potential methods of tackling them.

Evolutionary medicine can answer the “why” questions

Why do diseases develop and persist in humans? Let us use chronic obstructive pulmonary disease (COPD) as an example. COPD is a common disease and causes millions of annual deaths worldwide. Recent studies have revealed that the heritability of COPD is 37%, meaning that an individual with a genetic predisposition for COPD has a 37% chance to pass that predisposition on to their offspring. Why did humans acquire this genetic trait in the first place, and why has such a negative genetic predisposition persisted? The evolutionary biologist perspective can provide some insight to both these questions.

In a 2015 publication, Aoshiba et al. discuss some intriguing reasons why COPD developed in humans, based on current evolutionary medical theories.

i) Evolutionary constraints and the inability to correct a basic design flaw

Since humans have a long generation time of about 20 years or more, we are unable to rapidly adapt to “fast” changes like general uptake of tobacco smoking or increased air pollutants, the leading causes of the historically recent disease COPD. Although inhaled particles are detrimental to our health, our low number of offspring and long generational cycles has not led to any real shift in our physiology in the past few hundred years to better cope with this selection pressure. As a point of comparison: it took the human population about 10,000 years to acquire the widespread ability to digest cow’s milk, an ability that was absent in most of our ancestors and is still absent in many cultures today where milk products were not traditionally part of the general diet.

ii) Co-evolution of the immune system and microorganism

Given our long lifespan and low number of offspring, we experience a higher frequency of repeated invasion by the same microorganisms as compared to shorter living animals. This increases the need for a better immune system, especially in the airways which are frequently exposed to microorganisms. This active immune system in our lungs, which is key to ward off invasion by microorganisms, is also activated by cigarette smoke and other airborne substances. Scientists have also identified that airway inflammation by viral pathogens causes a similar biological reaction as COPD. The system which has protected us for millions of years is now also causing us harm.

iii) Life history trade offs

According to Darwinian theory, traits that lead to more surviving offspring are naturally selected for and passed on more frequently to the next generation. This means that traits that are beneficial to the health of young organisms are positively selected for, even when they are detrimental to the health of the elderly. This seems to be the case for COPD, where strong, reactive immune systems increase the survival rate of the young and are therefore kept in the population despite causing issues for older individuals. Another gene variant associated with a genetic predisposition to COPD is one which increases protease activity. While high proteolytic activity is a genetic risk factor for COPD, it is advantageous for the removal of microorganisms and also promotes reproduction chances by helping sperm penetration of the zona pellucida of the ovum at fertilisation. Therefore, a trait which increases the chances of COPD nevertheless persists and even flourishes in the population. Other examples of reproductive success at the expense of health can be found in oncology, where people with higher testosterone or oestrogen levels are generally more fertile, but also more susceptible to prostate and breast cancer.

Looking at the bigger picture

It goes without saying that evolutionary medicine does not give us the answers how to treat or diagnose a disease in a specific patient. It is also ethically impossible to experimentally prove the effect of natural selection and the trade-offs made during evolution in humans. However, by looking outside the box and considering the evolutionary perspective, we can generate new understandings and insights on a range of human afflictions.

When diagnosed, many patient’s ask their physicians the difficult question: why me? Evolutionary explanations can help shed some light on this otherwise unanswerable question, hopefully helping patients to better cope with their personal situation. A deeper understanding of the development of diseases can also help us find new solutions to these healthcare challenges.

V-Bio Ventures, a leading Belgian life sciences VC, invests in Biodol Therapeutics, a French biotech specialized in next-generation chronic pain treatments. Biodol Therapeutics receives EUR 4.5 million to develop novel FLT3 inhibitors for the treatment of chronic and neuropathic pain, aiming to reach the clinic by early 2023.

Ghent, Belgium, 31 August, 2020 – It is estimated that 1 in 5 people in developed countries will encounter chronic pain (defined as pain lasting longer than 3 months) during their lifetime. This results in immense suffering and a significant reduction in the quality of life. Despite more than USD 20 billion spent on pain medication annually, efficacy is underwhelming and most patients only ever obtain partial relief from their pain. In addition to the limited efficacy of current treatments, opioid analgesics come with significant dangers of addiction and overdosing. In this context, the search for novel and innovative pain medications is more pressing than ever.

Biodol Therapeutics, a biotechnology company located in Montpellier and Strasbourg (France), is based on the seminal work of Dr. Jean Valmier, Professor at the University of Montpellier and the INSERM Institute for Neurosciences of Montpellier (INM), and Dr. Didier Rognan, Research Director at CNRS and Director of the Laboratory for Therapeutic Innovation (LIT) at the University of Strasbourg. Dr. Pierre Sokoloff, the company’s CSO, is the former director of the INSERM Unit of Molecular Neurobiology and Pharmacology at Hospital Ste-Anne in Paris and former Director of Exploratory R&D for Neurology-Psychiatry at Pierre Fabre Laboratories. Biodol was founded in 2015.

The company discovered that FLT3 (a known hematopoietic receptor) is expressed on sensory neurons and is instrumental in the generation and maintenance of a pain response. The receptor has been shown to integrate signals from both the nervous and immune systems to modulate pain sensation and is emerging as a promising target for drug development. Biodol has identified a novel class of allosteric, highly selective modulators of FLT3, without the safety limitations of classical RTKi. The company will develop these molecules as a next-generation treatment for chronic pain.

Thanks to the investment by V-Bio Ventures, the company now has the means of developing their novel molecules towards the clinic and confirm their first translational data showing the potential in humans. The investment will allow further optimization of the lead compounds and prepare the company for IND filing by the end of 2022.

Fabien Granier (CEO, Biodol):

“We are delighted to announce the investment of V-Bio Ventures. Their knowledge and advice will bring our company to the next level. Thanks to our IP portfolio and following our multiple discussions with pharma, we are now uniquely positioned to finalize the key set of data expected by the pain management industry. Biodol Therapeutics is without a doubt moving forward in providing patients struggling with neuropathic pain the safe and specific treatments they have been waiting for.”

Ward Capoen (Principal, V-Bio Ventures):

“The neuro-immune interface is an exciting new area for therapeutics, and we strongly believe that the next generation of pain therapeutics will come from this direction. We are very impressed by the work done at Biodol so far and look forward to help the company bringing their exciting new medicines to patients.”

About Biodol Therapeutics

Biodol Therapeutics (www.biodol.eu), founded in 2015, develops first-in-class compounds for the treatment of chronic pain (CP). Biodol Therapeutics has identified the Receptor Tyrosine Kinase (RTK) FLT3 as a key player for triggering and maintaining the chronic neuropathic pain (NP) state. The company is focused on the development of allosteric inhibitors of the FLT3 receptor for the treatment of chronic pain. Biodol Therapeutics already owns the exclusive rights on a portfolio of 4 patents. The company has been supported by BPIFrance, Satt AxLR, Inserm Transfert, Region Occitanie, the French National Research Agency, SEMIA Incubator and Montpellier Business and Innovation Centre.

About V-Bio Ventures

Cabinet Carrel advised Biodol Therapeutics and V-Bio Ventures on this funding round.

__________________________________________________________________________________

For more information, contact:

V-Bio Ventures
Ward Capoen
ward.capoen@v-bio.ventures

Biodol Therapeutics
Fabien Granier
fabien.granier@biodol.eu

In August 2020, V-Bio Ventures announced their investment in Biodol Therapeutics, a French start-up looking to make a difference to people suffering from chronic pain. The company is developing a drug to treat neuropathic pain by addressing the interplay between nerves and the immune system. In a billion-dollar market dominated by ineffective and dangerous painkillers, their unique approach could reduce the suffering of millions.

By Amy LeBlanc

Everyone knows the feeling of pain. Whether from a papercut, bruise or serious injury, we’ve all experienced how distracting and consuming the sensation can be. For many unfortunate people, pain has become a part of their everyday existence, limiting their daily activities and overall quality of life. Chronic pain, defined as lasting more than three months, can be a debilitating experience and affects over 225 million people in the world today.

For many, their condition is treated with opioids analgesics, which can in themselves lead to even greater issues such as addiction. But for others, such as the 30% of chronic pain patients suffering from neuropathic pain, even opioids aren’t effective. Instead, patients with neuropathic pain are limited to taking repurposed drugs such as antidepressants and antiepileptics to try to calm their firing nerves. These repurposed drugs are less than ideal: only one in two patients find their pain reduced by even 30%, and one in every three experiences side effects. Chronic pain remains an unsolved public health and societal problem with a huge medical need for better treatment options.

Connecting nerves and immunology

A striking feature of the $23 billion chronic pain market is that most drugs only address symptoms, without attempting to solve the root cause of the problem. For two thousand years, since the Roman medical writer Aulus Cornelius Celsus first described the four hallmarks of inflammation (redness (rubor), heat (calor), swelling (tumor), and pain (dolor)), we have known of the connection between the immune system and pain. However, it is only recently that the neuro-immunology link has been examined more closely.

It wasn’t until 2018 that the underlying cause of the [neuropathic pain] cascade was uncovered by the scientists who would go on to found Biodol Therapeutics. – Fabien Granier

The link between immunology and neurology is precisely what French start-up Biodol Therapeutics is looking to address. This company aims to develop the first-ever specific treatment for neuropathic pain and believes its technology will also be able to address other forms of chronic pain. It’s an example of true innovation, where a small company is looking at a longstanding challenge from a different angle. Biodol CEO Fabien Granier explains how the company came to be:

“Neuropathic pain occurs when a nerve has been damaged, through a lesion or by a treatment like chemotherapy, but the pain response persists even after the original injury has been healed. The cascade of events from nerve damage to neuropathic pain has long been known, but it wasn’t until 2018 that the underlying cause of the cascade was uncovered by the scientists who would go on to found Biodol Therapeutics. Their research, published in Nature Communications (1), found that the underlying cause of the cascade was an interaction between immune cells and the nervous system which led to the stimulation of a receptor called FLT3 on the damaged nerve. This in turn triggers the events that lead to the development of neuropathic pain.”

Old target, new possibilities

The FLT3 receptor has long been known as a target for another disease: cancer. There are multiple types of leukemia treatments that work by blocking FLT3 receptors. These treatments, only used in the deadly scenario of blood cancer, are “dirty” therapies with a range of side effects, only tolerated due to the high-risk profile of the disease they are being used to combat. However, Granier believes that FLT3 inhibitors may nevertheless be the solution neuropathic pain patients have been waiting for:

“At Biodol, we are developing a small molecule drug that works by inhibiting FLT3 receptors. This has never been done for pain, as it wasn’t until the seminal work by Biodol’s scientists that we even knew this receptor might be a target for chronic pain. We are also confident that we can overcome the side effects and long-term use issues of oncological FLT3 inhibitors, as they target the intracellular part of the receptor. Our small molecule compounds are instead targeting the extracellular part of FLT3. This makes them more selective and safe for continual use, which is necessary for a chronic condition like neuropathic pain.”

Using FLT3 inhibitors in combination with opioids eliminates the buildup of opioid resistance in animal models. A combination therapy in humans may therefore be a safer and more sustainable alternative to current opioid treatments for inflammatory pain. – Fabien Granier

Granier also tells us there is an indication that FLT3 inhibitors also have the potential to play a vital role in the global opioid crisis:

“Our researchers have found that using FLT3 inhibitors in combination with opioids eliminates the buildup of opioid resistance in animal models. A combination therapy in humans may therefore be a safer and more sustainable alternative to current opioid treatments for inflammatory pain.”

Taking a chance on change

The company is still in the early stages of drug development, working on the chemistry and lead optimization in preclinical studies. Granier is however confident they will find a good candidate for the clinic by 2023 at the latest. At that point, he believes pharmaceutical companies will be immensely interested in the treatment they’ve developed. Ward Capoen, Principal at V-Bio Ventures, agrees:

“Pain is an interesting market to tackle, because people are a bit afraid of the field. It’s considered a difficult area to work in, because there have been a couple of famous failures on safety lately, mostly related to one target. This is because any pain drugs need to be clean and safe for long-term use. Interestingly, in terms of risk management and likelihood of approval, pain is generally in the same range as oncology.

We decided to take the leap and invest in this company’s vision. It’s what V-Bio does best: we support young companies with good science, who are simply too early-stage for others, and nurture them through to the next stage of their journey. – Ward Capoen

When Biodol approached us, they had a lot of interest from other investors and pharma, who thought the target had a huge potential but were still too hesitant to get involved. Unlike them, we decided to take the leap and invest in this company’s vision. It’s what V-Bio does best: we support young companies with good science, who are simply too early-stage for others, and nurture them through to the next stage of their journey.”

According to Capoen, Biodol now has the funds to progress through the preclinical phases and get their lead to the clinic. Once the FLT3 inhibitor is ready for in-human trials, he is confident the interest from pharma will be intense.

One thing is for sure: early-stage or not, Biodol’s neuro-immunology based approach to pain management is in line with a general scientific trend towards tackling medical challenges in a more holistic manner. The aim is not to treat symptoms in isolation, but rather to understand the whole system and address the root cause of the disease. At Biodol, they aren’t just attempting to develop a new and better drug; they’re trying break the pain cycle.

(1) Rivat et al., Inhibition of neuronal FLT3 receptor tyrosine kinase alleviates peripheral neuropathic pain in mice. Nat Commun, (2018) 9:1042.

Many of our current antiviral, antibacterial and anti-tumour medications are comprised of combinations of two or three active substances, selected on the basis that these combinations slow down emergence of drug resistance. We are currently witnessing a rapid expansion of disease indications for which exploratory drug combos are being tested, as well as of the rationales for combining drugs. In this article, we examine the drivers behind this trend and the inherent caveats and complexities of drug combo development.

This article was authored by Willem Broekaert from V-Bio Ventures.

A long history of combining approved drugs

The value of using combinations of approved drugs has long been recognized in antibiotic treatments. Already in 1948, a controlled clinical trial established that a combination of para-aminosalicylic acid and streptomycin results in better control of tuberculosis and less antibiotic resistant bacteria compared to treatment with each drug alone. A quadruple combo of antibiotics (isoniazid, rifampicin, pyrazinamide and ethambutol) is today part of the standard tuberculosis treatment regimen. With the rising threat of antimicrobial resistance, drug combinations are being used to try to slow the widespread emergence of antibiotic-resistant bacterial strains.

Combinations of approved drugs are also being used in other disease areas. The underlying rationale is that a combination of selected medicines, each acting on a different molecular circuit, simultaneously pulls multiple strings. This, in turn, ideally results in both improved efficacy and less side effects, due to lower doses of the active substances being used. Drug combinations can either be administered as separate drugs or as fixed-dose combinations formulated in one pill, with the latter option ensuring better patient compliance.

Although identification of effective drug combos was largely based on patient experience in the past, modern methods have moved one step ahead and started testing new combinations in rigorous clinical trials.

These days, most patients with severe hypertension use at least two different antihypertensive drugs. A full quarter of patients even take a triple combination. For antihypertensive drug combos, figuring out which approved drug classes made effective combos was historically based on empirical observations by individual clinicians. Large-scale studies have been run a posteriori to confirm or disprove proposed combinations. Current hypertension guidelines reflect these studies by, for instance, advocating for combinations of angiotensin-converting enzyme inhibitors with calcium antagonists (for safe and effective hypertension management), while advising against combinations of beta-adrenergic blockers with non-dihydropyridine calcium antagonists (due a greater risk for certain cardiac events). Although identification of effective drug combos was largely based on patient experience in the past, modern methods have moved one step ahead and started testing new combinations in rigorous clinical trials.

Trialling combos of investigational drugs

Until recently, drug combinations were mainly applied in those fields where underlying disease mechanisms are relatively simple. The development of antivirals, for example, revolves around a handful of viral protein targets that are markedly different from host cell proteins. For instance, the anti-HIV drug Biktarvy combines two compounds that inhibit viral reverse transcriptase and one that blocks viral integrase

However, for multifactorial diseases with a complex pathophysiology, the number of contributing biological pathways increase dramatically, as do the number of cell types, tissues or organs involved. With modern technology we have been able to deepen our understanding of these mechanistic circuits at the genomic, proteomic and metabolomic level. Combined with computational modelling approaches, it has now become possible to investigate hypothesis-driven drug synergies, rather than relying on empiric combinations.

An example of this is in non-alcoholic steatohepatitis (NASH), a complex disease which involves concurrent excess fat deposition, inflammation, and fibrosis in the liver. Similarly, neurodegenerative diseases like Alzheimer’s disease feature synaptic transmission loss, inflammation and cell degeneration in an interplay between neurons and glial cells. Any successful therapies for these multifactorial diseases will have to act on all pathways simultaneously. Unfortunately, single compound drugs capable of selectively modulating multiple defined pathways are unlikely to exist. However, combinations of selective drugs could potentially do the job.

Exploring investigational drug combos is inherently more complex than combining approved drugs… Nevertheless, many such studies are currently taking place, with the benefits of successful combinations deemed worth the trouble.

In a vast range of disease areas, including immuno-oncology, autoimmunity, pain, neurodegenerative and metabolic diseases, trials are underway to examine combinations of investigational drugs with either approved drugs or even other investigational compounds. An example of the latter is a seven arm Phase II trial in NASH run by Gilead, with different two-by-two combinations of an investigational farnesoid X Receptor agonist, an Acetyl-CoA carboxylase inhibitor and an ASK1 kinase inhibitor. Regulators require a compelling biological rationale for any proposed combination treatment, backed up by a set of nonclinical data and clinical data on both the monotherapies and combination therapies. Obviously, exploring investigational drug combos is inherently more complex than combining approved drugs, since clinical data for the individual drugs are lacking at the outset of the study. Nevertheless, many such studies are currently taking place, with the benefits of successful combinations deemed worth the trouble.

The many challenges with combination therapies

To develop combination therapies, substantial nonclinical data need to be gathered. These data need to demonstrate not only the synergistic effects of the drugs, but also the absence of synergistic toxicities and untoward drug-drug interactions. Part of the challenge is the availability of animal models: these studies require models that replicate all the pathological cues of the human disease that the drugs combo is supposed to act upon. Additionally, the dynamic range of the animal models needs be large enough to discriminate between single compounds that work well and which combinations (if any) work even better. Better models will need to be developed to fully meet these needs.

We at V-Bio Ventures believe that high-risk trials of investigational drug combos are here to stay, despite the likely significant failure rates, because the long-term outcome will be significantly better therapies for patients.

A next hurdle arises at the clinical stage. Phase I studies of combination therapies tend to be lengthy and expensive, particularly for combinations of investigational drugs. Establishing toxicity thresholds requires dose escalations for both drugs and, as moving to the next dose can only be done sequentially, this can take a lot of time. When one of the drugs is already approved, then this component can be maintained at its safe and effective dose, or one dose level below, which obviously speeds up such studies. Phase II studies require creative adaptive trial designs, as they have to show the efficacy of each individual agent, as well as improved efficacy of the combo, on an appropriate endpoint. Only once the efficacy of the combo versus the single drugs has been established in a Phase IIb study, negotiation with the regulators will determine if a Phase III study can begin with just the combo at the selected dose. The whole clinical process is magnitudes more complex than a normal clinical trial for a single compound, which is already a challenging undertaking in itself.

Our thoughts on drug combos

The attempts of the biotech industry to evaluate combination therapies, even before single drugs have been approved, are testimony to their strong commitment to find effective solutions for hard-to-treat diseases. Some may judge that such endeavors as premature and therefore a waste of resources. We at V-Bio Ventures believe that high-risk trials of investigational drug combos are here to stay, despite the likely significant failure rates, because the long-term outcome will be significantly better therapies for patients.

Ghent, Belgium, 28 July 2020 – Today V-Bio Ventures announces its investment in a EUR 23 million Series A financing into ExeVir Bio. The round was led by Fund+, with the participation, next to V-Bio Ventures, of VIB, UCB Ventures, SFPI-FPIM, and several Belgian family offices. ExeVir Bio has been established by Belgian partners combining world class science, antibody engineering, manufacturing, blue-chip venture capital investment and Flemish Government financing, which have joined forces in a unique collaboration to boost the development of new therapies to combat Covid-19.

ExeVir Bio, a spin-out of VIB, the world-leading Belgium-based life sciences research institute, is harnessing its Llama-derived antibody (VHH) technology platform to generate robust antiviral therapies providing broad protection against coronaviruses. After early pre-financing by the Flemish Government, UCB, a multinational biopharmaceutical company, assisted in the generation of the lead candidate and is producing the GMP batches for clinical trials. Fund+, a leading Life Sciences-focused investment firm in Belgium, led the financing and was instrumental in setting up ExeVir Bio.

ExeVir Bio is using a highly innovative and clinically validated VHH technology to develop treatments for viral infections that may pose a significant global threat. Lead asset VHH72-Fc binds to a unique epitope that is conserved in SARS-CoV-1 and SARS-CoV-2 viruses and this binding prevents these viruses from entering the cell. The importance of this approach is that it could be used both as a therapeutic and prophylactic. Therapeutic use could help slow viral replication in the lungs, reduce inflammation, and give patients valuable time to raise their own productive immune response. Prophylactic use could support the ringfencing of an outbreak, protect healthcare workers, and support those at increased risk of severe illness from Covid-19.

Torsten Mummenbrauer, CEO of ExeVir Bio, said: “We are committed to the international effort against Covid-19 to support healthcare systems and to offer global access to our new treatment. With this Series A financing we can rapidly advance the development of our lead compound into clinical studies by the end of the year. We are confident our Llama-derived antibodies hold a key to saving the lives of patients who can become seriously ill with coronavirus.”

The technology platform was developed by VIB-UGent scientists, Professors Xavier Saelens and Nico Callewaert with the help of VIB’s drug discovery team at VIB Discovery Sciences, and national and international scientific collaborators. The team has shown that Llama-derived single-domain antibodies can neutralize SARS-CoV-2 in preclinical studies and SARS-CoV-1 in in vitro assays. As Llama antibodies are smaller than human antibodies, they can attach to parts of the coronavirus that would otherwise be inaccessible. The antibodies were derived from a Llama called ‘Winter’. A paper on the platform was published on 28 May 2020 in the journal Cell, on ‘Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies’ by Wrapp et al.

Torsten Mummenbrauer, CEO of ExeVir Bio, Philippe Monteyne, Partner at Fund+, Erica Whittaker, Head of UCB Ventures, Jérôme Van Biervliet, Managing Director, VIB and Katja Rosenkranz, Partner at V-Bio (observer) will join the Board of ExeVir Bio. Further board appointments will be announced in the future.

About ExeVir Bio

ExeVir Bio (https://exevir.com/) is harnessing its VHH technology platform to generate robust antiviral therapies providing broad protection against viral infections, including coronaviruses. It is a spin out from VIB, the world class Belgium-based life sciences research institute, based on the work of Professor Drs Xavier Saelens and Nico Callewaert from VIB in collaboration with: Laboratory of Jason McLellan – University of Texas at Austin; Laboratory of Barney Graham – NIAID (Vaccine Research Center); Laboratory of Johan Neyts – KU Leuven (Rega Institute). ExeVir Bio is led by a team of experts that combines international biotech and pharma experience with a successful track record of developing and bringing products to market. It is backed by blue chip investors led by Fund+, VIB, UCB Ventures, FPIM, V-Bio and several Belgian Family Offices.