Opinion

Start-up Story

Juvabis – Too deadly to ignore

Leaders worldwide have been awakened to the fact that the bottom of the barrel has been scraped with regards to antibiotics. As new antimicrobials are fewer and farther between and resistances are mounting, new approaches are garnering more and more attention. A Swiss start-up has developed a unique technology platform to design new drugs to fight bacteria.

Juvabis’ founding story is everything but unique, muses co-founder Sven Hobbie. A group of Swiss researchers develop a new technology, file the patent, and decide to commercialise their IP. That’s how it goes...however, reality is rarely that straightforward. It took a seven-year detour across the world before Hobbie got the company off the ground. “I worked at MIT, both in Singapore and Boston,” he explains. There, he was exposed to a vigorous commercialisation of science. Hobbie felt inspired. He knew that back in Zurich, there was great potential to address the increasing problem of antibacterial resistance.

He returned to Zurich, but not without misgivings. “I left a lot behind to venture into this start-up,” he says with a smile. “But the risk of antimicrobial resistance is too deadly to do nothing.” Together with his Zurich colleagues Erik Böttger and Andrea Vasella, as well as David Crich at Wayne State University, Hobbie founded Juvabis – with a seemingly simple approach. “We focus on those bacterial drug targets that have proven most successful in medical history and apply innovative chemistry to develop new therapeutics. Since both the drug targets and the compound classes have been clinically validated, there is a high chance of efficacy in humans and limited safety concerns.” These characteristics will allow Juvabis to rapidly process its leads into clinical trials, Hobbie points out. It is crucial that drug candidates circumvent all relevant resistance mechanisms known to date. Of course, there is no guarantee that new resistances will not emerge, but that is true for any new antibiotic, Hobbie stresses. 

Today, new antibiotics are used much more carefully than in previous decades. This is exactly why big pharma has been hesitant to invest for some time. “You cannot flood the market with a new antimicrobial,” says Hobbie. New drugs would be held back to function as a last resort: this is not a profitable outlook. However, policies worldwide are beginning to change in light of dwindling anti-bacterial resources. “In [the] future, economic models will be put in place to make sure that revenue will not depend on [the] volume sold but on how the antimicrobial performs, for example, by being able to set a high price on new drugs, or by market entry rewards.” Where big pharma companies are still afraid to tread, smaller biotechs like Juvabis are picking up the slack – and the risk. “It’s true. Policy changes to incentivise antimicrobial drug development are an ongoing process,” says Hobbie. “We anticipate changes for the better, but critical details have yet to be finalised.” So far, though, he is not worried.

“We have a big advantage,” Hobbie explains. “Our preclinical development projects have greatly benefitted from support by the ENABLE programme.” The IMI project seeks to promote the development of new antibiotics against gram-negative bacteria. Juvabis is still in the pre-seed stage, working from Zurich University, though now, everything is set to move quickly. The company expects to be fully funded by the end of the year, with the first product scheduled to move to clinical trials as early as next year.

Until then, much work still needs to be done. CEO Hobbie, is especially on the job 24-7, but he tackles it with humour. “With a start-up, you need funding for hiring people, but you need manpower to maximise the chances of getting funding,” he says. “It is a Catch-22.” 

How are you going to change the world?

We are going to save lives
by bolstering the treatment options
for infectious disease. 


Company Profile

Juvabis GmbH
Founded in 2015
Based in Zurich
CEO: Sven Hobbie
www.juvabis.com

Hipromine – A creepy crawly business

Researchers are scouring the oceans and soils to get their hands on new bio-active compounds and nutrients. An unexpectedly productive source might be closer than we think: in those little bugs many consider a pest. Polish start-up Hipromine is using insects to produce everything from fish food to antimicrobials.

Damian Józefiak

Some coincidences are too peculiar not to be true. When HiProMine was looking for a place to open their R&D facility, they ended up on an old family farm of their co-founder Damian Józefiak. Here, HiProMine’s insect armada would churn out bio-active compounds for use in feed, cosmetics, and pharmaceuticals. The name of the place? Robakowo, literally Bugsville. “HiProMine has brought the bugs back to Bugville,” Józefiak, an Associated Professor at Poznan University of Life Sciences, says with a grin. Beetles, crickets, cockroaches – around 30 species live on HiProMine’s farm today.

It all started one country over, at a symposium on poultry nutrition in Germany. Talk turned to using insects as an alternative in poultry feed. After all, bugs produce high-quality proteins that can easily match up those from soy or fish, and they are produced in a more sustainable manner. The idea stayed with Józefiak, and only grew from there. 

Apart from being diligent suppliers of proteins, insects are an abundant source for compounds pharmaceutical companies are hunting for. The six-legged creatures create enzymes and fats with properties that cosmetics companies find highly appealing. Insect droppings also make perfect fertilisers. 

Józefiak saw a business opportunity –  after all, he is an entrepreneur as well as a researcher and had founded companies before. In early 2015, he managed to secure pre-seed funding from Startup Hub Poland and Giza Polish Ventures. Two months later, the Polish National Centre for R&D joined the backers and HiProMine was founded. Józefiak considers himself lucky to have found financiers. “In Poland, it is hard to find investors who understand the business, and who appreciate it will take years before a company becomes profitable.”

Big run on bug products

That is why HiProMine is focused on becoming profitable in the short term. Collaborations with the livestock industry show that the demand is there, and, for the products, going through the roof. “Actually, we cannot produce enough of the high-quality proteins suit the requests coming in from all corners of the world. That is why our next step is to scale up.”

Longer term, the projects become more varied. For instance, HiProMine collaborates with M.A.R.S., which develops research stations for space exploration. “You cannot keep a cow in space,” says Józefiak. “But insects...they are robust, they are versatile. They can get rid of waste and produce proteins and fats good enough to eat.”

Biopharmaceuticals are also in the cards. Some insects provide novel antimicrobials, for example. So, when will the first insect-born medicine hit the shelves? Józefiak laughs. “Maybe it’s not so far off,” he says. “Recently, I was in Switzerland to discuss a collaboration with a pharma company. I cannot talk about specifics, but this is definitely one of the directions we are pursuing.”

For Józefiak, it seems incredible that many people find using insects as a resource in any way unusual. “It is not new or strange,” he points out. “It is happening on every farm, in every park and every forest. HiProMine is just converting it to a controlled process.” 

Eligo Bioscience - A sniper among shotguns

In the face of rising resistances, scientists around the world are racking their brains on how to keep bacterial pathogens in check. Eligo Bioscience has found the perfect tool in the genome editing technology CRISPR/Cas9. With it, they are creating ultraprecise anti biotics that will leave the human microbiome intact.

Xavier Duportet, CEO Eligo Biosciences

Perhaps it’s true what they say and people who love their work don’t need hobbies. “I do have an ant farm,” says ­Xavier Duportet a little apologetically. “I’ve had one since I was little.” Ants aside, the young synthetic biologist and entrepreneur spends a lot of time in the lab, in the office, on the road. And with success: only one year after its foundation, his company has accumulated an astounding amount of fame.
It all started in 2013 across the Atlantic: Duportet, then a PhD student at MIT and INRIA, and his colleague David Bikard from Rockefeller University tried to selectively eradicate bacteria with the help of the brand new CRISPR/Cas9 technology. Together with Timothy Lu, MIT professor for Biological Engineering, and Luciano Marraffini from Rockefeller Uni, they felt they had a solid foundation to spin off a company – back home in France.

To get initial funding, Duportet, the newly minted CEO, got creative and applied for awards and to competitions. A big chunk came from the ‘Worldwide Innovation Challenge’ which was launched in December 2013 by the French government. It netted Eligo an award, and €200,000 – enough to get the company off the ground. This year, Eligo has already raised €2m in seed investments from Seventure Partners, and another €400,000 from Business Angels. Investors seem happy to invest. “They can tell our vision has promise,” ­Duportet assures.
Kill the bad, keep the good

Eligo’s method employs the CRISPR/Cas9 technology that makes it very easy to identify and modify strands of DNA. It inserts a pair of “genomic scissors” into a bacteriophage capsid which acts as a transport vehicle. Inside the bacteria, the Eligo­biotics (as they have been nicknamed) search out unique gene sequences and cut them up, effectively destroying the microbes. Thus, Eligo­biotics can be highly specific. For example, they can find and destroy just the virulent or resistant strains, leaving the microbiome largely intact. A huge difference to customary antibiotics, which target bacteria indiscriminately and thus do long-time damage to the beneficial and harmful alike. “We are like snipers. If we kill the bad strains, the good strains can flourish.”

And eligobiotics are not bent on killing, either. It is also possible to find bacteria that are a danger to human health and turn them into harmless variants. Currently, the company is developing two lead candidates in gut and skin applications. A stopover, nothing more. “In the long run, we want to churn out a drug a day based on the platform we are developing,” Duportet stresses. “There would be countless applications for that technology. We could nip antibiotics resistance in the bud!”
Duportet is not the type to let grass grow under his feet. Parallel to Eligo, the scientist turned businessman runs ­Hello Tomorrow, a non-profit business accelerator for science start-ups, which he founded three years ago. Among other awards, the 27-year-old has won French Innovator of the Year by the MIT Technology Review. He has been portrayed in Le Monde and La Tribune. Has the fame gone to his head? “I don’t think so,” Duportet says with a grin. “Who has time for that?”

As far as he is concerned, Eligo still has a long way to go. Duportet’s dream is to be able to hone the microbiome to perfection. “Research shows that many diseases are driven by the human microbiota. Just imagine what we could do if we could engineer microbiomes! We could change healthcare for good.”

How are you going
to change the world?

We are going to put a
check on widespread
diseases by finetuning
the microbiome.

Company Profile

Eligo Bioscience S.A.S.
Founded in 2014
Based in Paris, France
CEO: Xavier Duportet
Web: www.eligo-bioscience.com

Tilt Biotherapeutics - Express to solid tumours

Solid tumours have long resisted cellular immunotherapy-based treatment attempts. A Finnish oncologist feels certain he has found a way to get to the heart of the cancer. He founded Tilt Biotherapeutics to ensure his oncolytic virus therapy gets to the patient in record time.

Akseli Hemminki, CEO Tilt Biotherapeutics Ltd

“Immunotherapy can work, and it will work. I have seen it work in patients, and I am certain of it,” Akseli Hemminki states. If it was up to him, his technology would be available to patients tomorrow, and not a day too soon. Three years ago, the professor of oncology founded Tilt, and its lead product, an oncolytic virus, has made rapid progress towards the clinic. The first clinical trials are scheduled for 2017. “For me, this seems very, very slow,” Hemminki admits.

The scientific rationale for the founding of Tilt Biotherapeutics Ltd had been growing for years, Hemminki explains. In an advanced therapy access programme, he had already treated more than 200 patients, and he saw that oncolytic viruses had the potential to enable successful T-cell therapy. Hemminki subsequently armed an oncolytic adenovirus with immunostimulatory cytokines interleukin 2 (IL-2) and Tumour Necrosis Factor alpha (TNFα). In several studies (doi: 10.1371/journal.pone.0131242, 10.1158/2326-6066), he and his team from Helsinki University’s Gene Cancer Group showed that this technology could do something other immunotherapy approaches could not: make T-cells fight solid tumours. It combines oncolysis with TNFα and IL-2 to remove the tumour’s ability to suppress an immune response and activate T-cells locally. The virus is injected directly into the tumour, where it replicates resulting in systemic effects. This oncolytic virus became the first product of Tilt, TILT-123. “The outcome we had observed in patients treated with oncolytic viruses was so compelling that a new company was the logical next step.”
Full speed ahead

It was not the first company Hemminki launched. Back in 2008, he was one of the founders of Oncos, another developer of oncolytic viruses created as part of his research at Helsinki University. Seven years later, Oncos merged with Norwegian Targovax. Most would consider Oncos a success story, yet Hemminki was not entirely satisfied. “In 2008, I was happy to advise and be CSO, but in 2013, I wanted to see if my own vision worked.” Key to his vision was to have the patient at the centre of the research – thus his impatience to get products to the market fast. And so, Tilt Bio­therapeutics was born, Hemminki at the helm, CEO and CSO rolled into one.

The start was all but easy. Initial financial support came from Hemminki himself, friends and family. There is hardly any venture capital available for Finnish biotechs, Hemminki explains. One of the few VCs that do invest in life sciences in this region, Lifeline Ventures, eventually came onboard. Tilt has managed to raise around €4m, from Lifeline Ventures, Business Angels, EU grants, and the Finnish government’s funding agency TEKES.

Hemminki, who plays bass guitar in his spare time and loves to excercise, says he has always been passionate about his research. But even his dedication has bounds, he found. “Over the last year, everything has been happening quite rapidly.” The last six months saw additions to the Tilt team every other month or so. “It is a good thing that I am not a micromanager,” he grins. “Instead, I try to get people excited about their work. And it is working well – I have a great team!”
Oncolytic viruses are a hot topic in immuno-oncology, Hemminki knows. But he does not fear the competition. “There are not many companies out there with our scientific background and  experience from human patients,” he says. “Our position in this field is unique.”

How are you going
to change the world?

We will cure cancer,
plain and simple.

Company Profile

Tilt Biotherapeutics Ltd
Founded in 2013
Based in Helsinki, Finland
CEO: Akseli Hemminki
Web: tiltbio.com

Glycemicon – A delectable find

How are you going to change the world? – We are going to develop an early-stage mechanism to counter the onset of diabetes – the epidemic of our time.

Nadja Mrosek, CEO Glycemicon

The growing social and financial threat of diabetes is keeping healthcare insurers and politicians up at night. Swiss researchers have found a way to possibly ward off the disease before it manifests. A nutriceutical may be the last bulwark against overeating and underexercising.

“It was a textbook spinoff,” says Nadja Mrosek. Researchers from the Swiss Federal Institute of Technology (ETH) in Zurich happened across a molecule that effected the development of fat cells. They went looking for the inhibitor of the molecule, and found it. With the help of a serial entrepreneur, the scientists then founded a company. “Obviously, founding a company is never a picnic,” laughs CEO Mrosek. “But all in all, it went smoothly.”

The Swiss start-up Glycemicon targets one of the major diseases of our times: diabetes. “It’s an epidemic,” said Mrosek. In a society where overeating is the norm and getting sufficient exercise the exception, diabetes type 2 runs rampant. “It used to be an old people’s disease. Today, even young children acquire diabetes,” Mrosek explains. Yet, it still takes a while for the disease to develop, and that is where Glycemicon steps in. In prediabetic patients, fat cells are often enlarged, and sensitivity to insulin is reduced.

Elemental for this process is RORγ, which in turn is inhibited by tetrahydroxylated bile acids (THBA), a bile acid that occurs naturally in humans and in various food products. When THBA is given to mice, it blocks ROR γ activity. Thus, it promotes the formation of new, smaller fat cells and restores insulin sensitivity.

Intriguingly, that holds true even if the mouse continues to eat a high-fat diet. Overall, the mouse’s weight stays the same. “The higher number of fat cells does not equal more fat overall,” says Mrosek. “However, the small fat cells are much more sensitive towards insulin.” 

It took six to found

When two ETH professors Erick Carreira and Christian Wolfrum and two researchers discovered the blocker, the foundation of a company to bring the tech to market was the natural next step. Strengthening the founding team were Mrosek herself and Peter Harboe-Schmidt, start-up coach at the Swiss federal innovation agency Commission for Technology and Innovation (CTI) who had already co-founded SpiroChem and Xigen Pharma. The two were hooked right off the bat.

Initially, the funding came from the founders’ own pockets, but that money was soon supplemented by the startup competition Venture Kick and a CTI grant. The ETH, as well, offers support to its spin-outs. “Having the infrastructure to do proof of concept is a great boon to a fledgling company,” Mrosek knows.

Meanwhile, the company has managed to raise €4m. Enough to get them through preclinical studies. There is currently another fundraising round under way to finance clinical trials, which are scheduled to start in 2017. Not quite a pharmaceutical drug, the compound will get to patients as a so-called nutraceutical. Medical foods, a certain form of nutraceuticals, can be prescribed by a physician, and patients will have to be monitored by their doctor, similar to regular drugs. But with a little luck, the road to the market is slightly less rocky. The safety of the naturally occurring compound in particular is unlikely to be an issue, Mrosek believes. “So far, THBA has shown an excellent safety profile. We are not worried.”

In 2019, Mrosek hopes, the product will be ready to get to patients. “We have a completely novel mechanism on hand,” she says. “There is nothing comparable on the market at the moment.”

Company Profile

Glycemicon AG
Founded in 2013
Based in Technopark Aargau, Brugg, Switzerland
CEO: Nadja Mrosek
Web: www.glycemicon.com

Immunethep - Banishing bacteria

Long-standing research by Porto University has shown that infection-causing bacteria rely on a particular method to circumvent the immune system. On this scientific basis and backed by a catalyst company, Immunethep was founded to take away the microbes’ bag of tricks.

Pedro Madureira, CSO Immunethep

Pedro Madureira had never considered founding a company and bringing his research to the market. “To be honest, the thought never occurred to me,” the young biologist laughs. At the time, Madureira was working on his postdoc in immunobiology at the University of Porto, researching a specific virulence mechanism in bacteria frequently causing sepsis in newborns. But when Bruno Santos contacted him with the idea to found a company, he was all for it. “I knew I had to do it,” says Madureira today.

The pathogen’s arsenal

He and his fellow researchers discovered exactly why bacterial infections can be so dangerous, sometimes leading to sepsis and even death. It is not only the bacteria themselves, Madureira explains. “In fact, our immune system could easily deal with the microbes.” But the micro­organisms have a secret weapon in their arsenal that prevents their host from fighting back. They shut down their host’s immune system.
Madureira and his team showed that the bacteria that most often cause sepsis in humans all excrete a particular molecule, glyceraldehyde 3-phosphate dehydrogenase or GAPDH for short. The enzyme stimulates the host’s production of immunosuppressive cytokine interleukin-10 (IL-10). The same virulence mechanism is employed by S. pneumoniae, E. coli, S. aureus and other pathogens. More than 95% of all sepsis cases in newborns are caused by these types of bacteria.

After they had decoded the mechanism, the researchers asked themselves whether introducing antibodies to GAPDH would block the infection-inducing properties of the bacteria. In a mouse model, Madureira and his team showed that pregnant mice vaccinated with ­GAPDH antibodies indeed produced offspring that was immune to Group B Streptococcus (doi: 10.1371/journal.ppat.1002363).
The team’s research caught the attention of the tech transfer company Venture Catalyst. Its co-founder and serial entrepreneur Santos saw the practical applications of Madureira’s research. After all, with more and more antibio­tics failing, there is an urgent need for novel approaches. “We desperately need viable solutions,” says Santos.

So with backing from Venture Catalyst, Santos suggested founding a company to bring a peptide-based immunotherapy to the market, and Madureira was hooked. Two years and a research grant were spent in order to find out if the theoretical knowledge could be translated into products fit for the pharmaceutical market. In 2014, the patent was secured and Immunethep SA took shape, with Madureira as Chief Scientific Officer and Santos serving as CEO. At the beginning of last year, Portugal Venture funded the fledgling company with more than €700,000.
Next on the list is the clinical development. “We would have liked to start out with a vaccine for pregnant women, as sepsis in neonates is most severe,” says Madureira. “But it simply makes more sense to lead with other applications.” Potentially fatal infections are also common in the elderly and patients with chronic illnesses like diabetes.

The business man and scientist agree that they will not start clinical tests without a strong ally. “We are already in talks with potential partners for the clinical development,” Santos says. Immunethep is also working on a bacterial infection antibody treatment, based on the same principle. Santos is confident that Immune­thep is going to thrive. “Everything is going exactly according to plan.”

How are you going
to change the world?

We will help solve one
of the biggest health
issues out there:
antibiotics resistance.

Company Profile 

Immunethep SA
Founded in 2014
Based in Cantanhede, Portugal
CEO: Bruno Santos
Web: www.immunethep.com