French biotech Generare speeds up hunt for new drugs by cloning natural molecules

French biotech startup Generare has closed a €5 million seed round (around $5.5 million at current exchange rates) to step up development of what it touts as a highly scalable approach to identifying promising compounds for drug discovery that already exist in nature. It’s focused on sifting for molecules that are produced by microorganisms but could be repurposed as treatments in humans.

Such molecules were once a rich source of drug discovery using early chemistry-based discovery techniques. The cardinal example is Penicillium’s antibiotic effect that was spotted after the mold happened to grow in a lab petri.

But finding less common molecules that could become the basis for new antibiotics, anticancer or other drugs requires a new kind of approach that can sift through large amounts of genetic material, says Generare co-founder and chief science officer Dr Vincent Libis.

“We are really interested in discovering chemical molecules produced by bacteria,” he explains. “They encode them in genes — which is basically [a] genetic recipe for [a] molecule. And so what we are hunting for is these genetic recipes. And our technologies are all focused on detecting novel genetic recipes and then manipulating them to obtain the molecules that they encode.”

“So [it’s] a lot of molecular biology to sequence DNA, to cut and paste DNA, and bioinformatics, or computational biology, to triage which one of these genetic recipes you want to go after first, and what do you expect the molecules that they encode are gonna be like.”

Drug hunting ‘on a planetary scale’

Founded in October 2022, the startup says it’s devised a technique that relies upon cloning and biosynthetics to break up the genetic material of microorganisms into millions of fragments to allow for speedier analysis — making it much quicker and easier to identify new molecules of interest.

Although still young for a biotech, Generare has already been able to identify more than 1,000 “genetic recipes”, as it calls the molecules of interest, since it began operating its discovery platform 12 months ago. Part of this early haul includes more than 100 “novel” chemical molecules with a handful that have antibiotic activities.

The approach it’s taking depends on scaling this up to cast a very wide net so it can crunch through masses of genetic material to find the minority of useful compounds hiding amid the dirt.

“Because these molecules are very successful, the more you find, the more chances you have of finding the next billion dollar drug, basically,” CEO and co-founder Guillaume Vandenesch tells TechCrunch. “It’s like you’re playing a board game and you’re trying to get a double six — but you’re throwing like 100 or 1000 dice at a time.

Generare is drawing on around a decade of work by Libis in genetic engineering which underpins its approach. Essentially the method involves taking DNA extracted from a microorganism that codes for a natural molecule, putting the genetic recipe into a lab host and producing (he calls it printing) the molecule in a test tube — “where you can really interrogate it”.

The startup says this method allows it to explore the entire chemical diversity of microbes. It also talks about its platform enabling scanning for novel genetic recipes “on a planetary scale” as a result of how efficiently it’s able to conduct the search.

“If you want to explore the entire map of natural molecules that are produced by microbes you need to have a technology that is extremely efficient, extremely cost efficient,” stresses Vandenesch.

DNA sequencing has been used in drug development for around 15 years, per Libis. More recently, about five years ago, a wave of startup began using DNA sequencing to mine natural molecules specifically. Generare is aiming to improve on earlier efforts by accelerating the analysis of the genetic material.

It’s patenting its approach and what Libis refers to as “the most mathematically efficient implementation” of it.

“What we bring to the table, the really differentiating technology, is at which scale we can do this,” he tells TechCrunch. “We really have orders of magnitude faster ability to get from a genetic recipe — unknown — to a molecule in a test tube. And this is enabled by our, let’s call it, cloning technology, which just pieces out the strands of DNA that contains this genetic recipe very quickly into a laboratory strain so that we can express and then characterize the activity.”

He likens the process to removing a blindfold which reveals the genetic diversity of the molecules. By doing that at scale the startup can organize and group compounds into groups which looks the same; groups which make already patented molecules (which it avoids); and groups which look like they might encode promising molecules. “So you have a much more orderly search that is enabled by this — by using DNA as a guide,” he adds.

“I worked for pretty much 10 years on finding a solution to the speed at which we could take a piece of DNA and bring it to another laboratory strain, which was the bottleneck of this whole process,” Libis continues. “We stumbled on a solution — where we gained orders of magnitude faster ability to transfer these genes. And so that’s what motivated the start of the company.

“That’s our really differentiating element… So it’s just a lot of research,” he adds.

Digging in the dirt

Soils are Generare’s initial choice for scaling this natural molecules search on account of how many microorganisms they contain and the ancient “war” of survival/supremacy that’s been waged between the countless microscopic entities living in the ground. It encourages the development of novel chemical protections against things like bacteria or fungi or other threats.

“In the soil, you have 1,000 species [of bacteria] per gram and it’s on the whole planet,” says Libis, adding: “This war is [waged] through chemical weapons — which are these molecules — and so they’ve been ‘innovating’, the war has been going on for hundreds of millions of years.”

Identifying more of the “really powerfully chemistry” that’s evolved through natural processes, whereby one biological entity develops a tool “to mess with the biology of another organism”, and putting it to “good use” in the human body is Generare’s core mission.

“These bacteria evolved for 400 million years. They’ve probably invented a lot of things that could be very valuable to us,” adds Vandenesch. “There’s so many different organic organisms that are adapted to so many different conditions… basically there is a treasure trove that’s ready to be discovered.”

Beyond soil microbes, the startup says marine environments offer another vast hunting ground where it can apply its approach.

“Really the exciting thing, in a way, is we know only 3% of all these chemicals that are made by microbes,” Libis adds.
“[Humanity has] only discovered 3%… so a large reservoir still needs to be explored.”

“We know that we only found 3% because we see 97% more genes than we see known molecules.”

Industrializing a decade of research

So far Generare has secured an agreement with French biotech company Aurobac Therapeutics to pilot its technology. It’s a company that’s focused on developing new antibiotics.

The new seed funding will be used to industrialize its gene transfer approach so it can figure out how to scale up by turning its lab-based processes into more of a factory-style production line — that’s as lean and streamlined as possible.

“The vision is to go planetary scale exploration of what used to be the most successful modality in the history of pharma and agrochemistry as well,” says Libis. “But basically, the next two years, we are just trying to make it ready for the prime time — where we go after the whole world, basically.”

Its business model will see it engaging in “co-development” of drugs with pharmaceutical companies — with the goal of earning a return on any “valuable bioactive molecules” it has brought to the attention of its partners.

Given the long timescales involved in bringing new drugs to market, Generare confirms the startup will be looking to raise further funding, likely in a couple of years.

“Our dream is like, in 18 months, we have the blueprints of the faculty, you know, meter per meter, exactly what each step is doing and what equipment is needed,” he adds. “Then that’s what we will be fundraising for — to build this in real life.”

The company also believes its platform could also have applications in other sectors, such as supporting development of new agri-chemicals with natural molecules to replace traditional pesticides and insecticides. There could even be uses in the cosmetics industry. But its initial focus is on pharmaceuticals where there is a pressing need.

Antibiotics resistance is a growing problems so there’s a clear need to rethink drug discovery. However Libis also warns the key issue is the broken business model which needs governments to step in with subsidies if humanity is to avoid a full-blown crisis of treatment failure.

“Antibiotics are just a broken market,” he says. “Economically, it’s very hard to have a viable business model when you discover antibiotics. It’s such a commodity once you have them. And also, people don’t use the most powerful ones, so companies that discover them have a hard time getting back their R&D expenses. So what we need is, in fact, mostly a governmental answer — at the EU scale, at the US scale — that will inject some guarantee that the company that invests in R&D and antibiotics will get a return on their investment.”

“There’s hope,” he adds. “There’s the PASTEUR Act in the U.S. that might pass and offer this kind of guarantee, and the EU as well is working actively. But it’s really urgent that something happens there. So for now, we are taking the risk, and we managed to convince our investors that we should be working on this activity, that the landscape is going to change and that there’s going to be, like, subsidies to compensate. But it’s daily struggle.”

“For two years we will manage to bend their mind. But in five years, if nothing has changed at some point we will be forced to also refocus on more guaranteed indications.”

Investors in Generare’s seed include Teampact.ventures, Galion.exe and EU-backed VIVES Partners. Synbioven, Saras Capital and Better Angle also participated, along with a number of business angels. 

With so many molecules lurking somewhere out there waiting to be discovered, Generare doesn’t sound worried about competitors raiding nature’s treasures before its had a chance to apply its high scale sifting methodology. But it name-checks the likes of U.S.-based Hexagon Biosciences and LifeMine Therapeutics as playing in the same arena.