French biotech startup Generare has announced a funding of 5 million euros (at current exchange rates) to step up the development of what it touts as a scalable approach to identifying promising compounds for drug discovery that already exist in nature. Closed a seed round of approximately $5.5 million. It focuses on screening molecules produced by microorganisms that have the potential to be repurposed as human treatments.
Such molecules were once a rich source for drug discovery using early chemistry-based discovery techniques. A major example is the antibiotic efficacy of Penicillium, which was discovered after the mold was accidentally grown in a Petri dish in the laboratory.
But discovering less common molecules that could form the basis of new antibiotics, cancer drugs, and other drugs requires a new kind of approach that can sift through large amounts of genetic material. It's necessary, says Dr. Vincent Libis, Generale's co-founder and chief scientific officer.
“We are very interested in discovering chemical molecules produced by bacteria,” he explains. “They encode them in their genes – it's basically [a] genetic recipe for [a] molecule. And what we're looking for are these genetic recipes. And all of our technologies are focused on detecting new genetic recipes and manipulating them to obtain encoded molecules. ”
“So [it’s] A lot of molecular biology to sequence DNA, cut and paste DNA, and a lot of bioinformatics and computational biology to triage which of these genetic recipes to pursue first; A lot of molecular biology is needed to determine what the molecules encoded are expected to do. Like. “
“Global” drug hunt
Founded in October 2022, the startup has devised a technology that relies on cloning and biosynthesis to break down microbial genetic material into millions of fragments, allowing for faster analysis and the creation of new molecules of interest. The company says it has made it easier and faster to identify people.
Although still young for a biotech, Generare has already identified more than 1,000 “genetic recipes” (as the company calls molecules of interest) since it began operating its discovery platform 12 months ago. is completed. Some of this early collection contained more than 100 “novel” chemical molecules, a small number of which had antibiotic activity.
The approach the research team is taking is whether they can scale this up and cast a very wide net, breaking up large amounts of genetic material and finding the few useful compounds hidden in the soil. It's taking place.
“These molecules have been so successful that basically the more we discover, the more likely we are to discover the next billion-dollar drug,” said Guillaume Vandenesch, CEO and co-founder. told TechCrunch. “It’s like playing a board game and trying to roll a double six, but you’re rolling 100 or 1000 dice at once.
Generare leverages Libis' nearly 10 years of research in genetic engineering to underpin its approach. Essentially, the method involves extracting DNA from a microorganism that encodes a naturally occurring molecule, putting that genetic recipe into a host in the lab, and producing the molecule in a test tube “where you can actually look it up,” he said. printing).
The company says this method allows it to explore the entire chemical diversity of microorganisms. He also talks about how the platform will enable scanning for new genetic recipes “on a global scale” due to how efficiently searches can be performed.
Generare co-founders Dr. Vincent Libis (left) and Guillaume Vandenesch Image credit: Generare
“If we want to explore the entire map of natural molecules produced by microorganisms, we need highly efficient and cost-effective techniques,” Vandenesch emphasizes.
According to Libis, DNA sequencing has been used in drug development for about 15 years. More recently, about five years ago, a wave of startups began using DNA sequencing to specifically mine natural molecules. Generare aims to improve on previous efforts by accelerating the analysis of genetic material.
The company has patented its approach and what Libis calls “the most mathematically efficient implementation.”
“What we bring to the table, the technology that really differentiates us, is how much scale can we do this?” he told TechCrunch. “We actually have the ability to go from an unknown genetic recipe to a molecule in a test tube orders of magnitude faster, and this is made possible by our so-called cloning technology. , we can very quickly cut out the DNA strand containing this genetic recipe into a laboratory strain and express and characterize its activity.”
He likens the process to removing blinders that reveal the genetic diversity of molecules. By doing this at scale, startups can organize and group compounds into similar-looking groups. Groups that make molecules that are already patented (and get away with it). and a group that appears to encode promising molecules. “So using DNA as a guide allows for a more orderly search,” he added.
“I've been working for nearly 10 years to find a solution to the speed at which you can take a piece of DNA and bring it into another experimental strain, and this has been the bottleneck of this whole process,” Ribis continues. “We came up with a solution that gave us the ability to transfer these genes orders of magnitude faster, and that's what motivated us to start the company.
“That's our real differentiator…so it's just a lot of research,” he added.
dig the soil
The search for this natural molecule takes into account the number of microorganisms contained in soil and the ancient “war” for survival/supremacy that has been waged between the countless microscopic entities that live underground. Generale's first choice for expansion. Facilitate the development of new chemical protection against bacteria, fungi, and other threats.
“There are 1,000 species of living things in the soil. [of bacteria] per gram, and that's across the entire planet,” Libis said, adding: [waged] Through chemical weapons (these molecules), and they continue to “innovate”, wars have continued for hundreds of millions of years. ”
They further identify a “very powerful chemistry” that has evolved through natural processes, allowing one biological entity to develop tools to “disrupt the biology of another” and make it “effective” within the human body. Generale's core mission is to utilize
“These bacteria evolved over 400 million years. They probably invented a lot of things that are very valuable to us,” Vandenesh added. “There are so many different organic organisms that are adapted to so many different conditions. There's basically a treasure trove at your fingertips.”
Beyond soil microbes, the company says the marine environment provides another vast hunting ground to which its approach can be applied.
“In some ways, what's really interesting is that we only know that 3% of all these chemicals are made by microorganisms,” Ribis adds.
“[Humanity has] Only 3% have been discovered…therefore, large reservoirs still need to be explored. ”
“We see 97% more genes than any known molecule, so we know we only found 3%.”
Industrializing 10 years of research
So far, Generale has secured a contract with French biotech company Aurobac Therapeutics to pilot its technology. The company is focused on developing new antibiotics.
The new seed funding will be used to industrialize the company's gene transfer approach, scaling it by turning the lab-based process into a more factory-style production line, one that is as lean and streamlined as possible. We can find ways to expand.
“The vision is to explore on a global scale what was once the most successful method in the history of pharmaceutical and agricultural chemistry,” says Ribis. “But basically, over the next two years, we're just trying to set ourselves up for a prime time where we're going after the whole world.”
The company's business model involves engaging in “co-development” of drugs with pharmaceutical companies, with the goal of profiting from “valuable bioactive molecules” that attract the attention of its partners.
Given that it takes a long time to bring new drugs to market, Generale acknowledged that the startup is likely looking to raise further funding within the next few years.
“Our dream is that within 18 months we will have a teacher blueprint for every meter, knowing exactly what each step is doing and what equipment is needed. That’s it,” he added. “That’s what we’re raising money for, to actually build this.”
The company also believes its platform has potential applications in other areas, such as supporting the development of traditional insecticides and new agrochemicals using natural molecules to replace insecticides. It could also be used in the cosmetics industry. But its initial focus is on medicines with urgent needs.
Antibiotic resistance is a serious problem and it is clear that we need to rethink drug discovery. But Libis also warned that the key problem is that the business model is broken, and that governments need to intervene with subsidies to avoid a full-blown crisis of treatment failure. .
“Antibiotics are just a broken market,” he says. “Economically, it's very difficult to have a viable business model if antibiotics are discovered. Once you have them, it's such a commodity. Also, people don't use the most powerful ones, so Companies that discover them will have a hard time recouping their R&D costs. So what we really need is to ensure that companies that invest in R&D and antibiotics get a return on their investment. Most of the responses are from governments at the EU and US scales.
“There is hope,” he added. “The US has the Pasteur Act that could pass and provide this kind of guarantee, and the EU is actively working on it as well. But it's really urgent that something happens there. So, So far, we have been able to convince investors that we should take the risk and engage in this activity, that the situation will change and that there will be subsidies and so on to cover it. It’s a daily struggle.”
“For two years, we will manage to bend their minds. But after five years, at some point, if nothing has changed, we will have to refocus on more robust indications as well. .”
Generare’s seed investors include Teamact.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 waiting to be discovered, Generale worries that competitors will raid nature's treasures before he has a chance to apply his large-scale sifting techniques. Apparently not. However, US-based companies such as Hexagon Biosciences and Lifemine Therapeutics have been named as playing in the same arena.