Loopworm, a startup ramping up production at a facility in Bangalore capable of churning out 6,000 tons of insect protein meal a year, is now working in parallel on a platform using silkworms as mini bioreactors to produce recombinant proteins.
Founded by engineering graduates Abhi Gawri and Ankit Alok Bagaria in 2019, Loopworm raised $3.4m from investors including Omnivore and Titan Capital in September 2022, which it has supplemented with government grants, and is now gearing up for a series A round.
Rather than farming silkworms, Loopworm is using a dry rendering approach to process worms supplied by a network of established insect farmers into protein meal and oil, and plans to use the proceeds to help get its value-added business off the ground.
“We have an aggregator who collects from silkworm breeders and a few black soldier fly farmers,” Bagaria told AgFunderNews. “We are currently operating at about 10% capacity, but once we are at capacity we will be able to supply 500 tons a month of insect meal with a revenue potential of $15 million per year.
“This year, we’ll be closing at around a million dollars in revenues from supplying companies primarily in aquaculture [including CP Feeds and Ananda Group] and we have trials with many other companies in aquaculture and pet food.”
Transient expression systems for recombinant protein production
While most black soldier fly larvae processors are vertically integrated, handling breeding, farming and processing on one site, said Bagaria, “India already has a large number of silkworm producers and Bangalore is the silk hub of India, so it makes sense for us to focus on processing and building markets for value-added products rather than farming.
“What we are essentially trying to do is build a business that generates cash from animal nutrition, pet nutrition and value-added products, and then use that cash to scale our biorefinery approach.
“Insect meal or oil value is anywhere between $1.5 to $4 per kilo. But if you look at insect protein hydrolysates that can be used for pet nutrition and biostimulants [for crops], or higher value products such as [growth factors] EGF and FGF, you’re looking at completely different numbers.”
Rather than developing genetically modified silkworms that pass on on their capability to express recombinant proteins to their offspring, Loopworm is using transient expression systems. Here, silkworms are injected with viral vectors enabling them to produce the target proteins before they are processed a few days later, said Bagaria.
Commonly used in biotechnology to deliver genetic material into cells, viral vectors are modified viruses that can introduce specific genes into a host. In the case of silkworms, the vectors carry the genes necessary for the production of target proteins, effectively turning the silkworms into protein-producing factories for a short period, he said.
“Maybe you’re a diagnostics company and you need a viral antigen for the diagnostic kit that you are trying to manufacture. You give Loopworm a gene of interest that will go into our viral vector, we’ll inject the silkworms, and basically produce the antigen in our system, purify it, and sell it to you, like a CDMO approach.”
‘It’s actually super-scalable’
If this sounds tricky given that you have to keep injecting every generation of silkworms, he said, “It’s actually super-scalable, because once you know how to do it, it becomes an engineering problem. The silkworm pupae [the stage after the larval stage, just before they reach the adult moth stage] are on trays on a conveyor belt and we will have a microfluidics based approach to have them injected. A fixed volume of the viral recombinant virus goes into their bodies, and then we move to the next tray of silkworms.
“In four days or five days we’ll harvest them, homogenize them, and extract and purify the proteins. According to our calculations, it’s 40 times cheaper [than using a precision fermentation approach with engineered microbes to express the same recombinant proteins].”
Asked how novel this approach is, he said, “We are certainly not the first to do it, but we are the first one to optimize it so that we can commercialize it. Handling silkworm pupae is far easier than handling silkworm larvae as they are stationary, so it’s easy to inject them.”
While the downstream processing is much the same if you make recombinant proteins using microbes vs insects, he said, there is far less liquid to deal with in the latter production system. “If you have made the recombinant protein in a bioreactor, you have tons and tons of liquid whereas we have the same amount of protein concentrated [in the form of homogenized silkworms], which reduces the cost.”
According to Bagaria: “We have already filed one patent on this platform and we’re about to file a second one. To date, we have expressed green fluorescent protein [a protein found in jellyfish used as a marker in molecular and cell biology], FGF (fibroblast growth factor), TGF-beta (transforming growth factor), EGF (epidermal growth factor), and human serum albumin at significantly higher yield vs conventional cell culture systems.
“We have regulatory approvals from the Indian government to make these at R&D scale, but we are not authorized to sell them yet. If we raise our Series A funds, we’re planning to set up our own facility to do this commercially with a view to first sales in around two years.”
As selling these proteins for therapeutics would involve a lengthy regulatory process, it’s more straightforward to sell them for diagnostic kits, cosmetics, industrial chemicals, drug discovery or vaccine research, he said.
Funding: ‘We’ve achieved a lot with not very much [money] very quickly’
As for funding, he said, “We are still educating and creating awareness, but what is giving investors confidence is that we are already selling 50 tons of insect meal and oil to aquaculture feed manufacturers per month.
“We have a factory team in place, the certifications are secured, and we have a business development team in place. So we’ve achieved a lot with not very much [money] very quickly.
“At the same time, we have a layer of innovation and value addition on top of that with the protein hydrolysates and recombinant proteins.”
Funding rounds in insect agriculture, 2024 (US dollars):
- Entosystem (black soldier flies, Canada): $42 million
- Protix (black soldier flies, Netherlands): $40 million
- Tebrio (mealworms, Spain): $32.6 million
- FreezeM (black soldier fly neonates for breeding, Israel): $14.2 million
- Nasekomo (insect ag franchisor, black soldier fly neonate supplier, Bulgaria): $8.7 million
- Entocycle (enabling tech for insect ag, UK): $2.6 million
Source: Preliminary AgFunder data [disclosure: AgFunder is the parent company of AgFunderNews)