Insilico Medicine says the Boston region’s large talent pool and critical mass of potential business development partners have convinced the discoverer and developer of drugs based on generative artificial intelligence (AI) to relocate its headquarters there from New York City and Hong Kong.

Insilico has moved the first dozen of an eventual 25 staffers to a 3,000-square-foot suite at 1000 Massachusetts Avenue. The company will retain operations in New York at the Cure, the Deerfield-owned life sciences and healthcare campus at 345 Park Avenue South.

“We have relocated ultra-high level pros, basically the brains of the operation,” Insilico founder and co-CEO Alex Zhavoronkov, PhD, told GEN Edge. “Most of the target selection, product selection strategy, business development strategy, toxicology, some high level strategic medicinal chemistry are going to be there—and of course, partnering.”

In an interview on the sidelines of the recent Biotechnology Innovation Organization (BIO) International Convention held in San Diego, Zhavoronkov said Insilico wanted to address one of its priorities, namely scaling up operations in the United States, within a region that has attracted major hubs for global biopharmas. Boston/Cambridge has been a longtime leader of GEN’s nationally-quoted A-List of Top 10 U.S. Biopharma Clusters, though last summer the region narrowly lost the top spot to the San Francisco Bay Area after a falloff in venture capital financings reflecting 2022’s post-pandemic bear market.

1000 Massachusetts Avenue is a four-story, 105,217-square-foot office building owned by Intercontinental Real Estate, a Boston-based real estate investment management firm.

Zhavoronkov said Insilico’s new headquarters will also include “a really nice showroom.”

“We are going to launch a few more software products and maybe, just maybe, hardware products which will allow you to compute on site. That’s why having a showroom is very important,” Zhavoronkov added.

The company has yet to disclose details on its planned future software and possible hardware products, though Zhavoronkov said the software will be a “confidential compute” offering designed to let biopharma users design drugs using AI but without storing their data in the cloud.

Software solutions accounted for just 6.6% or $3.362 million of Insilico’s total $51.18 million in revenues last year. Software revenues more than doubled year-over-year, zooming 124% from $1.499 million in 2022.

“My target for this year is substantial: At least 15% of sales has to be coming from software,” Zhavoronkov said. “I want to continue with software plus drugs, because we are not a biotech. Once you are going to just focus on biotech, you are no longer an AI.”

He said Insilico is looking to reposition its business development efforts by innovating on “really ultra-high quality data packages”: “Every program, particularly for the United States, needs to be of ultra superior quality so that when pharma looks at it, they need to be extremely impressed,” Zhavoronkov said. “When you are selling cookies to the cookie makers, they know how to make cookies, right?”

Fabergé eggs of AI

He likens his company’s development of AI drug candidates to the jeweled Fabergé eggs created by Peter Carl Fabergé’s House of Fabergé in Saint Petersburg, Russia. Between 1885 and 1917, nearly 70 such eggs were crafted, of which 57 survive—including 46 of the 52 “Imperial” eggs made as Easter gifts for the wives and mothers of Russian czars Alexander III and Nicholas II.

“We want to become a Faberge factory where we take the egg, design and properly decorate it, then go and take it for the show so people can bid for it,” Zhavoronkov explains.

Just as Faberge egg customers customize their selections with a jewel maybe some music, Insilico envisions customizing its generative AI drug candidates, then putting them up for bids to eager biopharma customers.

“We want to be the super high-end jeweler who puts all of those assets on display for purchase. Our job is, at the very least, to offer best in class chemistry,” Zhavoronkov said. “If anyone who is looking at the asset tells me, I actually saw a better molecule somewhere else in this target class, I would be very disappointed, and I might deprioritize the program.”

“I need to make sure that they are at least best in class and then for many, I have first in class, so there is nothing to compare. You’d have to compete on biology,” Zhavoronkov added. “We are taking those Faberge eggs to the prom, so to speak, right?”

Insilico has built a pipeline of 31 programs aimed at 29 targets. Seven programs have received IND approval from the FDA and advanced into clinical phases, starting with lead candidate INS018_055, a small-molecule TRAF2- and NCK-interacting kinase (TNIK) inhibitor that is in Phase IIa trials for idiopathic pulmonary fibrosis (IPF) in the United States (NCT05975983) and China (NCT05938920). The company expects to release its first Phase II data for INS018_055 later this year.

On Tuesday, Insilico announced that it completed enrollment of 71 patients at 29 sites across China in the Chinese Phase IIa study, designed to evaluate the safety and tolerability of oral INS018_055 for up to 12 weeks in adults with IPF compared to placebo. and that the company is preparing to launch a Phase IIb proof-of-concept study in 2025 to explore the efficacy and further safety of INS018_055.

The American Phase IIa study, designed to enroll 60 patients, is “ongoing and actively accruing patients,” Insilico’s chief medical officer Sujata Rao, MD, stated.

An inhalable form of INS018_055 for IPF is in the IND-enabling phase, as is a program to develop the candidate as a treatment for kidney fibrosis.

In a paper published in Nature Biotechnology, a team of 30 researchers led by Zhavoronkov detailed how they used generative AI to discover INS018_055, with a novel target discovered by Insilico’s target identification engine, PandaOmics, and a novel molecular structure designed by its generative chemistry engine, Chemistry42. Both are specific-function platforms within the company’s AI platform, Pharma.AI.

“Golden target”

“We’re constantly expanding the indications. I think that this is a golden target, and people should be looking at this not as fibrotic target, but also as a cancer target as well. We want to ensure that it gets established as a fibrotic agent or a cancer agent,” Zhavoronkov said.

Zhavoronkov led a team of seven researchers from Insilico and academic partner ETH Zurich in publishing a paper in Trends in Pharmacological Sciences concluding that TNIK was a suitable target for treatments against several aging-related diseases, including fibrosis, cancer, obesity, and Alzheimer’s disease.

“TNIK signaling appears to converge on four critical hallmarks of aging, cellular senescence, deregulated nutrient sensing, chronic inflammation, and altered intercellular communication. TNIK’s contribution to these processes implicate it as a possible contributor to aging-related pathology, particularly by promoting conditions like cancer and metabolic dysregulation,” the researchers observed. “An interesting hypothesis would be whether TNIK dysregulation contributes to the aging process itself or is a consequence of it.

How did Insilico come to identify several potential indications for TNIK?

“We used aging research as a platform for target discovery,” Zhavoronkov explained. “We didn’t just use AI. We were looking for common mechanisms that work in aging and disease. We think that if something works in multiple areas of aging, multiple hallmarks of aging, it should be powerful enough to work in multiple diseases. Now, independent groups have implicated TNIK in Alzheimer’s and neurodegeneration.”

Alzheimer’s has been a notoriously challenging disease for which to develop drugs; a landmark Cleveland Clinic study pegged at 99% the failure rate of drug candidates targeting the memory-robbing ailment. But Eisai and Biogen won FDA approval last year for the anti-amyloid antibody Leqembi® (lecanemab-irmb), and last week an FDA advisory panel recommended agency approval of Eli Lilly’s amyloid plaque-targeting therapy donanemab.

In obesity, INS018_055 would compete with a growing number of newer treatments led by glucagon-like peptide 1 (GLP-1) receptor agonists such as Novo Nordisk’s semaglutide, marketed for type 2 diabetes treatment as Ozempic® and for obesity as Wegovy®—as well as Eli Lilly’s tirzepatide, marketed as Mounjaro® for type 2 diabetes and as Zepbound® for obesity.

Last year a research team from University of Copenhagen and research partner institutions reported associations of TNIK variants with blood glucose, HbA1c, body mass index, body fat percentage, and feeding behavior in a paper published in Science Advances: “These results define an untapped paradigm of TNIK-controlled glucose and lipid metabolism.”

Using genetically modified Drosophila and mouse models, the researchers studied the role of TNIK in obesity and metabolic dysfunction. In experiments with mice, researchers eliminated the gene for TNIK, which enabled the mice not to gain weight, no matter how much high-fat food they were fed.

“Like Schwarzenegger”

“The beauty of this paper was that if you look at mice on high fat, high sugar diets, TNIK wild type, they look so muscly, like Schwarzenegger. Inhibiting TNIK makes them thin. Now we are figuring the biology, the why. We don’t know, nobody knows yet,” Zhavoronkov said “We are very, very happy that it worked on obesity in that group.”

Insilico’s most recent clinical candidate is ISM3412, a treatment for methylthioadenosine phosphorylase (MTAP) deleted cancers, which account for 15% of all cancers. In April, Insilico won FDA IND approval to begin a Phase I multicenter, open label study (NCT06414460) of ISM3412, a small molecule selective methionine adenosyltransferase 2A (MAT2A) inhibitor designed to target cancers with MTAP deletion. The study, which has not yet begun recruiting patients, is designed to assess the drug in patients with locally advanced and metastatic solid tumors.

Insilico is one of several companies focused on treating cancer by inhibiting MAT2A. Furthest along is Ideaya Biosciences with its Phase II candidate IDE397, while Servier has listed a MAT2A inhibitor, S95035, as being in Phase I/II development; a Phase I trial (NCT06188702) is now recruiting patients, according to

In addition to Cambridge, MA, and New York, Insilico has operations in:

  • Abu Dhabi, UAE, one of the company’s two hubs for its Pharma.AI scientific team
  • Hong Kong, which oversees Insilico’s R&D collaboration and software solution businesses.
  • Montreal, the company’s other hub for its Pharma.AI scientific team, and a business development location.
  • Shanghai, one of two sites where the company focuses on drug discovery, R&D collaboration, and business development.
  • Suzhou, China, home to Insilico’s wholly owned, generative AI-driven automated laboratory, launched in December 2022.
  • Taipei, the company’s other drug discovery and business development site.

Since its founding in 2014, privately held Insilico has raised more than $400 million, the company stated in an updated prospectus filed in March with the Hong Kong Exchange. The company has applied to the Exchange for approval to carry out an initial public offering (IPO). The company applied for a listing in June 2023 but allowed its application to lapse.

According to its updated filing, Insilico’s $51.18 million in 2023 revenue marked a 70% increase from the $30.147 million the company generated in 2022. Most of Insilico’s revenue, $39.022 million or 76%, came from pipeline drug development, which includes R&D and out-licensing of some drug candidates to biopharmas, while another 17% or $8.976 million came from drug discovery services, such as collaborations with biopharma partners to discover targets associated with diseases using Pharma.AI, identify those targets, and conduct R&D.

Insilico is one of two AI-based drug developers that have sought to go public through the Hong Kong Stock Exchange in recent months.

XtalPi launched its IPO on Friday, raising HKD $989.3 million ($126.8 million)—the third largest IPO raised to date this year on the Hong Kong exchange, and the first to list there under a new rule designed to attract “strategic” startups in industries that include biotech. Established in 2015 by three postdoctoral physicists at MIT, XtalPi also has a U.S. site in Cambridge, MA, as well as Chinese sites in Beijing, Shenzhen, and two in Shanghai.

“Leveraging our Pharma.AI platform and automated laboratory, we plan to advance our pipeline in a rapid and focused manner. We plan to utilize our network of over 40 CROs [contract research organizations] and CDMOs [contract development and manufacturing organizations] for our nominated preclinical candidates and advance those programs into the clinical stage,” Insilico stated in its IPO. “We expect to advance our internal discovery-stage programs and nominate four to five additional preclinical candidates in the next 12 months.

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