BOSTON--(BUSINESS WIRE)--Jan 6, 2026--
1910, the only AI-native biotech pioneering small and large molecule therapeutics discovery, today announced the publication of PEGASUS™, a multimodal AI model that achieves state-of-the-art accuracy in predicting and designing cell-permeable macrocyclic peptides.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20260106491372/en/
As featured in the Journal of Medicinal Chemistry, PEGASUS™ generated the first reported macrocyclic peptides containing more than two polar or charged fragments that demonstrate in vitro cell permeability, addressing a longstanding barrier in peptide drug design. The publication, titled “PEGASUS: Unlocking Polarity in Cell-Permeable Cyclic Peptides Using AI Models Built on Massively Parallel Biological Assays,” is available here.
Macrocyclic peptides are a promising therapeutic class with the potential for oral bioavailability and intracellular activity, yet efforts to design them have been constrained by the intrinsic difficulty of achieving cell permeability. And although AI could help overcome this barrier, progress has been limited by a lack of permeability data: existing datasets are scarce, sparse, and biased toward hydrophobic peptides, limiting the ability of AI models to generalize beyond a narrow chemical space.
PEGASUS™ overcomes these challenges by integrating three data modalities:
These combined datasets enable PEGASUS™ to learn permeability-relevant features across the full landscape of macrocyclic peptide chemistry, including regions with high polarity and charge that have historically been inaccessible to rational design. Access to this space is critical: limiting designs to low-polarity, hydrophobic peptides both increases the risk of off-target binding and in vivo toxicity, and shrinks the number of allowable peptide sequences by 96.7%, excluding peptide structures that more closely resemble existing FDA-approved therapeutics.
“In drug discovery, AI has always been constrained by the lack of large, high-quality biological datasets,” said Jen Asher, Ph.D., Founder and CEO of 1910. “PEGASUS™ closes that gap. By generating billions of experimental data points and integrating them with physics-based simulations, we built a model that expands the therapeutic possibilities for macrocyclic peptides.”
In retrospective validation, the PEGASUS™ predictive framework improved hit rates by 13.1% when used as a pre-synthesis filter, outperforming existing deep learning approaches. The integrated generative component (CycPepVAE) produced 33 macrocyclic peptides that resemble FDA-approved therapeutics in polarity and charge; among those synthesized and tested, four achieved permeability consistent with in vivo oral bioavailability – a first for peptides in this chemical regime.
“Cell permeability is essential for oral drug delivery, yet there remains limited chemical overlap between macrocyclic peptides that are routinely designed to be permeable and those that have achieved clinical success,” said Cole Baker, AI Research Scientist II at 1910 and lead author of the publication. “Our work helps bridge this gap to enable the design of orally bioavailable macrocyclic peptide therapeutics.”
Developed within 1910’s ITO™ platform, PEGASUS™ functions both as a high-accuracy predictor of permeability for large, polar macrocyclic peptides and as a generative system that designs drug-like peptide candidates with improved solubility, polarity, and charge characteristics.
The publication establishes PEGASUS™ as the most comprehensive AI system for macrocyclic peptide permeability to date and provides a blueprint for using multimodal data integration to advance new therapeutic modalities.
About 1910
1910 is the only AI-native biotech pioneering small and large molecule therapeutics discovery by integrating massive multimodal data, frontier AI models, and high-throughput lab automation into an infrastructure for AI-enabled drug discovery.
1910 Publishes PEGASUS™, a Multimodal AI Model that Engineers Novel Drug-Like Macrocyclic Peptides
U.S. Secretary of State Marco Rubio said he plans to meet with Danish officials next week after the Trump administration doubled down on its intention to take over Greenland, the strategic Arctic island that is a self-governing territory of Denmark.
President Donald Trump has argued that the U.S. needs to control the world’s largest island to ensure its own security in the face of rising threats from China and Russia in the Arctic, and the White House has refused to rule out using military force to acquire the territory.
Rubio told a select group of lawmakers that it was the administration’s intention to eventually purchase Greenland, as opposed to using military force.
The remarks, first reported by the Wall Street Journal, were made in a classified briefing Monday evening on Capitol Hill, according to a person with knowledge of his comments who was granted anonymity because it was a private discussion.
On Wednesday, Rubio told reporters that Trump has been talking about acquiring Greenland since his first term. “That’s always been the president’s intent from the very beginning,” Rubio said. “He’s not the first U.S. president that has examined or looked at how we could acquire Greenland.”
He was on Capitol Hill for a briefing with the entire Senate and House, where questions from lawmakers centered not only on the administration’s operation to capture former Venezuelan leader Nicolás Maduro — but also on Trump’s recent comments about Greenland.
Tensions with NATO members escalated after the White House said Tuesday that the “U.S. military is always an option.” Danish Prime Minister Mette Frederiksen warned earlier this week that a U.S. takeover would amount to the end of NATO.
“The Nordics do not lightly make statements like this,” Maria Martisiute, a defense analyst at the European Policy Centre think tank, told The Associated Press on Wednesday. “But it is Trump, whose very bombastic language bordering on direct threats and intimidation, is threatening the fact to another ally by saying ‘I will control or annex the territory.’"
Rubio did not directly answer a question about whether the Trump administration is willing to risk the NATO alliance by potentially moving ahead with a military option regarding Greenland.
“I’m not here to talk about Denmark or military intervention, I’ll be meeting with them next week, we’ll have those conversations with them then, but I don’t have anything further to add to that," Rubio said, telling reporters that every president retains the option to address national security threats to the United States through military means.
The leaders of France, Germany, Italy, Poland, Spain and the United Kingdom joined Frederiksen in a statement Tuesday reaffirming that the mineral-rich island, which guards the Arctic and North Atlantic approaches to North America, “belongs to its people.”
Danish Foreign Minister Lars Løkke Rasmussen and his Greenland counterpart, Vivian Motzfeldt, have requested a meeting with Rubio in the near future, according to a statement posted Tuesday to Greenland's government website. Previous requests for a sit-down were not successful, the statement said.
Thomas Crosbie, an associate professor of military operations at the Royal Danish Defense College, said an American takeover would not improve upon Washington's current security strategy.
“The United States will gain no advantage if its flag is flying in Nuuk versus the Greenlandic flag,” he told the AP. “There’s no benefits to them because they already enjoy all of the advantages they want. If there’s any specific security access that they want to improve American security, they’ll be given it as a matter of course, as a trusted ally. So this has nothing to do with improving national security for the United States.”
Denmark’s parliament approved a bill last June to allow U.S. military bases on Danish soil. It widened a previous military agreement, made in 2023 with the Biden administration, where U.S. troops had broad access to Danish airbases in the Scandinavian country.
Rasmussen, in a response to lawmakers’ questions, wrote over the summer that Denmark would be able to terminate the agreement if the U.S. tries to annex all or part of Greenland.
But in the event of a military action, the U.S. Department of Defense currently operates the remote Pituffik Space Base, in northwestern Greenland, and the troops there could be mobilized.
Crosbie said he believes the U.S. would not seek to hurt the local population or engage with Danish troops.
“They don’t need to bring any firepower. They don’t to bring anybody.” Crosbie said Wednesday. “They could just direct the military personnel currently there to drive to the center of Nuuk and just say, ‘This is America now,’ right? And that would lead to the same response as if they flew in 500 or 1,000 people.”
The danger in an American annexation, he said, lies in the “erosion of the rule of law globally and to the perception that there are any norms protecting anybody on the planet.”
He added: “The impact is changing the map. The impact I don’t think would be storming the parliament.”
French Foreign Minister Jean-Noël Barrot said he spoke by phone Tuesday with Rubio, who dismissed the idea of a Venezuela-style operation in Greenland.
“In the United States, there is massive support for the country belonging to NATO – a membership that, from one day to the next, would be compromised by … any form of aggressiveness toward another member of NATO,” Barrot told France Inter radio on Wednesday.
Asked if he has a plan in case Trump does claim Greenland, Barrot said he would not engage in “fiction diplomacy.”
While most Republicans have supported Trump’s statement, Senators Jeanne Shaheen and Thom Tillis, the Democratic and Republican co-chairs of the bipartisan Senate NATO Observer Group, have criticized Trump’s rhetoric.
“When Denmark and Greenland make it clear that Greenland is not for sale, the United States must honor its treaty obligations and respect the sovereignty and territorial integrity of the Kingdom of Denmark,” their statement on Tuesday said. “Any suggestion that our nation would subject a fellow NATO ally to coercion or external pressure undermines the very principles of self-determination that our Alliance exists to defend.”
Kim reported from Washington. Geir Moulson in Berlin, Mark Carlson in Brussels and Ben Finley in Washington contributed to this report.
FILE - Danish military forces participate in an exercise with hundreds of troops from several European NATO members in the Arctic Ocean in Nuuk, Greenland, Sept. 15, 2025. (AP Photo/Ebrahim Noroozi, File)
FILE - A plane carrying Donald Trump Jr. lands in Nuuk, Greenland, Jan. 7, 2025. (Emil Stach/Ritzau Scanpix via AP, file)
FILE - United States Homeland Security Advisor Stephen Miller reacts on the sidelines of the ASEAN Summit in Kuala Lumpur, Malaysia, Sunday, Oct. 26, 2025. (AP Photo/Mark Schiefelbein), File)
CORRECT THE ORDER OF SPEAKERS, FILE - Denmark's Prime Minister Mette Frederiksen, right, and Greenland's Prime Minister Jens-Frederik Nielsen, left, speak on April 27, 2025, in Marienborg, Denmark. (Mads Claus Rasmussen/Ritzau Scanpix via AP, File)
