Circle Pharma, Inc.

As interest grows in the ability to leverage certain ringed molecules as drugs, Orbis Medicines has raised €90 million in new funding less than a year since the company unveiled its seed round. Orbis’ goal is to develop oral drugs for biologic targets using what are called macrocycles, which are rings made of the same building blocks as proteins but that are far smaller than typical proteins. The biotech’s focus is blockbuster targets that already have antibody drugs on the market, particularly in chronic diseases where patients might prefer to take a pill regularly rather than getting their treatment via injections or IV. The €90 million Series A was led by New Enterprise Associates. It included other investors such as Eli Lilly, Cormorant Capital, and the Export and Investment Fund of Denmark — a government-backed fund that backs Danish companies — as well as founding investors Novo Holdings and Forbion. While Orbis is still several years away from human studies, macrocycles have garnered renewed interest over the prospect of making small molecule drugs or pills, which are simpler to make and administer, that can go after highly specific targets usually only accessible using antibodies. Newly-minted CEO Morten Døssing said that the company went out after launching publicly to increase its seed round “a little bit.” The biotech announced a €26 million seed round from Forbion and Novo Holdings in February. “There was a significant amount of interest, and then that spurred this discussion, ‘Well, if we are raising, why don’t we just raise for something more substantial?’” said Døssing, who served as executive chair of Orbis’ board for the past three years as a partner at Novo Holdings, the investment arm of Novo Nordisk’s parent foundation. Macrocycles have long been the basis of drugs, including antibiotics and antifungals, but most were based on existing macrocycles found in nature. Startups developing these next-generation macrocyclic drugs are now leveraging newer technologies including high-throughput screening and machine learning to engineer and design different peptide rings. Orbis’ science comes from Sevan Habeshian and Bicycle Therapeutics co-founder Christian Heinis out of the Swiss Federal Institute of Technology in Lausanne. It’s also working with another biotech called Vivtex to screen the oral bioavailability of drugs. Orbis is using unnatural amino acids, drawing from a library of some 400 fully synthesized building blocks as opposed to the 20 protein building blocks found in nature. “The chemical diversity is much greater, but in a much smaller footprint,” said Døssing, noting that macrocycles using natural amino acids are typically eight to 12 amino acids in size, meaning they are large and not ideal for oral drugs. He added that Orbis is looking at targets primarily in immunology at this point, but noted that there’s interest in developing oral peptide drugs for cardiometabolic conditions — a category that includes obesity. He pointed to AbbVie’s recent $200 million acquisition of Nimble Therapeutics , a biotech that is likewise developing oral peptide drugs in immunology. Other macrocycle startups include Vilya — its name comes from “The Lord of the Rings,” and it was launched by Nobel Laureate and protein design pioneer David Baker and ARCH Venture Partners — and Circle Pharma, which last year raised a $54 million Series D . Merck last year also signed a small macrocycle deal with Unnatural Products. Orbis plans to use part of its Series A to build out a team in Copenhagen, where the company that also has a team in Switzerland announced a new site in October. Døssing said that Orbis currently has 15 employees but hopes to have around 40 workers by the end of the year.

Dive Brief:Orbis Medicines, a European biotechnology startup, has raised 90 million euros, or about $93 million, in a Series A round announced Monday that will fund development of oral peptide drugs.Orbis is focused on macrocycles, a class of medicines that blends the strengths of small molecule and biologic drugs. The company aims to construct oral macrocycles that work against disease targets already validated by successful injectable medicines, but hasnt specified which it will go after.Incubated by Novo Holdings, Orbis emerged from stealth last year with 26 million euros in seed funding. The company was co-founded by Sevan Habeshian and Christian Heinis, the latter of whom helped start Bicycle Therapeutics, a publicly traded macrocycle drug developer.Dive Insight:Biologic medicines are a huge and still-growing segment of pharmaceutical research. A report last year from Future Market Insights noted the market for biologics was expected to reach about $521 billion in 2024 and could more than double by 2034.Yet biologics are generally delivered by injections or infusions, making them less convenient than small molecule drugs that are taken orally. That limitation leaves an opportunity for drugmakers able to develop medicines that pack the power of biologics into a pill. Switching people from injections to oral drugs could also help with patient adherence, said Morten Graugaard Dssing, Orbis CEO and a partner at Novo Holdings.Morten Graugaard Dssing is a partner at Novo Holdings specializing in seed investments, and now CEO of Orbis Medicines.Permission granted by Orbis MedicinesOne solution that has gained traction in recent years are macrocyclic peptides, which are a newer twist on macrocycle drugs, dozens of which have won approval. Shaped like rings, macrocyclic peptides can slip into cells the way small molecules do, but are big enough to interfere with protein interactions, making them possible solutions for some undruggable targets. They also appear resistant to degradation by enzymes or stomach acids.Those characteristics may mean macrocyclic peptides retain biologic-like potency while administered orally, a goal Orbis and other companies like Vilya and Circle Pharma hope to achieve.Pharmaceutical companies have shown interest, too. Merck & Co. has in late-stage testing an oral macrocyclic peptide drug for heart disease it claims could rival marketed injectable medicines.There's a need for better technologies around making truly orally available macrocycles for a lot of these hard-to-drug targets and transitioning from biologics into an all-oral format, Graugaard Dssing said.Orbis work is based on research from Heinis and Habeshian that showed how to produce a library of macrocyclic compounds and engineer them so theyre smaller, and better absorbed by the body than existing drugs.The company hasnt disclosed which diseases or targets it is pursuing. Graugaard Dssing said Orbis platform could be used for any target and is right for any indication, broadly.Orbis' Series A round was led by NEA. Lilly Ventures, Cormorant Asset Management, Novo Holdings, Forbion and the Export and Investment Fund of Denmark were also involved. '

The funds will support the development of Orbis’ pipeline of next-generation oral macrocycle drugs. Credit: sanjeri via Getty Images. Denmark-based biotech Orbis Medicines has raised €90m ($94m) in a Series A funding round to advance the development of its next-generation orally dosable macrocycle drugs, which the company calls ⁿCycles. The financing was led by New Enterprise Associates (NEA) with participation from new investors, including Eli Lilly, Cormorant, and the Export and Investment Fund of Denmark. The company – which launched in February 2024 with $28m (€26m) in seed funding from Novo Holdings and Forbion – is focused on creating oral alternatives to injectable biologics, particularly for chronic diseases, according to Orbis CEO Morten Graugaard. Orbis aims to address longstanding challenges in developing macrocycles – large ring-like compounds made from amino acids or other building blocks – into oral drugs. These compounds have strong therapeutic potential due to their ability to bind selectively to biological targets such as the immunosuppressant cyclosporine and the antibiotic erythromycin, but have historically faced issues with stability, absorption, and bioavailability. The biotech’s initial focus is on programmes against targets that are already validated by blockbuster biologic drugs to provide oral alternatives for patients who might prefer to take a pill rather than having treatments injected or by intravenous (IV) infusion. In September 2024, Orbis announced a research collaboration with Vivtex to leverage its gastrointestinal robotic interface system (GI-ORIS), a platform designed to assess gut permeability, which is crucial for determining the oral bioavailability of Orbis’ ⁿCycles portfolio. A month later, the company announced a significant expansion of its operations and capabilities by joining Symbion’s new biotech startup hub in Fuglebakken, Copenhagen. The macrocycle space is gaining some momentum across the pharmaceutical industry. MSD is in late-stage clinical development for macrocyclic peptide drug MK-0616 (enlicitide decanoate) targeting PCSK9 in patients with hypercholesterolemia. The candidate, which is currently being investigated in several Phase III studies, is forecast to generate $1.5bn by 2030 if approved, according to GlobalData. GlobalData is the parent company of Pharmaceutical Technology. MSD further displayed its interest in the space by entering a $220m deal with Unnatural Products (UNP), an AI-based biotech developing macrocyclic candidates. Competitors such as Circle Pharma have also made progress, raising $54m in a Series D round in July 2024 and signing a deal with Boehringer Ingelheim in October. “We have a clear strategy for rapid value creation that leverages the unique capabilities of our ⁿGen platform and are excited to advance this important new class of drugs for patients,” said Graugaard in the announcement accompanying the funding.