With New Funding, Orbis Medicines to Develop Oral Macrocycles as Alternative to Biologic Drugs

Editor's note: this story was originally published on BioPharmInternational.com.

Denmark-based biotech startup Orbis Medicines recently won major funding to support its pursuit of developing oral alternatives to current biologic drugs, which are primarily administered parenterally.

The company announced on Jan. 6, 2025 that it closed a Series A funding round of $94 million (€90 million), which will go toward development of Orbis’ pipeline of next-generation oral macrocycle drugs, which the company has termed “nCycles”. This latest funding round brings the total amount raised by the company to $121 million (€116 million).

Macrocycles bind to targets with higher affinity and selectivity than small-molecule drugs, but they have been historically challenging to develop as oral drugs. Orbis Medicines’ technology platform, nGen, systematically delivers macrocycle candidates—nCycles—that are optimized for oral bioavailability. It has been this lack of oral bioavailability that has hindered therapeutic development of this class of molecules in the past (1). The nGen platform comprises multiple proprietary integrated elements in a “lab in a loop” system. It starts with hit-finding libraries containing 100 billion compounds. Using automated chemistry, the platform can synthesize and analyze up to 100,000 distinct synthetic macrocycles in weeks, which allows the company to discover candidates with the right properties to enable oral dosing and intracellular targeting.

The company’s pipeline is initially focused on nCycle candidates aimed against targets validated by blockbuster biologic drugs, which are delivered by injection, a route of administration that is not favorable with patients. The biopharma industry has been bending its efforts toward developing alternative routes of administration for biologics that bypass the parenteral route, such as oral and inhaled biologic formulations (2). However, because biologics have more structural sensitivities than small-molecule drugs to factors such as pH and temperature, there are limits to their delivery, especially orally, such as degradation in the alimentary tract and an inability to overcome intestinal cell or mucosal barriers and first-pass metabolism (2). These limitations therefore open a path to alternative orally bioavailable drugs, such as nCycles.

“The Orbis Medicines team has impressed us with the data supporting nGen, which we believe is the world’s leading discovery engine for oral macrocycle drugs. We are thrilled to support not only their journey to the clinic, but also their longer-term vision as a leader in their field,” said Ed Mathers, partner, New Enterprise Associates (NEA), in the press release (1). NEA led the financing.

In addition to NEA as the lead financer, others that participated in the funding round include new investors Eli Lilly and Company, Cormorant, and the Export and Investment Fund of Denmark as well as founding investors Novo Holdings and Forbion. Morten Graugaard has been appointed as CEO of Orbis Medicines after having served nearly three years as executive chair of its board of directors.

“The company is advancing the potential of macrocycles by developing orally available nCycles—a format preferred by patients, physicians, and healthcare systems, particularly for chronic diseases,” said Graugaard in the release. “The interest we have received demonstrates the market appetite for nCycles as an oral approach to both validated biologic targets and targets undruggable by other modalities. 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.”

References

1. Orbis Medicines. Orbis Medicines Raises EUR 90 Million Series A Funding Round to Develop Pipeline of Oral Macrocycles. Press Release. Jan. 6, 2025.
2. Mirasol, F. Exploring Innovative Means for Biologics Delivery. BioPharm International 2024, 37 (8), 7–9.