Unnatural Products Raises $45M to Build Oral Macrocyclic Peptides for 'Undruggable' Targets

Unnatural Products, a biotech company developing orally delivered macrocyclic peptides, closed a $45 million Series B financing on March 16, 2026. The round was led by The Venture Collective (TVC), with participation from argenx, Droia Ventures, Merck Global Health Innovation Fund, ARTIS, First Spark Ventures, and existing investors including LongeVC.

Who They Are and Why It Matters

Founded in Santa Cruz, California, and led by CEO Cameron Pye, Unnatural Products is building a platform to engineer synthetic macrocyclic peptides — ring-shaped molecules that occupy a unique pharmacological sweet spot. They are large enough to bind protein surfaces with the specificity of an antibody, yet small and stable enough to survive the gastrointestinal tract and be absorbed orally.

The company's thesis: roughly 85% of the human proteome remains "undruggable" by conventional small molecules or monoclonal antibodies. Macrocyclic peptides can potentially reach these targets — including protein-protein interactions, allosteric sites, and intracellular receptors that have resisted decades of drug discovery efforts.

The Novartis Connection

The Series B follows a potential $1.7 billion research collaboration with Novartis, announced earlier in 2026. That deal — one of the largest peptide-platform partnerships in recent memory — gave Novartis access to Unnatural Products' macrocyclic peptide engineering capabilities across multiple therapeutic areas, including cardiometabolic, inflammatory, and oncology targets.

The size of the Novartis deal underscores how seriously Big Pharma is taking the macrocyclic peptide modality. For years, these molecules were considered academic curiosities — difficult to synthesize at scale and hard to optimize for oral delivery. Advances in computational chemistry and high-throughput screening have changed that calculus.

Pipeline and Next Steps

Unnatural Products plans to use the Series B to advance its internal pipeline of macrocyclic peptide candidates into preclinical and early clinical development. The company has not disclosed specific therapeutic targets for its internal programs, but its Novartis collaboration spans cardiometabolic, inflammatory, and oncology indications.

The funding also supports continued investment in the company's peptide engineering platform, which combines synthetic chemistry, computational design, and biological screening to generate orally bioavailable macrocyclic candidates faster than traditional medicinal chemistry approaches.

A Growing Oral Peptide Ecosystem

Unnatural Products joins a wave of companies proving that oral peptide delivery is not a niche concept — it is becoming a mainstream drug modality. In the past month alone, the FDA has approved ICOTYDE (an oral cyclic peptide for psoriasis) and Foundayo (an oral GLP-1 agonist for obesity), while Pinnacle Medicines raised $89M for its own oral peptide platform. The investment thesis is clear: the era of peptides-require-injection is ending.