Macrocyclic peptide therapeutics are gaining serious momentum, and the new partnership between Novartis and Unnatural Products proves it. Announced on February 18, 2026, this collaboration focuses on advancing macrocyclic peptide therapeutics for cardiovascular disease.
The agreement could reach up to $1.8 billion in upfront payments, milestones, and royalties. Clearly, large pharmaceutical companies now see macrocyclic peptide therapeutics as a viable platform for high value chronic disease targets.
This alliance highlights a shift in cardiovascular drug discovery. Traditional small molecules and biologics have limitations. However, macrocyclic peptide therapeutics aim to bridge that gap. Novartis is betting that this modality can unlock difficult targets that were previously considered undruggable.
Macrocyclic peptide therapeutics sit between small molecules and biologics in size and function. Typically composed of 5 to 14 amino acids, these molecules usually range from 500 to 2000 Daltons. Because of their cyclic structure, they often show improved stability compared to linear peptides. As a result, they resist enzymatic degradation more effectively.
Unlike small molecules, macrocyclic peptide therapeutics can target complex protein protein interactions. These interactions are central to many cardiovascular pathways. Meanwhile, compared to antibodies, macrocycles may offer improved tissue penetration. In some cases, they may even allow oral administration.
This balance makes macrocyclic peptide therapeutics especially attractive for chronic diseases. Cardiovascular conditions require long term treatment. Therefore, improved safety, stability, and patient convenience matter significantly.
Unnatural Products uses an AI enhanced discovery platform to design macrocyclic peptide therapeutics. The system integrates computational modeling, rapid synthesis, and direct biological screening. Consequently, it can explore chemical space more efficiently than traditional methods.
AI plays a key role here. Instead of random screening, algorithms guide molecular design toward potency and selectivity. This approach increases the probability of identifying macrocyclic peptide therapeutics suitable for clinical development. It also reduces time and cost during early discovery.
For additional background on AI drug discovery, see our internal guide to AI powered peptide platforms.
By combining computational precision with laboratory validation, macrocyclic peptide therapeutics can be optimized for permeability and target engagement. That is particularly important for intracellular cardiovascular targets.
Cardiovascular disease remains a leading global cause of mortality. Despite many approved therapies, unmet needs persist. Certain signaling pathways remain difficult to modulate with conventional drugs. This is where macrocyclic peptide therapeutics may offer an advantage.
Novartis has a strong cardiovascular portfolio, including Entresto, which has generated multi billion dollar annual revenue. Therefore, expanding into macrocyclic peptide therapeutics aligns with its strategic focus. If successful, this partnership could redefine cardiovascular treatment paradigms.
For more analysis on cardiovascular pipelines, visit our cardiovascular drug development coverage page.
Importantly, the specific target in this collaboration has not been publicly disclosed. However, it is described as involving challenging protein interactions. That suggests a differentiated mechanism rather than incremental innovation.
The Novartis and Unnatural Products collaboration is currently in the preclinical stage. Novartis will lead IND enabling studies and manage clinical development if the program advances. This includes manufacturing, regulatory submissions, and commercialization.
Financially, the deal structure includes up to $100 million in upfront and early milestone payments. Additional payments could bring the total to $1.8 billion if development and commercial milestones are achieved. Tiered royalties in the low double digit range are also included.
Such financial commitment validates the promise of macrocyclic peptide therapeutics. Large pharmaceutical companies do not allocate this level of capital lightly. Therefore, the agreement reflects strong internal confidence in the modality.
A useful comparison is Merck’s oral PCSK9 macrocyclic peptide candidate, MK 0616. That program advanced into Phase 3 for atherosclerosis after demonstrating significant LDL cholesterol reduction in Phase 2 studies. Even with modest oral bioavailability, high potency enabled meaningful clinical impact.
This precedent strengthens the outlook for macrocyclic peptide therapeutics in cardiovascular care. It shows that oral delivery of macrocycles is achievable. More importantly, it confirms that regulators and clinicians are open to this modality.
You can read our detailed breakdown of MK 0616 in our oral macrocyclic peptide analysis article.
The growing pipeline activity suggests that macrocyclic peptide therapeutics are transitioning from experimental chemistry to validated drug class.
The next milestone for this collaboration will be submission of an Investigational New Drug application. An IND submission includes preclinical safety data, manufacturing details, and clinical trial protocols. If approved, Phase 1 studies can begin.
Regulators will likely evaluate pharmacokinetics, immunogenicity risk, and manufacturing consistency. Because macrocyclic peptide therapeutics combine features of peptides and small molecules, they require careful characterization. Nevertheless, previous approvals of cyclic peptide drugs provide regulatory precedent.
Manufacturing scalability is another key factor. Cardiovascular therapies are often prescribed long term. Therefore, cost effective production will influence commercial viability.
The cardiovascular market is competitive. Many mechanisms already have established treatments. As a result, new macrocyclic peptide therapeutics must demonstrate clear differentiation.
This differentiation may come from improved safety, enhanced selectivity, or oral administration. For patients, oral therapy can significantly improve adherence compared to injectables. Consequently, convenience alone can drive adoption.
Furthermore, targeting previously inaccessible protein interactions may unlock entirely new pathways. That would provide both clinical and commercial advantage.
In the short term, attention will focus on preclinical progress and IND clearance. Any disclosure of the specific molecular target will attract investor and scientific interest. Early safety data will also be critical.
In the long term, success depends on clinical validation. Macrocyclic peptide therapeutics must show meaningful improvement over existing therapies. If they achieve that, milestone payments and royalties will follow.
More broadly, this partnership reinforces macrocyclic peptide therapeutics as a growing pillar in drug development. The modality is no longer niche. Instead, it is entering mainstream pharmaceutical strategy.
Macrocyclic peptide therapeutics represent a strategic evolution in drug discovery. They combine structural precision with functional versatility. Moreover, partnerships like Novartis and Unnatural Products demonstrate growing institutional confidence.
If clinical data supports the early promise, macrocyclic peptide therapeutics could reshape cardiovascular treatment. For now, this $1.8 billion alliance marks an important milestone in the maturation of the field.
All human research must be overseen by a qualified medical professional.
All human research MUST be overseen by a medical professional.
