New Blue Ocean in Pharmaceuticals: Why Are Industry Giants Betting Big on Oral Cyclopeptides?
I. Technological Breakthrough: Solving the Dual Dilemma of Oral Administration and Targeted Therapy
Why are industry giants so excited? Because oral cyclic peptides theoretically solve two long-standing pain points in drug development.
Traditional small-molecule drugs are easy to administer orally, yet they struggle to bind to complex and flat protein surfaces. In contrast, biological agents such as antibodies feature precise targeting but are generally only available via injection, resulting in low patient compliance.
Cyclic peptides possess superior structural rigidity and metabolic stability compared with linear peptides due to their cyclic structure. More importantly, through sophisticated chemical modification and rational design, scientists can now endow them with satisfactory oral bioavailability.
For example, LUNA-18 from Chugai Pharmaceutical, a cyclic peptide targeting intracellular KRAS protein, achieves an oral bioavailability of 21%–47% without the use of special formulations. Acting like a custom-designed key, it can precisely insert into protein binding sites that are inaccessible to conventional small molecules, thereby holding great promise for tackling historically "undruggable" targets.
II. Clinical Frontline: Multiple Candidate Drugs Enter Critical Stages
The potential of this technology is being rapidly validated in clinical practice. At present, multiple oral cyclic peptide programs have advanced swiftly from the laboratory into clinical development. The table below summarizes some representative drug candidates that have attracted widespread attention.
It can be seen from the table that the R&D of oral cyclic peptides is concentrated in fields traditionally requiring injectable therapies and has entered a harvest period, as exemplified by JNJ-2113 and MK-0616. Meanwhile, for more challenging targets such as KRAS, the R&D pathway is undergoing rapid trial-and-error and iterative optimization.
III. Future Outlook: Reshaping the Landscape of Chronic Disease and Tumor Therapy
The rise of oral cyclic peptides heralds a major shift in the future form of drugs and therapeutic models.
In chronic disease areas such as cardiovascular and metabolic disorders, oral cyclic peptides are expected to deliver the therapeutic efficacy of biologics that currently require frequent injections, in the form of capsules or tablets patients can take at home.Merck’s Enlicitide serves as a prime example; it has the potential to completely transform the treatment experience for hyperlipidemia and significantly improve patient compliance.
In the field of oncology treatment, oral cyclic peptides represented by LUNA-18 are challenging the most intractable intracellular targets. Meanwhile, bicyclic peptide–drug conjugates have demonstrated potential for precision delivery, maintaining potent antitumor activity while reducing the toxicity associated with traditional antibody-drug conjugates.
Looking ahead, artificial intelligence is gaining in-depth involvement in this field. From AI-guided compound design and large-scale parallel synthesis to direct biological screening, intelligent platforms are greatly boosting the efficiency of cyclic peptide drug discovery and optimization, accelerating the entry of more candidate drugs into clinical development.
Faced with this new blue ocean that may reshape the landscape of the pharmaceutical industry, China’s innovative players are actively participating.
Haisco currently takes the lead; its molecule HSK47388 has obtained approvals in both China and the United States, and its Phase II clinical trial application for the treatment of psoriasis in China has also been approved.
Jiangsu Hansoh’s relevant molecular patents have been published, and its candidate is expected to enter clinical development soon.
In addition, Xianggen Biotech’s SG-6001 is still in the preclinical stage, with an IND filing projected for 2026.
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