Bi-XDC: The 'Two-Handed' Peptide Drug Conjugate Platform Enabling Precision Targeting and Enhanced Efficacy

If the cell therapy sector has been as hot as a blazing fire in recent years, the peptide sector can be described as lukewarm.

Peptide drugs have a long history. Since the first clinical application of insulin in 1922, the development of peptides over the past century has not been rapid. As of this year, approximately 118 peptide-based drugs have been marketed, accounting for only about 2% of all new drugs. The peptide sector has rarely experienced intense competition among investors vying for investment opportunities; rather, it has remained relatively lukewarm.

However, the peptide sector is by no means lacking in star products. Annual sales of several GLP-1 drugs in the peptide field, such as liraglutide and semaglutide, have already exceeded $10 billion. If traditional insulin drugs are also included in the category of peptide therapeutics, the annual sales volume would reach approximately $30–40 billion. Furthermore, tirzepatide, a dual GLP-1/GIP receptor peptide agonist approved by the FDA only this May for Eli Lilly, is projected to achieve peak annual sales of $25 billion, underscoring the superior efficacy advantages of dual-target therapies.

CBP’s Bi-XDC technology also incorporates peptide-based approaches. Similar to the characteristics of the peptide therapeutic sector, CBP is an innovative pharmaceutical company that has pursued steady and pragmatic growth. Over the six years since its establishment, CBP has witnessed both the heyday of antibody-drug conjugates and the downturn in the biopharmaceutical market. Throughout these cycles, the company has remained calm and low-profile, focusing diligently on technological development while pursuing steady progress.

Unlike companies in hot sectors that prioritize “speed,” CBP stands out in the peptide space as a model of “stability.” Achieving stability first requires robust core technologies and an experienced, highly competent team, enabling the company to maintain a solid foothold in a dynamic market.

Dr. Huang Baohua believes that the field of peptide drugs requires a technological revolution.Traditional peptide drugs and peptide-drug conjugates (PDCs) offer numerous advantages, including rapid tissue penetration and rapid systemic clearance. However, compared with antibody drugs and antibody-drug conjugates (ADCs), they still exhibit certain limitations, such as poor stability, weak targeting capability, and limited resistance to competition from endogenous ligands. These shortcomings have constrained the development of peptide drugs and PDCs.

Bi-XDC technology breaks through the design limitations of traditional peptide drugs and Peptide-Drug Conjugates (PDCs), addressing their shortcomings while preserving the advantages of peptide therapeutics. The core of this technology lies in its dual-targeting synergistic effect: Dr. Huang vividly likens Bi-XDC to equipping a drug with two hands, whereas traditional PDCs have only one. Many tasks that are unattainable for one-armed individuals, such as rock climbing, become effortless for those with two hands. Consequently, Bi-XDC achieves therapeutic effects that are beyond the reach of conventional peptide drugs.

Bi-XDC is a multifunctional peptide-drug conjugate. Unlike traditional peptide therapeutics, the peptide moiety of the Bi-XDC molecule (e.g., a TRPV6 antagonist ligand) can either directly engage target receptors to exert pharmacological effects or serve as a targeting guide to deliver the drug payload to specific cells. Meanwhile, peptide-like toxins (such as MMAE) can function as the payload.

Moreover, the ingenious design of Bi-XDC enables dual-targeting synergistic effects to be manifested at multiple levels, thereby enhancing its druggability.

First, Bi-XDC effectively enhances target specificity and affinity through the pairing of two ligands, achieving a synergistic “1+1>2” effect. This approach transforms two previously undruggable single targets into an ideal dual-ligand target pair, significantly improving the specific targeting capability of peptide drugs and thereby enabling the targeting of a broader range of previously undruggable targets.

Bi-XDC can also effectively resist competition from endogenous ligands, addressing the challenge of long-term tumor accumulation for peptide drugs. Most receptors targeted by peptide drugs have their natural endogenous ligands, and competitive binding by these endogenous ligands reduces the accumulation of peptide drugs within tumors. Bi-XDC resolves this issue through a dual-targeting synergistic effect. Experimental data indicate that due to competition from endogenous ligands, only 10% of single-ligand peptide drugs retain receptor binding, whereas under the same conditions, more than 80% of Bi-XDC remains bound to the receptors. Meanwhile, Bi-XDC molecules are comparable in size to conventional peptide drugs, enabling them to rapidly penetrate tumor tissue, undergo swift cellular internalization to exert cytotoxic effects, and be quickly cleared from the systemic circulation, similar to most peptide drugs.

Bi-XDC technology has received preliminary clinical validation. CBP-1008 is the first drug in the Bi-XDC pipeline. It employs a dual-ligand system targeting FOLR1 and TRPV6, delivering a microtubule inhibitor as its payload, with primary indications for breast cancer and ovarian cancer. It has demonstrated superior efficacy and safety compared to investigational drugs targeting similar pathways. CBP-1008 is currently in Phase II clinical trials. Concurrently, CBP-1018 is also undergoing clinical evaluation. It utilizes a dual-ligand system targeting FOLR1 and PSMA, with primary indications for prostate cancer and lung cancer, and preliminary efficacy has been observed in its Phase I safety assessment trial.

Bi-XDC technology features exceptional scalability. CBP has developed three major technology platforms based on Bi-XDC, including the BEST™ platform, the C-PROTAC platform, and the Chronic Disease platform. The BEST platform primarily addresses targeted tumor delivery; the C-PROTAC platform focuses on the targeted delivery of PROTAC drugs; and the Chronic Disease platform enables efficient tissue-targeted delivery. CBP drives drug iteration through upgrades to its technology platforms. In addition to the two first-generation drugs mentioned earlier, the next-generation (second-generation) Bi-XDC products include CBP-1019, CBP-1029, and CBP-1039, which are conjugated with topoisomerase inhibitors. Their primary indications include pancreatic cancer, colorectal cancer, and other solid tumors. IND applications for CBP-1019 were submitted in both China and the United States this year, with the first patient dosing expected to be completed in 2023.

CBP was established in 2016 and settled in Suzhou BioBAY. Since its inception, the company secured exclusive Series A financing from Allpharma Capital. Beyond the direct impact of its Bi-XDC platform (initially known as the Ligand-Drug Conjugate [LDC] technology platform for multi-target ligands), the founder and the continuously evolving core team have laid a solid foundation of experience for the company’s development. In the field of drug development, such extensive expertise enables startups to avoid many common pitfalls.

Dr. Huang Baohua, the company’s founder and CEO, was admitted to Peking University in 1978, where he majored in catalytic chemistry for his undergraduate degree and shifted to bioorganic chemistry for his master’s studies. In line with the choices of most scientists of that era, Dr. Huang pursued further education abroad after graduation. In 1987, he went to the United States to pursue a Ph.D. in biochemistry, formally launching his career in drug research. In early 1995, to gain hands-on experience in new drug development, Dr. Huang conducted postdoctoral research in the laboratory of Dr. Stephen W. Fesik at Abbott, following the completion of his doctorate. Dr. Fesik is the inventor of SAR-by-NMR fragment-based drug design. During this period, Dr. Huang published multiple articles in Nature and its subsidiary journals.

Dr. Shao Jun, a close friend of Dr. Huang Baohua from their undergraduate days at Peking University, began conducting research on peptide drugs at the Shanghai Institute of Organic Chemistry in 1982, making him one of the earliest scholars in China to study peptides. Also in 1987, by chance, he moved to Germany to pursue his doctoral degree. In 1992, Dr. Shao joined Vanderbilt University in the United States as a postdoctoral fellow, where he engaged in research on the conjugation of peptides and macromolecules. In late 1995, Dr. Shao also joined Abbott, focusing on process development and GMP manufacturing of peptide drugs.

In a remarkable coincidence, two former classmates and close friends reunited at Abbott more than a decade after leaving Peking University. This enduring bond led Dr. Huang Baohua to immediately think of his friend Dr. Shao Jun, who had many years of experience in peptide drug development, when he was upgrading the team at CBP Pharmaceuticals over ten years later.

Following his tenure at Abbott, Dr. Baohua Huang joined Tularik, an emerging innovator in novel drug development (later acquired by Amgen), where he established the company’s fragment-based drug design laboratory. He subsequently pursued an MBA at Cornell University, marking his entry into the business sector.

2011 marked a significant turning point for Dr. Huang Baohua. With over two decades of experience in drug design and business, Dr. Huang believed he was well-positioned to make meaningful contributions to the industry. Coinciding with this period, Adcetris, the world’s first second-generation antibody-drug conjugate (ADC), received approval from the U.S. FDA. Dr. Huang was greatly inspired by this milestone, recognizing that ADCs, often referred to as “biological missiles,” had resolved many druggability challenges. This breakthrough renewed the potential for developing numerous previously stalled “semi-finished” projects. It was against this backdrop that the concept of bispecific ligand-drug conjugation (bi-XDC) technology was conceived.

CBP was established in 2016 and settled in the Suzhou Industrial Park. Around 2019, Dr. Huang Baohua recognized that the team needed to be upgraded in line with the company’s growth, and thus invited his former classmate and close friend, Shao Jun, to join the CBP team.

By this time, Dr. Shao Jun had amassed extensive experience in the research and development, manufacturing, regulatory registration, and quality management of peptide drugs. He had previously held positions at major Chinese and American pharmaceutical companies, including Hisun Pharmaceutical, Yangtze River Pharmaceutical Group, Hengrui Medicine (USA), Procter & Gamble Pharmaceuticals, and AbbVie.

A drug design expert and a peptide drug expert, both of whom have accumulated extensive networks and resources over several decades. With the addition of clinical expert Dr. Teng Yan, business expert Mr. Yan Mingming, and other professionals, along with Dr. Wang Guitao who had previously joined CBP, the core team of CBP was officially formed. This marks CBP’s formal entry into an accelerated phase of development.

CBP’s solid technical foundation and the team’s robust capabilities have shielded it from significant impact during the market downturn.

CBP’s partners include CDMO service providers such as WuXi STA, Asymchem, and Ambeed. Principal Investigators (PIs) collaborating with CBP are based at Peking University Hospital, Fudan University Hospital, and the Cancer Hospital of the Chinese Academy of Medical Sciences. Despite having no marketed products to date, CBP invests approximately RMB 200–300 million annually in clinical development.

Similar to some companies that chose to “cut costs and increase efficiency” during the market winter, CBP reduced its team from 130 to around 100 employees in response to market shifts amid the financial crisis, thereby conserving capital.

During the Series B funding round last year, valuations were severely inflated, and CBP spent considerable time on financing matters. Dr. Huang Baohua, CEO of CBP, stated that the company could have initiated fundraising earlier, advising biotech firms to make decisive moves, raise as much capital as possible, and complete financing rounds at the earliest opportunity.

Fortunately, CBP, which has advanced steadily and methodically, has made substantial financial preparations. Dr. Huang studied financial budgeting and planning during his MBA program and previously managed the profit and loss (P&L) for a biotech company, giving him a solid financial background. He has shared with peers that bank credit facilities should be secured proactively when a company is performing well, as they serve as a critical operational tool: providing working capital during emergencies and facilitating mergers and acquisitions (M&A) during periods of strong performance.

Beyond the philosophy of proactive preparedness, what is more important is that while peers are feeling the chill of the biopharmaceutical winter, CBP has continued to strengthen its clinical development, thereby sustaining a steady flow of funding even in these challenging times.

Addressing the industry’s widespread concerns about the survival of biotech firms, Dr. Huang and Dr. Shao believe that encountering difficult periods is an inevitable part of growth, akin to adolescence in human development—a necessary stage in life. Meanwhile, for both the industry and the capital markets, this represents a critical period for returning to rationality after the rush of entrepreneurial fervor.

When discussing the future of the peptide field and CBP, Dr. Huang and Dr. Shao expressed strong confidence. In the realm of peptide drug development, beyond the currently popular indications for diabetes and weight loss, they are particularly optimistic about the application of peptide drugs in the central nervous system (CNS) sector. Examples include treating depression, managing pain, and anti-aging through signal modulation, thereby replacing potentially addictive drugs such as morphine and dopamine.

Furthermore, the integration of peptides with other pharmaceutical domains enables various drug molecules to function more effectively through peptide carriers. The peptide moiety of such molecules not only exerts its own pharmacological effects but also facilitates the efficient delivery of other pharmacophoric structures via the targeting action of peptide ligands.

CBP’s R&D platform and pipeline are also actively expanding to include candidate drugs with other molecular structures. On this basis, CBP is accelerating its overseas license-out of drug rights, seeking collaborations with major international pharmaceutical companies to leverage their market expertise in driving CBP’s commercial growth.

Regarding the upcoming financing plans, Dr. Huang Baohua stated, “If the data from the ramp-up phase of our second drug next year are favorable (which currently appear promising), and if we make progress in business development (BD) deals, we should launch a pre-IPO funding round next year, preparing for an IPO in 2024.”