CDH17: The Next Claudin18.2? Emerging Target Attracts Global Drug Developers with Diverse Modalities
Hansoh Pharma
Pharmaceutical Research, Production, and Sales
© Amino Observation - Innovative Drug Team Original Production
Author | Zheng Xiao
CDH17 Target: From the Beginning of the Year to the End.
At the beginning of the year's AACR conference, the CDH17 target was arguably the most eye-catching presence, with nearly 20 preclinical molecules making their debut, presenting a competitive landscape akin to "a clash of the titans."
This is indeed the case. According to OncologyPipeline data, there are currently more than 30 CDH17-related molecules in development worldwide—not only have mainstream technology platforms such as ADCs, multi-specific antibodies, and CAR-T all entered the field, but subsequent companies are also continuously innovating, attempting to develop "improved" molecules. The level of competition within the field has reached new heights.
BD deals further fuel the fire in this field.
On October 17, Hansoh Pharma announced a collaboration agreement with Roche: Roche will obtain the global rights outside of China for the CDH17 ADC drug HS-20110. As consideration, Roche is required to pay an upfront payment of $80 million and up to $1.45 billion in milestone payments.
For a molecule still in Phase I clinical trials, such an upfront payment scale is already considered substantial.
From the current热度, BD deals in the CDH17 field may have just begun. So, can CDH17, like "Claudin18.2,"成就a group of companies?
/ 01 /
Similar Logic in Proprietary Medicine
CDH17 is regarded as the nextClaudin18.2。
CDH17 is a non-classical member of the calcium-dependent protein CDH superfamily. Current research has found that it is expressed to varying degrees in various tumor tissues, including gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, and cholangiocarcinoma.
Although some studies have shown that the high-level expression of CDH17 is closely related to patient prognosis and risk assessment, an awkward reality is: the mechanism of CDH17's association with tumors has not been fully elucidated so far.
This also led to the lukewarm research and development of the CDH17 target in the medical community in the past. At least before 2022, it was still an extremely niche target. It was only in recent years that CDH17 unexpectedly gained popularity.
As for the reasons behind the recent popularity of CDH17, it appears to be similar to the star target Claudin18.2, with the external world viewing it as an ideal druggable target.
Almost all pharmaceutical companies mentioned the same viewpoint when developing CDH17-related molecules:
In normal tissues, CDH17 is highly restricted to the lateral membrane, hidden in the inaccessible intestinal tight junctions. In contrast, in 50%-90% of gastrointestinal cancers, CDH17 is overexpressed and redistributed, leading to its exposure on the surface of cancer cells, thus becoming more accessible for antibody drugs to target.
The above differences make CDH17 a promising target for antibody-based therapies. For instance, ADC drugs can leverage the advantage of being "precision missiles" to deliver targeted strikes against tumor cells.
It is in this context that CDH17 has attracted many companies to enter the field, and it has even reached a new level of competition.
/ 02 /
Reached a new level of intensity
The competition in CDH17 target development is not only reflected in the large number of molecules being developed, but also across multiple dimensions.
The most direct feeling is that pharmaceutical companies have extremely diverse ideas, ranging from ADC to bispecific antibodies and then to CAR-T, showing a state of saturated research and development. Among the nearly 20 molecules announced at the AACR conference, the most popular is the ADC route, followed closely by bispecific antibodies and CAR-T.
The same company may bring more than one R&D direction. For example, at this year's AACR conference, Levena Biopharma and Chia Tai Bio proposed two different models targeting CDH17 respectively.
V立志博 introduced the ADC drug LBL-054 and the TCE molecule LBL-054-CD3.
Tavot Bio brought ADC drug TAVO307A and γ-δ T cell engager TAVO307B.
Of course, the R&D approaches vary among different companies. For instance, although LBL-054 and TAVO307A are both ADC drugs, they carry different toxins; TAVO307B, on the other hand, uses pan-γδTCR, which is reportedly less likely to trigger cytokine storms compared to mainstream CD3-based T-cell engagers.
This also reflects one point: although everyone is on the same starting line, the competition has already begun. This competition is not only limited to the CDH17 target but may also include confrontations with other drugs.
Innovent Biologics has set its sights on tri-specific antibodies, with its IBI3019, a novel tri-specific antibody targeting EGFR, CDH17, and CD16A for the treatment of colorectal cancer, making an appearance at the AACR conference.
The core concept of this molecule is to enhance tumor-specific EGFR inhibition by targeting CDH17, which is highly expressed in tumors, while reducing the common skin toxicity associated with EGFR therapy.
Moreover, IBI3019 has begun to benchmark against currently mainstream EGFR antibody drugs. According to the company's description, IBI3019 demonstrated stronger anti-tumor effects than Cetuximab (EGFR monoclonal antibody) and Amivantamab (EGFR/c-Met bispecific antibody) in both in vivo and in vitro experiments. This might also be a consideration for the future if IBI3019 can become a drug, as it will face direct competition with EGFR antibody drugs.
Obviously, as the low-hanging fruits of innovation are being exhausted and competition intensifies, the race among innovative pharmaceutical companies is becoming more preemptive. This also means that, for targets as nascent as CDH17, pharmaceutical companies have no choice but to invest more effort, making the entire market more competitive and bustling.
/ 03 /
Still Need to Work Hard to Achieve Success
Of course, competition is fierce,CDH17More efforts are still needed to reach the target.
The logic is that, although the drug development rationale for the CDH17 target appears clear, it has not been fully validated by human data. Even BI-905711, the TRAILR2/CDH17 bispecific antibody with the most advanced progress, has only released Phase 1a clinical data, showing relatively good safety but unimpressive activity data.
Therefore, whether this field can yield viable drugs remains to be validated. Furthermore, even if drug development is possible, pharmaceutical companies may still need to make greater efforts, as the CDH17 target is bound to be one of the most competitive.
Currently, the main players in the research and development of the CDH17 target are Chinese pharmaceutical companies. At this year's AACR conference, in addition to the aforementioned Toca Bio, Vibe Therapeutics, and Innovent Biologics, other companies such as Huadong Medicine and Simcere Pharmaceutical also made appearances, accounting for over 80%.
This is due to the engineer红利, but at the same time, it is also because Chinese pharmaceutical companies are becoming more and more creative. Chinese innovative pharmaceutical companies have jumped out of the "problem solver" category and become disruptors in the global innovative drug market. Given the efficiency of Chinese pharmaceutical companies, the iteration in this field may exceed imagination.
Therefore, this also means that a batch of CDH17 molecules may be eliminated before they even reach the global market.
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