CDE issued a sword pointing to ADC, another pharmaceutical innovation "golden track" to "inner volume"?

Recently, the Drug Evaluation Center (CDE) of the State Drug Administration issued the Technical Guidelines for the Clinical Development of Anti-tumor Antibody Conjugated Drugs (Draft for Comment) (hereinafter referred to as the "Guiding Principles"), pointing out that the development of biopharmaceutical technology has promoted antibody conjugated drugs (ADCs) into a stage of rapid development, making it one of the current hot spots in the research and development of
new anti-tumor drugs.

Make it one of the current hot spots in the research and development of
new anti-tumor drugs.

Zhang Xiaolei, co-founder and CEO of Oulu Pharmaceutical, said in an interview with the 21st Century Business Herald that the significance of the "Guiding Principles" is that from the policy level, the state hopes that in the ADC market layout, enterprises should use cutting-edge technology platforms to focus on the indication field
of "the moat is relatively wide and the city wall is relatively high".

As an ADC enterprise layoutr, we must use cutting-edge technology to aim at differentiated targets, and do not pile up hot indications
.

ADC brings "fresh air outlet"

ADC brings "fresh air outlet"

ADC drugs are coupled by linkers between antibody drugs targeting specific antigens and payloads (such as small molecule cytotoxic drugs), which combines the powerful killing effect of traditional small molecule cytotoxic drugs and the tumor targeting of
antibody drugs.

As a result, based on the fact that ADCs are more toxic than chemotherapy drugs, the new generation of ADCs has obtained clinical treatment data
that are significantly better than chemotherapy therapies.

This has also led to the launch of many ADC drugs and achieved rapid growth
in sales.

CITIC Securities Research Report also shows that by 2026, the global ADC drug market is expected to exceed $40 billion
.

Gilead Sciences acquired Immunomedics for about $21 billion

In addition to multinational pharmaceutical companies, many local innovative pharmaceutical companies are also methodically exploring the ADC field
.

Enterprises with Trop-2 ADC drugs in China include Fudan Zhangjiang, Shanghai Shijian, Kelun Pharmaceutical, BIOTEC and Junshi Biologics
.

One is that ADCs are a very good mechanism, and antibodies can be linked to chemotherapy drugs that can integrate two classic, years-proven tumor treatment options
.

One is that ADCs are a very good mechanism, and antibodies can be linked to chemotherapy drugs that can integrate two classic, years-proven tumor treatment options
.

Third, bispecific antibody of dual targets is considered a major trend
.

"The pharmaceutical industry is an industry that has accumulated science and research, and is based on the understanding of the
field of disease.

How to differentiate the competition?

How to differentiate the competition?

Therefore, in the ADC industry, more exploration is underway
.

However, it is not easy to walk out of a differentiated path, due to the challenges of R&D and production technology, many ADC drug R&D companies can only blindly follow the successful cases, and some R&D companies even pin their hopes on the end-to-end and one-stop service platform
of production.

The "Biological Missile" Antibody Conjugation Drug Insight Report released by Wisdom Bud shows that from the perspective of indications and target distribution, tumors are the core direction
of the current focus.
But the center of gravity has shifted from hematological tumors to solid tumors, and HER2 remains a popular target, but the exploration of new targets is becoming more and more diverse
.

The center of gravity has shifted from hematological tumors to solid tumors, and HER2 remains a popular target, but the exploration of new targets is becoming more and more diverse
.

Zhang Xiaolei introduced that ADC drug R&D companies want to take the road of differentiation, first of all, they can innovate from the target or connector and payload, which has the possibility of
producing clinical differentiation.
At the same time, for ADC drug research and development companies, the core is still to sort out the differentiation, not necessarily to innovate on the target, but also to solve technical challenges
.
Even if HER2 is a mature target, innovation on connectifiers and small molecule toxins could lead to differentiated clinical outcomes
.

Judging from the market research of Oulu, there are many ADC companies in China, but most of them are concentrated in several targets
such as Her2 and Trop-2.
Because the two parts of small molecules and antibodies are very low from a technical point of view, the new targets make pharmaceutical companies "flock to the market", it is difficult to differentiate, and it is easy to catch up with the competitive advantage of only two or three years
.
Therefore, from the perspective of Biotech itself, we must carry out differentiated innovation, and we need to make the world's "First-in-class" to become the most valuable and highest return on investment company in
China.

There are many companies in China that do ADCs, but most of them are concentrated in several targets
such as Her2 and Trop-2.

"In the ADC track layout, each company's technology platform is different, and when working with ADC Therapeutics (a drug discovery company focused on the development of ADC drugs), we start from its toxin, that is, payload, focusing on PBD (pyrrol and benzene diazepine dimer cytotoxin) research, PBD is also recognized as the highest toxin in the ADC industry, and in terms of target selection, the target CD19 we focus on is a target
that no company has focused on in the ADC industry 。 Zhang Xiaolei said that PBD toxin is very toxic, has a rapid onset of action in the blood, and can form a "painful blow"
on DNA.
But because the dose is controlled in a small range, the balance of treatment can be mastered
.
In the choice of indications, Oulu also needs to be different from other pharmaceutical companies to focus on solid tumors, more focused on the field of hematology, and from the existing data, it can be found that Loncastuximab tesirine currently responds more ideally
in the field of hematology.

In fact, according to the 21st Century Business Herald reporter, although the target of CD19 itself is more common, there are not many corporate layouts
in the development of ADC at present.
Loncastuximab tesirine is the first ADC product on the CD19 target, which is also in line with the direction
of ADC focus under research.
Wisdom Bud believes that from the perspective of the research and development pipeline of domestic and foreign enterprises, ADC drugs have become the key direction of the layout of global innovative pharmaceutical companies, and may usher in a new peak within 3-5 years; From the indications and target distribution, tumors are the core direction of the current focus, but the focus has shifted from hematologic tumors to solid tumors, HER2 is still a popular target, but the exploration of new targets is becoming more and more diversified
.

From the perspective of the research and development pipeline of domestic and foreign enterprises, ADC drugs have become the key direction of the layout of global innovative pharmaceutical companies, and may usher in a new peak within 3-5 years

Some clinical experts also said in an interview with the 21st Century Business Herald reporter that the drug research and development of ADC has developed to the third generation, and there are some differences
in efficacy and safety.
Clinically, it is also particularly hoped that drugs with better efficacy and higher safety will be put on the market
.

The "Guiding Principles" also pointed out that when selecting innovative targets, we also need to pay attention to the
differences in efficacy between different drugs in the same target antigen, the difference in the efficacy of the same drug for different target antigen expression states, the determination of the optimal drug delivery strategy, the safety risk of off-target, and the combination of drugs.

How to avoid risks?

How to avoid risks?

At present, in addition to focusing on differentiation, ADC drug R&D companies how to avoid risks, how to compete well, and how to do a good strategic layout are also crucial
.

Northeast Securities Research Report pointed out that at this stage, ADC drugs are widely distributed in the field of tumors, and from a general point of view, the total number of local pipelines under research is small, the indications and target distribution are relatively concentrated, and the popular target HER2 accounts for more than 30%.

In addition, some enterprises are already exploring innovative targets, and the target track has not yet formed a clear competitive pattern and still has great potential
for development.

Because ADC drug development and production has very strict requirements for plant equipment, environment, and personnel operation, the proportion of CDMO services used is much
higher than that of general biological drugs.
As a result, established ADC R&D companies, including Seattle Genetics, are advancing the R&D process
in partnership with CDMO.
This approach is more efficient and allows R&D companies to focus on the early stages of R&D and clinical trials that they are good at
.

On the one hand, the process pain points of ADC drugs are highlighted
.
The process of combining large molecules and small molecules is more complex, and the amount of process development is 2-3 times
that of traditional antibodies.
And the antibodies and small molecules must have their own complete processes, and then couple them together, the analysis workload is large
.

The process of combining large molecules and small molecules is more complex, and the amount of process development is 2-3 times
that of traditional antibodies.

On the other hand, the formulation of ADC drugs is more complex
.
At present, the ADC drugs that have been listed mainly use the lyophilization process, and the lyophilization preparation of biological drugs means that the stability is not good
enough.
However, the reason for lyophilization is because ADC drugs have both hydrophilic and hydrophobic components, and it is difficult to maintain long-term stability
in a liquid environment.
This is also why the proportion of R&D and production outsourcing of ADC drugs is higher than that of ordinary biologics, and most companies do not have the ability to complete the entire production process
independently.

On the other hand, the formulation of ADC drugs is more complex
.

This also makes many ADC drug development companies blindly follow the successful case, or many ADC drug research and development companies will hope to produce end-to-end, one-stop service platform
.

In addition, under normal circumstances, the ADC drug industry chain is mainly led by upstream R&D enterprises, entrusting CMO companies to specialize in the production of ADC drugs, and agreeing on drug sales models with CSO
companies.
For example, the upstream innovative pharmaceutical company Seagen develops drugs and technologies; Then CMO companies such as ABZENA and Novasep specialize in the production of ADC drugs, and pharmaceutical companies pay for manufacturing and process optimization; During the sales process, Seagen licensed sales shares to Takeda outside of
North America.
This industrial model reduces the cost of drug development by innovative enterprises, reduces the risk and difficulty of drug production, and also promotes cooperation and transactions
between enterprises.

When talking about how to avoid the potential risks of the ADC market, Zhang Xiaolei mentioned, "Whether there are different technologies and different targets for ADCs, and detailed planning
is required from the strategic layout of the enterprise.
At the same time, a professional team has also become the key to victory, in the field of high technical threshold, enterprises need to improve the operational efficiency of the team, have a high ability to execute, and respond to the market challenges
at any time with a senior and professional team configuration.
”