CDE posting sword refers to the healthy development of the ADC market. Where is the competition point in the second half of the "Golden Circuit"?

21st Century Business Herald reporter Ji Yuanyuan intern Hong Xiaolan Shanghai report

Recently, the State Drug Administration's Drug Review Center (CDE) again released the "Principles of the Principles of the Technical Guidance of the Clinical R & D of Anti -tumor Antibody Pharmaceuticals (Draft for Solicitation)" The antibody coupling drug (ADC) has entered a stage of high -speed development, making it one of the current hot topics of anti -tumor new drugs. Especially in the field of tumor treatment, the continuous growth of ADC's research and development is leading a new era of targeted therapy. The "Guidance Principles" aims to make suggestions for special attention in clinical research and development of ADC anti -tumor drugs.

The "Guidance Principles" proposes that clinical R & D should pay attention to the main points of efficacy differences between different drugs of the same target antigen and the best dating plan exploration. In addition, with the advancement of science and technology, new ADC products will continue to be developed and applied to clinical trials, such as dual -surface or dual -target ADC. But it is expected that, like the current ADC drug, each component may directly affect the safety and effectiveness of the product.

Zhang Xiaolei, co -founder and chief executive officer of Luolu Pharmaceutical, said in an interview with the 21st Century Business Herald that the significance of the "Guidance Principles" is that from the policy level, the state hopes to use the ADC market layout. , Focus on the field of indications that "the moat is relatively wide and the city walls are relatively high". The proposal of "Guidance Principles" also requires the entry enterprise in the ADC track to take strategic value as a direction for long -term consideration. As an ADC enterprise layout, it is necessary to use cutting -edge technologies to target differentiated targets, and do not tie the layout of popular indications.

"On the one hand, in the application of technical platforms, we must consider toxins, Linker, whether it can increase the treatment window, whether the toxicity is small, whether the efficacy can be improved, and whether the treatment cycle can be shortened; on the other hand, in the target, in the target In terms of choice, HER2 has blossomed everywhere, and it may become the next PD-1 in the future, which may be a waste of patient resources and medical resources. Therefore, the ADC track needs more differential target layout. "Zhang Xiaolei said.

ADC brings "new air outlet"

ADC drugs are made of antibody drugs with targeted specific antigen with effective loads (such as small molecular cytotoxic drugs) by connecting couples by connecting subdains. Essence The main goal of developing ADC drugs is to target the valid load and deliver to a specific part to achieve relatively low system exposure of effective load and effectively increase the risk of benefit of anti -tumor treatment.

As a result, based on ADC's more controllable toxicity than chemotherapy drugs, the new generation ADC has obtained clinical treatment data of chemotherapy therapy. Compared with traditional targeted therapies, ADC further broaden the treatment population and can be applied to new targets that are not covered by traditional targeting therapies.

This has also spawned a lot of ADC drugs and achieved rapid sales. IQVIA data shows that from 2016 to 2020, the US ADC market sales increased from US $ 329 million to US $ 1.47 billion, with an average annual compound growth rate of 45%. According to the Nature subsidy market forecast, by 2026, the global ADC drug market size will reach 16.4 billion US dollars. CITIC Securities Research Report also shows that by 2026, the global ADC drug market is expected to exceed $ 40 billion.

Continuously beyond expected clinical success, superimposed market space, igniting the enthusiasm of domestic and foreign pharmaceutical companies, making ADC the hottest segment of the innovative pharmaceutical industry. In September 2020, there were two striking transactions, highlighting the strong interest in the ADC field in the field of ADC. Among them, Geilyda science acquired Immunomedics for about $ 21 billion and obtained Trodelvy, a FIRST-in-CLASS antibody puppet medicine targeted at Trop-2, which was used to treat adult patients with metastatic metastical breast cancer who had received at least 2 therapies in the past. ; Seattle Genetics and Meridon have achieved cooperation in the field of tumor, which will jointly develop and promote the antibody coupling drug Ladiratuzumab Vedotin, which targeted LIV-1.

In addition to multinational pharmaceutical companies, many Chinese local innovation pharmaceutical companies are also exploring the ADC field in an orderly manner. The "Clinical Research Research Research Research on New China Anti-tumor New Drugs in 2021" released in the first half of 2022 shows that many products from domestic and foreign pharmaceutical companies enter the clinical and pre-clinical stage. Shijian, Coron Pharmaceutical, Biotet and Junshi creatures. There are more than 10 clinical studies, 4 of which are international multi -center studies, and 4 are phase III clinical studies. Comparing the opening of DATO-DXD among the cancer subjects and researchers and researchers, the open III study (Tropion-Breast01) and so on.

In response to the hot investment in the R & D of ADC drugs and the booming pipeline, some analysts of the securities institutional pharmaceutical industry pointed out to the 21st Century Business Herald that with the continuous iteration of antibody coupling technology, the increasing potential of ADC drugs will be tapped. There are quite a few exploration opportunities in the ADC field: First, ADC is a very good mechanism. The antibody connection chemotherapy drugs can integrate two classic and after many years of verified tumor treatment plan. However, in different tumor diseases, its target biological characteristics may be different. Therefore, for the biological characteristics of different diseases, the target also needs to be explored and studied more.

Second, ADC combined treatment is a very important treatment strategy. For example, ADC connecting small molecules and connecting immunotherapy need to be explored in the future.

Third, the BISPECICICFIC ANTIBODY (double -specific antibody) of the dual -target is considered a major trend. There may be different targets on a tumor cell. How to connect chemotherapy drugs with different target drive gene dual -resistance in the future to produce a larger effect. That is to promote the development of dual -target ADC research may also be a trend.

"The pharmaceutical industry is an industry accumulated in science and research, and is also based on the cognition of the disease field. This also requires enlisted to deepen the cognition of the disease Biomarker (biomarkers) and target genomics through continuous scientific research exploration . "The aforementioned analyst said.

Focus on differentiated competition

Therefore, in the ADC industry, more explorations are in progress. Especially nowadays, the ADC field has entered a high time of highlights. Market demand has made countless enterprises enter the bureau. To some extent, how to change its tie and fierce competition in the industry has also become the focus of the industry.

However, it is not easy to get rid of a differentiated path. Due to the challenges in R & D and production technology, many ADC drug R & D companies can only follow the successful cases. Some R & D companies even want to pin on the production end and one -stop service platform. Therefore, how to find a breakthrough in fierce competition, or find out a suitable path in many other targets, has become a matter of thinking that every company is worth thinking about.

The "Bio -missile" antibody coupling drug insights released by the smart buds show that from the perspective of indications and target distribution, tumors are currently focused on the core direction. However, the center of gravity has shifted from hematoma to physical tumors. HER2 is still a popular target, but the exploration of new targets has become more diverse.

According to Zhang Xiaolei, the ADC drug R & D enterprise wants to take a differentiated path, first of all, it can innovate in terms of targets or connectors and effective loads. These innovations have the possibility of differentiation in clinical sense. At the same time, for the ADC drug research and development enterprise, the core is to understand the differentiation. It is not necessary to innovate in targets and solve technical challenges. Even if HER2 is a mature target, if you can innovate on connecting sub -and small molecular toxins, differentiated clinical treatment effects may be produced.

Judging from the survey of the Lu Road market, there are many companies in China, but most of them are concentrated in several targets such as HER2 and Trop-2. Since the two parts of small molecules and antibodies are technically, the threshold is very low. After the new target comes out, it makes pharmaceutical companies "come together", which is difficult to differentiate. Essence Therefore, from the perspective of BIOTECH companies itself, we must carry out differentiated innovation. It is necessary to make the world's "First-in-Class" and become the most valuable and investment return company in China.

"On the layout of the ADC track, each company's technical platform is not the same. When cooperating with ADC therapeutics (drug research and development company focusing on developing ADC drugs), we are from its toxins, that is, Payload, focusing Study of benzodiamine hybrid diodes) research, PBD also recognizes the highest toxins in the ADC industry, and in terms of target selection, the target CD19 we focus on is the target that the ADC industry has not yet focused on. " PBD toxins are very poisonous, and it takes effect quickly in the blood, which can form a "pain blow" for DNA. However, because the dose is controlled in a small range, the balance point of treatment can be grasped. In the choice of indications, the road also needs to distinguish between other pharmaceutical companies that focus on physical tumors and focus on the field of hemoma. From the existing data, it can be found that LonCastuximab Tesirine currently responds ideal in the field of blood tumors.

In fact, according to the 21st Century Business Herald reporter, although the target of CD19 itself is more common, there are no many companies in the development of the ADC field. Loncastuximab Tesirine is the first ADC product on the CD19 target, which is also in line with the direction of the research ADC focus. In terms of smart buds, from the perspective of the R & D pipelines of domestic and foreign companies, ADC drugs have become the key direction of global innovative pharmaceutical companies, and they may usher in a new peak within 3-5 years. From the perspective of indications and target distribution, tumors It is currently focusing on the core direction, but the center of gravity has shifted from hematoma to physical tumors. HER2 is still a popular target, but the exploration of new targets has become more diverse.

Some clinical experts said in an interview with the 21st Century Business Herald that the drug research and development of ADC has developed to the third generation, and there are some differences in the efficacy and safety. Clinically also hopes that there are better effects and more safety drugs to go public. The "Guidance Principles" also pointed out that when choosing innovative targets, it also needs to be paid attention to. The differences between the efficacy between different drugs of different drugs of the same target antigen, the difference in the efficacy of the same medicine for different target antigen expressions, the best administration strategy to determine, pay attention to the decisive target Safety risks, combined medication and other aspects of concern.

Do a good job of avoiding risk strategic layout

Right now, the ADC drug research and development enterprise wants to take a differentiated path. In addition to focusing differentiated, it is crucial to avoid risks, how to compete, and how to do a good job of strategic layout.

Northeast Securities Research Report pointed out that at this stage, ADC drugs are widely deployed in the field of tumor. On the whole, the total number of local research pipelines is small, and the distribution of indications and targets is more concentrated. Popular target HER2 accounts for more than 30%. In addition, some companies have explored innovative targets. The target track has not yet formed a significant competitive pattern, and it still has greater development potential.

Because ADC drugs have very strict requirements for plant equipment, environment, and personnel operations, the proportion of them using CDMO services is much higher than ordinary biopharmaceuticals. Therefore, the old ADC R & D companies, including Seattle Genetics, promote the research and development process through the form of cooperation with CDMO. This method is more efficient and enables R & D companies to focus on the early R & D and clinical trials that they are good at.

On the one hand, the pain points of ADC drugs are prominent. The process of combining macromolecules and small molecules is more complicated, and the process development volume is 2-3 times that of traditional antibodies. And both antibodies and small molecules must have their own complete process, and then use them together to analyze the workload.

On the other hand, the preparation of ADC drugs is more complicated. At present, ADC drugs that have been listed are mainly frozen -drying processes. Biotechnology is made into frozen drying preparations that the stability is not good enough. However, the reason why it is frozen and dry is because ADC drugs have both hydrophilic ingredients and hydrophobic components, and it is difficult to maintain long -term stability in the environment of the liquid. This is why the proportion of outsourcing and outsourcing for ADC drugs is higher than ordinary biopharmaceuticals, and most companies are unable to independently complete the entire production process.

This has also made many ADC drug research and development enterprises blindly imitate successful cases, or many ADC drug research and development companies will want to pin on the production end and one -stop service platform.

In addition, under normal circumstances, the ADC drug industry chain is mainly led by upstream R & D enterprises and commissioned CMO to specialize in the production of ADC drugs and agreed to the drug sales model with CSO. For example, the upstream innovative pharmaceutical company Seagen develops drugs and development technology; then CMO, such as Abzena and Novasep, specialize in the production of ADC drugs, and the pharmaceutical company pays the cost of manufacturing and process optimization costs. In the sales session Sales are divided into. This industrial model reduces the cost of developing drugs for innovative enterprises, reducing the risk and difficulty of drug production, and also promoting cooperation and transactions between enterprises.

Talking about how to avoid the potential risks of the ADC market, Zhang Xiaolei mentioned, "Do you have different technologies for ADC and whether there are different targets. The team has also become the key to winning. In areas with higher technical thresholds, companies need to improve the team's operating efficiency, have high execution capabilities, and respond to market challenges with senior and professional team configurations. "

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