There are 13 PD-(L)1 models in China, and the competition is fierce. What can the late entrants rely on?

An expert predicted two years ago, "In five years, it is expected that more than 80 companies will be doing PD-(L)1 clinically.
At that time, it is not used for injections, but for bathing
.

" It is a joke, but it also reveals the cruelty of the homogenization of domestic PD-(L)1 product development

On March 25, 2022, Henlius (2696.
HK) announced that its first self-developed innovative biopharmaceutical PD-1 inhibitor H drug-Hanszoid® (generic name: slulimumab injection) Liquid) was officially approved by the State Food and Drug Administration for the indication of adult advanced solid tumors with unresectable or metastatic microsatellite instability-high (MSI-H) who have failed previous standard therapy
.

Slulimumab is the first innovative monoclonal antibody independently developed by Henlius, commonly known as "H drug" in the industry
.

With the approval of Henlius' slulimumab, up to now, there are 13 PD-(L)1 mAbs approved in China, of which there are 7 domestic PD-1 mAbs

At a time when the approval policies at home and abroad are getting tighter and tighter, how does Henlius PD-1 break through? There are more and more competing products, and prices are rolling in.
.
.
In the red sea, what innovation path has Henlius chosen, and how will it get out of the vicious circle of homogenization? Worth watching
.

1.
Another way - MSI-H solid tumor: subdivided track "blue ocean"

1.
Another way - MSI-H solid tumor: subdivided track "blue ocean"

According to statistics, there are currently 70 PD-(L)1 drugs and drug candidates entering the clinical stage in China
.

Sinolink Securities pointed out that in terms of indications, most of the products have adopted the strategy of "listing small tumor species + expanding large tumor species"

At present, PD-(L)1 products on the market have been approved for a number of indications, covering lung cancer, liver cancer, esophageal cancer and other indications with a large patient population in China
.

How to gain an advantage and break through in the current PD-1 Red Sea market? The PD-1 products listed later can only seek differentiated development, or have better performance in clinical data
.

This time, Henlius’ slulimumab has been approved for MSI-H solid tumor indications, which are not differentiated by cancer types, and can cover endometrial cancer, colorectal cancer, gastric cancer, renal cell cancer, and ovarian cancer.
Dozens of solid tumors
.

In this indication, Henlius has always been a pioneer
.

As early as in preclinical and early clinical studies, Drug H has delivered excellent PK and PD data, and demonstrated good antitumor activity and good safety in its pivotal Phase II clinical trials, significantly extending the period of time.

The preclinical study and structural characterization study of the product have been published in the international journal PLOS ONE.
The results of the study show that compared with Nivolumab and Pembrolizumab, drug H showed similar or better biological activity in vitro and in vivo, and was comparable to bevacizumab.
The combination of anti-hambetaxel (HLX04) has a synergistic anti-tumor effect
.

Through the structural analysis of the binding complex between the Fab segment of the H drug and the extracellular domain of PD-1, the product has a unique recognition pattern that is different from Pembrolizumab and Nivolumab, and has a similar binding epitope to Pembrolizumab

Phase II trial of slulimumab in treated, unresectable or metastatic high-grade microsatellite instability or mismatch repair deficient (MSI-H/dMMR) solid tumors, in the primary efficacy analysis population, confirmed by IRRC The estimated ORR was 39.
7% (95% CI: 28.
03, 52.
30; 3 complete responses, 24 partial responses)
.

The results of the study showed that H-drug monotherapy had significant benefit in the treatment of unresectable or metastatic MSI-H solid tumors that had failed previous standard therapy, met the prespecified primary endpoint, and had good safety and tolerability

According to the data, MSI-H solid tumor refers to a type of solid tumor with a highly unstable phenotype of microsatellites.
It was first discovered in hereditary colorectal cancer.
Later studies found that MSI-H is commonly found in patients with other cancer types.
, including endometrial cancer, gastric cancer, hepatocellular carcinoma, melanoma and other cancer cells
.

Studies have shown that the incidence of MSI-H in all cancers is about 14%, and these patients usually have a higher response rate to immune checkpoint inhibitors

According to the estimated incidence of various tumors in China and the incidence of various MSI-H tumors, there are about 300,000 new solid tumor patients with MSI-H in China every year
.

The popular indications on the PD-1 track are highly competitive, but there are still many sub-indications that have not yet been covered, such as MSI-H solid tumors, which have urgent clinical needs and a considerable market size

So far, only two PD-1 mAbs have been approved in China for MSI-H solid tumors
.
In addition to Henlius H, BeiGene's PD-1 monoclonal antibody, Bai Zean, was approved for this new indication on March 11 this year
.
The domestic MSI-H solid tumor field is still in the blue ocean and has yet to be developed
.

Zhang Wenjie, Chairman, Executive Director and CEO of Henlius, said that he hoped that everyone could jointly develop this blue ocean market and be confident in the clinical data of the company's products
.
In addition, the company's commercialization team is also ready to accelerate the commercialization of H medicine
.
It is understood that in terms of commercial operation, Henlius has completed the formation of a sales team of about 200 people in the first quarter of 2022.
After the product is launched, it will quickly implement a differentiated layout and fully penetrate the Chinese market
.
While actively implementing market promotion and sales layout, it will also plan to establish in-depth cooperation with genetic testing companies to jointly explore innovative solutions in the field of oncology, build a new patient service model, improve MSI testing standards and accessibility, and gradually Establish a patient diagnosis and treatment ecosystem around digestive tract tumors and gynecological tumors
.

On this basis, with the successive approvals of slulimumab for other indications (including sqNSCLC, ES-SCLC, etc.
), Henlius will also further consolidate the market and sales layout in lung cancer and other fields, and build a complete oncology patient care ecosystem
.

2.
Continue to expand differentiation and deepen SCLC and other fields

2.
Continue to expand differentiation and deepen SCLC and other fields

In addition to the first approved MSI-H solid tumor indication, the future of H medicine is also extremely promising
.

Zhu Jun, President of Henlius, said in an interview with the media that although the overall domestic competition for PD-1 is fierce, the clinical data varies greatly, and some subdivisions are still blue oceans
.

It is particularly worth mentioning that the international multicenter phase III study of slulimumab combined with chemotherapy in previously untreated extensive-stage small cell lung cancer (ES-SCLC) reached the primary endpoint in December last year
.

The results of the study showed that the combination of slulimumab and carboplatin-etoposide could prolong the median overall survival (OS) in the overall population and the Chinese subgroup, and the median overall survival (OS) in the slulimumab group and placebo group The OS was 15.
38 months and 11.
10 months, respectively, the overall population reduced the risk of death by 38% (41% in the Chinese subgroup), p<0.
001, and the 2-year overall survival rate (OSR) of the two drug groups was 43.
2%, respectively and 8.
0% with good safety
.

Henlius plans to submit the registration application for this indication in China and the EU in 2022.
If approved, Henlius' H drug is expected to become the world's first anti-PD-1 monoclonal antibody for the first-line treatment of SCLC
.

Public information shows that small cell lung cancer accounts for about 15%-20% of bronchogenic lung cancers.
When small cell lung cancer is diagnosed, about 30% of patients with tumors are in limited stage, and the rest are in extensive stage.
When the tumor spreads beyond the supraclavicular area is the broad period
.
Small cell lung cancer is often difficult to cure because the tumor is likely to have spread widely by the time it is diagnosed
.
The industry calls it a disease with complex and incomprehensible tumorigenesis and development mechanisms, short survival period and minimal therapeutic progress
.

At present, there are only two PD-L1 mAbs approved for the first-line treatment of SCLC in the world, and slulimumab is the first PD-1 mAb to achieve phase III positive results in the first-line indication of SCLC
.
Previously, two PD-1 mAbs, Bristol-Myers Squibb's O drug and Merck's K drug, have successively withdrawn their marketing applications for this indication due to negative OS results in confirmatory tests
.

The development of new drugs for small cell lung cancer is a long and bumpy road.
Henlius chose "knowing that there are tigers in the mountains, but preferring to travel in the mountains".
Now the H Medicine International Multicenter Phase III has reached the primary study endpoint of OS, and it has also given PD-1 monoclonal antibody.
Instill confidence in this area
.
Moreover, compared with the approved PD-L1 data, Henlius’ H drug also has certain advantages
.
Compared with the published clinical data, only 22.
9% of people with PD-L1 in the treatment of SCLC can live for more than two years, while the H drug can double the two-year survival rate
.

The 2020 Global Cancer Statistics Report shows that there are more than 810,000 new lung cancer cases in China, of which about 120,000 are small cell lung cancers
.
Compared with the current research and development status of "nine deaths and one life", the market space for small cell lung cancer is very large
.

In addition, other indications of Henlius H medicine have also ushered in important progress
.
In September 2021, the NDA of slulimumab combined with chemotherapy in locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC) was accepted by the NMPA; the registration application for H drug combined with chemotherapy in the first-line treatment of esophageal squamous cell carcinoma (ESCC) was also approved.
It is expected to be submitted in 2022
.

3.
Actively explore combination therapy and look at the global market

3.
Actively explore combination therapy and look at the global market

The reason why major pharmaceutical companies get together to develop PD-(L)1 products is that it is not only a broad-spectrum anticancer drug that can treat many types of cancer, but also a cornerstone drug for immunotherapy, which can be used in combination with a variety of drugs.
1+1>2 effect
.

It is understood that in addition to continuously covering more indications, especially key large tumor types, Henlius is also actively exploring combination therapy to provide patients with better treatment solutions
.
At present, Drug H has obtained clinical trial licenses in China, the United States, the European Union and other countries and regions, and 9 combined treatment programs have been launched simultaneously
.

Development of Henlius H pharmaceutical products

Among them, in the field of lung cancer, Henlius has achieved a comprehensive first-line clinical layout, in locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC), non-squamous non-small cell lung cancer (nsNSCLC) and small cell lung cancer ( SCLC) are conducting trials on H drugs, covering more than 90% of lung cancer patients
.
Henlius has launched an international multi-center phase III clinical trial for both indications of sqNSCLC and SCLC, with over 30% of overseas ethnic groups enrolled
.

The competition in the domestic market is fierce, and PD-(L)1 enterprises seeking overseas opportunities are also an important part of the strategic layout of each company
.
At the same time, going abroad and gaining recognition from the international market can also better illustrate the innovation of this product
.

It is reported that the drug has been enrolled in more than 2,800 subjects worldwide
.
The rich international clinical data can lay the foundation for the overseas application of H medicine and carry out subsequent commercialization
.

In addition, as early as 2019, Henlius entered into a cooperation with PT Kalbe Genexine Biologics (KG Bio), granting it the exclusive development and commercialization of its first monotherapy and two combination therapies in 10 countries in Southeast Asia.
rights, and will continue to expand overseas business to cover more countries and regions based on the clinical and approval progress of Drug H, and benefit more global patients with high-quality biological drugs
.

On the other hand, as an early domestic biopharmaceutical company that realized the overseas listing of its self-developed products, Henlius has trained the integration capabilities required for going overseas through the "pioneering force" of Hanquyou, and gradually established its own perfection.
R&D, production and commercialization system
.
This can also lay a solid foundation for the company's follow-up H medicine and other innovative products to "go overseas" and accumulate valuable experience
.

Recently, Henlius announced its 2021 results, achieving an operating income of 1.
683 billion yuan, a year-on-year increase of 186.
3%
.
The annual R&D investment increased to RMB 1,763.
7 million
.
Henlius has built a mature international R&D, production and commercialization system.
With the successive approval of innovative products such as H medicine in 2022, its hematopoietic capacity has been enhanced, and its pace of development towards biopharma is also accelerating
.

4.
Postscript

4.
Postscript

Since the first domestic PD-1 was approved for the market in December 2018, more than 3 years later, the PD-(L)1 market has ushered in more than ten products, and some changes are also happening quietly
.

With more and more products on the market, there are still a number of PD-(L)1s that are lining up for approval.
In 2019, medical insurance intervened, and domestic PD-(L)1 prices were gradually "generalized" in three years; in addition, In 2021, CDE will release a new policy on anti-tumor drugs to further crack down on pseudo-innovative and me-worse drugs.
.
.
The domestic competition boom has made PD-1 a new breakthrough point.
However, the FDA's review and approval is also tightening, with differentiated, Products with better efficacy can stand out
.

It can be seen that domestic PD-(L)1 is facing greater competitive pressure in terms of pricing, domestic and foreign approval policies,
etc.
Among them, how to break through the competition, how to find differentiated development, how to truly solve clinical pain points, and meet unmet clinical needs are the key to whether the current PD-(L)1 R&D pharmaceutical companies can achieve breakthroughs and turn cocoons into butterflies.
key
.