What is the "gold standard" of "life-saving drugs" vs. "high-level repetition" for anti-tumor drugs?

The development of first-in-class drugs has become one of the important criteria for evaluating the innovation ability and competitiveness of enterprises.

On August 30, the official website of the State Food and Drug Administration showed that the anti-PD-1 fully human innovative antibody drug sepalizumab (GLS-010) jointly developed by Yuheng Pharmaceutical and WuXi Biologics has been approved for marketing by NMPA for treatment Patients with relapsed or refractory classic Hodgkin lymphoma (r/r cHL) above second-line

Such news did not cause too much attention

The change from "1" to "6" is not only a change in numbers, but also indicates that full competition has brought about the full development of the PD-1 market

On the other hand, racetrack competition has entered the "Red Sea", whether it is more than 20 PD-1 products that may be marketed globally in the next 2-3 years, or 4 PD-1 products that have been listed and entered into the medical insurance for less than 20,000 yuan after reimbursement.

Homogenization, high investment, and commercialization pressure have intensified the "involution" of innovative drugs

01 "Inner Volume" breaks the question

The Frost & Sullivan research report shows that the number of cancer patients in China increased from 3.

According to the "Guiding Principles", products must have clear clinical value and differentiation: clinical value is the ultimate appeal of the product, and differentiation is the key to victory in medical insurance negotiations and fierce market competition, so as to avoid falling into PD- 1 The price is "inward-rolled"

The PD-1 event has entered the second half.

On September 5, Hengrui Medicine issued an announcement announcing that it had reached a cooperation agreement with Tianguangshi

This is Hengrui's second move in License-in recently

For the research and development of new drugs that are "billions of dollars, decades", License-in is undoubtedly an efficient, high-speed, and most cost-effective choice.

License-in has become the most common channel for pharmaceutical companies to own FIC and BIC

In summary, this model has three major innovations, namely, new product mechanisms, new indications selected, and new drug candidates market

Regarding the early development of the imported pipeline, Arnold adopted a combination of “radical” and “pragmatic”.

Arnold Pharma’s core product AN2025 (buparlisib) is an oral pan-PI3K inhibitor that targets all PI3K subtypes of class I and exhibits anti-tumor activity in hematological malignancies and solid tumors

Previously, in the global phase II randomized clinical trial of its combination with paclitaxel for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), the median survival time of patients was as high as 10.
4 months, which was granted a rapid rate by the US FDA.
Approve channel qualifications
.

AN0025 is an oral E-type prostate receptor 4 antagonist that changes the tumor microenvironment and promotes immunity by acting on EP4 receptors
.
The candidate drug has a wide range of indications.
In theory, after being used in combination with drug K, clinical trials for more than a dozen indications can be carried out simultaneously
.
Lu Yang said that Arnold did not advance at the same time, but narrowed the scope based on scientific and market considerations, and chose 5 indications, namely non-small cell lung cancer, triple-negative breast cancer, and colorectal cancer, which are in high demand in the market.
Cancer, and cervical cancer and bladder cancer, which are scientifically lower risk
.
At present, Arnold’s 3 clinical-stage products are almost all the early introduction of global or most regional rights.
Among them, AN2025 has global rights, AN0025 has global rights (excluding Japan, South Korea and some Southeast Asian countries), and AN1004 has large Rights and interests in China, Singapore and South Korea
.

With the profound changes in the medical and medical system, the pharmaceutical industry has gradually changed from sales-driven to product-driven and innovation-driven, especially those "good products" that can truly meet clinical needs
.
"Good product" is also the basis for a company's ability to transform and upgrade
.

02 The Rising Biopharma

Biopharma is a unique biopharmaceutical enterprise model in China, between Big Pharma and small Biotech
.
Compared with Big Pharma, it has a lighter weight but faster development.
Compared with Biotech, it has stronger commercialization capabilities
.
A group of companies that have achieved large-scale sales of products, such as Cinda Biological, BeiGene, Betta Pharmaceuticals, and Junshi Biological, are typical representatives of Chinese->
.

On August 6, BeiGene announced its results for the second quarter and first half of 2021.
Total product revenue reached 1.
58 billion yuan, an increase of 108% year-on-year; R&D investment in the first half of the year was US$677 million, an increase of 14.
66% year-on-year
.

Cinda, also in the first echelon, is not far behind.
In the first half of the year, Cinda achieved total revenue of 1.
942 billion yuan, a year-on-year increase of 97.
3%; of which product revenue was 1.
855 billion yuan, a year-on-year increase of 101.
4%
.

Biopharma has become a transit point for biopharmaceutical companies towards Big Pharma, but this road is not easy to follow
.
Not only requires pharmaceutical companies to have global leading R&D capabilities and high-investment R&D, but also international capabilities, a sound management system, and commercialization capabilities
.

After rapid development, policy support, and talent return in recent years, domestic innovative drugs have begun to catch up with Europe and the United States, especially the number, scale, and quality of products under research have been considerable
.
However, most Biotech companies start from R&D based on technology or products, lacking production, management, and commercialization capabilities.
Few companies can successfully go to Biopharma, and more will exit through mergers and acquisitions
.

Just like the two sides of a coin, the harsh conditions and requirements will accurately screen the next up-and-coming star that can stand on the "trend" for the market
.
Taking Arnold Pharma as an example, judging from its previous IPO prospectus in Hong Kong, it has the potential to stand out from Biotech
.

Secondly, "internationalization" is also one of Biopharma's essential labels.
Whether it is Baekje, Cinda, Betta or Junshi, it is not difficult to see that they can gain the favor of the market.
The most important point is the differentiated clinical layout.
And internationalization strategy
.

In the introduction of products, Arnold has global development rights for multiple varieties, and has obtained a number of overseas clinical research approvals
.
As mentioned above, take the fastest-growing product AN2025 (buparlisib) of Arnold Pharma as an example.
AN2025 is authorized by Novartis to develop Arnold globally.
From the targets and indications of this phase III study, the product is globally competitive.

.

In the past 20 years, although the CDK4/6 inhibitor, which was later called the anti-cancer "nova", obtained Phase III clinical results at the same time, it was not satisfactory.
Even if it rushed to market, it would be difficult to find a market
.
However, PI3K has a significant correlation with tumor progression, increased tumor microvessel density, and enhanced chemotaxis and invasiveness of cancer cells due to its overactive signaling pathways.
It has become one of the key targets for the development of tumor therapeutic drugs.
PI3K inhibits The clinical development of the drug has made considerable progress
.

PI3K α and PI3K β are closely related to tumor growth, while PI3K γ and PI3K δ are related to immunity
.
The incidence of certain types of specialized subunit mutations in head and neck squamous cell carcinoma is relatively low, and there are pathological disorders caused by this, so it is more suitable for treatment with pan PI3K inhibitors
.

It is precisely because the head and neck squamous cell carcinoma is more in line with the role of multiple subtype signaling pathways in mechanism, so that this pan-PI3K can play a better role, thus obtaining the best history of second-line treatment of head and neck cancer in the second phase of clinical trials.
Data
.
Previous studies have found that PI3K inhibitors can also have a good synergy and anti-drug resistance mechanism with paclitaxel, an important chemotherapeutic drug for head and neck squamous cell carcinoma.
This is Arnold’s choice to combine buparlisib with paclitaxel for the treatment of head and neck squamous cell carcinoma.
One of the important reasons
.

Currently, no PI3K inhibitor has been approved in China.
Among the five products with the same target on the market abroad, except for Novartis’s alpelisib, which is indicated for breast cancer, Bayer’s copanlisib, Gilead’s idelalisib and Verastem’s duvelisib are all approved for breast cancer.
Blood tumors
.

Arnold’s AN2025 has conducted clinical studies on a variety of solid tumors other than breast cancer.
The current phase III study is also endorsed by past clinical data.
The results of the previously completed global phase II clinical trials show that AN2025 has good safety and Effectiveness
.

With the approval of PD-1 in the first-line head and neck squamous cell carcinoma in 2019, and the results of phase II clinical studies, Arnold Pharma believes that PD-1 will gradually replace chemotherapy and occupy the mainstream first-line head and neck squamous cell carcinoma.
It is in cooperation with the FDA and After clinical PI communication and recognition by all parties, Arnold Pharma adjusted to provide effective treatment options for patients who have progressed after PD-1 treatment during the global phase III clinical trial, filling this huge unsatisfaction Clinical needs
.

In addition, in order to achieve the goal of global development of more products, Arnold is also gradually increasing the proportion of independent research and development of products, because independent research and development product companies have global rights and international development will not be restricted by other partners.
The company also has greater initiative when products are added to cocktail therapy research
.

From the perspective of the team, the management of Arnold Pharma is somewhat "unconventional" compared with many innovative pharmaceutical companies
.
Although the founder Lu Yang does not have too deep a scientific research background, his background in science and many years of commercialization and continuous entrepreneurial experience have given Arnold Pharma as an innovative pharmaceutical company a gene with high execution power
.
From the perspective of the R&D team, Arnold Pharma has brought together a team of scientists from the world's top pharmaceutical companies, laying a strong R&D foundation for it to create a differentiated tumor treatment portfolio
.

For a company that has been transforming into innovative drugs for only 5 years, it can get pipelines from the world's top pharmaceutical companies such as Novartis and Eisai, promote global registration tests, and complete the IND application for self-developed products in the FDA.
It is not an easy task.
It not only requires strong innovation strength and sufficient financial support, but also depends on a strong global R&D, commercialization system and mature management system as the support
.

From the previous excessive pursuit of FIC, to no longer innovating for innovation, domestic pharmaceutical companies are returning to calm down on the clinical value and commercial value of drugs.
New technologies and new drugs are still the most important innovation entry points for domestic pharmaceutical companies, but there are differences.
The positioning and commercialization capabilities of enterprises will also determine the competitiveness and results of enterprises
.