Efan Pharmaceuticals transfers Shengbaiyao F-627 for RMB 210 million, and is expected to be the first to be listed in the United States

On August 30, Yifan Pharmaceutical issued an announcement stating that its holding subsidiary, Shanghai Yiyi, had agreed on August 26 to exclusively license all intellectual property rights and commercialization rights related to F-627 in China to CP Tianqing Pharmaceutical Group Co.

CSF includes two types, short-acting and long-acting.

According to the US business reporting website businessinsider, global chemotherapy-induced neutropenia (CIN) affects more than 8 million people every year, and about 1 million people are affected in the United States alone

According to public information, the global G-CSF market in 2019 reached US$4.

Participants of long-term G-CSF, organized by Head Leopard Research Institute

At present, the global R&D competition for Shengbaiyao is relatively good.

On May 7 this year, the National Medical Products Administration approved the pegylated recombinant human granulocyte stimulating factor injection (trade name: Shenlida) declared by Shandong New Times Pharmaceutical under Lunan Pharmaceutical Group to become the fourth domestic long-acting Sheng Baiyao

So far, there are 4 domestic pharmaceutical companies that have long-acting rhG-CSF production approvals, namely Shandong New Times Pharmaceuticals, CSPC Baike (Shandong) Biopharmaceuticals, Qilu Pharmaceuticals and Hengrui Pharmaceuticals

In 2020, the market structure of PEGylated recombinant human granulocyte stimulating factor injection will be Qilu Pharmaceutical and CSPC Baike (Shandong) Biopharmaceuticals

F-627 is the only clinical trial product that has been head-to-head with the long-acting original product Neulasta and the short-acting product Nupogen, and the results of the head-to-head trial have reached the preset primary efficacy endpoint

Southwest Securities predicts that the scale of the domestic Shengbaiyao market is expected to exceed 10 billion yuan, and long-acting dosage forms are expected to become mainstream in the future

Reference materials:

1.

2.

3.
Overview of the Shengbaiyao industry in Toubao Research Institute: https://pdf.
dfcfw.
com/pdf/H3_AP202103221474788138_1.
pdf?1616435901000.
pdf

On August 30, Yifan Pharmaceutical issued an announcement stating that its holding subsidiary, Shanghai Yiyi, had agreed on August 26 to exclusively license all intellectual property rights and commercialization rights related to F-627 in China to CP Tianqing Pharmaceutical Group Co.
, Ltd.
(hereinafter referred to as "CP Tianqing") and its wholly-owned subsidiary, CP Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co.
, Ltd.
(hereinafter referred to as "Tianqing Nanjing Shunxin")
.
Tianqing Nanjing Shunxin agreed to accept the transfer and entrust Beijing Yiyi to produce it.
Tianqing Nanjing Shunxin must pay Shanghai Yiyi a license fee of no more than 210 million yuan and a tiered net sales commission fee
.

The recombinant human granulocyte colony stimulating factor-Fc fusion protein (F-627) independently developed by the company's holding subsidiary Evive Biotech Ltd is used to prevent and treat neutropenia caused by cancer patients during chemotherapy
.
F-627 is an innovative biological drug product developed based on the existing Di-KineTM bimolecular technology platform with independent intellectual property rights of Yiyi Biotech
.
It is a rhG-CSF dimer expressed by CHO cells based on Fc fusion protein technology, with long-lasting and potent biological characteristics
.
At present, F-627 is mainly used in the prevention and treatment of neutropenia caused by chemotherapy in cancer patients.
It can rapidly proliferate and recover neutrophils in cancer patients undergoing chemotherapy, thereby enhancing the immune system 's ability to resist infection To prevent patients from dying of infection or other related complications during chemotherapy
.

Notice that, in October 2017, F-627 second international Phase III clinical trial (hereinafter referred to as "05 test") program with FDA agreement (SPA) binding, indicating that the FDA approved 05 clinical trials of the F-627 Protocols and statistical analysis methods of clinical results
.
In January 2018, Yiyi Biotechnology completed the first phase III clinical trial of F-627 in the United States (hereinafter referred to as the “04 trial”), and reached the preset primary efficacy endpoint.
The subjects are well tolerated and safe Achieved expectations; on January 5, 2020, Yiyi Biotechnology received the F-627 Phase III clinical trial "Collection of Statistical Data and Charts" in China, and the statistical results showed the effectiveness of the F-627 China Phase III clinical trial.
It has fully reached the preset evaluation standards of clinical trials, and its efficacy is equivalent to that of the control drug (recombinant human granulocyte colony stimulating factor of the original imported drug); in June 2020, Yiyi Biotech received the 05 trial "Statistical Data Chart" carried out in the United States and Europe "Collection", the results show that the second international phase III clinical trial successfully reached the preset primary efficacy endpoint and secondary efficacy endpoint, and the efficacy of the drug was equivalent to that of the control drug; in July 2020, the company completed the immunogenicity of the 05 trial.
And antibody test, the result was negative, indicating that there was no drug-related antibody production; since then, the phase I, phase II, and phase III clinical trials of F-627 at home and abroad have successfully reached the preset goals of clinical trials
.
March 30, 2021, F627 submitted to the US FDA BLA application, the evening of 27 May 2021 received US Food and Drug Administration Administration (FDA) acceptance letter, formally accepted the $ 110 biological BLA application of F627 into technology The review stage marked a further breakthrough in the innovative research and development of Yifan Pharmaceutical
.

Clinically, colony stimulating factor drugs such as granulocyte colony stimulating factor are used to treat this complication.
Although these drugs can increase the number of white blood cells, they are relatively insufficient in improving the function of white blood cells, and are expensive and accompanied by certain toxic side effects.
The application has certain limitations
.
White blood cell-increasing drugs (boosting white blood cells) can increase the number of white blood cells.
Common clinical white-boosting drugs include general white blood-boosting drugs (ie royal jelly, astragalus and other traditional Chinese medicines), hormone-based white blood-boosting drugs, and granulocyte colony stimulating factor (G-CSF), among which G -CSF has a quick effect and is the first therapeutic drug for radiotherapy and chemotherapy-related neutropenia recommended by clinical guidelines at home and abroad
.
G-CSF receptor activation must be through the G-CSF ligand bimolecular polymerization, F-627 contains two G-CSF molecules, it is easier to form a G-CSF ligand-receptor dimer complex from the spatial structure, and mAb carrying the Fc protein structure, the effect of addition of PEG and similar in theory, increase the molecular weight to reduce the half-life, which can be dimeric structure such that the reaction accuracy of higher
.

CSF includes two types, short-acting and long-acting.
Among them, short-acting G-CSF needs to be administered 1 to 2 times a day in each chemotherapy cycle, such as Amgen's Nupogen (filgrastim) and Chugai Co.
, Ltd.
's Lenograstim (Legramostim), long-acting G-CSF is mainly prepared by polyethylene glycol modification, and usually only needs to be administered once in a chemotherapy cycle, such as Amgen’s Neulasta (pefigrastim, glycosylation) Modification), Hengrui Medicine's Aido (thiopefigrastim)
.

According to the US business reporting website businessinsider, global chemotherapy-induced neutropenia (CIN) affects more than 8 million people every year, and about 1 million people are affected in the United States alone
.
The global neutropenia drug market is estimated to be US$6 billion, and more than 85% of patients are still using the first-generation rhG-CSF, while fewer than those using the second-generation rhG-CSF pegylated rhG-CSF 15%
.

Edited by Head Leopard Research Institute,

The first overseas launch of Shengbaiyao was Amgen.
At its peak in 2015, its two G-CSF products sold as high as 5.
7 billion U.
S.
dollars.
Even after the long-acting dosage form reached its peak sales, it still achieved 45.
34 in 2017.
The sales of USD 100 million was 8.
3 times that of the short-acting dosage form in the same year
.
A large number of approved products in this field include Sanofi’s Sargramostim (trade name: leukine) and Novartis’s generic drug plant Sandoz’s filgrastim (Biosimilar, trade name: Zarxio), but Neupogen and Neulasta The competitive advantage is obvious, and it has a monopoly position
.

According to public information, the global G-CSF market in 2019 reached US$4.
5 billion, of which long-acting formulations accounted for 88%
.
Neulasta accounts for 73% of the long-acting G-CSF market
.
Neulasta is the world's first long-acting recombinant human granulocyte colony stimulating factor (rhG-CSF) product developed by Amgen.
It was approved by the FDA in January 2002 to reduce the incidence of neutropenia-related infections during tumor treatment.
, Its global sales reached a peak in 2015, about 4.
715 billion US dollars
.
In recent years, due to the impact of biosimilars, Neulasta's sales have experienced a serious decline, falling to $2.
293 billion in 2020
.
Currently, 4 Neulasta biosimilars have been approved globally, namely Fulphila, Udenyca, Ziextenzo and Nyvepria
.
According to a report from the Head Leopard Research Institute, from 2017 to 2020, the high volume of biological agents will drive the rapid growth of the Shengbaiyao market.
At present, 85% of the market is occupied by biological agents and will expand steadily in the future
.

Participants of long-term G-CSF, organized by Head Leopard Research Institute

At present, the global R&D competition for Shengbaiyao is relatively good.
Yifan Pharmaceutical's products are expected to become the sixth or seventh long-acting Shengbaiyao marketed in the United States, and it is also the first domestic long-acting G-CSF marketed in the United States.
It is expected to seize a certain market share
.
Judging from the current domestic market, the market share of long-acting G-CSF has increased year by year, and has surpassed short-acting G-CSF since 2018, and currently holds about 70% of the market share
.
It can be seen that the long-acting dosage form of G-CSF has great potential
.

On May 7 this year, the National Medical Products Administration approved the pegylated recombinant human granulocyte stimulating factor injection (trade name: Shenlida) declared by Shandong New Times Pharmaceutical under Lunan Pharmaceutical Group to become the fourth domestic long-acting Sheng Baiyao
.

So far, there are 4 domestic pharmaceutical companies that have long-acting rhG-CSF production approvals, namely Shandong New Times Pharmaceuticals, CSPC Baike (Shandong) Biopharmaceuticals, Qilu Pharmaceuticals and Hengrui Pharmaceuticals
.
Among them, the related products of Shandong New Times Pharmaceutical, Sinopharm Biopharmaceuticals (Shandong) Biopharmaceuticals, and Qilu Pharmaceuticals are all PEGylated recombinant human granulocyte stimulating factor injections, and Hengrui's is Thiopefilgrastim injections.
Liquid
.

In 2020, the market structure of PEGylated recombinant human granulocyte stimulating factor injection will be Qilu Pharmaceutical and CSPC Baike (Shandong) Biopharmaceuticals
.
The addition of Shandong New Era Pharmaceuticals, a subsidiary of Lunan Pharmaceuticals, will have a certain impact on the current market structure
.

F-627 is the only clinical trial product that has been head-to-head with the long-acting original product Neulasta and the short-acting product Nupogen, and the results of the head-to-head trial have reached the preset primary efficacy endpoint
.
The company predicts that F-627 sales in the United States are expected to reach 200 to 300 million US dollars
.

Southwest Securities predicts that the scale of the domestic Shengbaiyao market is expected to exceed 10 billion yuan, and long-acting dosage forms are expected to become mainstream in the future
.
At present, the domestic long-acting G-CSF R&D competition is relatively good.
The product of Yifan Pharmaceutical is expected to be the first to be launched in China.
It is expected to become a large variety of more than 1 billion in the future and become a new growth point for performance
.
It is foreseeable that the competitive landscape of Shengbaiyao market will become more intense in the future
.

Reference materials:

1.
Yifan Pharmaceutical Announcement

2.
Qi Xiaotian, Zhang Jiaxiang, Zhang Xiaoliang, Huang Nana, Li Xiaoyu, Sun Rong.
Research progress in the treatment of chemotherapy-induced leukopenia with traditional Chinese medicine[J].
Chinese Herbal Medicine, 2019, 50(20):5088-5095

3.
Overview of the Shengbaiyao industry in Toubao Research Institute: https://pdf.
dfcfw.
com/pdf/H3_AP202103221474788138_1.
pdf?1616435901000.
pdf

4.
Merck Diagnosis and Treatment Manual: https:// href="https://" target="_blank" rel="noopener">https:// Southwest Securities Research Report: F-627 was accepted by the FDA, and innovative drug research and development achieved breakthroughs