Yifan Pharmaceutical (002019): F627 domestic third phase meets predetermined standards for overseas approval

Yifan Pharmaceutical (002019): F627 domestic third phase meets predetermined standards for overseas approval

Event: On January 5th, the company issued an announcement that the holding subsidiary Kennenglong’s research product F-627 domestic phase III clinical trial “Statistic Data Graph Collection” was released, and the effectiveness and safety reached the evaluation standards.

F-627 is a new generation of long-acting G-CSF drugs. It is an innovative biopharmaceutical product independently developed by Shanghai Jiannenglong using its own bi-molecular platform. This phase III clinical trial is a domestic multi-center, randomized, open-controlled trial.The first case entry group was completed in 4 years in 2018, and the final case tracking was completed in June 2019.

The effectiveness and safety have reached the benchmark evaluation standard for clinical trials, and it is indeed equivalent to the control drug (the original research imported drug regenerating human granulocyte colony stimulating factor).

The F-627 domestic phase III clinical trial was successful and provided the necessary and critical conditions for domestic declaration of production. This trial was developed using the latest FDA guidelines to lay an alternative basis for the FDA’s application for a biological product license.

Currently, the first phase III clinical trial in the United States (04-plan, and placebo-controlled trial) has reached the main clinical endpoint and obtained the expected evaluation standard; the second international phase III clinical trial (05-plan, controlled trial with the original research product, Neulasta)Using this “Special Program Evaluation” plan, the last visit stage is currently underway, and clinical results are expected to be available in the second quarter of this year.

In 2018, G-CSF had a global market of about 5 billion U.S. dollars, Amgen’s Neulasta accounted for about 80% of the market share; Neulasta US patents expired in June 2015, and European patents expired in August 2017.

At present, the United States market has approved two Neulasta biosimilars, including Mylan’s Fulphila (June 2018) and Coherus’s Udenyca (November 2018). SPPI’s innovative G-CSF drug Eflapegrastim is under FDA review. We expect F-627 is expected to be declared and listed overseas in the third quarter of this year. If it finally obtains 10% of the market and the price is based on a 20% discount on Neulasta, the sales scale of F-627 in the global market can reach about 400 million US dollars.

1 F-627 domestic phase III clinical results are not inferior to Nupogen, and global sales breakthrough is expected to reach 400 million US dollars.

Neutropenia is a common side effect of chemotherapy. Baisheng medicine can effectively increase its quantity. There are three common Baisheng medicines: general Baisheng medicine, hormone Baisheng medicine and granulocyte colony stimulating factor.

In general, there are many varieties of whitening drugs, and the whitening effect is poor. Those with severe leukopenia have no obvious effect. Therefore, patients with chemotherapy often use granulocyte colony-stimulating factor (G-CSF) directly.The gold standard for whitening chemotherapy patients is recommended jointly by ASCO, CNN and other guidelines.

The first-generation rhG-CSF is a single-molecule short-acting type, with a small molecular weight, short half-life, and easy removal by enzymes and kidneys. It requires multiple daily or weekly injections. Amgen’s Nupogen (Figerastine) and Japan and ChinaLenograstim Corporation is the first generation.

The second generation of G-CSF is a single-molecule long-acting type, which is Amgen’s Neulasta (pefigelastine, glycosylation modification). It is modified by adding PEG groups to Neupogen, and the half-life is increased. Each cycle is onlyNeed to be injected once.

G-CSF receptor activation must be through the bi-molecular polymerization of G-CSF ligands. Generon developed the F-627-recombinant human granulocyte colony-stimulating factor-Fc fusion protein (rhG-CSF-Fc) based on its own D-Kine platform.), Containing two G-CSF molecules, it is easier to form a G-CSF ligand-receptor dimer complex from the spatial structure, and it carries the Fc protein of the monoclonal antibody structure, which can theoretically achieve the same as the addition of PEGEffect, increasing the molecular weight and reducing the half-life, may also reduce the affinity of the receptor. Secondly, the mechanism reaction itself needs to form a dimer structure, which makes the reaction more accurate.

The domestic phase III clinical effect is not inferior to Neupogen.

This national phase III clinical trial is a domestic multi-center, randomized, open-controlled trial. The first case enrollment was completed in 4 years in 2018, and the last case breakthrough was completed in June 2019. The effectiveness and safety have fully reached the clinical trial index evaluation standards.The effect is comparable to the control drug Neupogen.

The F-627 domestic phase III clinical trial was successful, providing key conditions for domestic declaration of production. This trial was developed using the latest FDA guidelines to lay an alternative basis for the FDA’s application for a biological product license.

Currently the first phase III clinical trial in the United States (04-plan, with placebo-controlled trial) has reached the main clinical endpoint and obtained the expected evaluation standard; the second international phase III clinical trial (05-plan, with the original research Neulasta controlled trial) is usedThe “Special Program Evaluation” has started and has entered the final visit stage. It is expected to obtain clinical results in the second quarter of this year. We expect that it will be non-inferior to Neulasta.

F-627 sales are expected to reach $ 400 million.

According to relevant data statistics, G-CSF had a global market of about 5 billion U.S. dollars in 2018. Amgen Neulasta accounted for about 80% of the market share. Neulasta US patents expired in June 2015 and European patents expired in August 2017.

Currently, the United States market has approved two Neulasta biosimilars, including Mylan’s Fulphila (June 2018) and Coherus’s Udenyca (November 2018). SPPI’s innovative G-CSF drug Eflapegrastim is under review by the FDA. We expect F-627 is expected to apply for overseas listing in the third quarter of this year. If it finally obtains 10% of the market and the price is priced at 20% discount on Neulasta, the sales coverage of F-627 in the global market will reach about 400 million US dollars.

2 F652 has obtained orphan drug certification. It is expected that the sales will exceed US $ 100 million in the future. Another product under development is F-652, which has obtained FDA orphan drug certification.

F-652 is a recombinant human interleukin 22-FC fusion protein. It obtained FDA orphan drug qualification in October 2019—for GVHD (treatment of acute graft-versus-host 杭州桑拿网 disease), exempting property, waiving application fees, research and development funding, expediting approval, and7 years after listing, market exclusivity, etc. In addition to F652, there are also indications for research on acute diabetes, acute alcoholic hepatitis, etc. In the future, F652 will tend to enter the market as an orphan drug, expand the indications after enjoying the market exclusivity period, and fully explore the marketpotential.

According to the relevant IMS report, approximately 3,000 patients in the United States receive acute graft-versus-host disease each year. With reference to the annual cost of Rusotinib in the United States market, it is approximately $ 120,000. Based on this, the GVHD US market size is estimated to be approximately3.

6 billion US dollars / year, F-652 is expected to become the second drug approved for GVHD in the United States after rusotinib. Assuming that it can replace 25% of the market share in the future, the sales scale is expected to reach 90 million US dollars.In the case of other indications such as acute cancer, sales are expected to exceed $ 100 million with a high probability.

A reasonable estimate of the 63% equity interest of 300 million Fanneng Jiannenglong is about 7 billion yuan.

F-627 is currently given a reasonable estimate of 82 trillion, F-652 is given a reasonable estimate of 28 trillion, and Jiannenglong conservatively estimates that the current income exceeds 11 billion US dollars. Yifan holds 63% of Jiannenglong. A reasonable estimate is given to this part of equity.70 million.

4The price of calcium pantothenate has been stable recently. It is expected that the price of calcium pantothenate will start to reverse from the bottom of 2018 in the post-pig cycle. It will accelerate the price increase in April 2019 to the current 8 months. It experienced a stagnation period of 4 months, mainly due to swine fever.As a result, the price of calcium pantothenate went up slightly from September to October, and the wind showed that the current offer was 380 yuan / kg. Looking back at 2019, affected by swine fever, the downstream feed demand was weak, and the price rise of calcium pantothenate was not smooth.Entering 2020, with the breakthrough and stimulation of many national methods, the impact of swine fever will gradually weaken. The number of pigs slaughtered in each place will obviously increase in the future after the initial breeding period, and the demand for feed will gradually pick up, driving the prosperity of calcium pantothenate.It is expected that the transaction situation score will improve significantly in 2019, waiting for the post-pig cycle to start.

5 The preparation business is rapidly advancing, and the launch of the exclusive variety supplement medical insurance. The fast-volume preparation business is in line with expectations. It is expected to grow by 30% and contribute a profit of nearly 400 million US dollars. In November 2019, a new round of national medical insurance directory negotiations, the company ‘s exclusive medical insurance andThe base medicine product compound Huangdai Tablets again replaced the medical insurance through negotiation and renewal with a small decrease. Another exclusive product, the Mahuang Xiaoke Granules, was replaced for the first time with the National Medical Insurance Catalog, and the compound Huangdai Tablets and Macen Xiaoke Granules were used as companies. “531 “focuses on nurturing products and is expected to start rapid volume through national medical insurance.

Earnings forecast and investment rating: We estimate that the company’s operating income for 2019-2021 will be 51.

5.1 billion, 62.

6.7 billion, 70.

6.7 billion; net profit attributable to mothers was 10.

4.2 billion, 13.

02 ppm and 14.

97 ppm; EPS is 0.

86 yuan, 1.

08 yuan and 1.

24 yuan, maintain “highly recommended” level. Risk reminders: pressure on price reduction of calcium pantothenate; the preparation business fails to meet expectations; the development of innovative drugs fails to meet expectations; other risks.