Xin Litai (002294): 6.

200 million introduction of global innovative drugs for renal anemia extends product line in chronic disease

Xin Litai (002294): 6.

200 million introduction of global innovative drugs for renal anemia extends product line in chronic disease

Event: The company announcement intends to cooperate with Japan Japan Tobacco Inc.

(JT) agreement to obtain the exclusive license to use the “Enarodustat” related intellectual property rights, technical information in the Chinese market (ie Mainland, Taiwan, Hong Kong and Macau Special Administrative Region) in the field of renal anemia indications.

This includes the product’s exclusive rights in the area of renal anemia indications, exclusive technology development, production, marketing, and commercial operation in the Chinese market.

According to the product development progress, the company will pay the research and development budget with self-raised funds, and the total amount will not exceed USD 87.5 million (equivalent to RMB 6).

200000000).

  Comment: Enarodustat is an innovative oral small molecule renal anemia drug, which is clinically developed in Japan.

  ”Enarodustat” is an oral small molecule global innovative therapeutic drug for renal anemia developed by JT (has a global patent), and is a hypoxia-inducible factor prolyl hydroxylase inhibitor (hypoxia-inducible factor-prolyl hydroxylaseInhibitor, HIF-PHI).
), HIF-PHI can promote bone marrow red blood cell regeneration by stimulating endogenous EPO production and other mechanisms, so as to achieve the purpose of treating renal anemia.

Currently, a phase III clinical trial has been completed in Japan, and the NDA was declared in November 2019. It is currently under review.

  Renal anemia, as a common complication of CKD, has a severely low awareness and treatment rate in China.

Renal anemia is an important complication for patients with chronic kidney disease (CKD), leading to a severe reduction in the quality of life of patients, an increased risk of death, and a risk of cardiovascular disease.

Data from a recent epidemiological survey show that the prevalence of CKD in the adult population has reached 杭州夜网论坛 10.

8%, about 1.

200 million people, more than 50% of whom have anemia.

The prevalence and severity of renal anemia are gradually increasing in different populations of CKD patients. CKD 1?
The prevalence of anemia in stage 5 patients was: 22 in order.

0%, 37.

0%, 45.

4%, 85.

1% and 98.

At 2%, the prevalence of anemia in diabetic and non-diabetic CKD patients was 98.

2% and 52.

0%.

However, the awareness rate of renal anemia in CKD patients is only 67.

5%, and the treatment rate is low, starting treatment late.

Treatment of anemia in non-diabetic CKD patients in the United States44.

9%.

Third, the rate of compliance with CKD anemia is low. Among patients with chronic non-diabetes, the rate of compliance with treatment is only 12.
.

At 1%, the rate of compliance with anemia in hemodialysis patients was only 21.

3%, and European and American national standards are still at the same level (European and American treatment compliance rate is 55% -77%).

  Traditional ESAs + iron combination therapy has toxic limitations and is not highly compliant.

At present, ESAs + iron combination therapy is the only clinical treatment for renal anemia for decades, but it still has certain limitations including: ① some patients show low response to ESAs, and the use of ESAs is overdose, leading to increased side effects,Increased mortality.

② ESAs can be painful when injected subcutaneously or intravenously. Patients have poor compliance and discontinuous treatment.

③Inflammation and other conditions affect the treatment of ESAs and iron.

④ Some CKD patients may produce EPO antibodies due to the use of externally-derived EPO, resulting in a poor response to EPO treatment and even triggering antibody-mediated aplastic anemia, which further worsens the condition.
⑤ The use of ESA will accelerate iron consumption in the body, leading to functional iron deficiency, increasing hepcidin levels, exacerbating iron utilization barriers, and increasing the need for iron supplementation.

⑥ Intravenous iron supplementation can not completely improve the condition of iron utilization disorder, but it brings adverse reactions such as acute allergic reactions, oxidative stress, etc. In the case of acute infection, intravenous iron supplementation is not recommended. ES alone is used as a treatment for renal anemia.The effect is very limited.

Therefore, better clinical medicines and alternatives are urgently needed.
  HIF-PHI is a new target for the treatment of renal anemia, and its “oxygen perception mechanism” is based on the restoration of the 2019 Nobel Prize in Physiology or Medicine.

HIF-PHI drugs are emerging treatments for renal anemia.

  HIF-PHI (hypoxia-inducible factor proline amide hydroxylase inhibitor) is a new mechanism innovative drug for the treatment of renal anemia.

Its mechanism of action is to inhibit the function of “proline amide hydroxylase” (PH) by simulating the hypoxic environment, eliminate the degradation of “hypoxia-inducible factor-α” (HIF-α), and make the body “erythropoietin”(EPO) production increases, thereby achieving the goal of relieving anemia.

The “Oxygen Perception Mechanism” on which Enarodustat is based awarded the 2019 Nobel Prize in Physiology or Medicine.

  Enarodustat has the advantage of earlier target drugs and is a “global new” drug.

The HIF-PHI drugs Enarodustat developed by Japan’s JT Corporation have the following advantages over ESAs and other drugs with the same target: ① Enarodustat has higher activity than drugs with the same target, and the actual dosage is small, which theoretically reduces the probability of adverse reactions;② The once-daily usage increases the hemoglobin more slowly; ③ The risk of drug interaction of Enarodustat is lower than that of the same target drug, and the induction and inhibition of CYP enzymes is small and reversible; ④ The kidney burden of Enarodustat is lighter thanWith the same target drug, only 11% of Enarodustat was excreted from the kidney, and 46% of the same target drug was excreted through the kidney.

⑤ In terms of treatment compliance, once a day, the appropriate continuous treatment with the target drug is performed every other day.

  The company continues to deploy global innovative drugs and is expected to exert synergies in the field of chronic disease treatment.

Obtained the exclusive rights of the product in the Chinese market (including Mainland China, Taiwan, Hong Kong and Macau Special Administrative Regions), and plans to start the Phase III clinical trial in China in 2020, and is expected to obtain production approval by the end of 2022.

  Payments include: 1) the first domestic clinical trial; 2) Enarodustat successfully approved for listing in Japan; 3) the first submission of a listing application in the Chinese market; 4) the first approval of the product in the Chinese market.

Through this cooperation, the company is expected to achieve clinical trial data in Japan and accelerate internal R & D progress; after listing, it will provide patients with more convenient and effective medication choices to better meet the clinical needs met in the field of renal anemia, andExtend and expand the company’s innovative drug product line, and quickly enrich the company’s innovative products in the field of chronic diseases.

At the same time, it is expected to gradually take the opportunity to strengthen international cooperation in the development of innovative drugs, integrate the advantageous resources of all parties, and exert synergies.

  Profit forecast and estimation: Although the volume purchase has a continuous impact on the company’s existing business, the company’s core advantages are still solid, and the company has the ability and ability to select innovative drugs globally.

As a leader in the domestic cardiovascular field, in the future, we will be committed to continuous innovation in the field of chronic diseases, and the product echelon will be gradually strengthened. A variety of innovative drugs such as alisartan and teriparatide have entered or are about to enter the harvest period.bright future.

Maintaining EPS 1 for 19-21 years.

12/0.

93/0.

98 yuan, an annual increase of -20% /-17% / 6%, corresponding to 20X PE for 20 years.

Maintain the “overweight” rating.

  Risk reminder: Progress in volume procurement exceeds expectations; new product promotion exceeds expectations.