Welcome to the big exam OR touchstone! How did Cinda move from biotech to big pharma?

Source: Yaozhi Network/Red Pepper

On February 10, the FDA will convene an ODAC meeting (Oncology Drug Advisory Committee) for marketing applications for the PD-1 drug Cindalisumab in collaboration with Cinda/Eli. It may affect the FDA's attitude towards the review of PD-1/L1 products in China.

Welcome to the big exam OR touchstone?

According to public statistics, there are currently 6 PD-1 models listed in the United States, of which 5 have been approved for non-small cell lung cancer. Some industry experts said that the FDA is about to review more than 25 new drug applications that are completely or mainly based on Chinese data, and as the first application of Cinda and Eli Lilly, it is inevitable to face challenges from the FDA. At the same time, the United States is likely to tighten the approval of PD-1 monoclonal antibody due to the consideration of clinical resources and competitive landscape.

It is worth noting that based entirely on phase III clinical data conducted in China, the only innovative drug that has been successfully applied for marketing at the FDA is Zebutinib in BeiGene. However, as the first person to eat "crab", Innovent Biology will be the touchstone for the entire Chinese biomedical industry to go to sea, and accumulate experience for the exchange of follow-up innovative drugs with the FDA.

In fact, counting the innovation pipelines and clinical progress, Innovent Biologics is already in line with international standards and is moving forward side by side with international innovation giants.

Biotech is the only way to move towards bigsharma

In 2011, Cinda Bio was established. At that time, it was the first wave of PD-1 boom in China.

From the establishment of the project in 2012 to the 2019 PD-1 Xindili monoclonal antibody injection (Daboshu ®, English trademark: TYVYT®) was listed and became the first anti-PD-1 monoclonal antibody to enter the national medical insurance, Cinda successfully carded the first echelon of the PD-1 market. In the 2021 national health insurance negotiations, Daboshu ® (Xindili monoclonal antibody injection) successfully added three first-line indications to the national medical insurance directory (NRDL).

In addition, it is worth mentioning that Cinda Bio recently announced that Daboshu ® (Xindili Monoclonal Antibody Injection) achieved relevant sales revenue of about RMB 900 million in the fourth quarter of 2021.

Source: Cinda BioJPM Conference PPT

According to the statistics of Yaozhi data, as of now, Cinda Bio has 6 products including Xindili monoclonal antibody approved for listing. In June 2020, the biosimilar bevacizumab (trade name: Dayoutong ®, English trademark: BYVASDA®) was approved for marketing; in September, the biosimilar adalimumab (trade name: Su Lixin ®, English trademark: SULINNO®) was approved for listing; in September, the biosimilar rituximab (trade name: Daberva ®, English trademark: HALPRYZA®) was approved for marketing.

In June 2021, pemigatinib oral inhibitors (trade name: Dabtan ®, English trademark: PEMAZYRE®) were approved for listing; in November, orebatinib tablets (trade name: Nelik ®) were approved for marketing.

In addition to the 6 approved products, Cinda has 6 products with good results in the POC (Proof of Concept) stage, 4 products are ongoing, and more than 80 research projects are underway in terms of early research. In ten years, the growth of Cinda can be described as a step by step out of its own rhythm, from the initial biotech to the successful transformation of pharma, and gradually towards Bigpharma. The above strengths have provided sufficient reserves for them to successfully pass the FDA review on February 10.

The next wave of innovation is coming

In addition, from the perspective of R&D pipeline, Innovent Biology has a wide layout, involving tumors, autoimmune diseases, metabolic diseases and fundus diseases, etc. The project is mainly completed by internal research and development, cooperative development and external introduction.

Source of Cinda Bio's R&D pipeline: Cinda Bio's official website

IBI-306: Targeting PCSK-9, by specifically binding TO PCSK-9, blocking PCSK-9 binding to LDL-R epidermal growth factor-like domain A, reducing the degradation of LDL-R in lysosomes, promoting the degradation of LDL-C in the liver, reducing LDL-C in plasma, treating hyperlipidemia, and reducing the risk of cardiovascular disease. In August 2021, IBI-306 reached the primary study endpoint in the Phase 3 clinical study (CREDIT-2).

IBI-310: Taking CTLA-4 as the target, by upregulating the anti-tumor immune response mediated by human effector T cells and weakening the immunosuppressive activity mediated by regulatory T cells, it inhibits the immune escape of tumor cells and improves the body's own immune response to tumor cells, so as to achieve the purpose of treating a variety of tumors. Early clinical studies have shown that IBI-310 combined with sindilizumab has good safety and antitumor activity, suggesting potential in combination therapy for tumor therapy.

IBI-376 (parsaclisib): A potent, highly selective, new-generation PI3Kδ oral inhibitor introduced by Incite From Incyte, which plays an important role in inhibiting pi3Kδ in the growth and survival of malignant B-cell lymphoma. Currently, parsaclisib is conducting several Phase 2 trials in patients with non-Hodgkin lymphoma and autoimmune hemolytic anemia, as well as registered clinical trials in patients with myelofibrosis. The product has also been included in the Breakthrough Therapeutic Variety in China, with the proposed indications for recurrent or refractory follicular lymphoma.

IBI-326: A fully human-derived BCMACAR-T cell therapy developed jointly by Innovent Bio and Reindeer Medical. The latest results of the Phase 1 clinical study on the treatment of relapsed/refractory multiple myeloma (R/RMM) have been presented at the European Annual Meeting of Hematology (EHA) 2021. At present, the product has officially entered the key clinical study of Registration Phase 2. IBI-326 is also included in the Breakthrough Treatment Variety in China, with a proposed indication for relapsed/refractory multiple myeloma.

IBI-344 (taletrectinib): The next generation of tyrosine kinase (TKI) inhibitors introduced from Baoyuan Bio that target ROS1 and NTRK are effective in ROS1-positive NSCLC patients who have not been treated with TKI and have obvious differentiating advantages. With the potential for first-in-class (FIC) and best-in-class (BIC) new drugs, it is currently in Phase 2 research phase.

IBI-362: An innovative gastric acid modifier (OXM3) jointly promoted by Innovent Andy and Eli Lilly Pharmaceuticals, it is a GLP-1R and GCGR dual agonist with best-in-class potential. The effects of IBI-362 are thought to be mediated by the binding and activation of GLP-1R and GCGR, with a similar mechanism of action to OXM, so it is expected that it can improve glucose tolerance and reduce body weight. In addition to the effects of GLP-1R agonists in promoting insulin secretion, lowering blood sugar and reducing weight, IBI-362 may also have effects such as increasing energy expenditure and improving liver fat metabolism through GCGR activation.

IBI-188: is a CD47 antibody that induces tumor clearance through macrophages and can be coordinated with other tumor clearance therapies (chemotherapy, PD-1, HMA, etc.). It is highly responsive to the target, and 160 patients have participated in clinical trials, and the safety has been preliminarily verified.

IBI-302: Taking VEGF and C3b and C4b as targets, and combining the two targets of vascular endothelial growth factor (VEGF) and complement, the VEGF signaling pathway and complement activation are blocked. IBI-302 is used to treat age-related macular degeneration.

IBI-110: A recombinant all-human anti-lymphocyte activated gene 3 (LAG-3) monoclonal antibody, an anti-LAG-3 monoclonal antibody. Studies have shown that inhibiting LAG-3 can allow T cells to regain cytotoxic activity, reduce the function of regulating T cells to suppress the immune response, and thus enhance the killing effect on tumors.

IBI-323: is a PDL1/LAG-3 bispecific antibody, IBI-323 in addition to blocking the interaction of PD-L1/PD-1 and LAG-3/MHC-II activates the role of T cells, but also has the effect of drawing tumor cells (expressing PD-L1) and immune cells (expressing LAG-3), which is more beneficial for T cells to clear tumor cells. IBI323 has demonstrated the antitumor effect of dual antibodies 1+1>2 in preclinical studies, and has entered Phase I clinical studies.

IBI-322: Anti-PD-L1/CD47 dual antibody, IBI322 can simultaneously antagonize CD47 and PD-L1 two targets, by activating natural immune and acquired immune pathways, enhance the immune system's targeted recognition of tumors, exert anti-tumor effects, is currently in Phase I clinical research.

IBI-353: Is a potent and highly selective next-generation PDE4 inhibitor with a wide range of anti-inflammatory properties. In September 2021, it partnered with UNINONtherapeutics to obtain an exclusive licensing agreement in China, including Chinese mainland, Hong Kong, Macau and Taiwan.

IBI-315: The world's first recombinant fully human anti-programmed death receptor 1 (PD-1) and humanized anti-human epidermal growth factor receptor 2 (HER2) IgG1 bispecific antibody, jointly developed by Innovent Biotech and Hanmi Pharmaceuticals, and clinically developed in China by Innovent. According to preclinical studies, IBI-315 can also bridge T cells and tumor cells to promote the killing of tumor cells.

IBI-939: Is a recombinant fully human anti-immunoglobulin-containing motif and immune receptor tyrosine inhibition motif domain of T cell immune receptor (TIGIT) monoclonal antibody, mainly targeting T cells in the tumor microenvironment and TIGIT on the membrane of NK cells, which can prevent the binding of highly expressed CD155 on the cancer cell membrane with TIGIT, thereby restoring the activation of cytotoxic T cells and NK cells, and exerting tumor killing effect.

IBI-112: Is a recombinant anti-interleukin 23p19 subunit antibody injection that can specifically bind to the IL-23p19 subunit, blocking the IL-23 receptor-mediated signaling pathway by blocking the anti-inflammatory effect of IL-23 receptor binding to cell surface receptors. Preclinical data show that IBI112 has a clear target, a clear mechanism of action, and a significant anti-inflammatory effect, which is expected to provide more effective treatment options for patients with psoriasis and other autoimmune diseases.

IBI-102: Is an anti-GITR monoclonal antibody. GITR acts as a co-stimulatory receptor in regulatory T cells and at low levels in memory T cells, macrophages, dendritic cells, and NK cells. In August 2020, Innovent Biologics submitted its clinical trial application for IBI102 in China for the first time and was accepted for development for advanced malignancy.

IBI-319: An anti-PD-1/CD137 bispecific antibody developed by Innovent Biotech in collaboration with Eli Lilly Pharmaceuticals, it can simultaneously exert the dual effects of immune checkpoint PD-1 inhibitors and CD137 agonists. In November 2021, NatureCommunications published the results of the preclinical study of IBI-319, which showed that IBI-319 has a significantly better efficacy than PD-1 monoclonal antibody, and has good safety and no side effects such as hepatotoxicity.

IBI-321: PD-1/undisclosed target diagonist, its clinical trial application was accepted by NMPA on March 4, 2021.

IBI-351: A highly efficient oral new molecular solid compound that covalently and irreversibly modifies the Cysteine residue of the KRASG12C protein mutant, effectively inhibits the PROTEIN-mediated GTP/GDP exchange and thereby downregulates the KRAS protein activation level; preclinical cysteine selective tests also show the high selective inhibition effect of IBI351 on this mutation site. In addition, IBI351 inhibits the KRAS protein and then inhibits the downstream signaling pathway, effectively inducing tumor cell apoptosis and cell cycle blocking, and achieving anti-tumor effects. In September 2021, Cinda Bio and Jinfang Pharmaceutical reached a strategic cooperation to obtain the development and commercialization rights of IBI351 in China (including Chinese mainland, Hong Kong, Macau and Taiwan) as the exclusive partner, and have the option of global development and commercialization rights.

epilogue

From the beginning of its establishment, Innovent Biology has laid out early and blossomed in an all-round way, grasping the golden decade of the history of China's innovative drug development. Now Cinda is undoubtedly majestic and vigorous in this competition. In the future, with the continuous enrichment of products, international cooperation and talent blessing, Innovent Biology will eventually become a shining star in the sea of Chinese medicine stars.

Responsible editor: Three seven

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