Hold hands with Lilly!

On March 28, Innovent and Eli Lilly jointly announced that the two parties will deepen their strategic cooperation and have reached an agreement on the following matters: 1) Innovent obtains access to the import, sale, promotion and distribution of Cirana (Remoxicil) in mainland China.

This is the fifth time that Cinda and Eli Lilly have worked together

In this cooperation, ramucirumab is a blockbuster anticancer drug with global sales of more than 1 billion US dollars in 2020, while LOXO-292 and LOXO-305 are Eli Lilly's 2019 sales of about 8 billion US dollars The core assets of the anti-cancer targeted drugs acquired by the acquisition of Loxo Oncology have unlimited potential

At present, ramucirumab has been approved for marketing in China, and there is a new indication in the market application; and LOX-292 also submitted a marketing application in November last year, and is expected to be approved within this year

Ramucirumab

In recent years, studies have shown that the anti-vascular endothelial growth factor (VEGF) pathway is an important signaling pathway involved in tumor angiogenesis, and targeted therapy for gastric cancer has also made many attempts to target this pathway

Ciranaze® (ramucirumab) is a fully human IgG1 monoclonal antibody that specifically binds to VEGFR-2.

In the United States, ramucirumab is the first FDA-approved treatment for patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma after chemotherapy and the first FDA-approved treatment for advanced hepatocellular carcinoma ( Biomarker-driven therapy for patients with HCC)

FDA-approved indications for ramucirumab

From: Insight database (http://db.

In China, the first clinical application for ramucirumab was submitted as early as 2010, the first clinical application was initiated in 2014, and the first marketing application was accepted in January 2021

The NMPA has approved the drug in combination with paclitaxel in March 2022 for the treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma whose disease has progressed during or after fluorouracil- or platinum-containing chemotherapy, making it the first in China The only targeted drug approved for second-line treatment of advanced gastric cancer; in September 2021, ramucirumab was used as an alpha-fetoprotein (AFP) ≥ 400ng/ml and had previously received sorafenib for liver disease The new indication marketing application for second-line therapy in patients with cell carcinoma has been accepted and is expected to be approved within this year

Ramucirumab Program Overview

From: Insight database project progress module (http://db.

Gastric and liver cancers are the third and fifth most common cancers in China, with about 900,000 new cases each year

According to the Insight database, there are currently 4 biosimilar projects under development in China, from Kelun, Henlius, Chia Tai Tianqing, and Qilu Pharmaceuticals

Domestic competition of ramucirumab

From: Insight database project progress module (http://db.

"Pan-Cancer" Anticancer Drug: Sepretinib (LOXO-292)

Retsevmo® (Septinib, development code: LOXO-292) is a highly selective and potent inhibitor of transfection-rearranged gene (RET), the first FDA-approved drug specifically for the treatment of metastatic RET in adults Fusion-positive non-small cell lung cancer (NSCLC), advanced or metastatic RET-mutant medullary thyroid cancer (MTC) requiring systemic therapy in adults and children over 12 years of age, and advanced or metastatic radioactive iodine tolerance (if appropriate) requiring systemic therapy Therapy in patients with RET fusion-positive thyroid cancer

Genetic alterations in RET kinases, including fusion and activating point mutations, lead to hyperactive RET signaling and uncontrolled cell growth

In China, the NMPA accepted the new drug marketing application of Retsevmo® (septinib) for the above indications in August 2021, and granted priority review status, which is expected to be approved for marketing within this year
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LOXO-292 Project Overview

From: Insight database project progress module (http://db.
dxy.
cn/v5/home/)

The third-generation BTK inhibitor LOXO-305: potential BIC, one-on-three PK zanubrutinib, ibrutinib, acalatinib

In this cooperation, Eli Lilly also granted Innovent Biothe priority to negotiate the future commercialization rights of Pirtobrutinib in China
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Pirtobrutinib (LOXO-305) is an investigational oral, highly selective, non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor that retains activity under acquired resistance to the C481 mutation, Provides consistently high on-target coverage and avoids complications from off-targeting of other non-covalent BTK inhibitors
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In December 2021, Eli Lilly has submitted the drug's marketing application to the FDA on a rolling basis
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LOXO-305 is also the fastest-moving new generation of BTK inhibitors targeting the BTKC481S mutation
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Eli Lilly is confident in this new drug, and has launched 3 head-to-head randomized superiority global multi-center Phase III clinical trials in 2021 in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma.
Cancer (MCL) and 3 BTK inhibitors that have been marketed ) direct PK
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According to the Insight database, the Chinese part of two head-to-head clinical trials of BRUINCLL-321 and BRUINMCL-321 has also been initiated (CTR20212373, CTR20212310)
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In December 2020, Eli Lilly announced the global multicenter Phase I/II clinical data of LOXO-305 at the ASH meeting (abstract 542), which included 323 patients who had received at least two lines of therapy and had disease progression or intolerance.
CLL/SLL or other NHL patients with standard of care
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Eli Lilly LOXO-305 has published clinical data

From: Insight database (http://db.
dxy.
cn/v5/home/)

RESULTS: Among 139 CLL/SLL patients who could be evaluated for efficacy, the overall response rate (ORR) was 63% (95% CI: 55-71)
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Among the 121 patients who had failed prior BTK inhibitor therapy for efficacy evaluation, the ORR was 62% (95% CI: 53-71), and the ORR increased to 84% (21/25) with a follow-up of 10 months or longer
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The degree of remission increased over time
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ORR was similar in patients who had previously used a covalent BTK inhibitor and discontinued treatment due to disease progression, and discontinued covalent BTK inhibitor therapy for toxicity or other reasons
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According to the agreement, Innovent Biologics will pay Eli Lilly a total of after the approval and registration of cilanze® (ramucirumab) for hepatocellular carcinoma and Retsevmo® (septinib) for non-small cell lung cancer.
$45 million down payment
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Innovent will be solely responsible for the pricing, importation, marketing, distribution and sales promotion of these two products
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Innovent Bio has more than 20 strong anti-tumor pipelines in different stages of clinical research, industry-leading clinical development and registration professional teams, broad business channel coverage and a commercialization team of more than 3,000 people.
Successfully launched and sold Dabosu® (sintilimab) and Dabohua® (rituximab biosimilar) in China
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