Innovent and RemeGen Enter into Clinical Trial Collaboration Investigating Combination Therapy of TYVYT® (sintilimab injection) and Novel ADC Candidates for Advanced Solid Tumors in China

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ROCKVILLE, Md. and SUZHOU, China, June 25, 2023 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and RemeGen Co., Ltd. (688331.SH/09995.HK), today announced that they entered into a clinical trial collaboration and supply agreement with for the combination therapies of TYVYT® (sintilimab injection) with RC88, a novel mesothelin(MSLN)-targeting antibody-drug conjugate (ADC), or RC108, a novel c-Met-targeting ADC, respectively, as potential treatment options for advanced solid tumors in China.

Under the agreement, Innovent will provide clinical drug supplies of TYVYT® (sintilimab injection) during the clinical trial collaboration. RemeGen will conduct Phase 1/2a clinical studies to evaluate the anti-tumor activity and safety of the combination therapy of TYVYT® (sintilimab injection) with RC88 or RC108 in Chinese patients with advanced solid tumors.

TYVYT® (sintilimab injection) is an innovative PD-1 inhibitor co-developed by Innovent and Eli Lilly and Company. In China, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. TYVYT® (sintilimab injection) is the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types in the NRDL – including non-squamous NSCLC, squamous NSCLC, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer, as well as the first and the only immunotherapy medicine for gastric cancer in the NRDL.

RC88 is a novel MSLN-targeting ADC independently developed by RemeGen. RC88 is currently being investigated in an ongoing Phase 1 clinical trial, which was approved by the NMPA in November 2018. The preliminary results demonstrated anti-tumor activity and a manageable safety profile of RC88 monotherapy in MSLN-positive advanced solid tumors. Preclinical studies also showed that RC88 can selectively delivers a potent cytotoxic payload to MSLN-expressing cells through internalization, thus inducing G2/M arrest and apoptosis. When combined with PD-1/PD-L1 or other immune checkpoint inhibitors (ICIs), RC88 can induce immunogenic cell death (ICD), releasing a series of signaling molecules to further activate T cells, enhance tumor immune response, and synergistically exert a stronger anti-tumor effect.

RC108 is a novel c-Met targeting ADC independently developed by RemeGen. RC108 is currently being investigated in an ongoing Phase 1 clinical trial, which was approved by the NMPA in November 2020. The preliminary results demonstrated anti-tumor activity and a manageable safety profile of RC108 monotherapy in c-Met-positive advanced solid tumors. Preclinical studies also showed that RC108 can induce tumor-specific adaptive immunity and increase the infiltration of T cells into the tumor microenvironment, while anti-PD-1 monoclonal antibody can activate T cells to enhance anti-tumor killing effect. Therefore, it is expected that the combination therapy of RC108 and sintilimab can not only improve antigen presenting by dendritic cells , but also boost the tumor killing of T cells, therefore bringing in synergistic tumor inhibition effect.

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to collaborate with RemeGen to further explore the combination therapy potential of sintilimab injection and novel ADC candidates. Preclinical studies has suggested the synergistic anti-tumor effects, which supports the investigation of combining ADCs with an anti-PD-1 monoclonal antibody to improve patient outcomes and overcome drug-resistance. As immunotherapy advanced into next era of development, we hope to strengthen the leading position of sintilimab as a backbone immunotherapy as well as investigate the new opportunities of combination therapies, and provide better treatment options for more cancer patients. "

Ms. Na Su, Senior Vice President of RemeGen, stated "Collaborating with Innovent is an important advancement in the research and commercialization strategy for the combination therapy of RC88 and RC108. The combination of RC88 and RC108 with sintilimab provides an innovative treatment approach that targets two different targets simultaneously. The mechanisms are complementary and synergistic, helping to overcome or delay resistance, achieve multi-pathway targeting of tumors, and provide an efficient solution for unmet clinical needs."

About RC88 ADC

RC88 is a novel anti-mesothelin ADC developed by RemeGen, which is formed by a recombinant humanized anti-MSLN monoclonal antibody conjugated to the microtubule inhibitor MMAE via a Linker. It includes an MSLN antibody moiety (also known as RC88 naked antibody), a linker, and a small molecule moiety of the cytotoxic pentapeptide MMAE. RC88 binds hMSLN with high affinity and specificity and can compete with endogenous ligands. It can kill tumor cells with different expression levels of MSLN, and the killing effect is positively correlated with the expression of MSLN. Functional studies on the Fc fragment showed that the Fc-mediated effect was not a major role in the effect of this drug. Based on promising preclinical data, a phase 1 study has been moving forward quickly.

About RC108 ADC

RC108 is a targeted antibody-drug conjugate (ADC) developed by RemeGen for the treatment of solid tumors with positive expression of the cell-matrix epithelial transition factor (c-MET). RC108 consists of a c-MET targeting antibody, a linker, and a small molecule cytotoxin. Its mechanism of action is similar to RC48, as it can selectively bind to c-MET-positive tumor cells, mediate antibody internalization, and effectively deliver the cytotoxin to cancer cells, achieving a good tumor-killing effect. In November 2020, RemeGen received approval from the National Medical Products Administration to conduct Phase 1 clinical trials of RC108 targeting c-MET-positive advanced solid tumors in China. The trial is currently progressing smoothly, and preliminary results show that RC108 has anti-tumor activity against c-MET-expressing solid tumors and is well-tolerated. In December 2022, RC108 obtained clinical trial permission from the U.S. Food and Drug Administration (FDA) to conduct clinical research in patients with c-MET-positive solid tumors. In April 2023, a combination therapy involving RC108 was approved to conduct Phase 1b/2 clinical research in China, targeting patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations who have failed treatment with MET expression of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Preclinical study results showed that RC108 induces tumor-specific adaptive immunity, increases T-cell infiltration into the tumor microenvironment, and PD-1 monoclonal antibodies activate T-cells, enhancing anti-tumor immune responses. Therefore, it is expected that the combination of RC108 and PD-1 antibodies can enhance dendritic cell presentation of tumor antigens and strengthen T-cell killing of tumor cells, resulting in an enhanced synergistic anti-tumor effect.

About Sintilimab

Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells^[i]. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. The updated NRDL reimbursement scope of TYVYT® (sintilimab injection) include:

• For the treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
• For the treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
• For the treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
• For the treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
• For the treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
• For the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy.

Additionally, sintilimab has been approved in combination with bevacizumab and chemotherapy (pemetrexed and cisplatin) for the treatment of patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy.

Besides, two clinical studies of sintilimab have met their primary endpoints:

• Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
• Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines in the fields of oncology, metabolism, autoimmunity, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include:  TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor), olverembatinib (BCR-ABL TKI) , Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 3 assets are under NMPA NDA review, 6 assets are in Phase 3 or pivotal clinical trials, and 18 more molecules are in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Note:

TYVYT® (sintilimab injection) is not an approved product in the United States.

BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.

TYVYT® (sintilimab injection, Innovent)

BYVASDA® (bevacizumab biosimilar injection, Innovent)

HALPRYZA® (rituximab biosimilar injection, Innovent)

SULINNO® (adalimumab biosimilar injection, Innovent)

Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

CYRAMZA® (ramucirumab, Eli Lilly). CYRAMZA® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Retsevmo® (Selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Disclaimer: Innovent does not recommend any off-label usage.

About RemeGen

RemeGen Co., Ltd. (RemeGen) is a leading fully integrated biopharmaceutical company in China headquartered in Yantai, Shandong Province, China, and RemeGen has labs/offices in Beijing, Shanghai, California and Maryland. The company is committed to the discovery, development and commercialization of innovative and differentiated biologics for the treatment of autoimmune, oncology and ophthalmic diseases with unmet medical needs in China and globally. Currently, more than 20 biologics candidates are under development, and seven products with more than 20 indications are in clinical trials or have entered the commercialization stage. Among them, the first BLyS/APRIL dual-targeting fusion protein novel biologics globally for the treatment of SLE, Telitacicept was approved for marketing on March 9, 2021; and China's first domestically made antibody-drug conjugate Disitamab Vedotin was approved for marketing on June 8, 2021. RemeGen was listed on the Hong Kong Stock Exchange on November 9, 2020 (stock code: 09995.HK) and on the Science and Technology Board of the Shanghai Stock Exchange on March 31, 2022 (stock code: 688331.SH).

Innovent's Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

SOURCE Innovent Biologics