Innovent Biologics and Merck Announce Clinical Collaboration to Evaluate IBI351 (KRAS G12C Inhibitor) in Combination with Cetuximab for KRAS G12C-Mutated Non-Small Cell Lung Cancer

Rockville, USA and Suzhou, ChinaJune 2, 2023PR Newswire -- Innovent Bio (HKEX stock code: 01801), a biopharmaceutical company dedicated to the research, development, production, and commercialization of innovative drugs in major disease areas such as oncology, autoimmune diseases, metabolic disorders, and ophthalmology, today announced a clinical research and drug supply collaboration agreement with Merck KGaA to explore IBI351 (GFH925, KRAS).^G12CInhibitor) combined with Erbitux^®(Cetuximab Injection) is used forTreatmentCarrying KRAS^G12CMutatedAdvancedPatients with non-small cell lung cancer.

According to the cooperation agreement, Innovent Bio will conduct a Phase Ib clinical study to evaluate IBI351 in combination with Erbitux.^®(Cetuximab Injection) in ChinaCarryKRAS^G12CMutatedAdvancedSafety, Tolerability, and Preliminary Efficacy in Non-Small Cell Lung Cancer Patients. Merck will provide cetuximab for the trial; currently, cetuximab as a monotherapy or in combination therapies has not been approved for the treatment of non-small cell lung cancer patients.

Currently, IBI351 monotherapy for patients with KRAS mutations who have failed prior standard treatments^G12CA single-arm registrational study for mutant advanced non-small cell lung cancer is ongoing, with plans to submit a New Drug Application (NDA) by the end of 2023. In addition, IBI351 in combination with sintilimab (PD-1 inhibitor)For carriers ofKRAS^G12CA Phase Ib clinical study on mutant advanced non-small cell lung cancer is also underway. Previously, the Phase I clinical study data of IBI351 monotherapy for solid tumors was orally presented at the 2023 American Association for Cancer Research Annual Meeting (AACR 2023). IBI351 monotherapy showed efficacy in 67 patients with KRAS mutations who had failed or were intolerant to prior standard treatments.^G12CIn patients with advanced lung cancer harboring mutations, it demonstrated good safety, tolerability, and encouraging efficacy signals[Link]。

Dr. Hui Zhou, Senior Vice President of Innovent BioWe are pleased to have reached an agreement with Merck Group to jointly explore the combination of IBI351 and Cetuximab.Monoclonal Antibody TherapyCarrying KRAS^G12CThe Clinical Potential of Non-Small Cell Lung Cancer Patients with Mutations. Clinical studies suggest that KRAS^G12CInhibitorHomologous moleculesCombination of anti-EGFR monoclonal antibodies shows preliminary efficacy in previously treated patients with advanced colorectal cancer^[1],[2],[3]The preclinical study of IBI351 in combination with cetuximab also suggests potential synergistic enhancement of antitumor activity in non-small cell lung cancer. As a monotherapy, IBI351 has demonstrated encouraging efficacy and safety signals in Phase I clinical trials. We look forward to advancing the further development of this high-potential molecule as both a monotherapy and combination therapy, exploring new opportunities for frontline treatments. As cancer immunotherapy enters its next phase, we will continue to uphold our mission of "developing high-quality biologics that are affordable for the general public," benefiting more patients.

AboutIBI351/GFH925（KRAS^G12CInhibitor)

The RAS protein family is mainly divided into three subtypes: KRAS, HRAS, and NRAS. Among them, KRAS is the most common RAS protein subtype, with KRAS gene mutations found in nearly 90% of pancreatic cancer patients, 30-40% of colon cancer patients, and 15-20% of lung cancer patients; its mutation rate is higher than the total sum of ALK, RET, and TRK gene mutations.

As a highly efficient oral new molecular entity compound, IBI351 covalently and irreversibly modifies KRAS^G12CThe cysteine residue of the protein mutant inhibits the GTP/GDP exchange mediated by this protein, thereby downregulating the activation level of KRAS protein. Preclinical cysteine selectivity tests also demonstrated the high selective inhibitory potency of IBI351 for this mutation site. Moreover, after inhibiting the KRAS protein, IBI351 can further inhibit the downstream signaling pathway, induce tumor cell apoptosis and cell cycle arrest, achieving an anti-tumor effect.

In September 2021, Innovent Bio and Geforce Biomedicine announced a global exclusive licensing agreement, under which Innovent Bio, as the exclusive partner, obtained the development and commercialization rights of GFH925 (Innovent's R&D code: IBI351) in China (including mainland China, Hong Kong, Macao and Taiwan), and had the option for global development and commercialization rights.

IBI351 was granted Breakthrough Therapy Designation by the CDE in January 2023 and May 2023, respectively, for the treatment of patients with KRAS mutations who have received at least one systemic therapy.^G12CPatients with mutant-type advanced non-small cell lung cancer (NSCLC) and KRAS who have received at least two systemic treatments^G12CPatients with mutant-type advanced colorectal cancer (CRC).

About Erbitux^®(Cetuximab Injection)

Cetuximab is the world's first IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody drug, cetuximab differs from standard non-selective chemotherapy drugs in that it targets and binds to EGFR. This binding inhibits receptor activation and subsequent signaling, reducing tumor cell invasion of normal tissues and the spread of tumors to new sites.

In addition, cetuximab is considered to inhibit the ability of tumor cells to repair damage caused by chemotherapy and radiotherapy, as well as to suppress the formation of new blood vessels within tumors. Based on in vitro study evidence, cetuximab also exhibits antibody-dependent cellular cytotoxicity (ADCC) against EGFR-positive tumor cells.

As of now, Erbitux^®Approved in more than 100 countries/regions worldwide for the treatment of RAS wild-type metastatic colorectal cancer, locally advanced, and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). Erbitux^®Developed by ImClone (now a wholly-owned subsidiary of Eli Lilly), Merck acquired Erbitux in 1998.^®Exclusive rights in markets outside the United States and Canada.

About Innovent Bio

"Start with trust, achieve through action." Developing high-quality biologics that are affordable for the general public is the ideal and goal of Innovent Bio. Founded in 2011, Innovent Bio is committed to the development, production, and sales of innovative drugs in major disease areas such as oncology, autoimmune diseases, metabolic disorders, and ophthalmology. On October 31, 2018, INNOVENT BIOLOGICS(SUZHOU)CO LTD was listed on the Main Board of the Hong Kong Stock Exchange under the stock code: 01801.

Since its establishment, the company has stood out among many biopharmaceutical companies with its innovative achievements and internationalized operation model. It has built a product chain including 35 new drug varieties, covering multiple disease areas such as oncology, autoimmune diseases, metabolism, and ophthalmology. Among them, seven varieties have been selected for the national "Major New Drug Creation" project. The company has received approval for eight products to be marketed: Sintilimab Injection (Tyvyt®), Bevacizumab Injection (Byvasda®), Adalimumab Injection (Sulinno®), Rituximab Injection (Hanliko®), Pemigatinib Tablets (Pemazyre®), Olverembatinib Tablets (Besremi®), Ramucirumab Injection (Cyramza®), and Selpercatinib Capsules (Retsevmo®). Three varieties are under review by the NMPA, six new drug molecules have entered Phase III or pivotal clinical trials, and another 18 new drug varieties have entered clinical studies.

Innovent Bio has assembled a team of top-tier biopharmaceutical development and industrialization professionals with international advanced expertise, including numerous returned overseas experts, and has established 28 strategic collaborations with international partners such as Eli Lilly, Roche, Sanofi, Adimab, Incyte, and MD Anderson Cancer Center.

Innovent Bio, while continuously developing innovative drugs through self-research and pursuing its own growth, adheres to the development philosophy of economic construction centered on the people. Over the years, it has maintained a sincere commitment to science, upholding the principle of "patient-centeredness," caring for patients and their families, and actively fulfilling social responsibilities. The company has successively initiated and participated in multiple drug-related public welfare assistance programs, enabling more and more patients to benefit from advances in life sciences by gaining access to high-quality biologics at an affordable cost. As of March 2023, Innovent Bio's patient assistance program has benefited over 160,000 ordinary patients, with the total value of donated drugs reaching hundreds of millions of yuan.

Innovent Bio hopes to work together with everyone to enhance the development level of China's biopharmaceutical industry, in order to meet the public's access to medicines and people's pursuit of a better life and health.

For more details, please visit the company website: www.innoventbio.com or the company's LinkedIn account.www.linkedin.com/company/innovent-biologics/。

Statement:Innovent Bio does not recommend any unapproved drugs./Indications for use.

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References

[1] Yaeger R, Weiss J, et al. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Jan 5;388(1):44-54. doi: 10.1056/NEJMoa2212419. Epub 2022 Dec 21. PMID: 36546659; PMCID: PMC9908297.
[2] Kuboki Y et al. Sotorasib in combination with panitumumab in refractory KRAS G12C-mutated colorectal cancer: safety and efficacy for phase 1B full expansion cohort. ESMO Congress 2022, Abstract 315O
[3] Sae-Won Han et al. Phase Ib study of GDC-6036 in combination with cetuximab in patients with colorectal cancer (CRC)  with KRAS G12C mutation. AACR Congress 2023