On November 13, 2022 SK Biopharmaceuticals, a global innovative pharmaceutical company, reported that the state-run Korea Drug Development Fund (KDDF) has decided to support and finance the company’s development of SKL27969, which is being evaluated as potential treatment for patients with advanced solid tumors, widening SK Biopharmaceuticals’ area into oncology (Press release, SK biopharmaceuticals, NOV 13, 2022, View Source [SID1234623907]).

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The KDDF is a government fund that aims to support R&D for new drug development as part of efforts to advance Korea’s pharmaceuticals and biotechnology sectors.

A phase 1/2 clinical trial is being conducted under the US IND for SKL27969, a PRMT5 inhibitor, in adult patients with solid tumors for safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy.

SK Biopharmaceuticals said the KDDF’s two-year investment in the study will help the company and its U.S. subsidiary SK Life Science, Inc. to accelerate their clinical (Phase 1) and nonclinical trials, while expanding its oncology network.

SK Biopharmaceuticals will present its preclinical data of SKL27969 at the annual Society for Neuro-Oncology (SNO) conference in Tampa Bay, Florida, November 16 – 20, 2022.

About SKL27969

SKL27969 is a protein arginine methyltransferase 5 (PRMT5) inhibitor candidate that has shown activity in preclinical models of solid tumors, such as glioblastoma (GBM), non-small cell lung cancer (NSCLC), and triple negative breast cancer (TNBC).

On November 13, 2022 Akeso, Biopharma (9926. HK) ("Akeso") reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for Ivonescimab (PD-1/VEGF bispecific antibody, AK112) combined with docetaxel for the treatment of locally advanced or metastatic Non-Small-Cell Lung Carcinoma (NSCLC) patients who failed to respond to prior PD-(L)1 inhibitor combined with platinum-based doublet chemotherapy (Press release, Akeso Biopharma, NOV 13, 2022, View Source [SID1234623906]). This is the third BTD for AK112 for use with NSCLC patients, and AK112 is the only drug candidate granted BTD for PD-(L)1 resistant lung cancer treatment in China.

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The three BTDs of AK112 comprise:

AK112 combined with chemotherapy for the treatment of EGFR-mutated locally advanced or metastatic NSCLC patients who have failed to respond to EGFR-TKI treatment, which has completed Phase III clinical trials patient enrollment.
AK112 as the first-line treatment for locally advanced or metastatic NSCLC patients with positive PD-L1 expression, which has entered into Phase III clinical trials.
AK112 combined with docetaxel for the treatment of locally advanced or metastatic NSCLC patients who failed to respond to prior PD-(L)1 inhibitor combined with platinum-based doublet chemotherapy, which is the only drug candidate granted BTD for PD-(L)1 resistant lung cancer treatment in China.
Breakthrough Therapy Designations aim to accelerate development and regulatory review of new drugs to treat severe diseases which show encouraging preliminary clinical results. These drugs need to demonstrate a significant improvement in clinical endpoints over existing therapies, or fulfill unmet medical needs. Akeso believes that these three designations of AK112 for NSCLC will accelerate the R&D and marketing progress of AK112 in China.

PD-1/L1 monoclonal antibody combined with platinum-based chemotherapy is the standard of care for first-line therapy for patients with advanced NSCLC. However, the majority of patients do not benefit from the treatment or may relapse after a period of response, highlighting the need for more effective treatment. However, there are currently no immunotherapy regimens approved for NSCLC patients who failed to respond to prior PD-(L)1 inhibitor combined with platinum-based doublet chemotherapy.

Immunotherapy plus anti-angiogenesis therapy has proven its combined advantages in previous studies worldwide. Lung cancer is one of the mainstream exploration areas of this therapy. AK112 can potentially simultaneously block PD-1 and VEGF targets, and has demonstrated a favorable safety profile and promising anti-tumor efficacy in recent studies conducted by the Company. AK112 is expected to provide a valuable option for NSCLC patients to overcome immunotherapy resistance antibody therapy.

ABOUT IVONESCIMAB (PD-1/VEGF BI-SPECIFIC ANTIBODY, AK112)

Ivonescimab is a first-in-class and the first to enter phase III clinical trial PD-1/VEGF bi-specific antibody independently developed by Akeso Biopharma. Engineered with our unique Tetrabody technology, Ivonescimab blocks PD-1 binding to PD-L1 and PD-L2, and blocks VEGF binding to VEGF receptors. PD-1 antibody combined with VEGF blocking agents have shown robust efficacy in various tumor types (including renal cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma). In view of the co-expression of VEGF and PD-1 in the tumor microenvironment, Ivonescimab, as a single agent to block these two targets, may block these two pathways more effectively and enhance the antitumor activity, as compared to combination therapy.

Currently, Akeso is conducting a phase III clinical trial of AK112 monotherapy versus Pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression. In addition, a phase III clinical trial of AK112 plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy is ongoing. AK112 has started multiple clinical trials for various stages treatment of indications including non-small cell lung cancer and small cell lung cancer.

On November 13, 2022 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, reported the updated results of IBI351 (GFH925) (KRASG12C inhibitor) from a phase Ia clinical trial (NCT05005234) at the 2022 Chinese Society of Clinical Oncology (CSCO) Annual Meeting (Press release, Innovent Biologics, NOV 13, 2022, View Source [SID1234623905]).

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Phase Ia study of IBI351 (GFH925) monotherapy in patients with advanced solid tumors: updated results

IBI351(GFH925) is a novel, irreversible covalent inhibitor of KRASG12C mutation. The NCT05005234 study presented was a first-in-human study conducted in China to evaluate the safety, tolerability and efficacy of IBI351 monotherapy in patients with advanced solid tumors who failed or intolerant to standard of care treatment. As data cutoff (29 July 2022), 67 subjects were enrolled in the study, including 61 patients with non-small cell lung cancer (NSCLC), 5 colorectal cancer(CRC) and 1 pancreatic cancer. Approximately 50% patients received 2 lines or above prior systemic anticancer therapy. 37.7% of NSCLC patients had brain metastases. The highlights of the study results were as follows:

Of 55 evaluable NSCLC patients, 28 achieved partial response (PR), with investigator assessed ORR 50.9% and DCR 92.7%. As data cutoff, most patients remained on treatment. Sustained treatment response was observed at low dose of IBI351. Median duration of response (DOR) and median progression free survival (PFS) were not reached yet.
Of 21 patients with NSCLC treated at 600mg BID (the recommended phase 2 dose), better efficacy signal was observed, with investigator assessed ORR 61.9%(13/21) and DCR 100%.
Of 5 CRC patients, 3 achieved PR, with investigator assessed ORR and DCR 60%. 1 pancreatic cancer patient achieved PR in 1st tumor assessment, and remained on treatment.
As data cutoff, IBI351 was well tolerated. No DLT was reported and MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 92.5% (62/67) patients and the most common TRAEs were anemia, transferase increased, bilirubin increased, pruritus and fatigue. The majority of the TRAEs were grade 1-2 with 19.4% (13/67) of patients reporting grade 3 or higher TRAEs. There were no grade 5 TRAEs or TRAEs led to treatment discontinuation.
Favorable safety and tolerability and promising antitumor activity of IBI351 monotherapy were observed in previously-treated advanced NSCLC, CRC and pancreatic cancer harboring KRASG12C mutation. A single arm registrational trial of IBI351 monotherapy in previously-treated advanced non-small cell lung cancer is ongoing. More data will be presented at the future medical meeting.

Professor Yi-Long Wu from Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, stated: "KRAS mutation as the "undruggable" target for decades has become one of the most popular direction for clinical development recently. IBI351 is a novel, irreversible covalent inhibitor of KRASG12C mutation, whose preliminary data of safety and efficacy was reported at 2022 ASCO (Free ASCO Whitepaper). The update data shows the favorable safety and promising activity of IBI351 (GFH925) monotherapy in KRAS G12C mutated advanced solid tumor. We look forward to more positive clinical data from this study. "

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to present our clinical development updates at the 2022 CSCO, and that IBI351 monotherapy demonstrated encouraging efficacy and safety data in phase Ia study. A single arm registrational trial of IBI351 monotherapy in previously-treated advanced NSCLC is ongoing. We are working to advance into late stage clinical development to explore the potential of IBI351 as monotherapy and in combo-therapy. We are actively exploring next-generation immunotherapies, hoping to benefit more cancer patients."

About IBI351/GFH925 (KRASG12C Inhibitor)

Discovered by GenFleet Therapeutics, GFH925 (Innovent R&D code: IBI351) is a novel, orally active, potent KRASG12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRASG12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of IBI351 towards G12C. Subsequently, IBI351 effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest. In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of IBI351 in China (including mainland China, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.

On November 13, 2022 Shanghai Stock Exchange listed company HitGen Inc. ("HitGen", SSE:688222.SH) reported that it has entered into a research collaboration agreement with DAEWOONG PHARMACEUTICAL Co., Ltd ("Daewoong"), a global healthcare group in the Republic of Korea, dedicated to improving the quality of patients’ lives (Press release, Daewoong Pharmaceutical, NOV 13, 2022, View Source [SID1234623904]). HitGen will apply its DNA-encoded library (DEL) technology platform centered around the design, synthesis and screening of thousands of DELs that collectively comprise over 1.2 trillion small, drug-like molecules to discover compounds that bind to certain targets that Daewoong needs to discover for new drug development.

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"It is truly a privilege to work with Daewoong, one of the top pharmas in Korea, comprising a team of very innovative and collaborative researchers. We look forward to initiating the collaboration to identify novel small molecule starting points from DNA-encoded libraries, and we believe that successful results would lead to further expanded collaborations," said Dr. Jin Li, Chairman of the Board and Chief Executive Officer of HitGen.

"We are pleased to collaborate with HitGen which has the world’s best DEL screening platform. Daewoong will strengthen its innovative drug development capabilities and improve the quality of life of patients through cooperation with HitGen," said Seng-ho Jeon, Chief Executive Officer of Daewoong.

On November 13, 2022 InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on cancer and autoimmune diseases, reported 2022 third quarter results and latest corporate development (Press release, InnoCare Pharma, NOV 13, 2022, View Source [SID1234623902]).

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Dr. Jasmine Cui, Co-founder, Chairwoman and CEO of InnoCare said, "We successfully got listed on the STAR Board of the Shanghai Stock Exchange, which makes InnoCare become the double-listed biotech company and will inject new momentum to the Company’s long-term development. We further uplifted our commercialization capabilities with continued revenue growth of orelabrutinib after its inclusion in China’s National Reimbursement Drug List (NRDL). We accelerated the pace of innovation and clinical development in the field of malignant tumors and autoimmune diseases with 13 drug candidates entering clinical trials in a bid to meet the unmet clinical needs. Our Guangzhou site was approved for commercial production of orelabrutinib…We have achieved high-quality development in various fields, and we are committed to becoming a world leading biopharma company with innovations as the key driving force."

Financial Highlights

The revenue reached about RMB442 million in the first three quarters of 2022, including about RMB400 million from drug sales, a year-on-year increase of 129%, mainly due to the continuous growth of orelabrutinib sales after its inclusion in the NRDL;
The research and development expenses reached RMB475 million in the first three quarters of 2022 due to more on-going projects, with an increase of 30% year-on-year excluding the impact of the upfront payment to Incyte last year;
The cash and cash equivalents1 rose to RMB9.23 billion, an increase of 37.5% year on year in the first three quarters of 2022, mainly due to the fund raised from the STAR Board listing;
The total assets expanded to RMB10.4 billion in the first three quarters of 2022, an increase of 40.7% compared with the end of 2021;
Excluding the impact of foreign exchange loss, the loss for the first three quarters of 2022 was RMB444 million, mainly due to the increase of research and development expenses. The foreign exchange loss was RMB399 million, which had no actual impact on the Company’s business operations.

STAR Board Listing

On September 21, 2022, InnoCare got listed on the STAR Board of the Shanghai Stock Exchange, raising a total of RMB2.92 billion. The listing on the STAR Board will further enhance InnoCare’s innovative advantages in blood tumors, solid tumors and autoimmune diseases, and contribute to achieving its strategic goal of benefiting global patients with its self-developed innovative drugs.

Pipeline Progress

InnoCare has built a robust pipeline. Orelabrutinib was in commercial stage with NRDL inclusion, tafasitamab was approved for use in the Boao Lecheng International Medical Tourism Pilot Zone, with 13 drug candidates in clinical trials and several others in IND enabling stage. In addition to monotherapy, InnoCare is also exploring the potential of the drug pipelines in combination with standard therapy or other therapies. The followings are the latest developments:

Blood Tumor

Orelabrutinib

Orelabrutinib is expected to be approved by the Health Sciences Authority (HSA) of Singapore for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (R/R MCL) soon;
The supplemental New Drug Application (sNDA) for orelabrutinib for the treatment of patients with relapsed or refractory Waldenström’s Macroglobulinemia (R/R WM) is under review by the NMPA. A phase II study of orelabrutinib for the treatment of R/R WM patients was published in eClinicalMedicine, a journal owned by The Lancet. At a median follow-up of 16.4 months, the MRR was 80.9%, the overall response rate was 89.4%, and the PFS rate was 89.4% at 12 months2;
The sNDA of orelabrutinib for the treatment of R/R Marginal Zone Lymphoma (MZL) has been accepted and granted priority review by the NMPA. So far, no BTK inhibitor has ever been approved for treating patients with R/R MZL in China, and orelabrutinib is expected to fill the gap in this therapeutic area;
Phase III registrational trial of orelabrutinib for the first-line treatment of Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) is expected to complete patient enrollment by mid-year of 2023;
Phase III registrational study of orelabrutinib for the first-line treatment of MCD subtype diffuse large B lymphoma (DLBCL) is conducted in China. InnoCare has developed a comprehensive toolkit to treat all stages of DLBCL patients with combination therapies;
Phase II registrational trial for R/R Mantle Cell Lymphoma (MCL) is conducted in the U.S.
ICP-B04 (Tafasitamab)

The first prescription of tafasitamab in combination with lenalidomide was filled at the Ruijin Hainan Hospital at Bo’ao, who achieved complete response (CR) after 2 cycles of treatment;
Phase II registrational trial of tafasitamab in combination with lenalidomide in China has enrolled about 20% of patients;
The biologics license application (BLA) for tafasitamab in combination with lenalidomide was accepted by the Department of Health, the Hong Kong Special Administrative Region, China. Once getting approval, it will benefit the DLBCL patients in greater bay area;
Tafasitamab has been included in the overseas Special Drug list of commercial insurance in more than 10 provinces and cities, which improves the access of DLBCL patients in these regions.
ICP-490

Novel targeted protein degrader ICP-490 has entered clinical trial in China for the treatment of R/R multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL).
ICP-248

BCL2 inhibitor ICP-248 has entered clinical trial, developed to treat malignant hematological tumors such as NHL and acute lymphoblastic leukemia (ALL) as single drug or in combination with other drugs such as BTK inhibitor.
ICP-B02 (CM355)

ICP-B02, a CD20xCD3 bispecific antibody developed by InnoCare and Keymed, is in the clinical study for the treatment of CD20+ B-cell malignancies in China.
Solid Tumor

ICP-192 (Gunagratinib)

Initiate registrational trial in cholangiocarcinoma, and progress Phase II trial in urothelial cancer in China;
Progress basket trial, including gastric and head & neck cancer in China, Australia and U.S.
ICP-723

The first adolescent patient has been dosed in clinical trial with InnoCare’s second generation pan-TRK inhibitor ICP-723 at the Sun Yat-sen University Cancer Center. This is also the first time that ICP-723 will be evaluated in the clinical study of adolescent (12 to 18 years old) patients after showing good safety and efficacy in adult patients. InnoCare will also expand ICP-723 clinical study to treat pediatric patients (2 to 12 years old);
Based on the Proof-of-Concept (POC) data obtained, InnoCare will promote a registration clinical study of ICP-723 in China. The Company has also conducted a clinical study of ICP-723 in the United States.
ICP-B05 (CM369)

Monoclonal antibody ICP-B05 targeting CCR8 jointly developed by InnoCare and Keymed Biosciences has entered into clinical stage, developed as a monotherapy or combined with other therapies to treat advanced solid tumors, including lung cancer, digestive tract cancer, etc.
ICP-189

The clinical trials of Novel SHP2 allosteric inhibitor ICP-189 are conducted in China and the U.S., developed for the treatment of solid tumors as a single agent and/or in combination with other antitumor agents.
Autoimmune Disease

Orelabrutinib

Phase II trial for systemic lupus erythematosus (SLE) delivered positive results, and further clinical development of orelabrutinib in SLE has been initiated;
Phase II trial for multiple sclerosis (MS) in collaboration with Biogen is progressing to the final stage of patient enrollment;
Phase II clinical trials of orelabrutinib for the treatment of primary immune thrombocytopenia purpura (ITP) and Neuromyelitis Optica Spectrum Disorder (NMOSD) are undergoing in China.
ICP-488

Tyrosine kinase 2 (TYK2) JH2 allosteric inhibitor ICP-488 has completed single dose escalation study and started multi-dose escalation trial. ICP-488 is developed for the treatment of inflammatory diseases such as psoriasis, SLE and inflammatory bowel disease (IBD).
ICP-332

Phase II clinical trials of the novel TYK2 inhibitor ICP-332 for the treatment of atopic dermatitis (AD) of were initiated.
"In the challenging market environment, we still fulfilled the preset goals beyond expectations," said Dr. Cui. "Looking forward, we will continue to maintain our original aspiration, hold on the core value of ‘Science drives innovation for the benefit of patients’, strengthen the product pipelines, and accelerate the business development, in order to leverage our innovations achievements to generate greater values for the society."

To know more about the detailed financial data of InnoCare 2022 third quarter results, please log in View Source

Conference Call Information

InnoCare will host a conference call and webcast on Nov. 14, 2022 at 9:30 a.m. Beijing time.