[Translation] A phase II clinical study of SKB264 with or without KL-A167 in the treatment of patients with unresectable locally advanced, recurrent or metastatic HER2-negative breast cancer who have not received previous systemic treatment.

主要目的：评估SKB264联合或不联合KL-A167治疗不可手术切除的局部晚期、复发或转移性三阴性乳腺癌（TNBC）和激素受体阳性/人表皮生长因子受体2阴性乳腺癌（HR+/HER2- BC）患者的安全性和耐受性及初步的抗肿瘤活性。

[Translation]

Primary objective: To evaluate the safety, tolerability and preliminary antitumor activity of SKB264 with or without KL-A167 in patients with unresectable locally advanced, recurrent or metastatic triple-negative breast cancer (TNBC) and hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer (HR+/HER2- BC).

Start Date26 Aug 2022

Sponsor / Collaborator

Sichuan Kelun Botai Biomedicine Co., Ltd.

NCT05445908

/ RecruitingPhase 2

A Phase 2 Clinical Study of SKB264 With/Without KL-A167 in Patients With Unresectable Locally Advanced, Recurrent or Metastatic HER2-negative Breast Cancer Who Have Not Received Prior Systemic Therapy

The purpose of this study is to assess the safety and tolerability and preliminary antitumor activity of SKB264 with/without KL-A167 in patients with unresectable locally advanced, recurrent or metastatic TNBC and HR+/HER2- BC .The study is divided into three parts.Part 1（TNBC）: exploratory phase of the efficacy and safety of the combination treatment. Part 2（TNBC）: The subjects will be randomized to treatment group for SKB264 + KL-A167 or SKB264 . Part 3（HR+/HER2- BC）: The subjects will be randomized to treatment group for SKB264 + KL-A167 or SKB264 .

Start Date17 Aug 2022

Sponsor / Collaborator

Sichuan Kelun Botai Biomedicine Co., Ltd.

NCT05294172

/ Active, not recruitingPhase 3

KL-A167 Injection Combined With Cisplatin and Gemcitabine vs Placebo Combined With Cisplatin and Gemcitabine in the Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma: A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Clinical Trial

The study is to evaluate the efficacy of KL-A167 combined with cisplatin and gemcitabine vs placebo combined with cisplatin and gemcitabine in the treatment of recurrent or metastatic nasopharyngeal carcinoma, as measured by progression-free survival (PFS) per the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1

Start Date16 Jun 2022

Sponsor / Collaborator

Sichuan Kelun Botai Biomedicine Co., Ltd.

100 Clinical Results associated with Tagitanlimab

100 Translational Medicine associated with Tagitanlimab

100 Patents (Medical) associated with Tagitanlimab

Literatures (Medical) associated with Tagitanlimab

01 Jun 2019·Plant diseaseQ2 · AGRICULTURAL & FORESTRY SCIENCE

Compatible Mixture of Bacterial Antagonists Developed to Protect Potato Tubers from Soft Rot Caused by Pectobacterium spp. and Dickeya spp.

Q2 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Krychowiak, Marta ; Czajkowski, Robert ; Krzyzanowska, Dorota M. ; Maciag, Tomasz ; Siwinska, Joanna ; Jafra, Sylwia

Possibilities to protect potato tubers from rotting caused by Soft Rot Pectobacteriaceae (SRP) under disease favoring conditions were investigated using compatible mixtures of bacterial antagonists and tested with a newly developed stepwise efficacy-based screening protocol. Twenty-two bacterial antagonists were evaluated against a combination of five Pectobacterium and Dickeya strains representing species and subspecies most often associated with potato soft rot in Europe. To enable potential synergistic activity, the antagonists were initially tested against the combination of pathogens in 15 random mixtures containing up to 5 antagonists each. Three mixtures (M2, M4, and M14) out of 15 tested reduced tuber tissue maceration due to soft rot. The individual antagonists derived from M2, M4, and M14 mixtures were tested on potato slices and whole tuber injection assays. These five strains (S. plymuthica strain A294, E. amnigenus strain A167, R. aquatilis strain H145, S. rubidaea strain H440, and S. rubidaea strain H469) were combined to develop a tailored biological control mixture against potato soft rot. The new mixture, designated the Great Five (GF), was tested on seed potato tubers vacuum infiltrated with antagonists and subsequently with the combination of five SRP pathogens. In these experiments, the GF mixture provided stable protection of inoculated potato tubers, reducing soft rot by 46% (P = 0.0016) under high disease pressure conditions. The A294, A167, H145, H440, and H469 antagonists were characterized for features important for viable commercial applications including growth at different temperatures, resistance to antibiotics, and potential toxicity toward Caenorhabditis elegans. The implications for control of soft rot caused by SRP with the use of the GF mixture of antagonists are discussed.

01 Nov 2014·Bioorganic & medicinal chemistry lettersQ4 · MEDICINE

From the covalent linkage of drugs to novel inhibitors of ribonucleotide reductase: Synthesis and biological evaluation of valproic esters of 3′-C-methyladenosine

Q4 · MEDICINE

Article

Author: Hofer, Anders ; Meli, Maria ; Vodnala, Munender ; Torquati, Ilaria ; Vita, Patrizia ; D'Alessandro, Natale ; Grifantini, Mario ; Ferro, Arianna ; Tolomeo, Manlio ; Franchetti, Palmarisa ; Jayaram, Hiremagalur N ; Kusumanchi, Praveen ; Petrelli, Riccardo ; Del Bello, Fabio ; Cappellacci, Loredana

We synthesized a series of serum-stable covalently linked drugs derived from 3'-C-methyladenosine (3'-Me-Ado) and valproic acid (VPA), which are ribonucleotide reductase (RR) and histone deacetylase (HDAC) inhibitors, respectively. While the combination of free VPA and 3'-Me-Ado resulted in a clear synergistic apoptotic effect, the conjugates had lost their HDAC inhibitory effect as well as the corresponding apoptotic activity. Two of the analogs, 2',5'-bis-O-valproyl-3'-C-methyladenosine (A160) and 5'-O-valproyl-3'-C-methyladenosine (A167), showed promising cytotoxic activities against human hematological and solid cancer cell lines. A167 was less potent than A160 but had interesting features as an RR inhibitor. It inhibited RR activity by competing with ATP as an allosteric effector and concomitantly reduced the intracellular deoxyribonucleoside triphosphate (dNTP) pools. A167 represents a novel lead compound, which in contrast to previously used RR nucleoside analogs does not require intracellular kinases for its activity and therefore holds promise against drug resistant tumors with downregulated nucleoside kinases.

01 Jan 1993·Biological & pharmaceutical bulletinQ4 · MEDICINE

Mitogenic Activity and Lethal Toxicity of Lipid A Analogs, Glucosamine-phosphate Carrying Aromatic Alkyl Groups, in Mice.

Q4 · MEDICINE

Article

Author: Yanagihara, Yasutake ; Iwamoto, Yoshihisa ; Nakamoto, Shinichi ; Achiwa, Kazuo ; Shimizu, Tadayori ; Itoh, Hajime

The mitogenicity and lethal toxicity of four synthetic lipid A analogs, glucosamine-4-phosphate with a 7-hydroxy-heptanoyl group (A-166), with a 7-phenyl-heptanoyl group (A-167), or with a 8-(1-phenyl-hexanoyl)-nonanoyl group (A-168), at the C-2 and C-3 positions, and glucosamine-6-phosphate with the same substituents as A-168 at C-2 and C-3 (A-169), were compared. The compound A-166 exhibited no mitogenic activity at various concentrations ranging from 3.13 to 50 micrograms/ml in the splenocytes of BALB/c mice, but A-167 exhibited weak mitogenic activity at concentrations of 12.5 and 25 micrograms/ml. A-168 and A-169, as well as A-103, glucosamine-4-phosphate carrying (R)-3-tetradecanoyl-oxytetradecanoyl groups, have remarkable mitogenic activity at concentrations ranging from 12.5 to 100 micrograms/ml; the activity of A-169 (6-phosphate) was stronger than that of A-168 (4-phosphate). Compound A-167 failed to cause death at doses of 25 and 50 micrograms/mouse in galactosamine-loaded C57BL/6 mice while A-166 and A-169 were toxic to 2 out of 6 mice at 50 micrograms/mouse; no deaths were observed at 25 micrograms/mouse. A-168 showed the highest toxicity of any of the compounds tested at 25 and 50 micrograms/mouse. The lethal effect of A-103 appeared to be somewhere between that of A-168 and A-169. These findings indicate that lipid A analogs, carrying an aromatic alkyl group as well as a hydroxyacyl group, are mitogenic and lethal when given to mice.

News (Medical) associated with Tagitanlimab

23 Jan 2025

·pipelinereview.com

Kelun-Biotech's Product Tagitanlimab Approved for Marketing in Second Indication in Combination with Cisplatin and Gemcitabine For the First-line Treatment of Patients with recurrent or metastatic NPC

CHENGDU, China I January 23, 2025 I Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the “ Company “) announced that the Company received marketing authorization in China from National Medical Products Administration (NMPA) for the programmed cell death ligand 1(PD-L1)-directed innovative humanized monoclonal antibody (“ mAb “) tagitanlimab (formerly KL-A167) used in combination with cisplatin and gemcitabine for the first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer (NPC). The approval is based on a randomized, double-blinded, placebo controlled, multi-center, phase III clinical study evaluates the efficacy and safety results of tagitanlimab in combination with cisplatin and gemcitabine versus placebo in combination with cisplatin and gemcitabine for the treatment of recurrent or metastatic NPC, which was led by Professor Shi Yuankai of the Cancer Hospital Chinese Academy of Medical Sciences as the principal investigator. According to the study results, tagitanlimab used in combination with cisplatin and gemcitabine for the first-line treatment for recurrent or metastatic NPC could have better progression-free survival (PFS), higher objective response rate (ORR) and extended duration of response (DoR) compared with chemotherapy, where all the patients could benefit regardless of the PD-L1 expression. The median PFS for tagitanlimab in combination with chemotherapy is not reached compared to 7.9 months for placebo in combination with chemotherapy (HR=0.47, 95% CI: 0.33-0.66, p<0.0001), and the risk of disease progression and death is reduced by 53%; ORR is 81.7% vs 74.5%; median DoR is 11.7 vs 5.8 months (HR=0.48, 95% CI: 0.32-0.70), which has nearly doubled compared to placebo arm; currently the median overall survival (OS) is still not mature, however the beneficial trend for OS of tagitanlimab in combination with chemotherapy has already been observed (HR=0.62, 95％CI: 0.32-1.22), and its risk of death is reduced by 38% [1] . Tagitanlimab also showed a manageable safety profile. This is the second indication approved for tagitanlimab. Previously, NMPA has approved the marketing in China of tagitanlimab monotherapy for the treatment of patients with recurrent or metastatic NPC who have failed after prior 2L+ chemotherapy. Dr. Micheal Ge, CEO of Kelun-Biotech said, “We are pleased that the second indication of our self-developed PD-L1 monoclonal antibody was successfully approved for marketing and demonstrated statistically significant and clinically meaningful improvements in PFS. For domestic NPC patients, Tagitanlimab has realized a breakthrough in therapeutic coverage and innovation from the backline to the frontline, which once again strongly validates the excellent strength of Kelun-Biotech’s new drug research and development. In the future, the company will always be based on unmet clinical needs, source innovation, and explore more and more excellent clinical therapeutic solutions to benefit more patients.” About Kelun-Biotech Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs. At present, the Company has more than 30 ongoing key innovative drug projects, of which 2 projects have been approved for marketing, 2 projects are in the NDA stage, and more than 10 projects are in the clinical stage. The company has established one of the world’s leading proprietary ADC platforms, OptiDC™, and has 1 ADC project approved for marketing, 1 ADC project in NDA stage, and multiple ADC or novel ADC projects in clinical or preclinical research stage. For more information, please visit https://kelun-biotech.com/ . [1] Label of tagitanlimab SOURCE: Sichuan Kelun-Biotech Biopharmaceutical Co.

Drug ApprovalPhase 3NDAClinical ResultCSCO

23 Jan 2025

·www.prnewswire.com

CHENGDU, China, Jan. 23, 2025 /PRNewswire/ -- Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the " Company") announced that the Company received marketing authorization in China from National Medical Products Administration (NMPA) for the programmed cell death ligand 1(PD-L1)-directed innovative humanized monoclonal antibody (" mAb") tagitanlimab (formerly KL-A167) used in combination with cisplatin and gemcitabine for the first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer (NPC). The approval is based on a randomized, double-blinded, placebo controlled, multi-center, phase III clinical study evaluates the efficacy and safety results of tagitanlimab in combination with cisplatin and gemcitabine versus placebo in combination with cisplatin and gemcitabine for the treatment of recurrent or metastatic NPC, which was led by Professor Shi Yuankai of the Cancer Hospital Chinese Academy of Medical Sciences as the principal investigator. According to the study results, tagitanlimab used in combination with cisplatin and gemcitabine for the first-line treatment for recurrent or metastatic NPC could have better progression-free survival (PFS), higher objective response rate (ORR) and extended duration of response (DoR) compared with chemotherapy, where all the patients could benefit regardless of the PD-L1 expression. The median PFS for tagitanlimab in combination with chemotherapy is not reached compared to 7.9 months for placebo in combination with chemotherapy (HR=0.47, 95% CI: 0.33-0.66, p<0.0001), and the risk of disease progression and death is reduced by 53%; ORR is 81.7% vs 74.5%; median DoR is 11.7 vs 5.8 months (HR=0.48, 95% CI: 0.32-0.70), which has nearly doubled compared to placebo arm; currently the median overall survival (OS) is still not mature, however the beneficial trend for OS of tagitanlimab in combination with chemotherapy has already been observed (HR=0.62, 95％CI: 0.32-1.22), and its risk of death is reduced by 38%[1]. Tagitanlimab also showed a manageable safety profile. This is the second indication approved for tagitanlimab. Previously, NMPA has approved the marketing in China of tagitanlimab monotherapy for the treatment of patients with recurrent or metastatic NPC who have failed after prior 2L+ chemotherapy. Dr. Micheal Ge, CEO of Kelun-Biotech said, "We are pleased that the second indication of our self-developed PD-L1 monoclonal antibody was successfully approved for marketing and demonstrated statistically significant and clinically meaningful improvements in PFS. For domestic NPC patients, Tagitanlimab has realized a breakthrough in therapeutic coverage and innovation from the backline to the frontline, which once again strongly validates the excellent strength of Kelun-Biotech's new drug research and development. In the future, the company will always be based on unmet clinical needs, source innovation, and explore more and more excellent clinical therapeutic solutions to benefit more patients." About Kelun-Biotech Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs. At present, the Company has more than 30 ongoing key innovative drug projects, of which 2 projects have been approved for marketing, 2 projects are in the NDA stage, and more than 10 projects are in the clinical stage. The company has established one of the world's leading proprietary ADC platforms, OptiDC™, and has 1 ADC project approved for marketing, 1 ADC project in NDA stage, and multiple ADC or novel ADC projects in clinical or preclinical research stage. For more information, please visit . SOURCE Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalPhase 3NDAClinical Result

22 Jan 2025

·www.prnewswire.com

Akeso Received Payment for the Development Collaboration on Tagitanlimab

HONG KONG, Jan. 22, 2025 /PRNewswire/ -- On January 22, 2025, Akeso Inc. (9926.HK) announced that it had received payment from Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. ("Sichuan Kelun") for their collaboration on the development of tagitanlimab, an innovative humanized monoclonal antibody targeting PD-L1, following its recent marketing approval by China's National Medical Products Administration. In 2014, Akeso signed a cooperation agreement with Sichuan Kelun for the development of tagitanlimab. Under the terms of the agreement, Akeso will receive royalties from the commercial sales of tagitanlimab in addition to the development payment. Tagitanlimab marks Akeso's second oncology product to yield commercial royalties, following pucotenlimab, a PD-1 monoclonal antibody developed in collaboration with Lepu Biopharma in 2016. Dr. Yu Xia, founder, chairwoman, president, and CEO of Akeso, said: "Congratulations to our partners. We are thrilled about continuously successful approval of our innovative products, and truly anticipate their outstanding commercialization performance. This achievement highlights Akeso's strong R&D capabilities and our commitment to innovation. Since its inception, Akeso has established multiple external collaborations, including ivonescimab with Summit Therapeutics, quavonlimab with Merck and pucotenlimab with Lepu Biopharma. These partnerships not only benefit patients but also deliver significant returns for both Akeso and our collaborators. Looking ahead, Akeso will continue to pursue a diversified strategy for new drug development, leveraging global resources to drive the high-quality commercialization of our independently developed innovative therapeutics." SOURCE Akeso, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/inDrug Approval

100 Deals associated with Tagitanlimab

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Nasopharyngeal Carcinoma	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	25 Dec 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic HER2-Negative Breast Carcinoma	Phase 2	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	17 Aug 2022
Refractory Classic Hodgkin Lymphoma	Phase 2	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	17 Jul 2018
Relapsing classical Hodgkin lymphoma	Phase 2	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	17 Jul 2018
Diffuse Large B-Cell Lymphoma	Phase 1	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	19 Sep 2018
Extranodal NK-T-Cell Lymphoma	Phase 1	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	19 Sep 2018
Advanced Malignant Solid Neoplasm	Phase 1	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	28 Dec 2017
Non-squamous non-small cell lung cancer	IND Approval	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	11 Sep 2024
Hormone receptor positive HER2 negative breast cancer	IND Approval	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	27 Sep 2023
Triple Negative Breast Cancer	IND Approval	China	Sichuan Kelun Botai Biomedicine Co., Ltd.	11 Apr 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


CTR20220691 (NEWS) Manual	Phase 3	Nasopharyngeal Carcinoma	-	塔戈利单抗+顺铂+吉西他滨	ulzshskbcn(notdrlkqqo) = aihrcjltjr bmhuivtjdo (xrlvwuvfqj ) View more	Positive	21 Jan 2025
				安慰剂+顺铂+吉西他滨	ulzshskbcn(notdrlkqqo) = gqpghmhvdh bmhuivtjdo (xrlvwuvfqj ) View more
NCT05351788 (OptiTROP-Lung01, ASCO2024) Manual	Phase 2	Non-Small Cell Lung Cancer First line	103	SKB264 5 mg/kg Q3W + KL-A167 1200 mg Q3W	yciptffsfu(qotkhbcfuq) = zyfmarssda hdevmwflub (ufodgqcgin ) View more	Positive	24 May 2024
				SKB264 5 mg/kg Q2W + KL-A167 900 mg Q2W	yciptffsfu(qotkhbcfuq) = iumpqdvpke hdevmwflub (ufodgqcgin ) View more
NCT03848286 (KL167-2-05-CTP, Pubmed \| NEWS) Manual	Phase 2	Nasopharyngeal Carcinoma	153	KL-A167 900mg	ypcmfyqgvl(uvfsfnmlal) = csxabvjidc xjuwfobeol (jbyiqgeqyx, 19.2 - 34.9) View more	Positive	10 Oct 2022

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