作者: Yang, Hui‑Li ; Chang, Kai‑Kai ; Li, Ming‑Qing ; Mei, Jie ; Liu, Li‑Bing ; Ye, Jiang‑Feng ; Meng, Yi ; Li, Da‑Jin ; Yao, Li ; Wang, Ming‑Yan ; Lai, Zhen‑Zhen ; Zhou, Wen‑Jie ; Ha, Si‑Yao

Endometriosis (EMS) is a female hormone‑ dependent disease with controversial reports of its etiology and pathogenesis. Apoptosis is particularly important in the human endometrium due to the dynamic cycles of proliferation and shedding. Estrogen possessed antiapoptotic effects on endometrial stromal cells (ESCs), which appears to be exacerbated in women with EMS; however, the underlying mechanism of the antiapoptotic effects of estrogen on ESC remains unknown. The present study aimed to determine whether estrogen regulates the apoptosis of ESCs via thymic stromal lymphopoietin (TSLP) and the associated mechanism. An ELISA was conducted to detect TSLP content in the ESC culture medium treated with estrogen. Subsequently, the early apoptotic rate and expression of B‑cell lymphoma (Bcl‑2) of ESCs were analyzed by flow cytometry in the presence of recombinant human TSLP, anti‑human TSLP neutralizing antibody or estrogen. In the present study, it was reported that ESCs exhibited basal TSLP secretion in the absence of estrogen as reported in previous studies, and that estrogen promoted TSLP secretion of ESCs in a dose‑dependent manner. The results demonstrated that estrogen suppressed the apoptosis of ESCs associated with the promotion of Bcl‑2 expression, which may be partly reversed by inhibiting TSLP. Therefore, the findings of the present study revealed a novel mechanism of estrogen‑dependent apoptotic suppression of ESCs associated with TSLP secretion and Bcl‑2 regulation. Endogenous and estrogen‑induced endometrial TSLP may promote the initiation and development of EMS via the inhibition of apoptosis.

项与抗TSLP抗体(华润生物) 相关的新闻（医药）

2024-09-24

·Endpoints

Flagship’s AI biotech Generate lands $65M upfront in Novartis deal, as first clinical readouts near

The AI-focused biotech Generate:Biomedicines announced another pharma partnership Tuesday, agreeing to work on several protein therapies with the Swiss drugmaking giant Novartis. Novartis will pay $50 million in cash and put in a $15 million equity investment while lining up possible milestone payments of over $1 billion. The two didn’t disclose specifics like disease areas or the number of targets. Similar to an ongoing partnership with Amgen, the Generate-Novartis collaboration will focus on a range of protein-based therapeutics, which could include antibodies, peptides, enzymes, or cytokines. The deal is just the latest example of pharma’s growing interest in partnering with AI-focused biotechs. Novartis and Eli Lilly both announced research deals with Alphabet’s Isomorphic Labs at the start of 2024. This month, the California startup Genesis Therapeutics announced its third pharma partnership in four years with Gilead paying $35 million upfront , and Superluminal Medicines closed a $120 million Series A that included Eli Lilly among its backers. For Generate, Merck veteran Mike Nally has led a period of rapid growth since joining as CEO in 2021, including raising over $600 million and putting its first drugs into the clinic. Generate’s pipeline is now approaching 20 different programs, Nally said, and he expects to file three to six IND applications over the next 12 to 18 months. The Novartis deal will help the 320-employee biotech apply its AI-based technologies to more drug programs, he told Endpoints News . “We have a technology that is remarkably scalable in terms of molecular design capabilities that allows us to do more than we can ever prosecute on our own,” he said. The deal will further pad Generate’s already-lined coffers. Counting the Novartis deal, Generate now has over $350 million in cash, Nally said, which gives the company flexibility when weighing financing paths like a potential IPO. “If we believe that going public is the best path, we will pursue it,” he said. “But at the same time, we don’t think we need to go public to be successful. We have ample cash today and 25 different institutional investors that have really been great and supportive of us in the private sector.” Generate turned heads last November when it published on using its AI model called Chroma for de novo protein design . But the biotech’s lead programs, which are nearing early clinical data, are not de novo efforts. Instead, the company has used AI to help tackle the multi-parameter optimization challenge that is drug development, Nally said, in particular by boosting the binding affinity of a drug to its target while maintaining other key attributes like manufacturability. It already has two programs in the clinic: a Covid-19 antibody and an anti-TSLP antibody. For its Covid program, Generate will present interim Phase 1 data in October at the IDWeek conference in Los Angeles. Nally said they plan to pause that antibody’s development after the Phase 1 is completed, citing the uncertainty of the Covid market against the need to pay for and run large trials. The company is also on track to have initial data later this year from an ascending single-dose study of its TSLP program, GB-0895, in mild-to-moderate asthmatics. Generate expects six-month clinical data late in the first quarter or early in the second quarter of 2025, Nally said. The TSLP drug will be an early test of whether Generate’s AI approach to molecular design can translate to clinical benefit. Its lead programs are targeting well-studied proteins that already have approved treatment options, such as Amgen and AstraZeneca’s Tezspire for TSLP or Eli Lilly’s Ebglyss for IL-13 . Nally said its TSLP antibody showed a 20-fold improvement in binding compared to Tezspire, which he hopes will translate to less frequent dosing. Tezspire is a monthly injection, and Nally said he’s encouraged GB-0895 could be dosed every six months. The same pitch is behind several of Generate’s next antibodies, targeting IL-13, OX40L and TL1A. Nally said all three have “clear line of sight” to the clinic, with the IL-13 antibody set to enter the clinic early next year. These drugs have shown 20- to 40-fold improvements in the ability to bind to their targeted proteins, he added. Their internal programs are taking 18 to 24 months to reach the clinic, far quicker than an industry average of three to five years, Nally said. “More importantly than the time, what we really care most about is quality,” he said. “Are we getting different, better quality answers? We’re seeing that now with the first few programs we’re putting forth.”

蛋白降解靶向嵌合体高管变更临床1期IPO

2024-08-27

·PRNewswire

Keymed Biosciences Announces Interim Results for First Half of 2024

CHENGDU, China , Aug. 27, 2024 /PRNewswire/ -- Keymed Biosciences Inc. (HKEX: 02162) today announced its interim results for the first half of 2024, along with a corporate update. Rapid development of our pipeline products Stapokibart (CM310) (IL-4Rα antibody) In June 2024, the long-term efficacy and safety data from the Phase III clinical trial of Stapokibart injection for the treatment of moderate-to-severe AD were presented by way of oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024. The study showed that at week 52, the rates of achieving EASI-75 and EASI-90 for the Stapokibart group was 92.5% and 77.1%, respectively. The rates of achieving an IGA score of 0 or 1 point with a reduction of ≥ 2 points from baseline was 67.3%. Long-term treatment with Stapokibart can consistently improve dermatitis symptoms and quality of life in subjects with moderate-to-severe AD. In terms of safety, Stapokibart was safe and well-tolerated after 52 weeks of administration, with safety profiles consistent with those observed at week 16 and no new safety signals identified. Advanced and completed the 52-week treatment and safety follow-up of the Phase III clinical study of Stapokibart injection for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in the first half of 2024. In June 2024, the new drug application of Stapokibart injection for the treatment of CRSwNP was accepted by the NMPA and granted priority review. Advanced and completed the unblinding of data and the statistical analysis of the Phase III clinical study of Stapokibart injection for the treatment of seasonal allergic rhinitis (SAR) in the first half of 2024, with the clinical data meeting the primary endpoints. In April 2024, the new drug application of Stapokibart injection for the treatment of SAR was accepted by the NMPA. Launched a randomized, double-blinded, placebo-controlled Phase III clinical study to evaluate the efficacy and safety of Stapokibart injection in adolescent subjects with moderate-to-severe AD in February 2024. Launched a randomized, double-blinded, placebo-controlled Phase III clinical study to evaluate the efficacy and safety of Stapokibart injection in prurigo nodularis subjects in May 2024. Our partner CSPC initiated the critical Phase II/III clinical study for the treatment of moderate-to-severe asthma and moderate-to-severe COPD. CMG901/AZD0901 (Claudin 18.2 ADC) As of the date of this announcement, AstraZeneca has conducted multiple clinical studies regarding CMG901 (AZD0901) for the treatment of advanced solid tumors. Among these, an international multi-center Phase III study comparing CMG901 (AZD0901) monotherapy versus investigator's choice as second-line or later-line treatment in patients with advanced or metastatic gastric and gastroesophageal junction (G/GEJ) cancer expressing Claudin 18.2 was publicly announced on the drug clinical trial registration and information publicity platform in March 2024. The first patient has received the initial dose in April 2024. In June 2024, the latest data from a Phase I clinical study of CMG901 (AZD0901) in the treatment of advanced G/GEJ cancer were presented by way of oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024. The study results indicated that as of February 2024, among 89 evaluable patients with Claudin 18.2-high expressing (defined as Claudin 18.2 membrane intensity ≥2+ in ≥20% of tumor cells) G/GEJ cancer in three cohorts, confirmed objective response rate (ORR) and confirmed disease control rate (DCR) were 35% and 70%, respectively. In the 2.2 mg/kg dose group, the confirmed ORR was 48%. The median progression free survival (mPFS) for all 93 patients with Claudin 18.2-high expressing G/GEJ cancer was 4.8 months, and the median overall survival (mOS) was 11.8 months. CM313 (CD38 antibody) Continued to advance a multi-center, open-label, dose-escalation and dose-expansion Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of CM313 injection in patients with RRMM, lymphoma, and other hematological malignancies. Continuously proceeded with a randomized, double-blinded, placebo-controlled, dose-escalation, multiple-dose Phase Ib/IIa clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of CM313 injection in subjects with SLE. In June 2024, a research paper titled "A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia" was published in The New England Journal of Medicine. This is an investigator-initiated, single-arm, open-label, exploratory clinical study to evaluate the safety and preliminary efficacy of CM313 in adult patients with primary immune thrombocytopenia. The results showed that 95.5% of patients (21/22) achieved a platelet count of ≥50 × 109/L within 8 weeks upon the first acceptance of CM313 infusion, with a median cumulative duration for a platelet count of ≥50 × 109/L of 23 weeks (interquartile range: 17-24). Additionally, the durable platelet count response rate (defined as a platelet count of ≥50 × 109/L observed six or more times among the final eight platelet counts) was 63.6% (14/22). In June 2024, we have submitted an IND application to further assess the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of CM313 in patients with primary immune thrombocytopenia. CM326 (TSLP antibody) In May 2024, we initiated a randomized, double-blinded, placebo-parallel Phase II clinical study to evaluate the efficacy and safety of CM326 in patients with CRSwNP, further exploring the optimal dosage. Our partner CSPC initiated the Phase II clinical study for the treatment of moderate-to-severe asthma. CM355/ICP-B02 (CD20xCD3 bispecific antibody) Continuously proceeded with a Phase I/II clinical trial in the first half of 2024 to assess the safety, tolerability, pharmacokinetics, and the preliminary anti-tumor activity of CM355 in relapsed or refractory non-Hodgkin's lymphoma (NHL). As of the date of this announcement, dose escalation of the intravenous infusion formulation (IV) was completed and the subcutaneous formulation (SC) is in the process of patient evaluation. CM336 (BCMAxCD3 bispecific antibody) Continuously proceeded with a Phase I/II clinical study to assess the safety, tolerability, pharmacokinetics, and the anti-tumor activity of CM336 in RRMM. CM350 (GPC3xCD3 bispecific antibody) Continuously proceeded with a Phase I/II clinical study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of CM350 in patients with advanced solid tumors. CM369/ICP-B05 (CCR8 antibody) Continuously proceeded with a Phase I clinical study in the first half of 2024 to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of CM369 in subjects with advanced solid tumors and relapsed or refractory NHL. CM383 (Aβ protofibrils antibody) Initiated a Phase I clinical study of the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of single dose-escalation administration of CM383 in healthy subjects. The enrollment of the first subject was completed in June 2024. CM380 (GPRC5DxCD3 bispecific antibody) Submitted IND application, and planned to conduct a multi-center, open-label Phase I/II clinical study for evaluation of CM380 in treatment of patients with relapsed or refractory multiple myeloma. Financial and Business Highlights Actively carry out the out-licensing collaboration In July 2024, Chengdu Keymed and Belenos entered into an out-license agreement, which grants Belenos an exclusive right to develop, manufacture and commercialize the Group's drug candidates, CM512 and CM536, globally excluding the Greater China region. In return, Chengdu Keymed shall receive an upfront and nearterm payment of US$15 million, and iBridge HK Holdings Limited, a wholly-owned subsidiary of the Group, shall receive approximately 30.01% of the equity interest in Belenos as consideration. Subject to achievement of certain development, regulatory and commercial milestones, Chengdu Keymed may also receive additional payments of up to US$170 million. Chengdu Keymed is also entitled to receive tiered royalties from Belenos on net sales for a specified period of time commencing after the first commercial sale of CM512 and CM536. Expand manufacturing capacity and efficiently prepare for commercialization We continue to recruit talents to meet the growing needs of commercialization, research and development, clinical, production and operation of the Company. We further expanded our cGMP-compliant manufacturing capacity, efficiently prepared for the company to become a commercial organization. As of the date of this announcement, the production capacity of our production base has reached 18,600 litres in total, and all the designs thereof are in compliance with the requirements of cGMP of the NMPA and FDA. Financial highlights As of June 30, 2024, the Company held cash (including bank wealth management products) of RMB 2.58 billion. R&D expenses of the Group increased by RMB 81 million to RMB 331 million, from RMB 250 million for the six months ended June 30, 2023. During the Reporting Period, the Group's revenue amounted to RMB 54.6 million, mainly consisted of the 1st milestone revenue from AZ on the CMG901 license transaction. SOURCE Keymed

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100 项与抗TSLP抗体(华润生物) 相关的药物交易

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