作者: Nagao, Kohjiro ; Namba, Norihiro ; Kobayashi, Norihiro ; Sakai, Koto ; Morita, Izumi ; Yamaki, Kouya ; Fukui, Nodoka ; Kiguchi, Yuki ; Saito, Hiroyuki ; Oyama, Hiroyuki ; Nakano, Miyu ; Ohgita, Takashi

Apolipoprotein E (apoE) is a regulator of lipid metabolism, cholesterol transport, and the clearance and aggregation of amyloid β in the brain. The three human apoE isoforms apoE2, apoE3, and apoE4 only differ in one or two residues. Nevertheless, the functions highly depend on the isoform types and lipidated states. Here, we generated novel anti‐apoE monoclonal antibodies (mAbs) and obtained an apoE4‐selective mAb whose epitope is within residues 110–117. ELISA and bio‐layer interferometry measurements demonstrated that the dissociation constants of mAbs are within the nanomolar range. Using the generated antibodies, we successfully constructed sandwich ELISA systems, which can detect all apoE isoforms or selectively detect apoE4. These results suggest the usability of the generated anti‐apoE mAbs for selective detection of apoE isoforms.

2023-11-01·Cancer Science

Novel specific anti‐ESM1 antibodies overcome tumor bevacizumab resistance by suppressing angiogenesis and metastasis

Article

作者: Kang, Nannan ; Fan, Buxi ; Liu, Yu ; Sun, Yao ; Xue, Peilin

AbstractSuppressing tumors through anti‐angiogenesis has been established as an effective clinical treatment strategy. Bevacizumab, a monoclonal antibody, is commonly used in various indications. However, two major challenges limit the long‐term efficacy of bevacizumab: drug resistance and side effects. Bevacizumab resistance has been extensively studied at the molecular level, but no drug candidates have been developed for clinical use to overcome this resistance. In a previous study conducted by our team, a major finding was that high expression of ESM1 in bevacizumab‐resistant tumors is associated with an unfavorable response to treatment. In particular, an increase in ESM1 expression contributes to heightened lung metastasis and microvascular density, which ultimately decreases the tumor's sensitivity to bevacizumab. In contrast, the silencing of ESM1 results in reduced angiogenesis and suppressed tumor growth in tumors resistant to bevacizumab. We put forward the hypothesis that targeting ESM1 could serve as a therapeutic strategy in overcoming bevacizumab resistance. In this study, a variety of anti‐ESM1 antibodies with high affinity to human ESM1 were successfully prepared and characterized. Our in vivo study confirmed the establishment of a bevacizumab‐resistant human colorectal cancer model and further demonstrated that the addition of anti‐ESM1 monoclonal antibodies to bevacizumab treatment significantly improved tumor response while downregulating DLL4 and MMP9. In conclusion, our study suggests that anti‐hESM1 monoclonal antibodies have the potential to alleviate or overcome bevacizumab resistance, thereby providing new strategies and drug candidates for clinical research in the treatment of bevacizumab‐resistant colorectal cancer.

2023-10-01·Endocrinology, Diabetes & Metabolism Case Reports

Insulin autoimmune syndrome: not just one but two different diseases with therapeutic implications

Article

作者: Følling, Ivar ; Bolstad, Nils ; Nermoen, Ingrid ; Wammer, Anne Cathrine Parelius ; Tran, Hoa ; Medbøe Thorsby, Per ; Lima, Kari

SummaryWe present a young woman with treatment resistant insulin autoimmune syndrome (IAS) with a protracted course. Her serum insulin level was 6945 pmol/l (<160), C-peptide 4042 pmol/L (<1480), anti-insulin antibodies 5305 U/mL (<0.4) were monoclonal IgG kappa. After 12 h of fasting, her blood glucose fell to 1.2 mmol/L. Post-meal blood glucose peaked at 12.2 mmol/L with reactive hypoglycaemia below 2 mmol/L. Frequent meals and continuous blood glucose monitoring were helpful, but further treatments advocated in the literature with prednisolone, rituximab, plasmapheresis, cyclophosphamide and ciclosporin were without beneficial effect.Based on this case and a review of the literature, we propose that IAS is not one but two different diseases with different therapeutic strategies. The first disease, polyclonal IAS, predominates in Asia and is characterized by polyclonal anti-insulin antibodies, association with certain HLA genotypes and other autoimmune conditions, medications and viral infections possibly triggering the disease, a possible female predominance among young patients and a tendency towards spontaneous remission. The other disease, monoclonal IAS, predominates in Caucasians. Typical features are monoclonal anti-insulin antibodies, only weak HLA association, no drug predisposition, no sex difference, rare remission and conventional therapy often being without any clinical effect. We suggest that monoclonal IAS with IgG or IgA anti-insulin antibodies should receive therapy targeting plasma cells rather than lymphocytes.Learning points

IAS may be considered as two separate diseases, polyclonal and monoclonal.

The presence of either polyclonal or monoclonal antibodies should determine the choice of treatment for IAS.

In polyclonal IAS, discontinuation of a triggering medication and treatment of triggering conditions should be the backbone of therapy.

Monoclonal IAS should receive treatment targeting plasma cells.

项与 Anti-IGF monoclonal antibodies (Shin Nippon) 相关的新闻（医药）

2023-04-05

·BioSpace

9 Meters Biopharma Announces Successful Pre-IND Meeting with FDA Regarding Its GIP Antagonist NM-136 for Obesity

RALEIGH, NC / ACCESSWIRE / April 5, 2023 / 9 Meters Biopharma, Inc. (NASDAQ:NMTR), a clinical-stage company pioneering novel treatments for people with rare or debilitating digestive diseases, today announced receipt of a written response from the U.S. Food and Drug Administration (FDA) on the request for a Type B pre-IND (Investigational New Drug) meeting on the planned pre-clinical development of NM-136 for the treatment of obesity. Based on the response, the Company currently plans to submit an IND to the FDA for this indication in the second half of 2023 based on the completion of the preclinical program. An approved IND is a prerequisite for conducting Phase 1 clinical studies of NM-136 in the U.S. Completion of this interaction with the FDA represents an important milestone and provides greater regulatory clarity and direction on the data needed to support an IND submission including input on the nonclinical plans and a proposed design of the Phase 1 study. "We are pleased with the feedback from FDA regarding our plans to support an IND submission for NM-136," said John Temperato, President and Chief Executive Officer of 9 Meters. "Receipt of a written response provides us with the information needed to finalize our plans to support an IND for this promising product, the timing of which will be dependent upon our financial position going forward. We believe NM-136 provides a novel approach to treating obesity, an important health concern that affects over 40% of the U.S. population, and we look forward to potentially filing our IND and subsequently progressing this program into the clinic as early as late this year." NM-136 is a novel humanized monoclonal antibody antagonist targeting glucose-dependent insulinotropic polypeptide (GIP). The Company believes NM-136 is a first-in-class humanized monoclonal antibody specifically targeting and binding GIP in the systemic circulation. GIP plays a critical role in promoting nutrient uptake and storage and has been shown to promote fat accumulation in humans. Pre-clinical data has demonstrated that anti-GIP monoclonal antibodies can effectively produce weight loss in obese mice without affecting food consumption. About 9 Meters Biopharma 9 Meters Biopharma, Inc. is a clinical-stage company pioneering novel treatments for people with rare digestive diseases, GI conditions with unmet needs, and debilitating disorders in which the biology of the gut is a contributing factor. 9 Meters is developing vurolenatide, a proprietary long-acting GLP-1 agonist in Phase 3 development for short bowel syndrome as well as near clinical-stage assets including NM-136 for obesity disorders. For more information please visit or follow 9 Meters on Twitter, LinkedIn, and Facebook. Forward-Looking Statements This press release includes forward-looking statements based upon 9 Meters' current expectations. Forward-looking statements include, but are not limited to, statements that express our intentions, beliefs, expectations, strategies, predictions, anticipated milestones, and any other statements relating to our future activities or other future events or conditions. These statements are based on current expectations, estimates and projections about our business based, in part, on assumptions made by management. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation: our need to raise additional capital to fund our operations for at least the next 12 months as a going concern and to advance our product candidates and preclinical programs, including in light of current stock market conditions; risks related to our ability to successfully implement our strategic plans, including reliance on our lead product candidates; uncertainties associated with the clinical development and regulatory approval of product candidates; uncertainties in obtaining successful clinical results for product candidates and unexpected costs that may result therefrom; risks related to the failure to realize any value from product candidates and preclinical programs being developed and anticipated to be developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; intellectual property risks; risks related to delays in enrollment in and timing of clinical trials; reliance on collaborators; reliance on research and development partners; and risks related to cybersecurity and data privacy. These and other risks and uncertainties are more fully described in periodic filings with the SEC, including the factors described in the section entitled "Risk Factors" in 9 Meters' Annual Report on Form 10-K for the year ended December 31, 2022, as amended or supplemented by our Quarterly Reports on Form 10-Q and in other filings that 9 Meters has made and future filings 9 Meters will make with the SEC. You should not place undue reliance on these forward-looking statements, which are made only as of the date hereof or as of the dates indicated in the forward-looking statements. 9 Meters expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations with regard thereto or any change in events, conditions, or circumstances on which any such statements are based. Corporate and Media Contact Al Medwar SVP, Investor Relations & Corporate Communications 9 Meters Biopharma, Inc. investor-relations@9meters.com SOURCE: 9 Meters Biopharma, Inc. View source version on accesswire.com:

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2023-03-28

·BioSpace

9 Meters Biopharma Provides Business Update and Reports Financial Results for Fourth Quarter and Full Year 2022

RALEIGH, NC / ACCESSWIRE / March 28, 2023 / 9 Meters Biopharma, Inc. (NASDAQ:NMTR), a clinical-stage company pioneering novel treatments for people with rare or debilitating digestive diseases, today provided an overview of its recent achievements, upcoming milestones, and financial results for the fourth quarter and full year ended December 31, 2022. "Our priority for 2023 remains to progress our Phase 3 vurolenatide program for short bowel syndrome including securing a clinical development and commercialization partner," commented John Temperato, President and Chief Executive Officer of 9 Meters Biopharma. "We firmly believe vurolenatide can establish a new standard of care in the treatment of short bowel syndrome with the potential to address the full SBS patient population and offer a rapid onset of action, sustained response, and a potentially convenient dosing regimen." Mr. Temperato continued, "Our Board of Directors and management team remain focused on ensuring that the Company is positioned to execute on our clinical and preclinical milestones as our financial position allows us to do so. The current financial markets, particularly for small-cap pharmaceutical companies, have been challenging in recent months; however, we are pleased to have recently strengthened our balance sheet with an equity financing and have also implemented cost-saving measures to further our cash runway. We believe that these actions align our strategic and financial goals and will help move the Company forward." Clinical Development and Business Highlights Phase 3 study of vurolenatide in Short Bowel Syndrome (SBS) Phase 3 study of vurolenatide, VIBRANT 2 (VurolenatIde for short Bowel syndrome Regardless of pArenteral support requiremeNT), is a randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of vurolenatide 50 mg administered subcutaneously every two weeks in adults with SBS. VIBRANT 2 incorporates two primary endpoints to evaluate the efficacy of vurolenatide in SBS in patients dependent on parenteral support (PS) (on PS at least 3 times per week) and all other patients (on PS fewer than 3 times per week). In March 2023, we received additional clarifying comments from the FDA on the VIBRANT 2 study protocol. The comments provide additional clarification and direction on specific elements of the study protocol and design. Based on the comments received, the Company will align with the recommendations provided, including the use of a continuous variable endpoint and a 24-week study duration for both subgroups of patients in the trial. Approximately 120 patients will be enrolled in the study and an interim analysis will be conducted when 50% of patients reach 24 weeks. Use of a continuous variable endpoint is viewed by the Company as a more robust measurement of efficacy. Study design continues to address the entire SBS population, serving patients in need of improved therapeutic options as well as helping the more than 50% of patients who do not meet the PS requirement threshold and are currently not served by existing therapeutics and late-stage development GLP-2 agonists. Presentations on vurolenatide and SBS at ASPEN 2023 Nutrition Science & Practice Conference Two abstracts, Vurolenatide, a novel long-acting glucagon-like peptide-1 (GLP-1) analogue, for patients with short bowel syndrome: A randomized Phase 2 trial and Epidemiology of Short Bowel Syndrome in the United States, have been accepted for presentation at the forthcoming ASPEN 2023 Nutrition Science & Practice Conference to take place in Las Vegas, Nevada from April 20 - 23, 2023. NM-136 (anti-GIP humanized monoclonal antibody) NM-136 is a novel long-acting, humanized anti-GIP monoclonal antibody. The Company believes NM-136 is a first-in-class humanized monoclonal antibody specifically targeting and binding GIP in the systemic circulation. GIP plays a critical role in promoting nutrient uptake and storage and has been shown to promote fat accumulation in humans. A pre-IND meeting with the FDA in the first half of 2023 is expected to provide the Company with important regulatory guidance on the preclinical development plan to support an IND for NM-136 in obesity disorders. Further information is anticipated to be made available in early second quarter. An abstract, The prevention and treatment of obesity in wild-type (WT) and hyperphagic leptin-deficient (OB/OB) mice using monoclonal antibodies (mAbs) to glucose-dependent insulinotropic polypeptide (GIP) occurs independently of appetite suppression, has been accepted for presentation at the forthcoming Digestive Disease Week to take place in Chicago, Illinois from May 6 - 9, 2023. Corporate On March 15, 2023, 9 Meters announced the closing of a $5 million registered direct offering priced at-the-market under Nasdaq rules. Proceeds from the offering, together with other available funds, will support the development of the Company's pipeline programs as well as provide funds for working capital and general corporate purposes. The Board of 9 Meters approved a cost reduction plan to help extend the cash runway, which will reduce operating expenses and further align the Company's workforce with immediate business needs. Essential activities will be transferred to existing staff members with relevant experience, who will continue to support the Company's key development programs as well as any potential partnerships or collaborations. Key Anticipated Near-Term Milestones Presentation of Phase 2 study results of vurolenatide in SBS at ASPEN 2023 Nutritional Science & Practice Conference in April. Presentation of data on the prevention and treatment of obesity using anti-GIP monoclonal antibodies at Digestive Disease Week in May. Completion of a pre-IND meeting for NM-136 followed by potential IND submission in the second half of 2023. Fourth Quarter and Full Year 2022 Financial Results As of December 31, 2022, the Company had total cash and cash equivalents of approximately $29.7 million, compared to approximately $39.4 million as of September 30, 2022. Included in total cash and cash equivalents was approximately $17.0 million and $23.5 million of restricted cash as of December 31, 2022 and September 30, 2022, respectively. Subsequent to year-end December 2022, the Company amended its convertible note and repaid approximately $16.8 million that was previously classified as restricted cash. In March 2023, the Company raised $5 million in gross proceeds through a registered direct offering. The Company anticipates that its cash runway is sufficient to fund operations into the third quarter of 2023. 9 Meters reported a net loss of approximately $11.9 million and $43.8 million for the fourth quarter and full year 2022, respectively, compared to a net loss of approximately $9.6 million and $36.8 million, respectively in the fourth quarter and full year of 2021. This increase in net loss year over year was primarily due to the advancement of our clinical development programs. Net loss per share was $0.92 and $3.38 respectively, for the fourth quarter and full year 2022, compared with $0.04 and $0.15 ($0.80 and $3.03 per share on a post-split basis) for the comparable periods in 2021. About 9 Meters Biopharma 9 Meters Biopharma, Inc. is a clinical-stage company pioneering novel treatments for people with rare digestive diseases, GI conditions with unmet needs, and debilitating disorders in which the biology of the gut is a contributing factor. 9 Meters is developing vurolenatide, a proprietary long-acting GLP-1 agonist in Phase 3 development for short bowel syndrome as well as near clinical-stage assets including NM-136 for obesity disorders. For more information please visit or follow 9 Meters on Twitter, LinkedIn, and Facebook. Forward-Looking Statements This press release includes forward-looking statements based upon 9 Meters' current expectations. Forward-looking statements include, but are not limited to, statements that express our intentions, beliefs, expectations, strategies, predictions, anticipated milestones, and any other statements relating to our future activities or other future events or conditions. These statements are based on current expectations, estimates and projections about our business based, in part, on assumptions made by management. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation: our need to raise additional capital to fund our operations for at least the next 12 months as a going concern and to advance our product candidates and preclinical programs, including in light of current stock market conditions; risks related to our ability to successfully implement our strategic plans, including reliance on our lead product candidate; uncertainties associated with the clinical development and regulatory approval of product candidates; uncertainties in obtaining successful clinical results for product candidates and unexpected costs that may result therefrom; risks related to the failure to realize any value from product candidates and preclinical programs being developed and anticipated to be developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; intellectual property risks; risks related to delays in enrollment in and timing of clinical trials; reliance on collaborators; reliance on research and development partners; and risks related to cybersecurity and data privacy. These and other risks and uncertainties are more fully described in periodic filings with the SEC, including the factors described in the section entitled "Risk Factors" in 9 Meters' Annual Report on Form 10-K for the year ended December 31, 2021, as amended or supplemented by our Quarterly Reports on Form 10-Q and in other filings that 9 Meters has made and future filings 9 Meters will make with the SEC. You should not place undue reliance on these forward-looking statements, which are made only as of the date hereof or as of the dates indicated in the forward-looking statements. 9 Meters expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations with regard thereto or any change in events, conditions, or circumstances on which any such statements are based. Corporate and Media Contact Al Medwar SVP, Investor Relations & Corporate Communications 9 Meters Biopharma, Inc. investor-relations@9meters.com SOURCE: 9 Meters Biopharma, Inc. View source version on accesswire.com:

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100 项与 Anti-IGF monoclonal antibodies (Shin Nippon) 相关的药物交易

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