A Dose-escalation, Single-arm, Open-Label, Phase 1 Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of EU103 in an Advanced or Metastatic Solid Tumors Who Have Failed Standard Therapy

Phase 1 (dose escalation) of this study will evaluate:
The safety and tolerability of EU103 treatment are evaluated for patients with advanced or metastatic solid tumors who have failed standard therapy to determine the maximum tolerated dose and recommended Phase 2 dose.
And preliminary efficacy (tumor response), The pharmacokinetic characteristics are evaluated, and changes are investigated.

开始日期2023-08-08

申办/合作机构

Eutilex Co., Ltd.

100 项与 EU-103 相关的临床结果

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100 项与 EU-103 相关的转化医学

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100 项与 EU-103 相关的专利（医药）

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项与 EU-103 相关的文献（医药）

2015-02-01·Immunobiology4区 · 医学

Monitoring liver macrophages using nanobodies targeting Vsig4: Concanavalin A induced acute hepatitis as paradigm

4区 · 医学

Article

作者: Stijlemans, Benoit ; Devoogdt, Nick ; Muyldermans, Serge ; Sparkes, Amanda ; Zheng, Fang ; Schoonooghe, Steve ; Beschin, Alain ; De Baetselier, Patrick ; Lahoutte, Tony ; Raes, Geert ; Morias, Yannick ; Abels, Chloé

Kupffer cells (KCs) are liver resident macrophages which are important for tissue homeostasis and have been implicated in immunogenic, tolerogenic and pathogenic immune reactions depending on the insult. These cells and the biomarkers they express thus represent interesting in vivo sensors for monitoring liver inflammation. In the current study, we explored whether KCs can be monitored non-invasively using single-photon-emission computed tomography (SPECT) with (99m)Tc labeled nanobodies (Nbs) targeting selected biomarkers. Nbs targeting V-set and immunoglobulin domain-containing 4 (Vsig4) or macrophage mannose receptor (MMR) accumulated in the liver of untreated mice. The liver targeting of anti-Vsig4 Nbs, but not anti-MMR Nbs, was blunted upon depletion of macrophages, highlighting specificity of anti-Vsig4 Nbs for liver macrophage imaging. Ex vivo flow cytometry and immunohistochemistry analysis confirmed that anti-Vsig4 Nbs specifically targeted KCs but no other cell types in the liver. Upon induction of acute hepatitis using concanavalin A (ConA), down-regulation of the in vivo imaging signal obtained using anti-Vsig4 Nbs reflected reduction in KC numbers and transient modulation of Vsig4 expression on KCs. Overall, these results indicate that Nbs targeting Vsig4 as molecular imaging biomarker enable non-invasive monitoring of KCs during hepatic inflammation.

International Journal of Molecular Sciences

Antibodies Targeting Human or Mouse VSIG4 Repolarize Tumor-Associated Macrophages Providing the Potential of Potent and Specific Clinical Anti-Tumor Response Induced across Multiple Cancer Types

Article

作者: Ritter, Jessica ; Wahle, Joe ; Klebanov, Boris ; Zafari, Mohammad ; Nguyen, Phuong A ; Phennicie, Ryan T ; Sazinsky, Stephen ; Razlog, Maja ; Feldman, Igor ; Manfra, Denise ; Novobrantseva, Tatiana ; Kauffman, Kevin J

V-set immunoglobulin domain-containing 4 (VSIG4) is a B7 family protein with known roles as a C3 fragment complement receptor involved in pathogen clearance and a negative regulator of T cell activation by an undetermined mechanism. VSIG4 expression is specific for tumor-associated and select tissue-resident macrophages. Increased expression of VSIG4 has been associated with worse survival in multiple cancer indications. Based upon computational analysis of transcript data across thousands of tumor and normal tissue samples, we hypothesized that VSIG4 has an important role in promoting M2-like immune suppressive macrophages and that targeting VSIG4 could relieve VSIG4-mediated macrophage suppression by repolarizing tumor-associated macrophages (TAMs) to an inflammatory phenotype. We have also observed a cancer-specific pattern of VSIG4 isoform distribution, implying a change in the functional regulation in cancer. Through a series of in vitro, in vivo, and ex vivo assays we demonstrate that anti-VSIG4 antibodies repolarize M2 macrophages and induce an immune response culminating in T cell activation. Anti-VSIG4 antibodies induce pro-inflammatory cytokines in M-CSF plus IL-10-driven human monocyte-derived M2c macrophages. Across patient-derived tumor samples from multiple tumor types, anti-VSIG4 treatment resulted in the upregulation of cytokines associated with TAM repolarization and T cell activation and chemokines involved in immune cell recruitment. VSIG4 blockade is also efficacious in a syngeneic mouse model as monotherapy as it enhances efficacy in combination with anti-PD-1, and the effect is dependent on the systemic availability of CD8+ T cells. Thus, VSIG4 represents a promising new target capable of triggering an anti-cancer response via multiple key immune mechanisms.

项与 EU-103 相关的新闻（医药）

2023-05-09

·BioSpace

Sensei Biotherapeutics Reports First Quarter 2023 Financial Results and Recent Business Highlights

- Investigational New Drug (IND) application for SNS-101 cleared by U.S. Food and Drug Administration (FDA) with first patient dose in Phase 1/2 trial expected in mid-2023 - - Signing of key collaborations underscore potential of conditional activation and VISTA mechanism - - AACR presentation highlights progress of SNS-103 program targeting CD39 - - Strong balance sheet with cash runway into the second half of 2025 - BOSTON, May 09, 2023 (GLOBE NEWSWIRE) -- Sensei Bio Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, today reported financial results for the first quarter ended March 31, 2023, and provided recent business updates. “We are pleased with the progress across our pipeline, underscored by regulatory clearance to proceed with a Phase 1/2 clinical study of our lead candidate, SNS-101, in patients with advanced solid tumors. We look forward to commencing this trial in mid-2023 and expect to move swiftly to a recommended Phase 2 dose,” said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. “We are also maintaining superb progress and promising results from our other pipeline programs, each with breakthrough potential within their target classes, as we advance toward key decision points later this year.” Highlights and Milestones SNS-101 Sensei continues to advance SNS-101, a conditionally active antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation), which is implicated in resistance to cancer immunotherapy and whose expression correlates with poor survival across numerous cancers. Recent updates for SNS-101 include: In April 2023, the U.S. Food and Drug Administration (FDA) cleared Sensei’s Investigational New Drug (IND) application for the planned Phase 1/2 clinical trial of SNS-101 in patients with advanced solid tumors. The Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101 as both a monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo® (cemiplimab) in advanced solid-tumor cancer patients. Sensei expects to begin clinical trial enrollment and commence patient dosing at a starting dose of 0.3 mg/kg in mid-2023. In February 2023, Sensei CSO Edward van der Horst presented key preclinical data supporting the mechanism of SNS-101 at the Keystone Symposia on Next Generation Antibody Therapeutics. Under the recently signed CRADA with the National Cancer Institute (NCI), part of the National Institutes of Health, in February 2023, preclinical studies are in progress with the goal of further elucidating VISTA’s role in immune checkpoint resistance and expanding the potential of SNS-101 as a combination therapy beyond anti-PD-1. In addition, preparations are underway for the NCI to participate as a trial site in the clinical investigation of SNS-101. In a multi-dose GLP toxicology study, SNS-101 was well tolerated and displayed a favorable multi-dose pharmacokinetic profile, with linear elimination kinetics and an absence of target-mediated drug disposition. Additional TMAb™ Platform Updates Through its Tumor Microenvironment Activated biologics (TMAb) platform, Sensei is also advancing several conditionally active antibody programs, including SNS-102 targeting VSIG4 (V-Set and Immunoglobulin Domain Containing 4), SNS-103 targeting ENTPDase1 (ecto-nucleoside triphosphate diphosphohydrolase-1, also known as CD39) and a recently initiated fourth program. SNS-102: Eight parental pH-sensitive VSIG4 antibodies have been selected, which have undergone further lead optimization and are currently being characterized. SNS-103: In April 2023, Sensei presented new preclinical data on SNS-103 at the American Association for Cancer Research (AACR) Annual Meeting. Eight parental pH-sensitive CD39 antibodies have been selected, which have undergone further lead optimization and are currently being characterized. Sensei remains on track to select product candidates for both SNS-102 and SNS-103 in 2023. Sensei has initiated early discovery efforts for a fourth TMAB program focused on developing a conditionally active bispecific antibody. Upon successful candidate selection, Sensei expects to advance one product candidate to IND-enabling studies. First Quarter 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $95.5 million as of March 31, 2023, as compared to $107.1 million as of December 31, 2022. Sensei expects its current cash balance to fund operations into the second half of 2025. Research and Development (R&D) Expenses: R&D expenses were $5.2 million for the quarter ended March 31, 2023, compared to $7.5 million for the quarter ended March 31, 2022. The decrease in R&D expenses was primarily attributable to lower personnel costs due to the restructuring, lower expense relating to lab supply purchases and lower manufacturing related expense partially offset by higher expense associated with clinical trials. General and Administrative (G&A) Expenses: G&A expenses were $5.8 million for the quarter ended March 31, 2023, compared to $5.0 million for the quarter ended March 31, 2022. The increase in G&A expense was primarily attributable to external professional services, including $1.5 million of non-recurring expenses associated with stockholder activism related to our upcoming 2023 annual meeting of stockholders. Net Loss: Net loss was $10.2 million for the quarter ended March 31, 2023, compared to $12.4 million for the quarter ended March 31, 2022. About Sensei Biotherapeutics Sensei Biotherapeutics (Nasdaq: SNSE) is a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients. Through its TMAb™ (Tumor Microenvironment Activated biologics) platform, Sensei develops conditionally active therapeutics designed to disable immunosuppressive signals or activate immunostimulatory signals selectively in the tumor microenvironment to unleash T cells against tumors. Sensei’s lead investigational candidate is SNS-101, a conditionally active antibody designed to block the V-domain Ig suppressor of T cell activation (VISTA) checkpoint selectively within the low pH tumor microenvironment, where VISTA acts as a suppressor of T cells by binding the receptor PSGL-1. The company is also developing SNS-102, a conditional binding monoclonal antibody targeting V-Set and Immunoglobulin Domain Containing 4 (VSIG-4), as well as SNS-103, also a conditionally active monoclonal antibody targeting ecto-nucleoside triphosphate diphosphohydrolase-1 (ENTPDase1), also known as CD39. For more information, please visit , and follow the company on Twitter @SenseiBio and LinkedIn. Condensed Statements of Operations (Unaudited, in thousands except share and per share data) Three Months Ended March 31, 2023 2022 Operating expenses: Research and development $ 5,204 $ 7,455 General and administrative 5,804 5,032 Total operating expenses 11,008 12,487 Loss from operations (11,008 ) (12,487 ) Total other income 831 82 Net loss (10,177 ) (12,405 ) Net loss attributable to common stockholders (10,177 ) (12,405 ) Net loss per share, basic and diluted $ (0.33 ) $ (0.40 ) Weighted-average common shares outstanding, basic and diluted 30,866,087 30,647,679 Selected Condensed Balance Sheet Data (Unaudited, in thousands) March 31, 2023 December 31, 2022 Cash and cash equivalents $ 8,109 $ 17,795 Marketable securities 87,396 89,321 Total assets 107,933 118,375 Total liabilities 13,083 14,968 Total stockholders’ equity 94,850 103,407 Cautionary Note Regarding Forward-Looking Statements Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “believe”, “designed to,” “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Sensei’s current beliefs and expectations. These forward-looking statements include expectations regarding the development and potential therapeutic benefits of Sensei’s product candidates, the expected safety pro Sensei’s product candidates, the availability of data from Sensei’s preclinical studies, the timing of Sensei’s planned Phase 1/2 clinical trial of SNS-101, the timing of selection of product candidates, and its belief that its existing cash and cash equivalents will be sufficient to fund its operations at least into the second half of 2025. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the development of therapeutic product candidates, such as the risk that any one or more of Sensei’s product candidates will not be successfully developed or commercialized; the risk of delay or cessation of any planned clinical trials of Sensei’s product candidates; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical trials, will not be replicated or will not continue in ongoing or future studies or clinical trials involving Sensei’s product candidates; the risk that Sensei’s product candidates or procedures in connection with the administration thereof will not have the safety or efficacy pro we anticipate; risks associated with Sensei’s dependence on third-party suppliers and manufacturers, including sole source suppliers, over which we may not always have full control; risks regarding the accuracy of our estimates of expenses, capital requirements and needs for additional financing; and other risks and uncertainties that are described in Sensei’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) on March 29, 2023 and Sensei’s other Periodic Reports filed with the SEC. Any forward-looking statements speak only as of the date of this press release and are based on information available to Sensei as of the date of this release, and Sensei assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. Investor Contact: Michael Biega Senior Director, Investor Relations Sensei Biotherapeutics mbiega@senseibio.com Media Contact: Chris Railey Ten Bridge Communications chris@tenbridgecommunications.com

临床申请免疫疗法财报AACR会议

2023-03-28

·BioSpace

Sensei Biotherapeutics Reports Full Year 2022 Financial Results and Recent Business Highlights

- Investigational New Drug (IND) application submitted for lead candidate SNS-101, a conditionally active VISTA-blocking antibody - - New collaborations with Regeneron, the National Cancer Institute and Washington University in St. Louis will support development of SNS-101 - - Company anticipates advancing a second TMAb™ program to IND-enabling studies following successful candidate selection - - Strong balance sheet with cash runway into the second half of 2025 - BOSTON, March 28, 2023 (GLOBE NEWSWIRE) -- Sensei Bio, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, today reported financial results for full-year 2022 and provided recent business updates. “Over the last year the team has worked with urgency to test the biological rationale for our lead product candidate, SNS-101, as a potentially transformative therapeutic option for patients with solid tumors,” said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. “We remain committed to the belief that VISTA has tremendous potential as an immune checkpoint target and continue to take steps to prioritize the advancement of SNS-101. We are pleased that, despite industry headwinds, our work has culminated in the recent submission of an IND to begin a Phase 1/2 clinical trial with the support of our partners. We’re also excited about the overall progress of programs generated through our TMAb™ platform, including SNS-102 and SNS-103, and look forward to advancing other conditionally active antibodies that ignite and deploy the immune system’s full potential to fight cancer.” Added Mr. Celebi, “Following the streamlining and realignment of the Company’s resources to support its key indications and programs, including reductions in operating expenses, employee-related costs and occupancy costs, our programs are supported by a healthy cash position that provides runway into the second half of 2025. We are confident in our strategy and expect to continue achieving critical near-term milestones across our pipeline.” Highlights and Milestones SNS-101 Sensei continues to advance SNS-101, a conditionally active antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation), which is implicated in resistance to PD-1/PD-L1 therapy and whose expression correlates with poor survival across numerous cancers. Recent updates for SNS-101 include: In March 2023, Sensei submitted an IND application to the U.S. Food and Drug Administration for the planned Phase 1/2 clinical trial of SNS-101 in patients with solid tumors. In November 2022, Sensei presented preclinical data on SNS-101 at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, highlighting the antibody’s potentially improved safety, pharmacokinetic and efficacy pro non-conditionally active VISTA-blocking antibodies. Presented data showed a significantly lower risk of inducing cytokine release syndrome (CRS), linear elimination kinetics and avoidance of target-mediated drug disposition and significant enhancement of anti-tumor effects in combination with anti-PD-1 antibodies. Additional preclinical data presented at the Keystone Symposia on Next-Generation Antibody Therapeutics in February 2023 included crystal structure analysis further elucidating SNS-101’s mechanism of action, showing that the antibody directly blocks the pH-dependent interaction between VISTA and PSGL-1. New preclinical efficacy data support a rationale for SNS-101 both as monotherapy and in combination with PD-1 blockade for patients with solid tumors. Key Collaborations Supporting SNS-101 Sensei recently announced three collaborations key to the development of SNS-101 and the planned Phase 1/2 clinical trial in solid tumors: A Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), executed in February 2023, is designed to further demonstrate the role of VISTA in checkpoint resistance and will enable Sensei to explore SNS-101’s potential as a combination therapy beyond anti-PD-1. In January 2023, the Company signed a clinical supply agreement with Regeneron that will enable Sensei to evaluate SNS-101 in combination with the anti-PD1 therapy Libtayo® (cemiplimab). In November 2022, Sensei announced a Sponsored Research Agreement with Washington University in St. Louis to support research into the underlying molecular mechanisms that enable SNS-101 to overcome myeloid cell-driven immunosuppression within the tumor microenvironment. Additional TMAb Platform Updates Through its proprietary Tumor Microenvironment Activated biologics (TMAb) platform, Sensei is also advancing several pH-sensitive antibodies, including SNS-102 targeting VSIG4 (V-Set and Immunoglobulin Domain Containing 4) and SNS-103 targeting ENTPDase1 (ecto-nucleoside triphosphate diphosphohydrolase-1, also known as CD39). SNS-102: Eight parental pH-sensitive VSIG4 antibodies have been selected for lead optimization. Data on this program presented at SITC in November 2023 characterized endogenous expression patterns of VSIG4 in polarized macrophage populations and showed robust VSIG4-mediated suppression of primary human T-cells. Additionally, Sensei reported that a ligand receptor capture-trifunctional chemoproteomic (LRC-TriCEPS)-based proteomics strategy identified receptors on primary human T-cells that interact with recombinant VSIG4 protein. SNS-103: Sensei has identified eight parental pH-sensitive CD39 antibodies and begun further optimization on a lead antibody set. Upcoming Milestones Sensei will present preclinical data on its SNS-103 program at the American Association for Cancer Research (AACR) Annual Meeting in a poster session on April 18, 2023. Sensei remains on track to select product candidates for both SNS-102 and SNS-103 in 2023. Upon successful candidate selection, Sensei expects to advance at least one product candidate to IND-enabling studies. The Company has initiated early discovery efforts for a fourth TMAb program. Cost Savings Following the streamlining and realignment of the Company’s resources to support its key indications and programs, including reductions in operating expenses, employee-related costs and occupancy costs, Sensei projects it has a cash runway into the second half of 2025. As a result of the Company’s prudent fiscal strategy, Sensei expects significant cost savings while preserving the ability to fund development and continuation of programs for potential nearer-term data catalysts. Corporate Updates In December 2022, Sensei promoted Edward van der Horst, Ph.D., to Chief Scientific Officer. Year End 2022 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $107.1 million as of December 31, 2022, as compared to $147.6 million as of December 31, 2021. Sensei expects its current cash balance to fund operations into the second half of 2025. Research and Development (R&D) Expenses: R&D expenses were $30.4 million for the year ended December 31, 2022, compared to $21.7 million for the year ended December 31, 2021. The increase in R&D expenses was primarily attributable to increased manufacturing and early development activities for the Company’s lead program SNS-101, partially offset by a decrease in clinical trial expenses. General and Administrative (G&A) Expenses: G&A expenses were $19.8 million for the year ended December 31, 2022, compared to $15.8 million for the year ended December 31, 2021. The increase in G&A expense was primarily attributable to external professional services and personnel costs. Net Loss: Net loss was $48.6 million for the year ended December 31, 2022, compared to $36.8 million for the year ended December 31, 2021. Condensed Statements of Operations (Unaudited, in thousands except share and per share data) Twelve Months Ended December 31, 2022 2021 Operating expenses: Research and development $ 30,383 $ 21,662 General and administrative 19,805 15,820 Total operating expenses 50,188 37,482 Loss from operations (50,188 ) (37,482 ) Total other income 1,600 688 Net loss (48,588 ) (36,794 ) Net loss per share, basic and diluted $ (1.58 ) $ (1.33 ) Weighted-average common shares outstanding, basic and diluted 30,703,295 27,710,686 Selected Condensed Balance Sheet Data (Unaudited, in thousands) December 31, 2022 December 31, 2021 Cash and cash equivalents $ 17,795 $ 7,159 Marketable Securities 89,321 140,462 Total assets 118,375 153,225 Total liabilities 14,968 6,712 Total stockholders’ equity (deficit) 103,407 146,513 About Sensei Biotherapeutics Sensei Biotherapeutics (Nasdaq: SNSE) is an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients. Through its TMAb™ (Tumor Microenvironment Activated biologics) platform, Sensei develops conditionally active therapeutics designed to disable immunosuppressive signals or activate immunostimulatory signals selectively in the tumor microenvironment to unleash T cells against tumors. Sensei’s lead investigational candidate is SNS-101, a conditionally active antibody designed to block the V-domain Ig suppressor of T cell activation (VISTA) checkpoint selectively within the low pH tumor microenvironment, where VISTA acts as a suppressor of T cells by binding the receptor PSGL-1. The company is also developing SNS-102, a conditional binding monoclonal antibody targeting V-Set and Immunoglobulin Domain Containing 4 (VSIG-4), as well as SNS-103, also a conditionally active monoclonal antibody targeting ecto-nucleoside triphosphate diphosphohydrolase-1 (ENTPDase1), also known as CD39. For more information, please visit , and follow the company on Twitter @SenseiBio and LinkedIn. Cautionary Note Regarding Forward-Looking Statements Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “believe”, “designed to,” “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Sensei’s current beliefs and expectations. These forward-looking statements include expectations regarding the development and potential therapeutic benefits of Sensei’s product candidates, the expected safety pro Sensei’s product candidates, the availability of data from Sensei’s preclinical studies, the timing of selection of product candidates, and its belief that its existing cash and cash equivalents will be sufficient to fund its operations at least into the first quarter of 2025. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the development of therapeutic product candidates, such as the risk that any one or more of Sensei’s product candidates will not be successfully developed or commercialized; the risk of delay or cessation of any planned clinical trials of Sensei’s product candidates; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical trials, will not be replicated or will not continue in ongoing or future studies or clinical trials involving Sensei’s product candidates; the risk that Sensei’s product candidates or procedures in connection with the administration thereof will not have the safety or efficacy pro we anticipate; risks associated with Sensei’s dependence on third-party suppliers and manufacturers, including sole source suppliers, over which we may not always have full control; risks regarding the accuracy of our estimates of expenses, capital requirements and needs for additional financing; and other risks and uncertainties that are described in Sensei’s Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (SEC) on or about November 8, 2022 and Sensei’s other Periodic Reports filed with the SEC. Any forward-looking statements speak only as of the date of this press release and are based on information available to Sensei as of the date of this release, and Sensei assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. Investor Contact: Michael Biega Senior Director, Investor Relations Sensei Biotherapeutics mbiega@senseibio.com Media Contact: Chris Railey Ten Bridge Communications chris@tenbridgecommunications.com

财报免疫疗法AACR会议

2023-03-20

·药明康德

肿瘤细胞量降低超90%的新疗法；登上《自然》的靶向疗法... | 一周盘点

▎药明康德内容团队编辑本期看点1. 用于治疗携带NPM1突变或KMT2A重排的复发/难治性急性白血病（AML）的选择性小分子menin抑制剂revumenib登上《自然》杂志，53%的受试者对治疗有反应，12名患者争取到了接受干细胞或骨髓移植的机会。2. 新型合成微管不稳定药物AB8939在1例难治性AML患者中展现积极疗效，仅连续给药3天，接受治疗28天后就观察到白血病细胞的急剧减少，从55%降低到5%，降幅超过90%。3. Kiora Pharmaceuticals公司公布三项罕见眼科疾病的创新小分子疗法的积极数据。药明康德内容团队整理Revumenib：公布1/2期临床试验数据Syndax Pharmaceuticals公司公布了其选择性小分子menin抑制剂revumenib用于治疗携带NPM1突变或KMT2A重排的复发/难治性AML患者的积极结果，并发表在了权威学术期刊《自然》上。AML是成人中最常见的白血病之一，约占所有病例的三分之一。MLL基因重排和NPM1突变发生在大约40%的AML患者身上，这两种基因变异都需要menin蛋白质的参与来驱动癌症发生。Revumenib是一种有效的选择性小分子抑制剂，旨在抑制menin-MLL结合的相互作用以治疗白血病。研究共招募了68名AML患者。此次公布的数据显示，53%的患者对revumenib治疗有反应，30%实现了完全缓解或伴有部分血液学恢复的完全缓解。在获得缓解的患者中，超过78%患者的可测量残留病灶为阴性，表明即使通过最灵敏的方法，也无法检测到白血病。所有患者的整体中位缓解时间为9.1个月，中位总生存期为7个月（含对治疗无反应的患者）。12名原本无法进行移植手术的患者在出现病情缓解后进行了异体干细胞移植。总的来说，试验中观察到的副作用并不严重，没有患者因副作用而退出试验。AB8939：公布1/2期临床试验的初步数据AB Science公司公布了其针对血液恶性肿瘤开发的新型合成微管不稳定药物AB8939在1/2期临床试验中的积极初步结果。临床前数据表明，AB8939具有广泛的抗肿瘤活性，与靶向微管的标准化疗相比具有显著的优势，能够克服P-糖蛋白（Pgp）和髓过氧化物酶（MPO）介导的耐药性。此前，AB8939已被美国FDA授予AML的孤儿药资格。在这项研究中，一位未能事先接受阿扎胞苷治疗，并出现MECOM基因重排（一种对标准化疗耐药的生物标志物，与疾病进展的高风险和较差的预后相关）的AML患者在第一个治疗周期（即连续三天的AB8939治疗）一个月后，骨髓原始细胞（即白血病细胞）的水平从治疗前的55%急剧减少到5%。值得注意的是，这种反应是在AB8939的剂量非常低的情况下实现的，也就是1期剂量增量研究的第2个剂量（一共设计了13个待研究的剂量）。患者对AB8939的耐受性良好，没有出现治疗相关的毒性反应。在该低剂量下，第二个治疗周期后一个月时，患者的白血病细胞水平保持在10%（相当于相对于基线减少5倍）。考虑到迄今为止的总体研究，没有出现中度或严重毒性反应的迹象，大约50%的患者在第一个治疗周期和第28天的评估后请求继续接受AB8939的治疗。KIO-101：公布1期临床试验的新数据KIO-101是Kiora Pharmaceuticals公司的一种靶向二氢乳清酸脱氢酶（DHODH）的下一代非甾体类免疫调节小分子抑制剂，旨在克服市售的DHODH抑制剂的相关脱靶副作用和安全问题。该疗法的给药方式为玻璃体内注射，正在12名患有自身免疫性后部葡萄膜炎（posterior uveitis）的患者中接受评估。此次公布的结果显示，玻璃体内注射KIO-101是安全且可耐受的，具有治疗自身免疫性后部葡萄膜炎和黄斑囊样水肿（CME）患者的潜力。患者的视力呈剂量依赖性增加，前房细胞和玻璃体混浊的综合炎症评分在第2周下降了53.0%，并在第4周保持低水平。接受0.6 µg或1.2 µg治疗的5名患者中有3名（66.7%）的CME消退。在整个研究期间，所有组的眼压、视野和视网膜电图（ERG）都保持稳定，没有观察到不良事件。KIO-201：公布早期临床试验结果KIO-201是Kiora Pharmaceuticals公司的一种交联的、化学修饰的透明质酸，用于患有持续性角膜上皮缺损（PCED）的患者。该公司于近日报告了KIO-201在8名患者中的临床研究结果。数据显示，KIO-201是PCED的一种潜在的治疗方法。8只眼睛在治疗至少3周后通过重复荧光素染色进行评估，在治疗开始后4周，KIO-201使缺损的尺寸缩小>90.0%。8名患者中有5名（62.5%）在4周内达到了主要的愈合终点。该药物的安全性和耐受性良好，8名患者中有2名（25.0%）报告了6起非严重不良事件。研究人员报告的所有不良事件均与研究药物无关。KIO-301：公布首次人体试验数据KIO-301是Kiora Pharmaceuticals公司的一种小分子光控开关（Photoswitch），旨在治疗视网膜色素变性。该公司于近日公布了KIO-301的首次人体试验的初步数据。该试验作为正在进行的、更大规模临床试验的一部分，将初步评估KIO-301在晚期视网膜色素变性患者中的安全性、耐受性和疗效。试验的初始人群患有晚期色素性视网膜炎，伴有最低限度的光感或无光感。患者报告的结果表明，在注射KIO-301后，其感知光的能力、描绘明暗对比的能力以及整体视觉功能都有所改善。在研究过程中没有报告不良事件，包括眼部不良事件。CM24：公布1期临床试验的初步数据Purple Biotech公司公布了其靶向CEACAM1的单克隆抗体CM24用于治疗晚期实体肿瘤患者的初步临床数据。CEACAM1是一种免疫检查点蛋白，可通过多种途径支持肿瘤免疫逃逸和存活。NET是一种网状DNA结构，覆盖着由活化的中性粒细胞释放的致癌蛋白，已被证明可包裹肿瘤并促进免疫逃避、肿瘤进展和转移。当CEACAM1与NET结合时，它将成为癌症细胞粘附的重要位点，因此被认为是预防肿瘤转移进展和免疫逃逸的潜在治疗靶点。在临床前研究中，CM24已被证明可直接与NET结合，并抑制NET诱导的癌症细胞迁移。此次研究招募了14名晚期癌症患者，包括11名胰腺癌（PDAC）患者、两名结直肠腺癌患者和一名乳头状甲状腺癌患者。在八名可评估的PDAC患者中进行的分析表明，CM24联用纳武利尤单抗首次给药后和15天后，血清髓过氧化物酶（myeloperoxidase，一种NET的生物标志物）出现了具有临床意义的持续降低。此外，对来自可评估PDAC患者的肿瘤样本的分析表明，患者存活可能与肿瘤微环境中较高水平的CEACAM1+肿瘤浸润淋巴细胞呈正相关。Povetacicept（ALPN-303）：公布1期临床试验的初步数据Alpine Immune Sciences公司公布了其BAFF（B细胞激活因子）和APRIL（一种增殖诱导配体）的双重拮抗剂povetacicept（ALPN-303）在健康受试者中的初步临床数据。这些细胞因子在B细胞，特别是抗体分泌细胞的活化和存活中起着关键作用。Povetacicept正在被开发用于多种B细胞和/或自身抗体相关疾病。此次公布的研究结果表明，povetacicept在960 mg的剂量下耐受性良好，具有剂量依赖性的药代动力学特征，以及剂量依赖性的循环免疫球蛋白和抗体分泌细胞的减少。该结果支持在后续研究中使用每4周一次的剂量方案。EU103：IND申请获得韩国食品药品安全部许可EU103是Eutilex公司开发的靶向肿瘤相关巨噬细胞（TAM）表面的VSIG4的候选抗体药物，用于治疗标准治疗失败的晚期或转移性实体肿瘤。EU103旨在激活T细胞，并将诱导肿瘤生长的M2巨噬细胞转化为抑制肿瘤生长的M1巨噬细胞。近日，韩国食品药品安全部已经批准了EU103的IND申请，将在30例实体肿瘤患者中对该候选疗法的安全性和耐受性进行评估。ST316：IND申请获得FDA许可ST316是Sapience Therapeutics公司开发的潜在“first-in-class”的β-连环蛋白（β-catenin）拮抗剂，能够抑制β-连环蛋白与其共激活因子BCL9之间的相互作用。β-连环蛋白是Wnt信号通路的效应蛋白，该通路是最重要的致癌通路之一。BCL9是一种在多种癌症中驱动致癌基因表达的复合物，在这些癌症常常中观察到异常的Wnt/β-连环蛋白通路信号传导。β-连环蛋白和BCL9之间的相互作用以前被认为是一个“不可成药”的靶点，因为小分子无法抑制复合物的形成，而抗体无法进入细胞质或细胞核以破坏相互作用。ST316包含了允许进入细胞内的细胞穿透部分和设计用于结合β-连环蛋白第一个armadillo重复结构域的结构域，该位点仅与BCL9发生相互作用。ST316能将β-连环蛋白的生理活性和致癌活性分开，从而能够治疗Wnt驱动的肿瘤，同时保持正常的β-catenin功能完好无损。该研究的第1阶段剂量递增部分将在2023年上半年开展，招募可能患有Wnt/β-连环蛋白信号通路异常的肿瘤患者。TRE-515：公布1期临床试验数据Trethera Corporation公司公布了其口服潜在“first-in-class”的脱氧胞苷激酶（dCK）抑制剂TRE-515用于治疗高危、先前接受过多线治疗的恶性实体肿瘤患者的积极早期临床数据。TRE-515旨在抑制核苷补救通路中的关键酶dCK。实体恶性肿瘤中的肿瘤细胞和自身免疫性疾病中的病理免疫细胞的一个共同特征是需要升高的核苷酸水平来支持异常和加速的细胞分裂。而大多数健康成人细胞并不需要dCK活性。因此，由限速酶dCK介导的核苷补救通路有望在限制癌细胞和异常活化的淋巴细胞的快速增殖方面发挥关键作用。此次公布的临床结果显示，TRE-515的耐受性良好，不良事件有限、短暂且可控。其在40 mg至320 mg剂量范围内的暴露量几乎与剂量成正比，显示出良好的药代动力学特征，其特点是吸收快速（Tmax＜2小时）和超过6小时的血浆半衰期，支持每日一次口服给药。在研究的所有剂量水平中，根据RECIST v1.1标准报告了5例（n=5）达到疾病稳定（SD）的病例。这些患者中的大多数已经接受过至少5线的治疗，并伴有广泛的转移。血浆核苷浓度，即dCK的底物，提供了令人信服的靶标参与的证据（p<0.0001）。BSG005：公布1期临床试验数据Biosergen公司公布了其用于治疗毛霉菌病的候选药物BSG005的积极1期临床试验结果。毛霉菌病，也称为黑真菌病，是一种持续性且难以治疗的全身性真菌感染，死亡率高，因此迫切需要新的有效和安全的抗真菌疗法。BSG005是一种抗真菌化合物，此前已在毒理学研究中证明了安全性。此次双盲、安慰剂对照的1期临床试验结果显示，BSG005的安全性和耐受性良好，没有报告严重的不良事件，也没有关于肾脏和肝脏的负面安全信号。CT1812：IND申请获得FDA许可CT1812是Cognition Therapeutics公司开发的一种旨在穿透血脑屏障和血视网膜屏障的口服小分子，能够选择性地结合σ-2受体复合物，有望治疗干性年龄相关性黄斑变性（AMD）引起的地图样萎缩（GA）。σ-2受体复合物参与了一些关键的细胞过程，例如膜运输和自噬的调节，这些过程会因与可溶性β淀粉样蛋白（Aβ）低聚物、氧化应激和其他应激源的毒性相互作用而受损。在干性AMD中，这些细胞过程的受损会导致视力下降，最终导致视力丧失。CT1812的早期概念验证研究表明，σ-2受体调节剂能在拯救敏感的视网膜色素上皮细胞（RPE）免受致病蛋白和氧化应激等应激源的损害中发挥作用，从而保护黄斑中的这一重要组成部分。GRC 54276：IND申请获得FDA许可GRC 54276是Glenmark Specialty公司开发的一种口服小分子造血祖细胞激酶1（HPK1）抑制剂。HPK1调节的功能几乎参与癌症免疫循环的每一步，使其成为免疫肿瘤学的一个有吸引力的靶点。通过抑制HPK1，GRC 54276旨在潜在地增强患者自身的免疫系统以对抗癌症。GRC 54276正在一项1/2期临床试验中作为单一疗法或与抗PD-（L）1疗法联用治疗患有晚期实体肿瘤和淋巴瘤的成人患者。迄今为止，已有16名患有各种类型晚期癌症的患者参加了这项在印度进行的研究，该公司计划在接下来的几个月中在印度以外展开研究。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Karolinska Development’s portfolio company Biosergen presents positive results from phase 1 study of drug candidate to treat systemic fungal infection. Retrieved March 17, 2023, from https://www.globenewswire.com/news-release/2023/03/13/2625991/0/en/Karolinska-Development-s-portfolio-company-Biosergen-presents-positive-results-from-phase-1-study-of-drug-candidate-to-treat-systemic-fungal-infection.html[2] 유틸렉스, 'VSIG4 항체' 고형암 1상 "국내 IND 승인". Retrieved March 17, 2023, from http://biospectator.com/view/news_view.php?varAtcId=18492[3] 13/03/2023 – AB Science today announces a case report from the initial stage of its Phase I/II study (AB18001) evaluating AB8939, a microtubule destabilizer, in patients with refractory and relapsed acute myeloid leukemia (AML). Retrieved March 17, 2023, from https://www.ab-science.com/ab-science-reports-a-first-complete-bone-marrow-response-in-a-relapsed-refractory-acute-myeloid-leukemia-patient-from-the-very-low-dose-arm-of-its-ab8939-phase-i-ii-clinical-trial-ab18001/[4] ALX Oncology and Quantum Leap Healthcare Collaborative™ Announce First Patient Dosed in the I-SPY-P1 TRIAL in Breast Cancer. Retrieved March 17, 2023, from https://ir.alxoncology.com/news-releases/news-release-details/alx-oncology-and-quantum-leap-healthcare-collaborativetm-0[5] Sapience Therapeutics Receives IND Clearance from FDA to Proceed with Phase 1-2 Study of ST316 in Patients with Solid Tumors. Retrieved March 17, 2023, from https://www.prnewswire.com/news-releases/sapience-therapeutics-receives-ind-clearance-from-fda-to-proceed-with-phase-1-2-study-of-st316-in-patients-with-solid-tumors-301771021.html[6] TScan Therapeutics Announces First Patient Dosed in Phase 1 Umbrella Clinical Trial Evaluating TSC-100 and TS-101 for the Treatment of Hematologic Malignancies. Retrieved March 17, 2023, from https://ir.tscan.com/news-releases/news-release-details/tscan-therapeutics-announces-first-patient-dosed-phase-1[7] Albumedix and Heartseed announce Recombumin® as a critical excipient in the manufacture of Heartseed's HS-001 investigational cell therapy as its first in-human trial commences. Retrieved March 17, 2023, from https://www.prnewswire.com/news-releases/albumedix-and-heartseed-announce-recombumin-as-a-critical-excipient-in-the-manufacture-of-heartseeds-hs-001-investigational-cell-therapy-as-its-first-in-human-trial-commences-301769974.html[8] ITM, Helmholtz Munich and University Hospital Münster Announce Start of Phase I Clinical Trial with Radiotherapeutic ITM-31 for Glioblastoma. Retrieved March 17, 2023, from https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/ITM,_Helmholtz_Munich_and_University_Hospital_M%C3%BCnster_Announce_Start_of_Phase_I_Clinical_Trial_with_Radiotherapeutic_ITM-31_for_Glioblastoma-605/[9] Kiora Pharmaceuticals Announces the Acceptance of Three Abstracts at the 2023 ARVO Annual Meeting. Retrieved March 17, 2023, from https://www.newsfilecorp.com/release/157917[10] Dose Escalation Portion of Phase 1 Solid Tumors Trial Produces Favorable Results in Heavily Pretreated Solid Tumor Patients. Retrieved March 17, 2023, from https://www.globenewswire.com/news-release/2023/03/15/2627997/0/en/Dose-Escalation-Portion-of-Phase-1-Solid-Tumors-Trial-Produces-Favorable-Results-in-Heavily-Pretreated-Solid-Tumor-Patients.html[11] Syndax Pharmaceuticals Announces Two Publications in Nature of Data from the Phase 1 Portion of AUGMENT-101 in Acute Leukemia Patients. Retrieved March 17, 2023, from https://www.prnewswire.com/news-releases/syndax-pharmaceuticals-announces-two-publications-in-nature-of-data-from-the-phase-1-portion-of-augment-101-in-acute-leukemia-patients-301773322.html[12] ReCode Therapeutics Announces First Participants Dosed in a Phase 1 Healthy Volunteer Clinical Trial of Novel Disease-Modifying Genetic Medicine, RCT1100 for the Treatment of Primary Ciliary Dyskinesia. Retrieved March 17, 2023, from https://www.businesswire.com/news/home/20230315005163/en/[13] Cognition Therapeutics Announces Development Plans for Oral CT1812 in Geographic Atrophy Secondary to Dry AMD. Retrieved March 17, 2023, from https://ir.cogrx.com/news-releases/news-release-details/cognition-therapeutics-announces-development-plans-oral-ct1812[14] ORYZON announces First Patient In in FRIDA, a Phase Ib trial with iadademstat in relapsed/refractory FLT3-mutant acute myeloid leukemia patients. Retrieved March 17, 2023, from https://www.oryzon.com/en/news-events/news/oryzon-announces-first-patient-frida-phase-ib-trial-iadademstat-relapsedrefractory[15] Glenmark receives acceptance from U.S. FDA on its IND application for GRC 54276 to proceed with a Phase 1/2, first-in-human clinical study of the molecule for the treatment of patients with advanced solid tumors and lymphomas. Retrieved March 17, 2023, from https://www.prnewswire.com/news-releases/glenmark-receives-acceptance-from-us-fda-on-its-ind-application-for-grc-54276-to-proceed-with-a-phase-12-first-in-human-clinical-study-of-the-molecule-for-the-treatment-of-patients-with-advanced-solid-tumors-and-lymphomas-301774105.html[16] Clearmind Medicine Submits IND Application to FDA for its Proprietary CMND-100 Treating Alcohol Use Disorder. Retrieved March 17, 2023, from https://www.globenewswire.com/news-release/2023/03/16/2628683/0/en/Clearmind-Medicine-Submits-IND-Application-to-FDA-for-its-Proprietary-CMND-100-Treating-Alcohol-Use-Disorder.html[17] Purple Biotech Reports Biomarker Data from CM24 Phase 1 Dose Escalation Study. Retrieved March 17, 2023, from https://www.globenewswire.com/news-release/2023/03/16/2628495/0/en/Purple-Biotech-Reports-Biomarker-Data-from-CM24-Phase-1-Dose-Escalation-Study.html[18] Arbutus Doses First Subject in Phase 1 Clinical Trial with its Oral RNA Destabilizer, AB-161. Retrieved March 17, 2023, from https://investor.arbutusbio.com/news-releases/news-release-details/arbutus-doses-first-subject-phase-1-clinical-trial-its-oral-rna[19] Pyxis Oncology Announces Dosing of First Subject in Phase 1 Trial of PYX-201, a Novel ADC for Solid Tumors. Retrieved March 17, 2023, from https://ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-announces-dosing-first-subject-phase-1-trial-pyx[20] Matrivax Initiates Phase 1 Clinical Development of MVX01, a Novel Pneumococcal Vaccine Candidate. Retrieved March 17, 2023, from https://www.businesswire.com/news/home/20230316005723/en[21] Anaveon announces first patient dosed with ANV419 in a Phase I/II Study of ANV419 in patients with multiple myeloma. Retrieved March 17, 2023, from https://anaveon.com/anaveon-announces-first-patient-dosed-with-anv419-in-a-phase-i-ii-study-of-anv419-in-patients-with-multiple-myeloma/[22] Alpine Immune Sciences to Present Povetacicept (ALPN-303) Phase 1 (RUBY-1) Study Data at the 2023 American Academy of Dermatology Annual Meeting. Retrieved March 17, 2023, from https://www.businesswire.com/news/home/20230316005751/en/免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

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