A Phase Ib/II Trial of Zunsemetinib in Combination With Capecitabine in Patients With Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer With Bone Metastasis

This is a phase Ib/II study evaluating the safety and efficacy of zunsemetinib (ATI-450) with capecitabine in patients with hormone receptor-positive and HER2-negative (HR+/HER2-) metastatic breast cancer (MBC).

开始日期2024-09-30

申办/合作机构

Washington University School of Medicine

[+1]

EUCTR2022-000847-62-PL / Not yet recruiting临床2期

A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Zunsemetinib vs Placebo in Patients with Moderate-to-Severe Active Psoriatic Arthritis

开始日期2022-10-17

申办/合作机构

Aclaris Therapeutics, Inc.

NCT05511519 / Terminated临床2期

This is a Phase 2a study to investigate the efficacy, safety, tolerability, PK, and PD of ATI-450 versus placebo in patients with moderate to severe psoriatic arthritis.

开始日期2022-07-12

申办/合作机构

Aclaris Therapeutics, Inc.

100 项与 Zunsemetinib 相关的临床结果

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100 项与 Zunsemetinib 相关的转化医学

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100 项与 Zunsemetinib 相关的专利（医药）

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项与 Zunsemetinib 相关的文献（医药）

2023-10-01·International journal of radiation oncology, biology, physics

Investigating the Role of MK2 in Head and Neck Squamous Cell Carcinoma Growth, Metastasis and STING Pathway Activation.

Article

作者: Yelder, T ; Lominska, C E ; Schmidt, A ; Gao, H ; Okwuone, D D D ; Spiess, C ; Millington, G ; Markiewicz, M A ; Berggren, K ; Wang, J ; Morgan, D ; Smith, H ; Gan, G N

PURPOSE/OBJECTIVE(S):

Our prior work demonstrated that inhibition of MAPKAPK2 (MK2) can enhance radiation (RT)-mediated in vivo head and neck squamous cell carcinoma (HNSCC) tumor control and survival in preclinical immune incompetent models. The cytosolic DNA sensor cyclic GMP-AMP synthetase (cGAS) and its downstream adaptor protein, stimulator of interferon genes (STING), are conserved proteins within the innate immune signaling pathways and are important for mediating host defense against microbial infection and can play a role in anti-cancer immunity. We hypothesized that loss of MK2 enhances radiation-induced cGAS-STING pathway activation leading to improved tumor control and survival.

MATERIALS/METHODS:

MK2 shRNA knockdown human (Tu167, CAL27) and MK2 Cas9/CRISPR knockout (KO) syngeneic murine (Ly2, MLM3) HNSCC cell lines were treated with 10 Gy irradiation. Micronuclei were quantitated by DAPI-immunofluorescence (IF). Protein changes in cGAS-STING were evaluated by immunoblot. Inflammatory cytokine production including Type I IFNβ1 were evaluated by RT-qPCR. Ly2 and MLM3 cells were orthotopically or flank engrafted into immune competent mice (Balb/c, C57Bl/6, respectively) for animal tumor control-survival studies. Tumor immune cell infiltrate was examined using FACS and immunohistochemistry. Selected drug studies using the MK2 inhibitor, ATI-450, were performed with RT.

RESULTS:

Loss of MK2 in HNSCC (Tu167, CAL27, Ly2, MLM3) treated with RT led to a significant increase in micronuclei formation compared to control cells. MK2-enhanced micronuclei generation following RT could be inhibited with the actin filament polymerization inhibitor, cytochalasin B. RT treatment of MK2 shRNA cells led to increased cGAS and phospho-STING levels compared to either treatment alone. IFNβ1 levels were significantly higher in HNSCC cell lines treated with RT and with MK2 inhibited by an MK2 inhibitor (ATI-450) or genetic reduction compared to either treatment alone. In-vivo implantation of MLM3 cells into C57Bl/6 comparing control vs MK2 KO tumors treated with ±8 Gy RT demonstrated improved mouse survival favoring RT+MK2 KO over RT, MK2 KO or parental (63, 58, 58.5, 35 days, respectively). FACS analysis of MLM3 WT v KO tumors 3 days post RT showed an overall increase in the number of CD3/CD8 T-cells infiltrating into the tumor in all groups except for parental tumors. Further analysis demonstrated that loss of MK2 reversed CD8 T-cell exhaustion and when combined with radiotherapy led to increased CD8 T-cell activation. Furthermore, activated CD4 and CD8 T cells were reduced in WT+RT cells compared to WT tumors whereas no reduction was seen in the KO or KO+RT.

CONCLUSION:

HNSCC tumor MK2 inhibition enhances RT-mediated micronuclei formation and subsequent cGAS-STING-IFNβ1 levels. Loss of HNSCC MK2 leads to increased CD4-CD8 T-cell infiltration into the tumor and this effect is enhanced following RT. Targeting tumor MK2 may facilitate improved tumor control.

2023-02-01·ACR open rheumatology

Selective Inhibition of the MK2 Pathway: Data From a Phase IIa Randomized Clinical Trial in Rheumatoid Arthritis

Article

作者: Kivitz, Alan ; Burt, David ; Bangs, Madison C. ; Singhal, Atul ; Hope, Heidi Rath ; Monahan, Joseph B. ; Huff, Emma E. ; Gordon, David

Objective:

The study objective was to evaluate the safety, tolerability, pharmacodynamics, and preliminary efficacy of ATI‐450 with methotrexate in patients with rheumatoid arthritis (RA).

Methods:

A parallel‐assignment, placebo‐controlled, investigator‐blinded/patient‐blinded multicenter study evaluated patients with moderate‐to‐severe RA aged 18 to 70 years. Eligible patients were randomized (1:1) to ATI‐450 50‐mg oral tablets twice daily or placebo with a stable weekly dose of methotrexate for 12 weeks. The primary objective was to assess ATI‐450 safety and tolerability. The secondary objectives were to assess the median percentage change from baseline high‐sensitivity C‐reactive protein (hs‐CRP) levels, the mean change from baseline in Disease Activity Score in 28 joints based on CRP level (DAS28‐CRP) and Rheumatoid Arthritis Magnetic Resonance Imaging Score hand‐wrist assessments of synovitis or bone erosion at week 12, and the proportion of patients with American College of Rheumatology 20/50/70 (ACR 20/50/70) and with DAS28‐CRP scores of less than 2.6. The exploratory outcomes were change from baseline in endogenous and ex vivo–stimulated cytokine levels.

Results:

ATI‐450 was well tolerated with no severe adverse events reported. ATI‐450 reduced median hs‐CRP levels by 42% or more at all posttreatment timepoints. In the ATI‐450 group, a mean (median) decrease in DAS28‐CRP score of 2.0 (2.1) was observed at week 12; proportions of patients with an ACR 20/50/70 response in the per‐protocol population were 60%, 33%, and 20%, respectively, at week 12. Endogenous plasma levels of key inflammatory cytokines (tumor necrosis factor α, macrophage inflammatory protein 1β, interleukin 6, interleukin 8) were reduced across the 12 treatment weeks.

Conclusion:

This is the first clinical study demonstrating that selective mitogen‐activated protein kinase (MAPK)–activated protein kinase 2 (MK2) pathway blockade leads to a sustained antiinflammatory effect. This suggests that targeting the MK2 pathway mitigates the tachyphylaxis observed with p38 MAPK inhibitors in RA and supports further exploration.

2021-12-01·Science translational medicine1区 · 医学

The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress.

1区 · 医学

Article

作者: Monahan, Joseph B ; Wei, Qing ; Ruzinova, Marianna B ; Herndon, John ; Grierson, Patrick M ; Zhang, Daoxiang ; Dodhiawala, Paarth B ; Lim, Kian-Huat ; Chen, Timothy Hung-Po ; Li, Lin ; Cheng, Yi ; Khawar, Iftikhar Ali

Combination chemotherapies remain the cornerstone treatment for pancreatic ductal adenocarcinoma (PDAC), but de novo and acquired resistance is common. In this study, we aimed to identify and characterize resistance mechanisms to a FIRINOX chemotherapy regimen (a combination of 5-fluorouracil, irinotecan, and oxaliplatin) because it is the most aggressive regimen currently used clinically for patients with PDAC. Using an unbiased reverse-phase protein array, we detected phospho-activation of heat shock protein 27 (Hsp27) as the most up-regulated event after FIRINOX treatment in PDAC cells. Silencing HSP27 by RNA interference or by a small-molecule inhibitor enhanced apoptosis caused by FIRINOX in vitro. Mechanistically, FIRINOX up-regulated tumor necrosis factor–α (TNFα), causing autocrine phosphorylation and activation of transforming growth factor–β–activated kinase 1 (TAK1), MAPK activated protein kinase 2 (MAPKAPK2 or MK2), and, ultimately, Hsp27. Targeting MK2, the kinase that directly phosphorylates Hsp27, abrogated Hsp27 activation, sensitized PDAC cells to apoptosis, and suppressed SN-38–induced protective autophagy in vitro, in part by blocking phospho-activation of Beclin1. In an autochthonous PDAC mouse model, the MK2 inhibitor ATI-450 decreased PDAC development and progression. When combined with FIRINOX, ATI-450 eliminated most PDAC foci and marked prolonged mouse survival without causing additional toxicity. Last, we found that high phospho-MK2 expression in tumors was associated with poorer survival of patients with PDAC. Our study identified MK2 as a mediator of genotoxic stress–induced activation of prosurvival pathways and provides preclinical support for combining an MK2 inhibitor with FIRINOX-based chemotherapies to treat PDAC.

项与 Zunsemetinib 相关的新闻（医药）

2024-08-07

·GlobeNewswire-Health Care

Aclaris Therapeutics Reports Second Quarter 2024 Financial Results and Provides a Corporate Update

-Initiated Phase 2a Study Activities for ATI-2138 in Atopic Dermatitis--Strengthened Balance Sheet Through Sale of Future OLUMIANT® Royalties for Proceeds of up to $31.5 Million- WAYNE, Pa., Aug. 07, 2024 (GLOBE NEWSWIRE) -- Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, today announced its financial results for the second quarter of 2024 and provided a corporate update. "With study activities underway for our ATI-2138 Phase 2a trial in moderate to severe atopic dermatitis and the strengthening of our balance sheet through the completion of our royalty purchase agreement with OMERS, we're well-positioned to drive our strategic initiatives forward,” said Dr. Neal Walker, Interim President & CEO and Chair of the Board of Directors of Aclaris. “Our focus remains on leveraging our resources to maximize the potential of our innovative drug candidates, pursue available opportunities, and create long-term value for patients and shareholders alike." Research and Development Highlights: ITK Inhibitor Programs ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor ATI-2138-AD-201: Aclaris is activating clinical sites and expects to enroll patients in the coming weeks in this Phase 2a open-label trial to investigate the safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics of ATI-2138 in subjects with moderate to severe atopic dermatitis (AD). ITK Selective Compound Aclaris is progressing to development candidate selection a second generation ITK selective inhibitor for autoimmune indications. Lepzacitinib (ATI-1777), an investigational topical “soft” JAK 1/3 inhibitor In January 2024, Aclaris reported positive top-line results from its Phase 2b trial of lepzacitinib in atopic dermatitis (AD).Aclaris is currently seeking a global development and commercialization partner for this program (excluding Greater China). As previously announced, in 2022 Aclaris granted Pediatrix Therapeutics exclusive rights to develop and commercialize lepzacitinib in Greater China. Zunsemetinib (ATI-450), an investigational oral small molecule MK2 inhibitor Aclaris plans to support Washington University in St. Louis in its investigator-initiated Phase 1b/2 trials of zunsemetinib as a potential treatment for pancreatic cancer and metastatic breast cancer. Aclaris expects these trials to be primarily funded by grants awarded to Washington University. Financial Highlights: Liquidity and Capital Resources As of June 30, 2024, Aclaris had aggregate cash, cash equivalents and marketable securities of $149.9 million compared to $181.9 million as of December 31, 2023. In July 2024, Aclaris received an upfront payment of $26.5 million and is eligible to receive up to an additional $5.0 million upon the achievement of certain sales milestones in connection with the sale of OLUMIANT® royalties and milestones to OMERS Life Sciences. Aclaris anticipates that its cash, cash equivalents and marketable securities as of June 30, 2024 in combination with the $26.5 million from the sale of OLUMIANT® royalties and milestones will be sufficient to fund its operations into 2028, without giving effect to any potential new business development transactions, additional financing activities or the outcome of its strategic review. Financial Results Second Quarter 2024 Net loss was $11.0 million for the second quarter of 2024 compared to $29.6 million for the second quarter of 2023. Total revenue was $2.8 million for the second quarter of 2024 compared to $1.9 million for the second quarter of 2023. The increase was primarily driven by an increase in royalties under the Lilly license agreement during the three months ended June 30, 2024. Research and development (R&D) expenses were $8.8 million for the quarter ended June 30, 2024 compared to $25.3 million for the prior year period. The $16.5 million decrease was primarily the result of lower: Zunsemetinib development expenses associated with clinical activities for a Phase 2a trial for hidradenitis suppurativa which was completed in March 2023, a Phase 2b trial for rheumatoid arthritis which was completed in November 2023, a Phase 2b trial for psoriatic arthritis which was discontinued in December 2023, and drug candidate manufacturing costs;Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD which was completed in January 2024;ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial which was completed in September 2023 and other preclinical activities; andCompensation-related expenses due to a decrease in headcount and higher forfeiture credits. General and administrative (G&A) expenses were $4.8 million for the quarter ended June 30, 2024 compared to $8.3 million for the prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits, along with the recognition of bad debt expense recorded in the prior year period from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection. Licensing expenses were $1.3 million for the quarter ended June 30, 2024 compared to $0.6 million for the prior year period. The increase was due to an increase in royalties earned under the Lilly license agreement. Revaluation of contingent consideration resulted in a $0.2 million loss for the quarter ended June 30, 2024 compared to a gain of $1.5 million for the prior year period. Year-to-date 2024 Net loss was $27.9 million for the six months ended June 30, 2024 compared to $57.7 million for the six months ended June 30, 2023. Total revenue was $5.2 million for the six months ended June 30, 2024 compared to $4.4 million for the six months ended June 30, 2023. The increase was primarily driven by an increase in royalties under the Lilly license agreement during the six months ended June 30, 2024. R&D expenses were $18.6 million for the six months ended June 30, 2024 compared to $47.9 million for the prior year period. The $29.3 million decrease was primarily the result of lower: Zunsemetinib development expenses associated with clinical activities for a Phase 2a trial for hidradenitis suppurativa which was completed in March 2023, a Phase 2b trial for rheumatoid arthritis which was completed in November 2023, a Phase 2b trial for psoriatic arthritis which was discontinued in December 2023, and drug candidate manufacturing costs;Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD which was completed in January 2024;ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial which was completed in September 2023 and other preclinical activities; andCompensation-related expenses due to a decrease in headcount and higher forfeiture credits. G&A expenses were $11.6 million for the six months ended June 30, 2024 compared to $17.1 million for the prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits, a decrease in patent, legal and accounting related expenses, and the recognition of bad debt expense recorded in the prior year period from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection. Licensing expenses were $2.3 million for the six months ended June 30, 2024 compared to $1.6 million for the prior year period. The increase was due to an increase in royalties earned under the Lilly license agreement. Revaluation of contingent consideration resulted in a $3.0 million loss for the six months ended June 30, 2024 compared to a gain of $2.3 million for the prior year period. OLUMIANT® is a registered trademark of Eli Lilly and Company. About Aclaris Therapeutics, Inc. Aclaris Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates to address the needs of patients with immuno-inflammatory diseases who lack satisfactory treatment options. The company has a multi-stage portfolio of drug candidates powered by a robust R&D engine exploring protein kinase regulation. For additional information, please visit www.aclaristx.com. 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 such as “anticipate,” “believe,” “expect,” “intend,” “may,” “plan,” “potential,” “will,” and similar expressions, and are based on Aclaris’ current beliefs and expectations. These forward-looking statements include expectations regarding its plans for its development programs, including its plans to seek a development and commercialization partner for lepzacitinib, the clinical development of ATI-2138, its plan to support Washington University in St. Louis in its investigator-initiated Phase 1b/2 trials of zunsemetinib, the sufficiency of its cash, cash equivalents and marketable securities to fund its operations into 2028, as well as its strategic plans and strategic review. 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 conduct of clinical trials, Aclaris’ reliance on third parties over which it may not always have full control, Aclaris’ ability to enter into strategic partnerships on commercially reasonable terms, the uncertainty regarding the macroeconomic environment and other risks and uncertainties that are described in the Risk Factors section of Aclaris’ Annual Report on Form 10-K for the year ended December 31, 2023, and other filings Aclaris makes with the U.S. Securities and Exchange Commission from time to time. These documents are available under the “SEC Filings” page of the “Investors” section of Aclaris’ website at www.aclaristx.com. Any forward-looking statements speak only as of the date of this press release and are based on information available to Aclaris as of the date of this release, and Aclaris 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. Aclaris Therapeutics, Inc.Condensed Consolidated Statements of Operations(unaudited, in thousands, except share and per share data) Three Months Ended Six Months Ended June 30, June 30, 2024 2023 2024 2023 Revenues: Contract research $625 $875 $1,281 $1,764 Licensing 2,141 994 3,882 2,633 Total revenue 2,766 1,869 5,163 4,397 Costs and expenses: Cost of revenue (1) 624 1,042 1,433 1,850 Research and development (1) 8,759 25,275 18,604 47,862 General and administrative (1) 4,752 8,317 11,596 17,107 Licensing 1,285 550 2,316 1,611 Revaluation of contingent consideration 200 (1,500) 3,000 (2,300)Total costs and expenses 15,620 33,684 36,949 66,130 Loss from operations (12,854) (31,815) (31,786) (61,733)Other income, net 1,868 2,246 3,859 4,004 Net loss $(10,986) $(29,569) $(27,927) $(57,729)Net loss per share, basic and diluted $(0.15) $(0.42) $(0.39) $(0.84)Weighted average common shares outstanding, basic and diluted 71,291,400 70,633,528 71,183,129 68,763,542 (1) Amounts include stock-based compensation expense as follows: Cost of revenue $223 $473 $475 $772 Research and development 1,097 3,494 1,068 6,096 General and administrative 1,583 2,555 3,449 6,460 Total stock-based compensation expense $2,903 $6,522 $4,992 $13,328 Aclaris Therapeutics, Inc.Selected Consolidated Balance Sheet Data(unaudited, in thousands, except share data) June 30, 2024 December 31, 2023 Cash, cash equivalents and marketable securities $149,871 $181,877 Total assets $161,071 $197,405 Total current liabilities $15,682 $30,952 Total liabilities $27,249 $40,226 Total stockholders' equity $133,822 $157,179 Common stock outstanding 71,332,825 70,894,889 Aclaris Therapeutics, Inc.Selected Consolidated Cash Flow Data(unaudited, in thousands) Six Months EndedJune 30, 2024 Six Months EndedJune 30, 2023 Net loss $(27,927) $(57,729)Depreciation and amortization 485 416 Stock-based compensation expense 4,992 13,328 Revaluation of contingent consideration 3,000 (2,300)Changes in operating assets and liabilities (13,687) (722)Net cash used in operating activities $(33,137) $(47,007) Aclaris Therapeutics Contact:investors@aclaristx.com

临床2期引进/卖出财报临床1期临床结果

2024-05-07

·GlobeNewswire-Health Care

Aclaris Therapeutics Reports First Quarter 2024 Financial Results and Provides a Corporate Update

- Progressing ATI-2138 into Atopic Dermatitis -- Management to Host Conference Call at 5:00 PM ET Today - WAYNE, Pa., May 07, 2024 (GLOBE NEWSWIRE) -- Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, today announced its financial results for the first quarter of 2024 and provided a corporate update. “We are pleased to announce that following a review of the potential development pathways for ATI-2138, our investigational ITK/JAK3 compound with best-in-class potential, we have decided to progress ATI-2138 into a proof-of-concept Phase 2a trial in patients with moderate to severe atopic dermatitis,” stated Dr. Neal Walker, co-founder and Interim Chief Executive Officer & President of Aclaris. “Across all of our programs, we remain focused on executing a capital efficient strategy to advance novel immuno-inflammatory therapies.” Research and Development Highlights: ITK Inhibitor Programs ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor Aclaris plans to progress ATI-2138 into a Phase 2a trial in subjects with moderate to severe atopic dermatitis.In September 2023, Aclaris reported positive results from its Phase 1 multiple ascending dose (MAD) trial of ATI-2138. ITK Selective Compound Aclaris is progressing to development candidate selection a second generation ITK selective inhibitor for autoimmune indications. Lepzacitinib (ATI-1777), an investigational topical “soft” JAK 1/3 inhibitor In January 2024, Aclaris reported positive top-line results from its Phase 2b trial in atopic dermatitis (AD).Aclaris is currently seeking a global development and commercialization partner for this program (excluding Greater China). As previously announced, in 2022 Aclaris granted Pediatrix Therapeutics exclusive rights to develop and commercialize lepzacitinib in Greater China. Zunsemetinib (ATI-450), an investigational oral small molecule MK2 inhibitor Aclaris plans to support Washington University in St. Louis in its investigator-initiated Phase 1b/2 trials of zunsemetinib as a potential treatment for pancreatic cancer and metastatic breast cancer. Aclaris expects these trials to be primarily funded by grants awarded to Washington University. Financial Highlights: Liquidity and Capital Resources As of March 31, 2024, Aclaris had aggregate cash, cash equivalents and marketable securities of $161.4 million compared to $181.9 million as of December 31, 2023. A majority of cash expenditures in the first quarter of 2024 were related to payments associated with exit activities, including the wind down of discontinued R&D programs and the previously announced reduction in force. Aclaris anticipates payments associated with these activities to be substantially completed by the second quarter of 2024. As a result, Aclaris expects significantly lower quarterly cash expenditures in future quarters, without giving effect to any potential business development activities resulting from its ongoing strategic review of its business. Financial Results First Quarter 2024 Net loss was $16.9 million for the first quarter of 2024 compared to $28.2 million for the first quarter of 2023.Total revenue was $2.4 million for the first quarter of 2024 compared to $2.5 million for the first quarter of 2023. The decrease was primarily driven by lower contract research revenue during the three months ended March 31, 2024.Research and development (R&D) expenses were $9.8 million for the quarter ended March 31, 2024 compared to $22.6 million for the prior year period. The $12.8 million decrease was primarily the result of lower: Zunsemetinib development expenses associated with clinical activities for a Phase 2a trial for hidradenitis suppurativa, a Phase 2b trial for rheumatoid arthritis, and drug candidate manufacturing costs.Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD.ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial and other preclinical activities.Compensation-related expenses due to a decrease in headcount and higher forfeiture credits. General and administrative (G&A) expenses were $6.8 million for the quarter ended March 31, 2024 compared to $8.8 million for the prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits.Licensing expenses were $1.0 million for the quarter ended March 31, 2024 compared to $1.1 million for the prior year period. The decrease was due to the achievement of a commercial milestone during the three months ended March 31, 2023, offset by an increase in royalties earned under the Lilly license agreement.Revaluation of contingent consideration resulted in a $2.8 million loss for the quarter ended March 31, 2024 compared to a gain of $0.8 million for the prior year period. Conference Call and Webcast As previously disclosed on April 30, 2024, management will host a conference call and webcast, with an accompanying slide presentation, at 5:00 PM ET today to provide a corporate update. To access the live webcast of the call and the accompanying slide presentation, please visit the “Events” page of the “Investors” section of Aclaris’ website, www.aclaristx.com. The webcast will be archived for at least 30 days on the Aclaris website. About Aclaris Therapeutics, Inc. Aclaris Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates to address the needs of patients with immuno-inflammatory diseases who lack satisfactory treatment options. The company has a multi-stage portfolio of drug candidates powered by a robust R&D engine exploring protein kinase regulation. For additional information, please visit www.aclaristx.com. 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 such as “anticipate,” “believe,” “expect,” “intend,” “may,” “plan,” “potential,” “will,” and similar expressions, and are based on Aclaris’ current beliefs and expectations. These forward-looking statements include expectations regarding its plans for its development programs, including its plans to seek a development and commercialization partner for lepzacitinib, the clinical development of ATI-2138, and its plan to support Washington University in St. Louis in its investigator-initiated Phase 1b/2 trials of zunsemetinib, as well as Aclaris’ expectations regarding the wind down of discontinued R&D programs and costs associated with its recent reduction in force and the associated impact on anticipated cash burn, and its strategic review of its business. 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 conduct of clinical trials, Aclaris’ reliance on third parties over which it may not always have full control, Aclaris’ ability to enter into strategic partnerships on commercially reasonable terms, the uncertainty regarding the macroeconomic environment and other risks and uncertainties that are described in the Risk Factors section of Aclaris’ Annual Report on Form 10-K for the year ended December 31, 2023, and other filings Aclaris makes with the U.S. Securities and Exchange Commission from time to time. These documents are available under the “SEC Filings” page of the “Investors” section of Aclaris’ website at www.aclaristx.com. Any forward-looking statements speak only as of the date of this press release and are based on information available to Aclaris as of the date of this release, and Aclaris 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. Aclaris Therapeutics, Inc.Condensed Consolidated Statements of Operations(unaudited, in thousands, except share and per share data) Three Months Ended March 31, 2024 2023 Revenues: Contract research $657 $889 Licensing 1,741 1,639 Total revenue 2,398 2,528 Costs and expenses: Cost of revenue (1) 809 808 Research and development (1) 9,845 22,587 General and administrative (1) 6,844 8,790 Licensing 1,031 1,061 Revaluation of contingent consideration 2,800 (800)Total costs and expenses 21,329 32,446 Loss from operations (18,931) (29,918)Other income, net 1,990 1,758 Net loss $(16,941) $(28,160)Net loss per share, basic and diluted $(0.24) $(0.42)Weighted average common shares outstanding, basic and diluted 71,074,858 66,872,778 (1) Amounts include stock-based compensation expense as follows: Cost of revenue $252 $299 Research and development (29) 2,602 General and administrative 1,866 3,905 Total stock-based compensation expense $2,089 $6,806 Aclaris Therapeutics, Inc.Selected Consolidated Balance Sheet Data(unaudited, in thousands, except share data) March 31, 2024 December 31, 2023 Cash, cash equivalents and marketable securities $161,365 $181,877 Total assets $174,065 $197,405 Total current liabilities $20,080 $30,952 Total liabilities $32,051 $40,226 Total stockholders' equity $142,014 $157,179 Common stock outstanding 71,248,017 70,894,889 Aclaris Therapeutics, Inc.Selected Consolidated Cash Flow Data(unaudited, in thousands) March 31, 2024 March 31, 2023 Net loss $(16,941) $(28,160)Depreciation and amortization 243 198 Stock-based compensation expense 2,089 6,806 Revaluation of contingent consideration 2,800 (800)Changes in operating assets and liabilities (9,006) (4,397)Net cash used in operating activities $(20,815) $(26,353) Aclaris Therapeutics Contact: investors@aclaristx.com

临床1期临床2期财报临床结果引进/卖出

2024-03-14

·PRNewswire

Biotech's Role in Addressing the Pancreatic Cancer Emergency

FN Media Group Presents USA News Group News Commentary VANCOUVER, BC, March 14, 2024 /PRNewswire/ -- USA News Group - Known as one of the most deadly forms of cancer, pancreatic cancer still has the highest mortality rate of all major cancers today. However, researchers and the biotech sector are working diligently to improve the chances of those who receive this dire diagnosis. Recently, in late 2023, researchers at the Mayo Clinic made a discovery that advances knowledge of how pancreatic cancer spreads and identified a new potential therapeutic target along the way. With the American Cancer Society projecting a record year for new cancer cases in 2024, and Europe facing a pancreatic cancer emergency, it's important to focus on the advances being made in the biotech sector that are giving hope to patients and their families. Among the developers making gains include O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), Novartis AG (NYSE: NVS), ImmunityBio, Inc. (NASDAQ: IBRX), Aclaris Therapeutics, Inc. (NASDAQ: ACRS), and Nuvation Bio Inc. (NYSE: NUVB). There is a point of optimism to build upon, as the Pancreatic Cancer Action Network (PanCAN) has stated the five-year survival rate for pancreatic cancer has increased to 13%. Among the therapy developers that have garnered accolades and support from PanCAN is O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), which late last year took home a US$5 million Therapeutic Accelerator Award based on the promising results being delivered by its flagship asset, pelareorep. Since winning the award, Oncolytics has moved to make an amendment to its ongoing GOBLET gastrointestinal cancer study to include a new (fifth) cohort. This new cohort will evaluate the immunotherapy asset pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX) both with and without atezolizumab (Tecentriq®) in patients with newly diagnosed metastatic pancreatic ductal adenocarcinoma (PDAC). "We are enthusiastic to have the support of PanCAN to expand the evaluation of pelareorep in pancreatic cancer and explore mFOLFIRINOX as another combination that could improve outcomes for patients," said Dr. Matt Coffey, President and CEO of Oncolytics. "Evaluating pelareorep in combination with these widely used regimens is an important step in our broad clinical development program. Last fall, we reported a 62% objective response rate for the GOBLET PDAC cohort studying pelareorep in combination with the checkpoint inhibitor atezolizumab in addition to gemcitabine and nab-paclitaxel. This response is about three times that of historical controls and forms the basis of the registrational program, expected to begin this year." Oncolytics is conducting the GOBLET trial to investigate the effectiveness of pelareorep in enhancing the treatment of pancreatic cancer, a disease known for its poor 5-year survival rate. This is largely due to the cancer's ability to hide from the immune system and create an environment that suppresses immune response. In late 2022, the FDA granted pelareorep a fast track designation, acknowledging its potential to stimulate both the innate and adaptive immune systems and alter the tumor microenvironment. This makes pelareorep a promising candidate for combination therapy. "This study is designed to evaluate whether pelareorep can enhance outcomes in patients receiving mFOLFIRINOX, one of the most commonly used metastatic pancreatic cancer treatments," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics. "Combining pelareorep with mFOLFIRINOX represents an expansion of our existing pancreatic cancer program and maximizes the potential of pelareorep-based combination therapies to benefit pancreatic cancer patients." After discontinuing development of its monoclonal antibody NIS793 for the treatment of patients with pancreatic cancer, Novartis AG (NYSE: NVS) has opened 2024 with positive data from its Lutathera asset. In a mid-January release, Novartis announced that Lutathera significantly reduced the risk of disease progression or death by 72% as first-line treatment for patients with advanced gastroenteropancreatic neuroendocrine tumors. "These positive results for Lutathera are practice-changing and offer new first-line treatment data for patients who have a significant unmet need," said Dr. Simron Singh, Associate Professor of Medicine at the University of Toronto and co-founder of the Susan Leslie Clinic for Neuroendocrine Tumours at the Odette Cancer Centre, Sunnybrook Health Sciences Centre, Ontario, Canada. "This study confirms the clinical benefit of first-line radioligand therapy for newly diagnosed patients living with these types of advanced GEP-NETs. These findings should instill confidence among physicians in using Lutathera as a first-line treatment for patients with this life-threatening type of cancer." Back in early 2022, ImmunityBio, Inc. (NASDAQ: IBRX) showed promising results for its Nant Pancreatic Cancer Vaccine. Now, in February 2024, ImmunityBio has announced full accrual of its first two phases of a cancer vaccine trial in participants with Lynch Syndrome and the initiation of a randomized control phase of the trial. Lynch Syndrome is one of the most common hereditary cancer syndromes, occurring in 1 in every 300 Americans. People with Lynch Syndrome can not only develop colorectal cancer 20 years prior to the average age of diagnosis for that form of cancer but are also at an increased risk of developing many other types of cancers, including pancreatic. "We are encouraged by how rapidly this study has been able to enroll participants," said Asad Umar, D.V.M., Ph.D., a senior advisor to the Director for Translational Research in NCI's Division of Cancer Prevention (DCP) and a scientific lead for the trial. "It is a strong indication of an unmet need and of the willingness of participants to help science make new discoveries in the area of cancer prevention." Moving on from a disastrous year in 2023, Aclaris Therapeutics, Inc. (NASDAQ: ACRS) is resurrecting its asset zunsemetinib as a potential cancer treatment. As per the company's last corporate update of 2023, Aclaris now plans to explore zunsemetinib as a potential treatment for pancreatic cancer and metastatic breast cancer. "Throughout our history, Aclaris has remained focused on developing novel drugs where there is a lack of satisfactory treatment options," said Dr. Neal Walker, Co-Founder, Chairman, and Interim CEO of Aclaris in a January 2024 strategic business review. "We are well capitalized and we have recently taken the hard but necessary steps to streamline our operations to reduce costs and preserve capital in order to put Aclaris in an optimal position for the future." In early January 2024, the FDA cleared the investigational new drug (IND) application of Nuvation Bio Inc. (NYSE: NUVB) to evaluate its first clinical candidate from its novel drug-drug conjugate (DDC) platform, NUV-1511. "This IND clearance expands our clinical pipeline and validates the approach of our proprietary DDC platform to design potent oncology-focused chimeric small molecules which combine tumor-targeting specificity with the anti-cancer activity of known oncology agents," said David Hung, M.D., Founder, President, and CEO of Nuvation Bio. "We believe NUV-1511 has the potential to provide favorable clinical benefit for patients with various solid tumors and we look forward to initiating the Phase 1/2 study." The initial part of the Phase 1/2 study will assess safety and tolerability and investigate the potential effectiveness in patients with advanced solid tumors. It will focus on patients with pancreatic cancer, HER2-negative metastatic breast cancer, metastatic castration-resistant prostate cancer (mCRPC), and platinum-resistant ovarian cancer (PROC). Nuvation is already undergoing dosing in the Phase 1 monotherapy study of NUV-868 in solid tumors in patients with pancreatic cancer, ovarian cancer, metastatic castration-resistant prostate cancer (mCRPC), triple-negative breast cancer and other solid tumors. "We remain focused on strong clinical execution of our NUV-868 program for advanced solid tumors," said Hung in his company's Q3 2023 business update. Article Source: Article Source: USA News Group [email protected] DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. 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临床结果免疫疗法临床1期快速通道

100 项与 Zunsemetinib 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
骨转移癌	临床2期	美国	Aclaris Therapeutics, Inc.	2024-09-30
HR阳性/HER2阴性乳腺癌	临床2期	美国	Aclaris Therapeutics, Inc.	2024-09-30
银屑病关节炎	临床2期	美国	Aclaris Therapeutics, Inc.	2022-07-12
银屑病关节炎	临床2期	波兰	Aclaris Therapeutics, Inc.	2022-07-12
化脓性汗腺炎	临床2期	美国	Aclaris Therapeutics, Inc.	2021-12-29
Cryopyrin相关周期性综合征	临床2期	美国	Aclaris Therapeutics, Inc.	2020-10-23
类风湿关节炎	临床2期	美国	Aclaris Therapeutics, Inc.	2020-03-16

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05279417 (ATI-450-RA-202, Corporate Publications) 人工标引	临床2期	类风湿关节炎	251	ATI 450 (20 mg BID) + MTX	鏇築選構網構淵簾網顧(鏇鑰蓋獵築鑰鹽簾鑰繭) = ATI-450 20 mg BID and 50 mg BID did not differentiate from placebo in ACR20 and other measures 遞網鹽鏇餘廠選窪簾蓋 (壓襯壓製襯願憲願願艱 ) 未达到	不佳	2023-11-13
				ATI 450 (50 mg BID) + MTX
NCT04524858 (CTgov)	临床2期	Cryopyrin相关周期性综合征	1	ATI-450	餘蓋齋壓艱遞鏇顧鬱醖(鑰襯觸獵鑰夢選網獵顧) = 獵窪築選觸鏇製簾鏇顧廠蓋選鏇繭鹹鑰構襯齋 (鹹鑰築獵鹽艱壓鹹簾蓋, 艱憲艱蓋蓋繭繭齋廠鑰 ~ 願選願觸簾製鏇襯壓襯) 更多	-	2023-09-21
NCT04247815 (CTgov)	临床2期	类风湿关节炎	25	ATI-450+Methotrexate (ATI-450 Plus Methotrexate)	襯襯遞選觸餘選襯壓觸(積鹽顧範鏇築鬱齋醖範) = 膚衊襯壓淵窪膚範構獵壓範繭簾醖鹹憲襯鹹積 (鑰築壓鑰築襯鏇鹽簾獵, 餘艱襯積艱積鬱齋衊選 ~ 蓋窪淵糧鹽範網獵夢襯) 更多	-	2023-03-29
				Placebo oral tablet+Methotrexate (Placebo Plus Methotrexate)	襯襯遞選觸餘選襯壓觸(積鹽顧範鏇築鬱齋醖範) = 構鏇鬱膚鏇襯遞餘蓋壓壓範繭簾醖鹹憲襯鹹積 (鑰築壓鑰築襯鏇鹽簾獵, 築積夢簾衊網鬱製艱鬱 ~ 構糧積鹹衊顧願醖願廠) 更多
ACR2021	N/A	类风湿关节炎	-	ATI-450 + MTX	願醖製願窪觸齋糧壓鏇(製憲簾鑰糧壓繭鹹鹽獵) = 憲淵壓襯網構淵網構鹽積鏇積鑰網糧壓膚製遞 (繭餘構願簾範鹹鑰醖膚 ) 更多	-	2021-11-09
NCT04247815 (GlobeNewswire) 人工标引	临床2期	类风湿关节炎	19	Zunsemetinib	願鬱繭糧觸壓獵觸艱觸(積夢醖範鏇鏇夢構廠願) = urinary tract infection (UTI), elevated lipids and ventricular extrasystoles 繭築壓鬱淵構餘積鹹淵 (觸製膚獵積築壓積鹹鹽 )	积极	2021-01-19
				Placebo+methotrexate
EULAR2020	临床1期	phospho-HSP27 (pHSP27) \| TNFα \| IL1β ... 更多	77	ATI-450 10mg	衊鏇構遞繭簾壓鏇選獵(網窪艱鹹膚願繭鑰觸夢) = The most common adverse events (reported by 2 or more subjects who received ATI-450) observed during the trial were dizziness, headache, upper respiratory tract infection, constipation, nausea, and abdominal pain 網築憲選獵淵壓顧淵繭 (窪醖艱壓鹽觸鹹範鹹網 )	-	2020-06-03
				ATI-450 30mg