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).

Start Date31 Jul 2024

Sponsor / Collaborator

Washington University School of Medicine

[+2]

EUCTR2022-000847-62-PL / Unknown statusPhase 2

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

Start Date17 Oct 2022

Sponsor / Collaborator

Aclaris Therapeutics, Inc.

NCT05511519 / TerminatedPhase 2

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.

Start Date12 Jul 2022

Sponsor / Collaborator

Aclaris Therapeutics, Inc.

100 Clinical Results associated with Zunsemetinib

100 Translational Medicine associated with Zunsemetinib

100 Patents (Medical) associated with Zunsemetinib

Literatures (Medical) associated with Zunsemetinib

01 Oct 2023·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

Author: Yelder, T ; Lominska, C E ; Schmidt, A ; Okwuone, D D D ; Gao, H ; 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.

01 Feb 2023·ACR open rheumatology

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

Article

Author: Kivitz, Alan ; Burt, David ; Bangs, Madison C. ; Singhal, Atul ; Monahan, Joseph B. ; Hope, Heidi Rath ; 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.

01 Dec 2021·Science translational medicineQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: Ruzinova, Marianna B ; Monahan, Joseph B ; Wei, Qing ; Herndon, John ; Grierson, Patrick M ; Zhang, Daoxiang ; Lim, Kian-Huat ; Dodhiawala, Paarth B ; 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.

News (Medical) associated with Zunsemetinib

07 May 2024

·www.globenewswire.com

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

Phase 1Phase 2Financial StatementClinical ResultLicense out/in

14 Mar 2024

·www.prnewswire.com

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. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. USA News Group is Source of all content listed above. FN Media Group, LLC (FNM), is a third party publisher and news dissemination service provider, which disseminates electronic information through multiple online media channels. FNM is NOT affiliated in any manner with USA News Group or any company mentioned herein. The commentary, views and opinions expressed in this release by USA News Group are solely those of USA News Group and are not shared by and do not reflect in any manner the views or opinions of FNM. FNM is not liable for any investment decisions by its readers or subscribers. FNM and its affiliated companies are a news dissemination and financial marketing solutions provider and are NOT a registered broker/dealer/analyst/adviser, holds no investment licenses and may NOT sell, offer to sell or offer to buy any security. FNM was not compensated by any public company mentioned herein to disseminate this press release. This release contains "forward-loking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E the Securities Exchange Act of 1934, as amended and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. "Forward-looking statements" describe future expectations, plans, results, or strategies and are generally preceded by words such as "may", "future", "plan" or "planned", "will" or "should", "expected," "anticipates", "draft", "eventually" or "projected". You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events, or results to differ materially from those projected in the forward-looking statements, including the risks that actual results may differ materially from those projected in the forward-looking statements as a result of various factors, and other risks identified in a company's annual report on Form 10-K or 10-KSB and other filings made by such company with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and FNM undertakes no obligation to update such statements. Media Contact Information: FN Media Group, LLC Media Contact e-mail: [email protected] U.S. Phone: +1(954)345-0611 SOURCE USA News Group

Clinical ResultImmunotherapyPhase 1Fast Track

27 Feb 2024

·www.globenewswire.com

Aclaris Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides a Corporate Update

WAYNE, Pa., Feb. 27, 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 fourth quarter and full year of 2023 and provided a corporate update. “As we enter 2024, we are financially strong, focused and motivated,” stated Dr. Neal Walker, co-founder and Interim Chief Executive Officer & President of Aclaris. “Returning to the CEO role, I look forward to building on our strong foundation and deep expertise in kinase discovery and development as we look to shape the future of Aclaris.” Research and Development Highlights: 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, and is currently seeking a development and commercialization partner for this program. ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor Aclaris is assessing the most effective development pathway, including the lead indication, for ATI-2138. Aclaris reported positive results from its Phase 1 MAD trial of ATI-2138 in September 2023. 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.ATI-2231, Aclaris’ second MK2 inhibitor, was previously being developed for oncology and Aclaris was supporting Washington University in an investigator-initiated Phase 1a trial of ATI-2231 in patients with advanced solid tumor malignancies. However, Aclaris and Washington University agreed to instead study zunsemetinib in oncology in order to expedite the development timeline by eliminating the need to conduct the Phase 1a trial due to zunsemetinib’s more advanced clinical package. Discovery Aclaris plans to continue to advance discovery programs through KINect®, its proprietary drug discovery platform. Financial Highlights: Liquidity and Capital Resources As of December 31, 2023, Aclaris had aggregate cash, cash equivalents and marketable securities of $181.9 million compared to $229.8 million as of December 31, 2022. Financial Results Fourth Quarter 2023 Net loss was $1.5 million for the fourth quarter of 2023 compared to $27.6 million for the fourth quarter of 2022.Total revenue was $17.6 million for the fourth quarter of 2023 compared to $7.8 million for the fourth quarter of 2022. The increase was primarily driven by a one-time upfront payment under the license agreement with Sun Pharmaceutical Industries, Inc. (Sun Pharma) received in the fourth quarter of 2023. Research and development (R&D) expenses were $26.6 million for the quarter ended December 31, 2023 compared to $21.1 million for the prior year period. The $5.5 million increase was primarily the result of an increase in expenses associated with drug candidate manufacturing for zunsemetinib.General and administrative (G&A) expenses were $8.2 million for the quarter ended December 31, 2023 compared to $7.1 million for the corresponding prior year period. The increase was primarily due to an increase in personnel and stock-based compensation expenses. Licensing expenses were $5.7 million for the quarter ended December 31, 2023 compared to $0.6 million for the prior year period. The increase was primarily attributable to amounts payable to third parties in connection with amounts earned under the Sun Pharma license agreement. Revaluation of contingent consideration resulted in a $26.3 million gain for the quarter ended December 31, 2023 compared to a charge of $7.1 million for the prior year period. Intangible asset impairment charges were $6.6 million for the quarter ended December 31, 2023, representing the full balance of the in-process research and development (IPR&D) intangible asset. The impairment charge resulted from Aclaris’ decision to discontinue further development of the drug candidate for immuno-inflammatory diseases. Full Year 2023 Net loss was $88.5 million for the year ended December 31, 2023 compared to $86.9 million for the year ended December 31, 2022.Total revenue was $31.2 million for the year ended December 31, 2023 compared to $29.8 million for the year ended December 31, 2022. The increase was primarily driven by a one-time upfront payment under the license agreement with Sun Pharma received in the year ended December 31, 2023. The increase was partially offset by both a one-time upfront payment received under a license agreement with Eli Lilly and Company and a one-time upfront payment received under a license agreement with Pediatrix Therapeutics, Inc. in the year ended December 31, 2022. R&D expenses were $98.4 million for the year ended December 31, 2023 compared to $77.8 million for the prior year period. The $20.6 million increase was primarily the result of higher: Zunsemetinib development expenses, including costs associated with clinical activities for the Phase 2b trial for rheumatoid arthritis and drug candidate manufacturing costs;ATI-2138 development expenses, including costs associated with the Phase 1 MAD trial and other preclinical activities; andCompensation-related expenses due to an increase in headcount. G&A expenses were $32.4 million for the year ended December 31, 2023 compared to $25.1 million for the prior year period. The $7.3 million increase was primarily the result of higher compensation-related costs due to increased headcount and the impact of equity awards granted during the year ended December 31, 2023.Bad debt expense recorded from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection also contributed to the increase. Revaluation of contingent consideration resulted in a $26.9 million gain for the year ended December 31, 2023 compared to a charge of $4.7 million for the corresponding prior year period. Intangible asset impairment charges were $6.6 million for the year ended December 31, 2023, representing the full balance of the IPR&D intangible asset. The impairment charge resulted from Aclaris’ decision to discontinue further development of the drug candidate for immuno-inflammatory diseases. 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 development plans for its development programs, including its plans to seek a development and commercialization partner for ATI-1777 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.Consolidated Statements of Operations(unaudited, in thousands, except share and per share data) Three Months Ended Year Ended December 31, December 31, 2023 2022 2023 2022 Revenues: Contract research $566 $866 $3,035 $4,395 Licensing 17,004 6,722 28,214 25,100 Other — 165 — 257 Total revenue 17,570 7,753 31,249 29,752 Costs and expenses: Cost of revenue (1) 725 877 3,423 4,023 Research and development (1) 26,646 21,072 98,384 77,813 General and administrative (1) 8,214 7,146 32,412 25,133 Licensing 5,703 637 14,658 7,937 Revaluation of contingent consideration (26,300) 7,100 (26,900) 4,700 Intangible asset impairment 6,629 — 6,629 — Total costs and expenses 21,617 36,832 128,606 119,606 Loss from operations (4,047) (29,079) (97,357) (89,854)Other income, net 2,189 1,444 8,509 2,946 Loss before income taxes (1,858) (27,635) (88,848) (86,908)Income tax benefit (367) — (367) — Net loss $(1,491) $(27,635) $(88,481) $(86,908)Net loss per share, basic and diluted $(0.02) $(0.41) $(1.27) $(1.33)Weighted average common shares outstanding, basic and diluted 70,866,315 66,685,580 69,808,855 65,213,944 (1) Amounts include stock-based compensation expense as follows: Cost of revenue $337 $314 $1,456 $1,151 Research and development (2,367) 1,517 6,801 3,745 General and administrative 3,296 2,982 12,285 10,143 Total stock-based compensation expense $1,266 $4,813 $20,542 $15,039 Aclaris Therapeutics, Inc.Selected Consolidated Balance Sheet Data(unaudited, in thousands, except share data) December 31, 2023 December 31, 2022 Cash, cash equivalents and marketable securities $181,877 $229,813 Total assets $197,405 $254,596 Total current liabilities $30,952 $21,938 Total liabilities $40,226 $56,975 Total stockholders' equity $157,179 $197,621 Common stock outstanding 70,894,889 66,688,647 Aclaris Therapeutics, Inc.Selected Consolidated Cash Flow Data(unaudited, in thousands) Year EndedDecember 31, 2023 Year EndedDecember 31, 2022 Net loss $(88,481) $(86,908) Depreciation and amortization 863 797 Stock-based compensation expense 20,542 15,039 Revaluation of contingent consideration (26,900) 4,700 Intangible asset impairment charge 6,629 — Deferred taxes (367) — Changes in operating assets and liabilities 9,389 (1,195) Net cash used in operating activities $(78,325) $(67,567) Aclaris Therapeutics Contact: investors@aclaristx.com

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Indication	Highest Phase	Country/Location	Organization	Date
Bone metastases	Phase 2	US	Aclaris Therapeutics, Inc.	31 Jul 2024
Hormone receptor positive HER2 negative breast cancer	Phase 2	US	Aclaris Therapeutics, Inc.	31 Jul 2024
Arthritis, Psoriatic	Phase 2	US	Aclaris Therapeutics, Inc.	12 Jul 2022
Arthritis, Psoriatic	Phase 2	PL	Aclaris Therapeutics, Inc.	12 Jul 2022
Hidradenitis Suppurativa	Phase 2	US	Aclaris Therapeutics, Inc.	29 Dec 2021
Cryopyrin-Associated Periodic Syndromes	Phase 2	US	Aclaris Therapeutics, Inc.	23 Oct 2020
Rheumatoid Arthritis	Phase 2	US	Aclaris Therapeutics, Inc.	16 Mar 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05279417 (ATI-450-RA-202, Corporate Publications) Manual	Phase 2	Rheumatoid Arthritis	251	ATI 450 (20 mg BID) + MTX	wsskvgdfsc(gabfjvpfsy) = ATI-450 20 mg BID and 50 mg BID did not differentiate from placebo in ACR20 and other measures nvrphkeacu (iddxxbedyw ) Not Met	Negative	13 Nov 2023
				ATI 450 (50 mg BID) + MTX
NCT04524858 (CTgov)	Phase 2	Cryopyrin-Associated Periodic Syndromes	1	ATI-450	oxsrhnpqsu(fgqozwtmxz) = djipycgttg rpldrpveew (oonueyvcpf, flxhvskgrn - iofjsxrdet) View more	-	21 Sep 2023
NCT04247815 (CTgov)	Phase 2	Rheumatoid Arthritis	25	ATI-450+Methotrexate (ATI-450 Plus Methotrexate)	iubnkdkoic(liphxmwvaj) = xnzzyktvbs krethhgpoh (ocpuwzpjea, yizsovipff - sttuawdfwd) View more	-	29 Mar 2023
				Placebo oral tablet+Methotrexate (Placebo Plus Methotrexate)	iubnkdkoic(liphxmwvaj) = dpcunbbcrg krethhgpoh (ocpuwzpjea, rfagyskyiz - jgdcnkulbr) View more
ACR2021	Not Applicable	Rheumatoid Arthritis	-	ATI-450 + MTX	tlnpkvefgu(ofwinehwpe) = bcielwsdhm fqwoubcumo (rrmqoizfxx ) View more	-	09 Nov 2021
NCT04247815 (GlobeNewswire) Manual	Phase 2	Rheumatoid Arthritis	19	Zunsemetinib	zrwrjatryd(zxgxgxsfmg) = urinary tract infection (UTI), elevated lipids and ventricular extrasystoles whksmztdjb (zgtuvzzthn )	Positive	19 Jan 2021
				Placebo+methotrexate
EULAR2020	Phase 1	phospho-HSP27 (pHSP27) \| TNFα \| IL1β ... View more	77	ATI-450 10mg	mgjmjkaoli(amavjisjnu) = 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 mfjtufzwlv (etdhvffpdq )	-	03 Jun 2020
				ATI-450 30mg

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