Zunsemetinib

Follow-up plans to launch additional studies in arthritis alongside other areas of rheumatology, including ankylosing spondylitis, have been put on an indefinite hold according to XBiotech. Credit: Shutterstock / Yuri A XBiotech’s stock price has taken a hit after it announced a complete halt to its clinical program in rheumatological diseases while it “seeks to understand the outcome” from a Phase II study of its arthritis treatment Natrunix that failed to meet its primary endpoint. The Austin, Texas-based company’s stock value dropped by 27% after its Phase II trial (NCT05363917) saw what the company called “substantial irregularities that make unequivocal interpretation of the findings difficult.” Follow-up plans to launch additional studies in arthritis alongside other areas of rheumatology, including ankylosing spondylitis, have been put on an indefinite hold. The study’s primary endpoint sought a response rate of 50 measured using the American College of Rheumatology (ACR) response scale after 12 weeks of treatment with Natrunix. The Phase II study enrolled 230 subjects with moderate to severe rheumatoid arthritis and examined Natrunix in combination with methotrexate. However, the company says the trial was mired with issues at trial sites including some patients being enrolled multiple times prompting the company to hold back full results from the trial as it looks to see what it can salvage. In a statement the company said: “Although the study did not meet efficacy endpoints, discrepancies found during data analysis suggest caution in interpreting results. Findings of the study are still being analysed in order to better understand the implications of the findings and determine how these results can be used to guide potential further rheumatology studies for Natrunix.” Previously, GlobalData’s Pharmaceutical Intelligence Centre estimated that Natrunix, also known as bermekimab, was set to see global sales of $179m by the end of 2024, with that figure having been predicted to grow to $488m by the end of 2025. GlobalData is the parent company of Clinical Trials Arena . Elsewhere in the field of arthritis treatments, Bristol Myers Squibb has announced positive topline results from two Phase III trials evaluating the efficacy and safety of Sotyktu (deucravacitinib) in adults with active psoriatic arthritis, hitting both endpoints. Meanwhile, Aclaris Therapeutics’ stock also took a hit after it announced that it would discontinue the development of zunsemetinib after its Phase IIb trial failed to meet its endpoints.

– First Patient Dosed in ATI-2138 Phase 2a Trial in Atopic Dermatitis As Previously Announced;Top-line Data Anticipated in First Half of 2025 – WAYNE, Pa., Nov. 06, 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 third quarter of 2024 and provided a corporate update. "The third quarter of 2024 marked an important milestone for Aclaris with the dosing of our first patient in the Phase 2a trial of ATI-2138 for moderate to severe atopic dermatitis," said Dr. Neal Walker, Interim President & CEO and Chair of the Board of Directors of Aclaris. "This milestone, combined with our robust financial position, underscores our commitment to executing a capital-efficient development strategy." Research and Development Highlights: ITK Inhibitor Programs ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor Atopic Dermatitis (ATI-2138-AD-201): This Phase 2a open-label trial to investigate the safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics of ATI-2138 in patients with moderate to severe atopic dermatitis (AD) is ongoing. Aclaris continues to expect top-line data in the first half of 2025. ITK Selective Compound Aclaris is progressing a second generation ITK selective inhibitor to development candidate selection 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 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 September 30, 2024, Aclaris had aggregate cash, cash equivalents and marketable securities of $173.4 million compared to $181.9 million as of December 31, 2023. Aclaris anticipates that its cash, cash equivalents and marketable securities as of September 30, 2024 will be sufficient to fund its operations into 2028, without giving effect to any potential business development transactions, financing activities or the outcome of its strategic review. Financial Results Third Quarter 2024 Net loss was $7.6 million for the third quarter of 2024 compared to $29.3 million for the third quarter of 2023.Total revenue was $4.3 million for the third quarter of 2024 compared to $9.3 million for the third quarter of 2023. The decrease was primarily driven by higher milestones earned during the prior year period compared to the current year period.Research and development (R&D) expenses were $6.0 million for the quarter ended September 30, 2024 compared to $23.9 million for the prior year period. The $17.9 million decrease was primarily the result of: Zunsemetinib development expenses associated with clinical trials in 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 multiple ascending dose (MAD) trial which was completed in September 2023 and other preclinical activities, which were partially offset by clinical development expenses associated with a Phase 2a clinical trial which commenced in August 2024; andLower compensation-related expenses due to a decrease in headcount and higher forfeiture credits. General and administrative (G&A) expenses were $5.7 million for the quarter ended September 30, 2024 compared to $7.1 million for the corresponding 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 $1.8 million for the quarter ended September 30, 2024 compared to $7.3 million for the corresponding prior year period. The decrease was primarily due to higher milestones earned during the prior year period compared to the current year period.Revaluation of contingent consideration resulted in a $0.8 million loss for the quarter ended September 30, 2024 compared to a loss of $1.7 million for the prior year period. Year-to-date 2024 Net loss was $35.5 million for the nine months ended September 30, 2024 compared to $87.0 million for the nine months ended September 30, 2023.Total revenue was $9.5 million for the nine months ended September 30, 2024 compared to $13.7 million for the nine months ended September 30, 2023. The decrease was primarily driven by higher milestones earned during the prior year period compared to the current year period.R&D expenses were $24.6 million for the nine months ended September 30, 2024 compared to $71.7 million for the corresponding prior year period. The $47.1 million decrease was primarily the result of: Zunsemetinib development expenses associated with clinical trials in 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, which were partially offset by clinical development expenses associated with a Phase 2a clinical trial which commenced in August 2024; andLower compensation-related expenses due to a decrease in headcount and higher forfeiture credits. G&A expenses were $17.2 million for the nine months ended September 30, 2024 compared to $24.2 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 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 $4.1 million for the nine months ended September 30, 2024 compared to $9.0 million for the prior year period. The decrease was primarily due to higher milestones earned during the prior year period compared to the current year period.Revaluation of contingent consideration resulted in a $3.8 million loss for the nine months ended September 30, 2024 compared to a gain of $0.6 million for the corresponding prior year period. 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, including the timing of top-line data, 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 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 Nine Months Ended September 30, September 30, 2024 2023 2024 2023Revenues: Contract research $645 $705 $1,926 $2,469 Licensing 3,701 8,577 7,583 11,210 Total revenue 4,346 9,282 9,509 13,679 Costs and expenses: Cost of revenue (1) 654 848 2,087 2,698 Research and development (1) 5,956 23,876 24,560 71,738 General and administrative (1) 5,653 7,091 17,249 24,198 Licensing 1,754 7,344 4,070 8,955 Revaluation of contingent consideration 800 1,700 3,800 (600)Total costs and expenses 14,817 40,859 51,766 106,989 Loss from operations (10,471) (31,577) (42,257) (93,310)Other income: Interest income 1,991 2,316 5,850 6,320 Non-cash royalty income 894 — 894 — Total other income 2,885 2,316 6,744 6,320 Net loss $(7,586) $(29,261) $(35,513) $(86,990)Net loss per share, basic and diluted $(0.11) $(0.41) $(0.50) $(1.25)Weighted average common shares outstanding, basic and diluted 71,381,731 70,807,934 71,249,813 69,452,495 (1) Amounts include stock-based compensation expense as follows: Cost of revenue $232 $347 $707 $1,119 Research and development 1,124 3,072 2,192 9,168 General and administrative 1,648 2,529 5,097 8,989 Total stock-based compensation expense $3,004 $5,948 $7,996 $19,276 Aclaris Therapeutics, Inc.Selected Consolidated Balance Sheet Data(unaudited, in thousands, except share data) September 30, 2024 December 31, 2023Cash, cash equivalents and marketable securities $173,436 $181,877 Total assets $182,394 $197,405 Total current liabilities $18,816 $30,952 Total liabilities $52,243 $40,226 Total stockholders’ equity $130,151 $157,179 Common stock outstanding 71,417,513 70,894,889 Aclaris Therapeutics, Inc.Selected Consolidated Cash Flow Data(unaudited, in thousands) Nine Months Ended Nine Months Ended September 30, 2024 September 30, 2023Net loss $(35,513) $(86,990)Depreciation and amortization 664 635 Stock-based compensation expense 7,996 19,276 Revaluation of contingent consideration 3,800 (600)Changes in operating assets and liabilities 11,916 (3,885)Net cash used in operating activities $(11,137) $(71,564) Aclaris Therapeutics Contact: investors@aclaristx.com