MAPKAPK2

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

Investors sent Aclaris’ shares down 14% to $1.10 in pre-market trading. Aclaris Therapeutics has touted the latest phase 2 results for its “soft” JAK 1/3 inhibitor as a win for the beleaguered biotech, but investors appeared less enthusiastic about the wider set of mixed data. The phase 2b study involved 250 adults and children in the U.S. with mild to severe atopic dermatitis receiving either twice daily treatment with the therapy, called ATI-1777, as a spray at concentrations of 0.5%, 1% or 2%, or a once daily treatment of 2% or vehicle. At week four, the change in eczema from baseline as assessed by the Eczema Area and Severity Index (EASI) score was 69.7% for patients who received the 2% concentration twice daily compared with 58.7% for those who received the vehicle. The statistical significance of this difference, which equated to a p value of 0.035, met the trial’s primary efficacy endpoint, Aclaris said in a Jan. 10 release. However, while patients who received the once daily 2% concentration also saw a “trend toward significance”—with a 68.3% change compared to 59.5% among those receiving a vehicle—this was not “statistically superior,” the biotech admitted. Investors appeared dubious about the readout, sending Aclaris’ shares down 14% to $1.10 in pre-market trading from a Tuesday closing price of $1.28. While the trial had not been statistically powered for a response as measured by the Investigator Global Assessment Treatment Success, which the company noted is the FDA’s regulatory endpoint, Aclaris said the drug had shown improvement here as well, with changes of 37.2% and 36.6% for the once daily and twice daily 2% concentrations, respectively, compared to 27.1% and 26.3% in the respective vehicle cohorts. Aclaris did not share data on the efficacy of the 0.5% and 1% concentrations in the release. ATI-1777 had not produced any of the adverse events most commonly associated with JAK inhibitors, such as serious infections, malignancies, major adverse cardiovascular events or thromboses, according to the company. The most common adverse events among treated patients were nasopharyngitis and application site itch. “We are excited that ATI-1777 demonstrated response rates on par with existing market competition, along with a differentiated safety profile relative to JAK inhibitors given the low systemic absorption seen in both phase 2 studies,” Neal Walker, chairman of Aclaris’ board of directors, said in the release. “These results are particularly encouraging given the higher than anticipated vehicle response and the mid-study inclusion of a milder patient population,” Walker added. “The convenience of a spray formulation along with the potential to move to once-a-day dosing, potentially offer additional distinct advantages to patients suffering from atopic dermatitis.” Aclaris had been pinning its hopes on ATI-1777’s success after the company announced in the final weeks of the year that it was laying off almost half of its workforce as it resurrected plans to explore its MK2 inhibitor zunsemetinib despite a couple of mid-phase fails. At the time, Aclaris said that it would use a positive set of phase 2 data for ATI-1777 to hunt for a suitable partner for the asset.” In this morning’s release, the biotech’s CEO Douglas Manion, M.D., confirmed that the company would now “seek a development and commercialization partner for this program, which could include additional indications such as vitiligo.”

The company entered 2023 with 100 full-time employees, all of whom were based in the U.S. Aclaris Therapeutics has decided to give its MK2 inhibitor zunsemetinib a second chance—unfortunately, almost half of the biotech’s workforce won’t be so lucky. The Pennsylvania-based company is reducing its headcount by around 46%, with the changes to begin “immediately” and likely to be completed by the end of June next year. The company entered 2023 with 100 full-time employees, all of whom were based in the U.S. In a post-market release Dec. 19, CEO Douglas Manion, M.D., linked the decision to the reduction of zunsemetinib’s prospects after the drug failed to match placebo on any primary or secondary endpoints in a phase 2 rheumatoid arthritis trial last month. “With the discontinuation of development of ATI-450 for immuno-inflammatory disease indications, we are taking steps to reduce our spending and streamline our organization, which we expect to meaningfully preserve capital,” Manion said. When it first announced the zunsemetinib failure in November, Aclaris explained that it would halt all work on the MK2 inhibitor, also known as ATI-450, including a phase 2 trial in psoriatic arthritis. However, the biotech revealed in yesterday’s release that while the arthritis ambitions are gone for good, the company has decided to explore zunsemetinib as “a potential treatment for pancreatic cancer and metastatic breast cancer as well as in preventing bone loss in patients with metastatic breast cancer.” Aclaris was originally pursuing these indications via its other MK2 inhibitor, dubbed ATI-2231, undergoing a phase 1 trial in collaboration with Washington University. However, the company said yesterday that “due to ATI-450’s more advanced clinical development package” the lead asset was a better fit. In the meantime, the company will be holding out hope that better clinical news arrives when a 250-patient phase 2b trial of its topical JAK 1/3 inhibitor, called ATI-1777, reads out topline results in January. “If the results of the phase 2b trial are positive, we intend to seek a commercialization partner for the asset,” Manion said. It’s less clear what the future holds for ATI-2138. As recently as last month, Aclaris had been expecting to begin a phase 2 of the oral covalent ITK/JAK3 inhibitor in ulcerative colitis in “early 2024,” with further indications set to follow. Now, the company is apparently “reassessing the most effective pathway for ATI-2138 … including the indication selection due to the evolving competitive landscape within ulcerative colitis.” Against a backdrop of Eli Lilly’s mirikizumab joining the increasingly crowded ulcerative colitis market, Aclaris plans to provide further guidance on its plans for the drug in early 2024. November’s phase 2 fail wasn’t the first time that zunsemetinib disappointed in the clinic. Back in March, the drug failed to improve abscesses in patients with a chronic skin condition called hidradenitis suppurativa. Those mid-phase results halved the company’s stock to less than $6, with last month’s news taking the share price to new lows. The stock closed Tuesday trading at $1.02 per share.