On November 8. 2022 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported its financial results for the third quarter of 2022 and provided a corporate update (Press release, Aclaris Therapeutics, NOV 8, 2022, View Source [SID1234623423]).

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"The third quarter of this year marked another period of important milestone achievement – the successful completion of enrollment in the Phase 2a trial of zunsemetinib in hidradenitis suppurativa," said Dr. Neal Walker, Chief Executive Officer of Aclaris. "We also recently successfully completed the Phase 1 SAD trial for ATI-2138. We are very pleased with the results from the Phase 1 SAD trial which we believe support us proceeding to a multiple ascending dose (MAD) trial. Additionally, we have selected ulcerative colitis as the first target indication for ATI-2138 given the compelling pre-clinical profile and high medical need that persists for this debilitating disease."

Research and Development Highlights:

Clinical Programs

Zunsemetinib, an investigational oral small molecule MK2 inhibitor:
Currently being developed as a potential treatment for immuno-inflammatory diseases
Rheumatoid Arthritis (ATI-450-RA-202): This Phase 2b dose ranging trial to investigate the efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple doses (20 mg and 50 mg twice daily) of zunsemetinib in combination with methotrexate in subjects with moderate to severe rheumatoid arthritis (RA) is ongoing. Aclaris expects topline data in the second half of 2023.
Hidradenitis Suppurativa (ATI-450-HS-201): This Phase 2a trial to investigate the efficacy, safety, tolerability, PK and PD of zunsemetinib (50 mg twice daily) over 12 weeks in subjects with moderate to severe hidradenitis suppurativa (HS) has completed enrollment with 95 patients randomized and is ongoing. Aclaris expects topline data in mid-first half of 2023.
Psoriatic Arthritis (ATI-450-PsA-201): This Phase 2a trial to investigate the efficacy, safety, tolerability, PK and PD of zunsemetinib (50 mg twice daily) in subjects with moderate to severe psoriatic arthritis (PsA) is ongoing. Aclaris expects topline data in the second half of 2023.
ATI-1777, an investigational topical "soft" Janus kinase (JAK) 1/3 inhibitor:
Currently being developing as a potential treatment for moderate to severe atopic dermatitis (AD)
Atopic Dermatitis (ATI-1777-AD-202): This Phase 2b trial to determine the efficacy, safety, tolerability, and PK of ATI-1777 in subjects with moderate to severe AD is ongoing. Aclaris continues to expect topline data in the first half of 2023.
ATI-2138, an investigational oral covalent ITK/TXK/JAK3 (ITJ) inhibitor:
Currently being developed as a potential treatment for T cell-mediated autoimmune diseases
ATI-2138-PKPD-101: This Phase 1 first-in-human randomized, observer-blind, placebo-controlled single ascending dose (SAD) trial to investigate the safety, tolerability, PK and PD of ATI-2138 in healthy subjects is complete.
The primary objective was to assess the safety and tolerability of ATI-2138. Secondary endpoints included the assessment of PK, including the effect of food. The study also explored the PD response to ATI-2138. An additional cohort compared the capsule formulation to a tablet formulation.
Sixty-four male and female healthy volunteer subjects were randomized 3:1 into seven doses in eight cohorts. Each cohort consisted of eight randomized subjects (ATI-2138: n=6; placebo: n=2). Single dose levels were 1 mg, 3 mg, 5 mg, 15 mg, 25 mg, 50 mg, and 80 mg.

Preliminary data:
ATI-2138 was generally well tolerated at all doses tested in the trial. No serious adverse events or severe adverse events were reported. The most common adverse events in subjects treated with ATI-2138, headache (four subjects) and lightheadedness (two subjects), were mild and transient.
ATI-2138 demonstrated linear PK data and absorption with a favorable PK profile up to the 80 mg single dose.
There was no significant food effect at 15 mg (fasted versus fed) observed.
Similar PK was observed with the capsule versus tablet formulations at 25 mg.
Dose-dependent inhibition of both ITK and JAK3 exploratory PD biomarkers was observed; near complete inhibition of the dual ITK and JAK3-stimulated interferon production was observed at the 15 mg through 80 mg doses.
Aclaris has selected ulcerative colitis as the intended first clinical development target for ATI-2138. Aclaris is also exploring additional indications that are relevant to the mechanism of action.
Aclaris submitted a new IND for this program to the U.S. Food and Drug Administration’s (FDA) Gastroenterology Division in October 2022 for the treatment of ulcerative colitis. If allowed, Aclaris intends to initiate a Phase 1 MAD trial of ATI-2138 in healthy subjects by the end of 2022.
Preclinical Programs

ATI-2231, an investigational oral MK2 inhibitor compound:
Currently being explored as a potential treatment for pancreatic cancer and metastatic breast cancer as well as in preventing bone loss in patients with metastatic breast cancer
Second MK2 inhibitor generated from Aclaris’ proprietary KINect drug discovery platform and designed to have a long half-life.
IND-enabling studies are underway, and Aclaris expects to submit an IND by the end of 2022.
Financial Highlights:

Liquidity and Capital Resources

As of September 30, 2022, Aclaris had aggregate cash, cash equivalents and marketable securities of $248.1 million compared to $225.7 million as of December 31, 2021. Aggregate cash, cash equivalents and marketable securities as of September 30, 2022 included proceeds received during the quarter under a non-exclusive patent license agreement with Eli Lilly and Company (Lilly). Under the non-exclusive patent license agreement, Aclaris granted Lilly non-exclusive rights under certain patents and patent applications for the use of baricitinib, Lilly’s JAK inhibitor, to treat alopecia areata. Aclaris exclusively licenses patents and patents applications from a third party relating to the use of JAK inhibitors to induce hair growth and treat hair loss disorders.

Aclaris continues to anticipate that its cash, cash equivalents and marketable securities as of September 30, 2022 will be sufficient to fund its operations through the end of 2025, without giving effect to any potential business development transactions or financing activities.

Financial Results

Third Quarter 2022

Net loss was $20.0 million for the third quarter of 2022 compared to $21.1 million for the third quarter of 2021.
Total revenue was $19.0 million for the third quarter of 2022 compared to $1.7 million for the third quarter of 2021. The increase was driven by $17.9 million of licensing revenue in the quarter, including $17.6 million from the non-exclusive patent license agreement with Lilly.
Research and development (R&D) expenses were $23.7 million for the quarter ended September 30, 2022 compared to $14.0 million for the prior year period.
The $9.7 million increase was primarily the result of higher:
Zunsemetinib development expenses, including costs associated with clinical activities for a Phase 2b trial for RA, a Phase 2a trial for HS, and a Phase 2a trial for PsA.
ATI-1777 development expenses related to drug candidate manufacturing and other preclinical activities and costs associated with a Phase 2b clinical trial for AD.
IND submission preparation and preclinical development activities related to ATI-2231.
Compensation-related expenses due to an increase in headcount.
General and administrative (G&A) expenses were $5.8 million for the quarter ended September 30, 2022 compared to $6.0 million for the prior year period.
Licensing expenses were $7.3 million for the quarter ended September 30, 2022, resulting from separate third-party contractual obligations related to the non-exclusive patent license agreement with Lilly. There were no licensing expenses for the quarter ended September 30, 2021.
Revaluation of contingent consideration was $2.2 million for the quarter ended September 30, 2022, compared to a revaluation of contingent consideration expense of $0.9 million for the prior year period.
Year-to-date 2022

Net loss was $59.3 million for the nine months ended September 30, 2022 compared to $68.1 million for the nine months ended September 30, 2021.
Total revenue was $22.0 million for the nine months ended September 30, 2022 compared to $5.3 million for the nine months ended September 30, 2021. The increase was driven by $18.4 million of licensing revenue in 2022, including $17.6 million from the non-exclusive patent license agreement with Lilly.
R&D expenses were $56.7 million for the nine months ended September 30, 2022 compared to $29.7 million for the prior year period.
The $27.0 million increase was primarily the result of higher:
Zunsemetinib development expenses, including costs associated with clinical activities for a Phase 2b trial for RA, a Phase 2a trial for HS, and a Phase 2a trial for PsA.
ATI-1777 development expenses related to drug candidate manufacturing and other preclinical activities and costs associated with a Phase 2b clinical trial for AD.
IND submission preparation and preclinical development activities related to ATI-2231.
Compensation-related expenses due to an increase in headcount.
G&A expenses were $18.0 million for the nine months ended September 30, 2022 compared to $16.7 million for the prior year period.
The $1.3 million increase was primarily the result of higher compensation-related costs, including stock-based compensation, due to increased headcount and the impact of equity awards granted during the nine months ended September 30, 2022.
Licensing expenses were $7.3 million for the nine months ended September 30, 2022 resulting from separate third-party contractual obligations related to the non-exclusive patent license agreement with Lilly. There were no licensing expenses for the nine months ended September 30, 2021.
Revaluation of contingent consideration resulted in a $2.4 million reduction of expense for the nine months ended September 30, 2022, compared to a revaluation of contingent consideration expense of $22.1 million for the prior year period.