10-K: Actuate Therapeutics Files 10-K: Reports Positive Phase 2 Data and Outlines Future Plans

Actuate Therapeutics' 10-K filing highlights positive interim Phase 2 results for elraglusib in mPDAC and outlines plans for future clinical trials and development.

Summary

• Actuate Therapeutics, a clinical-stage biopharmaceutical company, filed its Form 10-K for the fiscal year ended December 31, 2024.
• The company is focused on developing therapies for difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 (GSK-3).
• Their lead drug, elraglusib, is being evaluated in a Phase 2 trial for metastatic pancreatic ductal adenocarcinoma (mPDAC) and a Phase 1/2 trial for refractory pediatric malignancies.
• Interim data from the Phase 2 mPDAC trial showed statistically significant increases in 1-year survival rate (43.6% vs 22.5%, p=0.002) and median overall survival (mOS of 9.3 months vs 7.2 months, hazard ratio of 0.63, p=0.016) with elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) compared to GnP alone.
• The combination treatment also resulted in increased Objective Response Rates (ORR) and Disease Control Rates (DCR) in the elraglusib/GnP combination arm versus the GnP control arm.
• The company plans to meet with the FDA to discuss the design of a Phase 3 registration study and the use of Phase 2 data to support potential registration.
• Elraglusib is also being evaluated in a Phase 1/2 study for pediatric cancer patients with recurrent/refractory solid cancers, with Ewing sarcoma identified as a potential second indication.
• The company is developing an oral tablet formulation of elraglusib and plans to initiate a Phase 1 study, subject to future funding.
• Actuate has licensed intellectual property related to GSK-3 inhibitors from the University of Illinois-Chicago (UIC) and Northwestern University (NU).
• The company intends to retain significant commercialization rights to its product candidates and may seek strategic partnerships to accelerate development.

Sentiment

Score: 6

Explanation: The document presents a mixed sentiment. Positive clinical trial results are tempered by concerns about financial stability and the need for future capital raises.

Positives

• Positive interim Phase 2 data for elraglusib in mPDAC, showing statistically significant improvements in survival rates and mOS.
• Favorable safety profile observed in the Phase 2 trial, with TEAEs and SAEs similar to the control arm.
• Development of an oral tablet formulation of elraglusib, offering a more convenient dose delivery option.
• FDA Fast Track and Orphan Drug Designations for elraglusib, providing regulatory benefits and incentives.
• The company has treated over 500 patients with Elraglusib Injection in Phase 1 and Phase 2 studies.

Negatives

• The company has a limited operating history and has incurred significant operating losses.
• The company's financial condition raises substantial doubt as to its ability to continue as a going concern.
• The company is dependent on the success of elraglusib, which is its only product candidate.
• The company will require substantial additional capital to finance its operations.
• The company has no products approved for commercial sale.

Risks

• Clinical trials may not yield sufficiently conclusive results for regulatory agencies to approve the use of the company's products.
• The company's products may fail to be more effective than current therapies, or to be effective at all.
• The company may discover that its products have adverse side effects, which could cause the products to be delayed or precluded from receiving regulatory approval.
• The company may fail to be able to enroll a sufficient number of patients in its clinical trials.
• The company may be unable to produce sufficient quantities of product to complete the clinical trials.
• The sites who conduct the company's clinical trials may fail to follow the trial protocols correctly, or there may be concerns regarding data integrity from one or more sites.
• The company's current elraglusib DS manufacturer is in China, and it is unknown how current or future geopolitical relationships with China may affect the company's ability to obtain DS.

Future Outlook

The company plans to meet with the FDA to discuss the design and execution of a Phase 3 registration study for elraglusib in mPDAC. Subject to future funding, the company plans to further investigate the activity of elraglusib in the Ewing sarcoma patient population and initiate a Phase 1 study of the Elraglusib Oral Tablet.

Management Comments

• Management believes elraglusib may improve outcomes in first-line mPDAC regardless of the chemotherapy backbone used.
• Management expects top-line data will be presented in the second quarter of 2025 based on the completion of enrollment in January 2024.

Industry Context

The document provides context on the competitive landscape in mPDAC, noting that current first-line chemotherapies have modest overall survival benefits and that several other targeted therapies are being evaluated in Phase 3 trials. The company believes elraglusib has the potential to treat a large segment of patients diagnosed with mPDAC.

Comparison to Industry Standards

• The mOS in patients with mPDAC treated with GnP ranged from approximately 3.6 to 9.8 months with an unweighted mOS of 6.9 months.
• The mOS in mPDAC patients is 11.1 months with NALIRIFOX, 11.2 months with FOLFIRINOX and 7 to 10 months with GnP, respectively, in the first-line setting.
• NALIRIFOX demonstrated superiority to GnP in the NAPOLI-3 trial (mOS 11.1 vs 9.2 months).
• The mOS for the EE and ITT were 15.3 months and 11.9 months, respectively. These compare favorably with the mOS for GnP alone of 8.5 months in the MPACT trial or more recently 9.2 months in NAPOLI-3 trial, which evaluated irinotecan liposomal injection (Onivyde) in combination compared to GnP, in the first-line mPDAC setting.

Related Party Transactions

• The Bios Equity Affiliated Funds and Kairos Venture Affiliated Funds participated in various financing transactions.
• The company issued convertible promissory notes to Bios Clinical Opportunity Fund, LP.
• The company incurred expenses for services provided by Pacific BioPharma Logistics, Inc., where a company employee's spouse is a shareholder.

Stakeholder Impact

• Positive clinical trial results could benefit patients with mPDAC and Ewing sarcoma.
• The company's financial condition and ability to raise capital could impact its ability to continue developing and commercializing elraglusib, affecting patients, employees, and shareholders.

Next Steps

• Meet with the FDA to discuss the design and execution of a Phase 3 registration study.
• Further investigate the activity of elraglusib in the Ewing sarcoma patient population.
• Initiate a Phase 1 study of the Elraglusib Oral Tablet, subject to future funding.
• Present top-line data from the Phase 2 mPDAC trial in the second quarter of 2025.

Key Dates