8-K: Xilio Therapeutics Announces Positive Phase 2 Data and AbbVie Collaboration in Year-End Report

Xilio Therapeutics reports encouraging Phase 2 data for vilastobart in MSS CRC patients and announces a collaboration with AbbVie to develop novel tumor-activated immunotherapies.

Summary

• Xilio Therapeutics announced its financial results for the fourth quarter and full year ended December 31, 2024, along with pipeline and business updates.
• The company reported encouraging initial Phase 2 combination data for vilastobart in patients with late-line MSS CRC, showing a preliminary 27% objective response rate in patients without liver metastases.
• Xilio is advancing masked T cell engager programs in novel ATACR and SEECR formats for PSMA, CLDN18.2, and STEAP1.
• A collaboration with AbbVie was announced in the first quarter of 2025 to develop novel tumor-activated, antibody-based immunotherapies, including masked T cell engagers, resulting in $52.0 million in upfront payments to Xilio.
• Cash and cash equivalents were $55.3 million as of December 31, 2024, and the company anticipates funding its operating expenses into the first quarter of 2026 with the AbbVie upfront payments.
• The net loss for the year ended December 31, 2024, was $58.2 million, compared to $76.4 million for the year ended December 31, 2023.

Sentiment

Score: 7

Explanation: The document presents a positive outlook due to encouraging clinical data and a significant collaboration agreement, but the company still faces financial challenges and development risks.

Positives

• Encouraging Phase 2 data for vilastobart in MSS CRC patients suggests potential as a differentiated anti-CTLA-4 therapy.
• The collaboration with AbbVie provides significant upfront funding and potential for substantial future payments and royalties.
• Advancement of multiple masked T cell engager programs demonstrates a robust pipeline.
• XTX301 showed evidence of sustained interferon gamma signaling without evidence of tachyphylaxis.
• The company's cash position is strengthened by the AbbVie collaboration, extending the funding runway into the first quarter of 2026.
• Net loss decreased year-over-year, indicating improved financial management.

Negatives

• The company reported a net loss of $58.2 million for the year ended December 31, 2024.
• The company will need to raise additional capital to fund operations beyond the first quarter of 2026.

Risks

• The success of clinical trials and regulatory approvals for Xilio's product candidates is uncertain.
• The company's ability to maintain its collaboration agreements with Roche, Gilead, and AbbVie is crucial for its future success.
• Xilio will need to obtain additional cash resources to fund its operations beyond the first quarter of 2026.
• Initial, preliminary or interim preclinical or clinical data or results may not be replicated in or predictive of future preclinical or clinical data or results.

Future Outlook

Xilio anticipates that its cash and cash equivalents as of December 31, 2024, together with the $52.0 million in upfront payments received in the first quarter of 2025 in connection with the collaboration agreement with AbbVie, will be sufficient to enable it to fund its operating expenses and capital expenditure requirements into the first quarter of 2026.

Management Comments

• We started 2025 with multiple promising updates across our pipeline, including encouraging initial Phase 2 combination data for vilastobart, our tumor-activated anti-CTLA-4, in patients with late-line MSS CRC, a difficult to treat, immunologically cold tumor type that is increasing in incidence, particularly in younger people, said Ren Russo, Pharm.D., president and chief executive officer of Xilio.
• Dr. Russo added, In addition, we are excited to be advancing multiple novel masked T cell engager programs internally and as part of our recently announced collaboration with AbbVie.

Industry Context

The collaboration with AbbVie highlights the increasing interest in tumor-activated immunotherapies and masked T cell engager technology within the biotechnology industry. The focus on MSS CRC, a difficult-to-treat cancer, aligns with the industry's pursuit of novel approaches for addressing unmet medical needs.

Comparison to Industry Standards

• The 27% objective response rate for vilastobart in combination with atezolizumab in MSS CRC patients without liver metastases is a notable result compared to historical data for this difficult-to-treat patient population.
• Companies like Bristol Myers Squibb (Opdivo) and Merck (Keytruda) have established PD-1/PD-L1 inhibitors as standard of care in various cancers, and Xilio's approach aims to improve upon these therapies by enhancing tumor selectivity and reducing systemic toxicity.
• The collaboration with AbbVie is similar to other partnerships in the immuno-oncology space, such as those between Roche and various biotech companies, where larger pharmaceutical companies invest in innovative technologies to expand their pipelines.

Management Changes

Stakeholder Impact

• Shareholders will benefit from the increased funding and potential for future revenue through the AbbVie collaboration.
• Employees will have increased job security due to the extended funding runway.
• Patients may benefit from the development of novel immunotherapies with improved efficacy and safety profiles.
• The collaboration with AbbVie could lead to increased opportunities for suppliers and partners.

Next Steps

• Report updated data from the Phase 2 clinical trial for vilastobart in the middle of 2025.
• Continue enrolling patients in Phase 1A monotherapy dose escalation and Phase 1B monotherapy dose expansion of the ongoing Phase 1 clinical trial of XTX301.
• Nominate a development candidate for its PSMA program in the ATACR format in the third quarter of 2025.
• Nominate a development candidate for its CLDN18.2 program in the ATACR format in the fourth quarter of 2025.
• Nominate a development candidate for its STEAP1 program in the SEECR format in the first half of 2026.
• Submit an IND application for XTX501 in the middle of 2026.
• Submit an IND application for its PSMA program in the first quarter of 2027.
• Submit an IND application for its CLDN18.2 program in the second quarter of 2027.
• Submit an IND application for its STEAP1 program in the second half of 2027.

Key Dates