Company Overview
Xilio Therapeutics, Inc. is a clinical-stage biotechnology company dedicated to discovering and developing novel tumor-activated immuno-oncology (I-O) therapies. The company's mission is to significantly improve outcomes for people living with cancer by harnessing the power of the immune system while minimizing systemic toxicity.
Xilio was founded in June 2020 and is headquartered in Waltham, Massachusetts. The company's platform technology is designed to engineer and develop tumor-activated molecules that can trigger anti-tumor immunity with limited systemic exposure. This approach aims to address the key limitations of traditional I-O treatments, which often result in severe side effects that can prevent or restrict their use. In its early years, Xilio focused on building its proprietary platform technology and advancing its initial pipeline of product candidates, conducting preclinical studies to validate its approach and prepare these candidates for clinical development.
Xilio's most advanced clinical-stage product candidates are vilastobart (XTX101), a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, and XTX301, a tumor-activated, engineered interleukin-12 (IL-12) therapy. Both candidates are being evaluated in ongoing clinical trials.
In March 2024, Xilio entered into a license agreement with Gilead Sciences, Inc. to develop and commercialize XTX301 globally. Under the terms of the agreement, Gilead paid Xilio a $30 million upfront payment and agreed to make additional payments upon the achievement of certain development, regulatory, and sales-based milestones, as well as tiered royalties on annual global net sales of XTX301.
Financial Position
Xilio's financial position has been bolstered by several funding rounds, including a $129.9 million initial public offering in October 2021 and subsequent private placements that have raised an additional $48 million. As of September 30, 2024, the company had $61.3 million in cash and cash equivalents.
In the first quarter of 2024, Xilio announced a strategic portfolio reprioritization and workforce reduction to align its resources with the advancement of its most promising programs. The company discontinued further investment in XTX202, its tumor-activated IL-2 product candidate, as a monotherapy and reduced its headcount by approximately 21%.
Vilastobart (XTX101) in Combination with Atezolizumab
Xilio's lead clinical-stage asset, vilastobart, is currently being evaluated in a Phase 1/2 clinical trial in combination with Genentech's atezolizumab (Tecentriq) in patients with advanced solid tumors. The Phase 1 portion of the study is assessing the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the combination.
In November 2024, Xilio reported initial data from the Phase 1C dose escalation portion of the study. The data showed that the combination of vilastobart and atezolizumab demonstrated encouraging early evidence of anti-tumor activity, including unconfirmed partial responses observed in two patients with difficult-to-treat, immunologically "cold" tumors. Notably, the data also included the complete resolution of a metastatic liver lesion in a patient with microsatellite stable colorectal cancer (MSS CRC).
The safety data indicated that the combination of vilastobart and atezolizumab was generally well-tolerated, supporting the potential of vilastobart to be a differentiated next-generation anti-CTLA-4 therapy when used in combination with PD-(L)1 inhibitors. Xilio plans to present these initial Phase 1C data in a late-breaker poster presentation at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting in November 2024.
Building on the Phase 1 results, Xilio is currently advancing the development of vilastobart in combination with atezolizumab in a Phase 2 clinical trial in patients with MSS CRC. The company expects to report initial Phase 2 data in the fourth quarter of 2024, with data on a total of approximately 40 patients expected in the first quarter of 2025.
XTX301: A Tumor-Activated IL-12 Therapy
Xilio's second clinical-stage candidate, XTX301, is a tumor-activated, engineered IL-12 therapy. IL-12 is a potent anti-tumor cytokine, but its systemic administration has been limited by severe toxicity. Xilio's approach with XTX301 is designed to localize IL-12 activity within the tumor microenvironment, potentially enhancing the therapeutic index.
XTX301 is currently being evaluated in a Phase 1 clinical trial, including ongoing Phase 1A monotherapy dose escalation and Phase 1B monotherapy dose expansion. Xilio expects to report initial Phase 1 safety, pharmacokinetic, and pharmacodynamic data for XTX301 in the fourth quarter of 2024.
Preclinical Programs and Platform
In addition to its clinical-stage assets, Xilio is leveraging its proprietary platform to advance a pipeline of earlier-stage tumor-activated I-O product candidates. This includes XTX501, a tumor-activated PD-1-targeted IL-2 bispecific, which is currently in IND-enabling activities.
Xilio is also developing a portfolio of tumor-activated immune cell engagers, known as the SELECTIVE EFFECTOR-ENHANCED CELL ENGAGER (SEECR) format. Preclinical data on this approach will be presented at the SITC Annual Meeting in November 2024.
Financials and Outlook
For the nine months ended September 30, 2024, Xilio reported total revenue of $4.6 million, primarily from its license agreement with Gilead. The company's net loss for the period was $45.1 million, with $32.4 million in research and development expenses and $18.3 million in general and administrative expenses.
As of September 30, 2024, Xilio had $61.3 million in cash and cash equivalents. The company has stated that its existing cash and cash equivalents are expected to fund its operations through the end of the second quarter of 2025.
For the most recent quarter, Xilio reported revenue of $2,263,000 and a net income of $0. The company's operating cash flow (OCF) for the quarter was -$13,672,000, while its free cash flow (FCF) was -$13,681,000. The decrease in OCF and FCF quarter-over-quarter was primarily driven by increased research and development expenses related to the ongoing clinical trials for the company's lead product candidates, vilastobart and XTX301.
Xilio has not provided formal financial guidance for the full year 2024. However, the company has outlined key milestones for the remainder of 2024, including the presentation of initial Phase 1 data for XTX301 and initial Phase 2 data for the vilastobart and atezolizumab combination in MSS CRC.
It's important to note that Xilio has not generated any revenue from product sales to date, as all of its programs are still in early clinical or preclinical development. The company currently only sells its products in the United States.
Liquidity
As of September 30, 2024, Xilio had $61,260,000 in cash and cash equivalents. The company's current liquidity position is expected to fund its operations through the end of the second quarter of 2025, providing a runway for advancing its clinical programs and achieving key milestones.
Xilio's debt-to-equity ratio stands at 0.4012, indicating a relatively low level of debt compared to equity. The company's current ratio and quick ratio are both 1.6651, suggesting that Xilio has sufficient short-term assets to cover its short-term liabilities.
However, the company notes there is substantial doubt about its ability to continue as a going concern, and it will need to secure additional capital through financing or other means in the near term to support its ongoing operations and research and development efforts.
Risks and Challenges
Xilio, like many clinical-stage biotechnology companies, faces several risks and challenges that could impact its future success. These include the inherent risks associated with the development of novel, first-in-class drug candidates, the ability to successfully complete clinical trials and obtain regulatory approvals, the potential for adverse safety events, and the ability to secure additional funding to support ongoing operations and research and development efforts.
Additionally, Xilio is exposed to the broader macroeconomic and geopolitical environment, which could affect its access to capital, supply chain, and overall business operations. The company's reliance on its CDMO partner in China, WuXi Biologics, also presents potential risks related to global trade tensions and disruptions.
Conclusion
Xilio Therapeutics is a clinical-stage biotechnology company at the forefront of tumor-activated immuno-oncology. With its lead programs, vilastobart and XTX301, the company is working to address the limitations of current I-O therapies and improve outcomes for people living with cancer. The promising early data on vilastobart in combination with atezolizumab, as well as the anticipated Phase 1 data for XTX301, underscores the potential of Xilio's innovative approach.
As the company continues to advance its pipeline and platform, it will need to navigate the inherent risks and challenges of drug development, while also maintaining a strong financial position to support its long-term growth. The company's current financial situation, with limited cash reserves and ongoing losses, presents a significant challenge that will need to be addressed through additional financing or strategic partnerships.
Investors will be closely watching Xilio's progress in the coming quarters and years as it seeks to deliver on its mission of transforming the I-O landscape. Key milestones to watch include the upcoming Phase 2 data for vilastobart in combination with atezolizumab, as well as the initial Phase 1 data for XTX301. The success of these clinical programs could potentially validate Xilio's tumor-activated approach and pave the way for future growth and potential partnerships in the competitive immuno-oncology space.