On July 24, 2025 Vir Biotechnology, Inc. (Nasdaq: VIR) reported that the first patient has been dosed in the Company’s Phase 1 clinical trial evaluating VIR-5525, an investigational dual-masked T-cell engager (TCE) targeting EGFR (epidermal growth factor receptor) (Press release, Vir Biotechnology, JUL 24, 2025, View Source [SID1234654516]). VIR-5525 will be evaluated for the treatment of a variety of EGFR-expressing solid tumors in areas of high unmet need such as non-small cell lung cancer (NSCLC), colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), and cutaneous squamous cell carcinoma (cSCC).

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The Phase 1 clinical trial (NCT06960395) is a first-in-human open-label, non-randomized study designed to assess the safety, pharmacokinetics, and preliminary anti-tumor activity of VIR-5525 as a monotherapy and in combination with pembrolizumab. VIR-5525 is Vir Biotechnology’s third dual-masked TCE in clinical trials. It incorporates the Company’s clinically validated in-licensed PRO-XTEN masking technology, which is designed to enable the selective activation of the TCEs in the tumor microenvironment, mitigating damage to healthy cells and reducing toxicity.

EGFR is a clinically validated target known to play a key role in cancer.1 Although EGFR-targeting therapies are available, they often face limitations due to the development of resistance mechanisms2 and high toxicities associated with treatment.3

"We are excited to bring our third PRO-XTEN dual-masked T-cell engager VIR-5525 to the clinic as we further our mission of transforming the lives of people living with hard-to-treat solid tumors," said Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology. "This achievement is a testament of Vir Biotechnology’s commitment to advancing innovative therapies that address substantial unmet needs in oncology."

"EGFR has been well characterized as a key oncogenic driver and a marker of poor prognosis in cancer. Traditional therapies have significant limitations, creating a substantial unmet need for highly efficacious and well-tolerated options," said Mark Eisner, MD, MPH, Chief Medical Officer, Vir Biotechnology. "VIR-5525 harnesses the anti-tumor power of T-cell engagers with a dual-masking approach designed to unlock an expanded therapeutic index. We look forward to evaluating the potential of this clinical candidate in our Phase 1 trial."

The first patient dosing of VIR-5525 triggers a $75 million milestone payment as part of the Company’s 2024 exclusive worldwide license agreement with Sanofi for the PRO-XTEN platform and clinical-stage T-cell engagers. This anticipated milestone payment has been held as restricted cash since the transaction closing and was excluded from the Company’s $1.02 billion in cash, cash equivalents and investments reported as of March 31, 2025. The payment will be recognized as a research and development expense in the third quarter of 2025.

Dose escalation continues for Vir Biotechnology’s dual-masked TCEs VIR-5818 (targeting a variety of HER2-expressing solid tumors) and VIR-5500 (targeting PSMA in metastatic castration-resistant prostate cancer). Initial Phase 1 data presented in January 2025 showed compelling early clinical response signals and promising safety profiles for both clinical candidates in heavily pretreated patients.

The Company is advancing multiple preclinical dual-masked TCEs against clinically validated targets with potential applications across a variety of solid tumors with high unmet need. These undisclosed candidates integrate the PRO-XTEN masking technology with novel TCEs discovered and engineered using Vir Biotechnology’s antibody discovery platform and the Company’s proprietary dAIsY (data AI structure and antibody) artificial intelligence engine.

About VIR-5525

T-cell engagers (TCEs) are powerful anti-tumor agents that can direct the immune system, specifically T-cells, to destroy cancer cells. VIR-5525 is an investigational dual-masked TCE currently being evaluated in an open-label, non-randomized Phase 1 clinical trial (NCT06960395) designed to assess the safety, pharmacokinetics and preliminary efficacy of VIR-5525 alone or in combination with pembrolizumab.

VIR-5525 combines a bispecific EGFR and CD3 binding TCE with the PRO-XTEN masking technology. The PRO-XTEN masking technology is designed to keep the TCEs inactive (or masked) until they reach the tumor microenvironment, where tumor-specific proteases cleave off the mask and activate the TCEs, leading to killing of cancer cells by T-cells. By confining the activity exclusively to the tumor microenvironment, we aim to circumvent the traditionally high toxicity associated with unmasked TCEs and increase their efficacy and tolerability. Additionally, the mask is designed to help drug candidates stay in the bloodstream longer in their inactive form, allowing them to better reach the site of action and potentially allowing for less frequent dosing regimens.