8-K: Instil Bio and ImmuneOnco Advance Bispecific Antibody 2510 in NSCLC Trials, Announce On-Track Enrollment and Promising Early Data

Instil Bio and ImmuneOnco announced significant progress in their clinical trials for the bispecific antibody 2510, including on-track enrollment for a Phase 2 NSCLC trial in China and plans for a US Phase 1b/2 trial.

Summary

• The Phase 2 trial of 2510 in combination with chemotherapy for first-line Non-Small Cell Lung Cancer (NSCLC) in China is on track to complete enrollment of approximately 60 patients in Q3 2025.
• Initial safety and efficacy results from this Phase 2 trial are anticipated in the second half of 2025.
• More than 30 NSCLC patients have been enrolled, with over 20 first-line NSCLC patients treated since the end of March 2025.
• Preliminary safety data as of May 9, 2025, indicated a reduction in infusion-related reactions (IRRs) in patients treated with 2510 in combination with chemotherapy (29.2%) compared to monotherapy (60.4%).
• In the safety analysis set from all solid tumor patients in monotherapy dose escalation and expansion (n=106), treatment-related adverse events (TRAEs) were observed in 94.3% of patients, with Grade 3 TRAEs accounting for 21.7% of cases, serious TRAEs in 12.3%, treatment discontinuation due to TRAEs in 4.7%, and TRAEs leading to death in 0.9%. Grade 3+ possible VEGF-related toxicities were rare.
• A Phase 3 trial of first-line 2510 in combination with chemotherapy in NSCLC is anticipated to start in mid-2026 in China, subject to regulatory discussions.
• Preliminary data from the Phase 1 monotherapy trial in heavily pre-treated relapsed/refractory NSCLC in China demonstrated an objective response rate (ORR) of 23.1% (efficacy evaluable n=13), including responses in patients with low (5%) PD-L1 tumor proportion score (TPS) and those previously treated with checkpoint inhibitors.
• 62% of NSCLC patients in the Phase 1 study experienced tumor shrinkage.
• Instil Bio expects to initiate a Phase 1b/2 monotherapy dose optimization trial of 2510 in relapsed/refractory solid tumors in the United States before the end of 2025, replacing the previously planned US combination trial to potentially accelerate the path to a global Phase 3 trial.
• Preclinical assays demonstrated cooperative binding of 2510 to PD-L1 in the presence of VEGF in vitro.

Sentiment

Score: 7

Explanation: The document provides generally positive updates on clinical trial progress, including on-track enrollment, promising preliminary efficacy data in a difficult-to-treat patient population, and a clear path to Phase 3. While safety data shows a high incidence of overall TRAEs in monotherapy, the reduction in IRRs in combination therapy and rarity of severe VEGF-related toxicities are positive. The strategic shift for the US trial is presented as an acceleration of the development pathway. Overall, the tone is optimistic regarding the drug's potential.

Positives

• Phase 2 trial enrollment for first-line NSCLC in China is on track to complete in Q3 2025, indicating good progress.
• Initial safety data showed a significant reduction in infusion-related reactions (IRRs) in combination therapy (29.2%) compared to monotherapy (60.4%).
• Preliminary Phase 1 monotherapy data in heavily pre-treated relapsed/refractory NSCLC demonstrated an objective response rate (ORR) of 23.1%, including responses in challenging patient populations (low PD-L1, prior checkpoint inhibitor treatment).
• 62% of NSCLC patients in the Phase 1 study experienced tumor shrinkage, indicating broad anti-tumor activity.
• A Phase 3 trial in China is anticipated to start in mid-2026, signaling advancement towards pivotal studies.
• The planned US Phase 1b/2 trial is intended to accelerate the path to a potential global Phase 3 trial, optimizing development strategy.
• Preclinical data supports a unique and potentially best-in-class mechanism of action for 2510.

Negatives

• Overall treatment-related adverse events (TRAEs) were observed in a high percentage of monotherapy patients (94.3%), although Grade 3 TRAEs were lower at 21.7%.
• Serious TRAEs occurred in 12.3% of the monotherapy study population.
• Treatment discontinuation due to TRAEs was observed in 4.7% of monotherapy patients.
• TRAEs leading to death were observed in 0.9% of monotherapy patients.

Risks

• Risks and uncertainties associated with in-licensing product candidates and clinical trial collaborations.
• The costly and time-consuming product development process and the uncertainty of clinical success.
• Risks inherent in relying on collaborators and other third parties, including for manufacturing and clinical trial operation.
• Risks and uncertainties related to successfully initiating, enrolling, completing, and reporting data from clinical studies.
• The risk that results obtained in clinical trials to date may not be indicative of results obtained in ongoing or future trials.
• The risk that Instil's product candidates may otherwise not be effective treatments in their planned indications.
• Risks related to macroeconomic conditions, including international conflicts, U.S.-China trade and political tensions, interest rates, and inflation.
• The time-consuming and uncertain regulatory approval process for product candidates across multiple indications and multiple regulatory authorities.
• The impact of product candidates that may compete with those developed by Instil.
• The sufficiency of Instil's cash resources.
• Other risks and uncertainties affecting Instil and its plans and development programs, including those discussed in the section titled 'Risk Factors' in Instil's Quarterly Report on Form 10-Q for the quarter ended March 31, 2025.

Future Outlook

Instil Bio and ImmuneOnco anticipate completing Phase 2 enrollment in China by Q3 2025, with initial results expected in 2H 2025. A Phase 3 trial in China is projected to begin in mid-2026, subject to regulatory discussions. Instil also plans to initiate a US Phase 1b/2 monotherapy trial before the end of 2025, which is intended to accelerate the path to a potential global Phase 3 trial.

Management Comments

• Bronson Crouch, CEO of Instil: "We are delighted with the significant clinical advancements by our collaborator, ImmuneOnco, with 2510 for NSCLC in China. We are confident that 2510 has the potential to emerge as a leading PD-(L)1xVEGF bispecific antibody, and we look forward to the initial results from the ongoing first-line chemotherapy combination trial in China. In parallel, we are advancing preparations to initiate U.S. clinical development later this year, and we look forward to bringing this potential important new medicine to patients globally."
• Dr. Tian Wenzhi, CEO of ImmuneOnco: "Our collaboration on 2510 has achieved meaningful progress. We are actively conducting a Phase 2 clinical trial of 2510 in combination with chemotherapy in patients with first-line NSCLC. The data generated to date underscore its best-in-class potential within the promising PD-(L)1xVEGF class. We anticipate sharing further clinical data in the second half of 2025."

Industry Context

The development of 2510, a PD-L1xVEGF bispecific antibody, positions Instil Bio and ImmuneOnco within the competitive and rapidly evolving field of oncology, specifically targeting non-small cell lung cancer (NSCLC). Bispecific antibodies represent a growing class of therapeutics designed to target multiple pathways simultaneously, potentially offering improved efficacy and reduced resistance compared to monotherapies. The focus on NSCLC, a leading cause of cancer deaths, highlights the significant market opportunity. The companies' claims of 'best-in-class potential' suggest an ambition to differentiate 2510 from other similar bispecific antibodies currently in development.

Comparison to Industry Standards

• The objective response rate (ORR) of 23.1% from the Phase 1 monotherapy trial in relapsed/refractory NSCLC is stated to be "similar to datasets from competitor PD-(L)1xVEGF bispecific antibodies at a similar stage of development," indicating comparable performance within the class.
• 2510 is differentiated from other PD-(L)1xVEGF bispecific antibodies by its VEGF trap, which binds multiple VEGF receptor ligands beyond VEGF-A, a bispecific structure leveraging PD-L1 as an anchor in the tumor microenvironment (TME), and enhanced antibody-dependent cellular cytotoxicity (ADCC) to direct killing of PD-L1-positive tumor cells.

Stakeholder Impact

• Shareholders: Positive impact due to clinical progress, potential for future value creation if trials are successful, and a clear development pathway for a key asset.
• Patients: Potential for a new and differentiated treatment option for Non-Small Cell Lung Cancer (NSCLC), particularly for those with relapsed/refractory disease or low PD-L1 expression.
• Employees: Continued work on a promising drug candidate, contributing to the company's strategic goals.
• Collaborators (ImmuneOnco): Continued successful collaboration and shared progress in advancing the 2510 program.

Next Steps

• Complete enrollment of approximately 60 patients in the Phase 2 trial in China in Q3 2025.
• Share initial safety and efficacy results from the Phase 2 trial in China in 2H 2025.
• Initiate a Phase 1b/2 trial of 2510 in the United States before the end of 2025.
• Start a Phase 3 trial of first-line 2510 in combination with chemotherapy in NSCLC in mid-2026 in China, subject to regulatory discussions.
• Present further preclinical datasets demonstrating the unique mechanism of action of 2510 at future medical or scientific conferences.

Key Dates

Recommendation

Keywords

Instil Bio, ImmuneOnco, AXN-2510, IMM2510, 2510, NSCLC, Non-Small Cell Lung Cancer, Bispecific Antibody, PD-L1xVEGF, Clinical Trial, Phase 2, Phase 1, Oncology, Biotechnology, Drug Development, Cancer Treatment, Clinical Data, Biopharmaceutical