Sensei Biotherapeutics: Virtual KOL Event for Solnerstotug PD-(L)1 Resistant Tumor Data

Sensei Biotherapeutics (Nasdaq: SNSE) is scheduled to host a virtual Key Opinion Leader (KOL) event on October 20, 2025, to present comprehensive dose expansion data for

(formerly SNS-101), a novel VISTA-targeting immunotherapy for patients with PD-(L)1 resistant tumors. This event represents a critical catalyst following promising Phase 1/2 clinical data presented at ESMO 2025, which demonstrated meaningful clinical activity in a heavily pre-treated patient population with significant unmet medical need.

• Clinical Efficacy
  : 6 total responses observed, with 5 occurring in PD-(L)1 resistant patients
• Dose Response
  : All responses occurred at 15 mg/kg dose level (50% 6-month PFS), none at 3 mg/kg
• Safety Profile
  : Favorable tolerability with only 6 mild cytokine release syndrome cases across 98 patients
• Market Opportunity
  : Targeting the growing PD-(L)1 resistant tumor market within the $230.3B global immune checkpoint inhibitor market
• Financial Position
  : Current market cap of $8.77M with cash runway into Q2 2026

Solnerstotug represents a breakthrough in cancer immunotherapy through its

. The therapy’s pH-selective binding mechanism allows activation only under low-pH conditions found in tumor microenvironments, providing:

• Target Selectivity
  : Blocks VISTA checkpoint selectively within tumors, minimizing systemic toxicity
• Novel Mechanism
  : VISTA acts as a T-cell suppressor by binding PSGL-1 receptor, representing an underexplored checkpoint pathway
• Conditional Activation
  : Reduces systemic toxicity compared to conventional antibodies

The Phase 1/2 dose expansion data reveals several critical insights:

• Study population: 35 efficacy-evaluable “hot tumor” patients
• Dose-dependent response: 15 mg/kg (n=19) vs 3 mg/kg (n=16)
• Response timing: 4 of 6 responders showed prolonged disease control with late-onset responses (18-54 weeks)

• Overall PD-(L)1 resistant patients: 37% 6-month PFS rate
• 15 mg/kg cohort: 50% 6-month PFS in PD-(L)1 resistant patients
• 3 mg/kg cohort: 24% 6-month PFS rate

• No dose-limiting toxicities observed
• Majority of adverse events were Grade 1-2 severity
• Favorable tolerability compared to conventional checkpoint inhibitors

• Global immune checkpoint inhibitors market projected to reach $230.3 billion by 2033 (CAGR 17.2%)
• PD-1 inhibitors represent 57.3% of global market share
• Over 50% of patients experience primary or acquired resistance to anti-PD-1 therapy

1. First-Mover Position
   : Among the most advanced VISTA-targeting candidates
2. Novel Target
   : Addresses resistance mechanisms not covered by existing therapies
3. Differentiated Mechanism
   : pH-selective activation provides unique safety profile
4. Specific Focus
   : Targets PD-(L)1 resistant populations with significant unmet need

• Second-line NSCLC patients who progressed on PD-(L)1 therapy
• PD-(L)1 resistant Merkel cell carcinoma patients
• Advanced solid tumors with “hot” tumor microenvironment characteristics

1. Dose-Response Correlation
   : The clear dose-dependent efficacy (responses only at 15 mg/kg) provides strong validation for the mechanism of action and supports the planned Phase 2 dosing strategy.

2. Late-Onset Response Pattern
   : The observation of delayed responses (18-54 weeks) suggests a unique immunological mechanism that may require longer treatment duration to achieve optimal benefit, potentially differentiating it from conventional checkpoint inhibitors.

3. Safety-Efficacy Balance
   : The favorable safety profile combined with meaningful efficacy in a resistant population positions solnerstotug as a potential best-in-class option for PD-(L)1 resistant patients.

1. Platform Validation
   : Success with solnerstotug would validate the TMAb technology platform, potentially enabling development of additional conditional activation therapies across multiple indications.

2. Combination Potential
   : The novel mechanism and favorable safety profile suggest significant potential for combination strategies with existing immunotherapies or targeted therapies.

3. Market Disruption Potential
   : As one of the first VISTA inhibitors, solnerstotug could establish a new therapeutic class and potentially change treatment paradigms for PD-(L)1 resistant cancers.

1. Financial Risk
   : Cash runway only until Q2 2026 requires additional capital financing for continued development
2. Regulatory Uncertainty
   : Novel mechanism may face additional regulatory scrutiny and potentially longer review timelines
3. Clinical Validation Risk
   : Phase 2 trials must confirm Phase 1/2 signals in larger patient populations
4. Competitive Landscape
   : Rapidly evolving immunotherapy field with multiple next-generation checkpoint inhibitors in development
5. Market Adoption
   : New mechanism may face physician acceptance challenges and require extensive education

1. First-Mover Advantage
   : Potential to become the first approved VISTA inhibitor, establishing market leadership
2. Partnership Potential
   : Novel technology attractive for larger pharmaceutical companies seeking to expand immunotherapy portfolios
3. Broad Applicability
   : VISTA expression across multiple tumor types enables expansion opportunities beyond initial indications
4. Acquisition Target
   : Innovative platform and promising clinical data make the company an attractive acquisition candidate
5. Market Need
   : Significant unmet need in PD-(L)1 resistant patients with limited treatment options

• October 20, 2025
  : Virtual KOL event with comprehensive dose expansion data presentation
• 2026
  : Planned Phase 2 trial initiations in 2L NSCLC and PD-(L)1 resistant MCC
• Regulatory Interactions
  : Potential for accelerated approval pathways based on unmet medical need

The virtual KOL event on October 20, 2025, represents a pivotal moment for Sensei Biotherapeutics and the development of solnerstotug. The comprehensive dose expansion data presentation will provide critical insights into the therapy’s potential to address the significant unmet need in PD-(L)1 resistant cancers.

With demonstrated clinical activity in a heavily pre-treated population, a favorable safety profile, and a novel mechanism of action, solnerstotug has the potential to become a first-in-class therapy for PD-(L)1 resistant tumors. However, the company faces significant challenges including financing requirements, regulatory uncertainty, and the need to confirm clinical signals in larger Phase 2 trials.

The upcoming KOL event will be instrumental in shaping investor sentiment, potential partnership discussions, and the overall development trajectory for this promising VISTA-targeting immunotherapy.