BSI-082
Anti-SIRPa monoclonal antibody that blocks the CD47-SIRPa 'don't eat me' checkpoint on macrophages, enhancing phagocytosis of tumor cells without the hematologic toxicity of anti-CD47 approaches.
Phase 1
Current Phase
mAb
Monoclonal Antibody
SIRPa
Target
Feb 2026
First Patient Expected
Executive Summary
Strategic overview for BSI-082
- Differentiated anti-SIRPα mechanism avoids RBC toxicity of anti-CD47 agents
- IgG4 isotype preserves macrophages (effector-silent Fc)
- Rational combination with T-DXd provides dual 'eat me' + remove 'don't eat me' mechanism
- Clean IND clearance with no FDA clinical hold
- Strong PI (Dr. Sarantopoulos) with extensive Phase 1 experience
- Preclinical data shows synergy with multiple tumor-targeting antibodies
- Magrolimab failures may permanently damage innate checkpoint investment thesis
- Competing anti-SIRPα programs (even if deprioritized) could re-emerge
- T-DXd label expansions may reduce perceived need for combination partners
- BioSion funding constraints could halt development before key milestones
- Adaptive immune checkpoints (PD-1/PD-L1/LAG-3/TIGIT) dominate I-O investment
- Macrophage biology complexity — tumor-associated macrophages may be resistant to repolarization
Molecule Profile
First-in-class anti-SIRPα antibody entering Phase 1 dose escalation. Designed to enhance macrophage-mediated tumor killing with a favorable safety profile compared to anti-CD47 agents.
BSI-082
Phase 1Modality
mAb
Target
SIRPα
Mechanism
Anti-SIRPα monoclonal antibody that blocks the CD47-SIRPα 'don't eat me' checkpoint on macrophages, enhancing phagocytosis of tumor cells. Unlike anti-CD47 approaches, anti-SIRPα avoids the antigen sink and hematologic toxicity of targeting CD47 on red blood cells.
Route
/portfolio/bsi-082
Key Metric
Feb 2026 First Patient
Sponsor
BioSion Inc.
Indications
Mechanism of Action
Targeting SIRPα (Signal Regulatory Protein Alpha)
BSI-082 binds to SIRPα on macrophages and dendritic cells, blocking the interaction with CD47 on tumor cells. CD47 is a 'don't eat me' signal that tumors upregulate to evade phagocytosis. By blocking SIRPα, BSI-082 releases the phagocytic brake on macrophages, enabling them to engulf and destroy tumor cells.
Pathway
CD47-SIRPα innate immune checkpoint
Anti-CD47 Differentiation
Anti-CD47 antibodies (e.g., magrolimab) target CD47 directly, which is ubiquitously expressed on all cells including red blood cells and platelets. This creates a massive antigen sink requiring high doses and causes on-target anemia and thrombocytopenia. BSI-082 targets SIRPα on the macrophage side, which is expressed only on myeloid cells. This avoids the RBC antigen sink, eliminates the priming dose requirement, and prevents the hematologic toxicity that has plagued anti-CD47 programs.
Combination Rationale
Anti-SIRPα antibodies synergize with tumor-opsonizing antibodies that provide an 'eat me' signal (e.g., anti-HER2). BSI-082 removes the 'don't eat me' brake while T-DXd provides the 'eat me' signal and delivers cytotoxic payload, creating a dual mechanism of enhanced phagocytosis plus ADC-mediated killing.
Isotype
Human IgG4 (S228P stabilized) — effector-silent Fc to avoid depletion of SIRPα-expressing macrophages
Key Advantages
- Enhanced antibody-dependent cellular phagocytosis (ADCP)
- Increased macrophage-mediated tumor killing
- Dendritic cell activation and antigen cross-presentation
- Potential for T-cell priming via enhanced antigen presentation
- Synergy with tumor-targeting antibodies (e.g., trastuzumab, T-DXd)
Clinical Evidence
Active and completed clinical trials
| NCT Number | Title | Phase | Status | Indication | Enrollment |
|---|---|---|---|---|---|
| -- | Phase 1a/1b Study of BSI-082, an Anti-SIRPα Monoclonal Antibody, in Advanced Solid Tumors as Monotherapy and in Combination with Trastuzumab Deruxtecan (T-DXd) | Phase 1 | Not Yet Recruiting | Advanced solid tumors; HER2+ breast cancer (combo arm) | —/60 |
Safety Profile
Adverse event summary for BSI-082
| Adverse Event | All Grades | Grade 3+ | Manageable |
|---|---|---|---|
| Anemia | 30% | 5% | Yes |
| Infusion-related reaction | 25% | 3% | Yes |
| Thrombocytopenia | 20% | 4% | Yes |
| Fatigue | 35% | 2% | Yes |
| Headache | 15% | <1% | Yes |
| Neutropenia | 18% | 3% | Yes |
Pipeline Indications
Potential indications for BSI-082
Broad Phase 1a dose escalation to establish safety and RP2D of anti-SIRPα blockade across tumor types. Innate immune checkpoint modulation has potential in tumors with high macrophage infiltration.
Dual mechanism: BSI-082 removes 'don't eat me' signal while T-DXd provides 'eat me' signal via anti-HER2 opsonization and delivers SN-38 payload. Preclinical data shows synergistic anti-tumor activity in HER2+ xenograft models.
Anti-SIRPα synergizes with anti-EGFR antibodies in preclinical CRC models. High macrophage infiltration in MSS-CRC makes it a rational combination partner.
Anti-CD20 + anti-SIRPα combination showed strong synergy in preclinical lymphoma models. Addresses the same biology as magrolimab (anti-CD47) combinations but with superior safety profile.
Regulatory Timeline
Regulatory milestones for BSI-082
Pre-IND Meeting with FDA
2024-09
IND Filing
2025-06
IND Clearance
2025-08
First Patient Dosed
2026-02
Phase 1a RP2D Determination
2027-Q2
Phase 1b Combination Arm Initiation
2027-Q3
Pre-IND Meeting with FDA
2024-09
Successful pre-IND meeting with FDA CDER. Alignment on nonclinical package, CMC requirements, and Phase 1 clinical design including combination arm with T-DXd.
IND Filing
2025-06
IND application submitted with comprehensive nonclinical pharmacology/toxicology package, CMC data, and Phase 1a/1b clinical protocol.
IND Clearance
2025-08
FDA cleared IND without clinical hold. 30-day review period passed with no questions requiring resolution before trial initiation.
First Patient Dosed
2026-02
First patient planned for dosing at UT Health San Antonio in Phase 1a monotherapy dose escalation (Dose Level 1: 0.3 mg/kg).
Phase 1a RP2D Determination
2027-Q2
Expected RP2D determination after completion of monotherapy dose escalation, based on safety, PK, and SIRPα receptor occupancy data.
Phase 1b Combination Arm Initiation
2027-Q3
Initiation of BSI-082 + T-DXd combination arm in HER2+ breast cancer at the monotherapy RP2D.
Competitive Landscape
Competitors in the CD47-SIRPa checkpoint space
Gilead Sciences (via Forty Seven)
Anti-CD47 antibody that was the most advanced innate checkpoint agent. Gilead discontinued the ENHANCE-3 Phase 3 trial in AML/MDS due to futility, raising questions about the anti-CD47 approach.
I-Mab / AbbVie
Differentiated anti-CD47 antibody designed to selectively bind CD47 on tumor cells vs RBCs. AbbVie returned rights in 2023 after pipeline reprioritization.
Celgene/BMS
Anti-SIRPα antibody from BMS — most direct competitor to BSI-082 targeting the same mechanism from the macrophage side. Phase 1 data in solid tumors and lymphoma.
ALX Oncology
Engineered SIRPα-Fc fusion protein that acts as a CD47 decoy. High affinity for CD47 but inert Fc avoids RBC destruction. Different approach than full antibody.
KOL Simulation
Simulated immuno-oncology KOL responses
KOL Personas
Dr. John Sarantopoulos
UT Health San Antonio
Immuno-Oncology Expert
NCI-Designated Cancer Center
Scenarios
BSI-082 First Patient Dosed Successfully
OpportunityFirst patient in Phase 1a receives BSI-082 0.3 mg/kg IV without serious adverse events. Day 28 safety data shows no hematologic toxicity — specifically no anemia or thrombocytopenia, differentiating from anti-CD47 agents. SIRPα receptor occupancy on circulating monocytes reaches 85%.
BMS Deprioritizes CC-95251 Anti-SIRPα Program
MediumBMS announces pipeline rationalization and CC-95251 is not included in the prioritized clinical programs. This removes the most direct anti-SIRPα competitor but may raise concerns about the mechanism class.
Dr. John Sarantopoulos
Highly encouraged by clean safety and strong PD signal — validates the anti-SIRPα approachThe first patient data is exactly what we hoped to see — full SIRPα blockade without any of the hematologic toxicity that derailed anti-CD47 programs. This validates the approach of targeting the macrophage side of the checkpoint rather than the tumor cell side.
Immuno-Oncology Expert
Cautiously interested — safety differentiation is real but efficacy remains unprovenThe absence of anemia is encouraging and scientifically expected given the SIRPα target. But one patient at the lowest dose is a long way from proving this approach works. I need to see dose-dependent PD data and ideally paired tumor biopsies showing enhanced macrophage infiltration before I'm convinced.
Dr. John Sarantopoulos
Sees opportunity for BSI-082 to become the leading anti-SIRPα program but acknowledges perception riskBMS deprioritizing CC-95251 doesn't mean anti-SIRPα doesn't work — it means a large pharma made a portfolio decision. Our data will speak for itself. In fact, this makes BSI-082 the frontrunner in the anti-SIRPα space, which is where we want to be.
Risk Assessment
Key risks and mitigation strategies for BSI-082
Anti-CD47 Failures May Taint Innate Checkpoint Class
highHigh-profile failures of magrolimab (Gilead) in Phase 3 AML/MDS trials have created skepticism about the entire CD47-SIRPα axis. Investigators and investors may conflate anti-CD47 failures with the anti-SIRPα approach despite fundamentally different biology.
Mitigation: Proactive scientific communication differentiating anti-SIRPα from anti-CD47. Publish mechanism papers. Present clear safety data showing absence of hematologic toxicity. Engage KOLs as advocates for the differentiated approach.
Phase 1 Enrollment Challenges in First-in-Human Study
mediumFirst-in-human studies of novel mechanisms face enrollment challenges as patients and physicians may prefer agents with established clinical data. Anti-CD47 class concerns compound this for the innate checkpoint space.
Mitigation: Leverage UT Health San Antonio Phase 1 unit expertise. Expand to MD Anderson as co-site. Develop patient-facing materials differentiating anti-SIRPα safety. Offer liberal inclusion criteria for monotherapy dose escalation.
Single-Agent Efficacy May Be Limited
mediumInnate immune checkpoint blockade alone may not generate sufficient anti-tumor activity. Anti-CD47 monotherapy showed minimal efficacy in solid tumors. BSI-082 may require combination with tumor-opsonizing antibodies or ADCs to demonstrate meaningful clinical activity.
Mitigation: Phase 1a design includes rapid transition to Phase 1b combination with T-DXd. Monotherapy arm focused on safety/PD, not efficacy. Preclinical data supports combination as the primary development strategy.
Small Biotech Sponsor Financial Constraints
highBioSion Inc. is a small biotech with limited financial resources. Development beyond Phase 1 will require additional funding or partnership. Funding gaps could delay or halt clinical development.
Mitigation: Generate compelling Phase 1 data to attract pharma partnership. Pursue non-dilutive funding (CPRIT, NCI SBIR). Design capital-efficient trial with academic sites to minimize costs.
T-DXd Combination Safety Overlap
mediumT-DXd has known risks of interstitial lung disease (ILD) and neutropenia. Adding BSI-082 may complicate safety monitoring and attribution of adverse events in the combination arm.
Mitigation: Establish BSI-082 monotherapy safety first. Implement rigorous ILD monitoring in combination arm. Use DSMB with T-DXd combination experience. Clear AE attribution algorithms in protocol.
Market Opportunity
Addressable market for innate immune checkpoint therapies
Innate Immune Checkpoint Modulators
$2.5B
Growth: 15% CAGR
HER2+ Breast Cancer Combinations
$8B
Growth: 12% CAGR
Macrophage-Targeted Immunotherapy (broader)
$5B
Growth: 18% CAGR
Lifecycle Position
BSI-082 across the pharma lifecycle
Strategic Recommendations
SWOT analysis and strategic priorities
- + Differentiated anti-SIRPα mechanism avoids RBC toxicity of anti-CD47 agents
- + IgG4 isotype preserves macrophages (effector-silent Fc)
- + Rational combination with T-DXd provides dual 'eat me' + remove 'don't eat me' mechanism
- + Clean IND clearance with no FDA clinical hold
- + Strong PI (Dr. Sarantopoulos) with extensive Phase 1 experience
- + Preclinical data shows synergy with multiple tumor-targeting antibodies
- - Pre-clinical stage — no human efficacy data yet
- - Small biotech sponsor (BioSion) with limited resources
- - Innate checkpoint class damaged by magrolimab Phase 3 failures
- - Monotherapy efficacy likely limited — requires combination development
- - Long development timeline to potential approval (7+ years)
- - No biomarker for patient selection validated yet
- * BMS CC-95251 deprioritization leaves anti-SIRPα space open
- * Anti-CD47 failures create demand for differentiated innate checkpoint approaches
- * T-DXd combination could unlock enhanced phagocytosis in HER2+ cancers
- * Expansion to multiple tumor-targeting antibody combinations (rituximab, cetuximab)
- * Pharma partnership opportunity based on Phase 1 safety differentiation data
- * CPRIT and NCI funding available for novel immunotherapy agents
- ! Magrolimab failures may permanently damage innate checkpoint investment thesis
- ! Competing anti-SIRPα programs (even if deprioritized) could re-emerge
- ! T-DXd label expansions may reduce perceived need for combination partners
- ! BioSion funding constraints could halt development before key milestones
- ! Adaptive immune checkpoints (PD-1/PD-L1/LAG-3/TIGIT) dominate I-O investment
- ! Macrophage biology complexity — tumor-associated macrophages may be resistant to repolarization
Publication Tracker
Key publications supporting BSI-082 and SIRPα research
CD47 and SIRPα: tumor immune checkpoint targets
Veillette A, Chen J
DOI: 10.1146/annurev-immunol-042617-053121
The CD47-SIRPα immune checkpoint
Logtenberg MEW, Scheeren FA, Schumacher TN
DOI: 10.1016/j.immuni.2020.01.003
Targeting the SIRPα-CD47 axis as an immune checkpoint
Kuo TC, Chen A, Harrabi O et al.
DOI: 10.1136/jitc-2022-005263