Pipeline Program

ANN-01P

ANN-01M is a bispecific antibody in pre-clinical development targeting mesothelin (MSLN) on pancreatic ductal adenocarcinoma (PDAC) and other MSLN+ tumors.

Indication: Mesothelin-expressing cancers (focus: PDAC) Status: Early Research and Development / Pre-clinical
ANN-01P
Platform concept highlighting mesothelin-focused development.

Pancreatic Ductal Adenocarcinoma Landscape

Pancreatic ductal adenocarcinoma (PDAC) accounts for >90% of pancreatic cancers and is on track to become the #2 cause of U.S. cancer death by 2030. The American Cancer Society estimates ~67,440 new U.S. cases and ~51,980 deaths in 2025, reflecting late presentation and limited screening options.

Most patients present with unresectable or metastatic disease. Despite intensive regimens (FOLFIRINOX; gemcitabine+nab-paclitaxel), median overall survival in advanced PDAC is typically <12 months. Dense desmoplastic stroma, immune exclusion, and early micrometastatic spread demand off-the-shelf mechanisms that do not rely on patient T-cell fitness and can function within a hostile tumor microenvironment.

Incidence Snapshot

U.S. annual cases (2025 est.) ~67,440 new diagnoses; ~51,980 deaths (American Cancer Society).
Global burden GLOBOCAN 2022: ~511,000 new cases; ~467,000 deaths worldwide; high incidence/mortality in Europe & North America.
Five-year survival (all stages) ~13% overall; stage-dependent (localized 44%, regional 16%, distant 3%) (SEER/ACS 2014-2020 cohort).

Mesothelin Biology & Relevance

Mesothelin (MSLN) is a surface protein found at very low levels in healthy tissues but highly expressed in most pancreatic cancers (around 80-90%). It binds to MUC16/CA125, helping cancer cells stick and spread. Because it’s common in tumors and rare in vital tissues, MSLN serves as both a useful biomarker and an effective target for drug delivery.

ANN-01P leverages MSLN internalization to ferry endogenous ApoL1 into tumor lysosomes, aiming for immune-cell-independent kill while avoiding systemic payload toxicities and manufacturing constraints typical of cell therapies.

ANN-01P Program & Research Plan

Mechanism & Rationale

  • ANN-01P bispecific architecture captures circulating ApoL1 and traffics it into mesothelin-positive PDAC cells, triggering lysosomal pore formation and tumor cell lysis independent of T cells or Fc-effector reliance.

Current Progress (pre-clinical)

  • In-vitro: Specific binding to MSLN+ PDAC lines, internalization, ApoL1-redirected killing; no activity in MSLN-negative controls.

Translational Models (in flight / planned)

  • Emory/Winship partnerships for PDAC biospecimens, PDXs.
  • Custom transgenic human ApoL1 x human mesothelin mouse models enabling exposure/efficacy and safety studies in a disease-relevant background.

Near-Term Milestones

  • Complete NSG mouse efficacy studies and ApoL1 / human mesothelin transgenic mouse evaluations.
  • Complete transgenic model characterization and pilot tox studies/efficacy studies.

Further Reading