Pipeline

Toward durable functional cures for persistent viral disease

At Perpetuu, we are developing AAV-delivered antibody therapies designed to address persistent viral diseases. Our pipeline focuses on durable therapeutic approaches that aim to move beyond lifelong treatment toward functional cures.

Perpetuu development pipeline programs, disease areas, development stages, status, and funding support.
Program Disease Antibody discovery AAV vector engineering Preclinical Clinical Status Funding Support
CMVZ01 Cytomegalovirus (CMV) in immuno-compromised patients Antibody discovery through AAV vector engineering Co-lead program
HBVZ10 Hepatitis B Antibody discovery through AAV vector engineering and Preclinical Co-lead, Preclinical PoC Funding support from the U.S. Department of Defense and NIH NIAID.
HDVZ35 Hepatitis D Antibody discovery Discovery
Colorized illustration of hepatitis B virus particles.

Chronic Hepatitis B

HBVZ10, one of Perpetuu’s two co-lead programs, targets chronic hepatitis B (CHB) and is designed to support a finite-treatment functional-cure strategy.

HBV persists in part because cccDNA can be maintained through intracellular replication and new rounds of infection. Standard-of-care nucleos(t)ide analogues such as entecavir potently inhibit intracellular viral replication but do not completely prevent extracellular virions from initiating new infection.

HBVZ10 is designed to provide sustained production of neutralizing anti-HBs antibodies from skeletal muscle, blocking the extracellular pathway of cccDNA replenishment.

Proof-of-conceptPublished preclinical validation of the Perpetuu platform

In humanized-liver mice with persistent HBV infection, a single administration of HBVZ10 produced sustained anti-HBs antibody titers ≥100,000 mIU/mL through study termination at 231 days.

As monotherapy, HBVZ10 reduced:

  • Serum HBV DNA by 78–93%
  • Serum HBsAg by 80–90%
  • Intrahepatic cccDNA approximately 5-fold versus control

When combined with entecavir, HBVZ10 produced:

  • HBsAg seroclearance in 8/9 animals (88.9%) vs. 1/10 (10%) with entecavir alone (p=0.001)
  • 100-fold greater reduction in hepatic cccDNA versus entecavir alone
  • 10-fold greater reduction in hepatic rcDNA versus entecavir alone

These findings support the potential of combining a durable extracellular virion blocker with an intracellular replication inhibitor as a new strategy toward functional cure.

Read the publication
Download the paper

The complete study data and supporting publications provide additional detail on the experimental design and results.

Zhang, B.H. et al. Molecular Therapy – Methods & Clinical Development 33 (2025): 4.

Infection Rebound after SOC Withdrawal

Line chart showing infection rebound after standard-of-care entecavir withdrawal.

HBVZ10 + Entecavir = Durable Suppression after SOC Withdrawal

Line chart comparing serum HBeAg levels in untreated animals and animals receiving HBVZ10 plus entecavir.
Line chart comparing serum HBsAg levels in untreated animals and animals receiving HBVZ10 plus entecavir.

Expanding Our Pipeline

Perpetuu is advancing co-lead programs in CMV and chronic hepatitis B, providing two complementary opportunities to demonstrate the potential of sustained in vivo antibody expression.

CMVZ01 targets prevention of CMV reactivation and disease in high-risk transplant patients, while HBVZ10 targets the persistent viral reservoir underlying chronic hepatitis B. Additional programs may extend the platform to other persistent viral diseases.

Colorized illustration of a cytomegalovirus particle surrounded by smaller viral particles.

CMVZ01: Co-lead program for transplant prophylaxis

A potential single-administration approach to durable CMV protection in high-risk transplant patients

CMVZ01 is being developed to provide sustained neutralizing antibody protection during periods of highest CMV risk following transplantation. The program offers concentrated high-risk patient populations, clinically meaningful endpoints, and an opportunity to validate Perpetuu’s antibody-expression platform in a focused clinical setting.

Current standard-of-care has important limitations.

High-risk populations:

  • Allogeneic stem cell transplant
  • Lung transplant
  • Solid organ transplant

Despite prophylaxis…

  • CMV reactivation remains common
  • Breakthrough infections occur
  • Daily dosing required
  • Significant drug-drug interactions
  • Resistance reported

CMV reactivation is driven by lifelong viral latency

Latent CMV

Immunosuppression

Reactivation

CMV Disease

Hospitalization

Graft Injury

Mortality

Perpetuu approach

Single administration

Skeletal muscle produces anti-CMV antibody

Sustained neutralizing antibody exposure

Designed to provide durable protection during the highest-risk period for CMV reactivation

Donor bone marrow transplants

  • CMV reactivation occurs in 50–70% of seropositive recipients
  • CMV drives 10–15% mortality with SOC
  • 25–40% of hospitalizations are due to CMV
  • 10–15% mortality linked to CMV

Lung transplants

  • 50–80% CMV infection rate
  • 30–50% hospitalized due to CMV
  • 10% mortality linked to CMV

Partner with us to advance the science

We are seeking strategic collaborations to advance our programs and expand application of our platform to additional chronic viral diseases.

Explore partnerships