A Yale School of Medicine spin-out · Connecticut
A functional cure for chronic hepatitis B.
CARG-201 is a replicating RNA immunotherapy built on our AVIDIO™ virus-like vesicle platform. One intramuscular injection expresses two HBV antigens, switches on innate immunity, and primes the CD8+ T cells that clear infected liver cells — the same engine the platform turns on tumors.
The platform
One self-amplifying RNA injection delivers two HBV antigens plus a built-in adjuvant.
CARG-201 is built on the AVIDIO™ VLV platform. A single intramuscular dose amplifies inside host cells, expresses the HBV surface and core antigens, and switches on innate immunity — priming the effectors that clear infected hepatocytes.
- Self-amplifying RNA — sustained antigen expression from one IM dose
- No meaningful pre-existing human immunity to SFV or VSV
- IND 31717 authorized; clinical lot released
- Drives anti-HBs antibodies, the established correlate of protection
- Target of the approved prophylactic HBV vaccine
- Primes HBc-specific CD8+ T cells
- The effectors behind spontaneous HBV clearance
- dsRNA triggers RIG-I → IFN-α/β in the cells presenting antigen
- Helps break immune tolerance; no exogenous adjuvant
CARG-201 construct: a VSV-G-enveloped vesicle carrying an SFV-replicase genome that expresses the HBV middle surface antigen (MHBs) and core antigen (HBc). dsRNA replication intermediates trigger RIG-I → IFN-α/β as an intrinsic adjuvant.
Rose et al. PNAS (2014) 111:16866 · Reynolds et al. J Virol (2015) 89:10407 · Yarovinsky et al. iScience (2019) 21:391
Preclinical proof
CARG-201 lowers HBsAg where non-replicating comparators show no effect.
In the hardest condition tested — a very high antigen-load AAV-HBV model — group-mean serum HBsAg fell by almost a full log over prime / boost / boost, while published data for a non-replicating arenavirus comparator showed no effect at the same load.
in responders. In the medium antigen-load study, 50% of CARG-201 mice reached undetectable HBsAg after the second boost (p<0.05 vs. GFP control).
group mean reduction in the very-high antigen-load study, where published GS-2829 / GS-6779 data show no effect.
per group, both studies. CD8+ T cells and anti-HBs antibodies were generated; serum ALT was preserved throughout.
Serum HBsAg, Exp. 2 (very high antigen load, 1×10⁷ PFU/mouse, i.m.), redrawn from CaroGen data. Arrows mark prime and two boosts. A separate medium-load study produced the deeper, ≥2 log responses.
Schmidt et al. J Infect Dis (2024) 229:1077 · Yarovinsky et al. iScience (2019) 21:391. Separate studies, not a head-to-head experiment. No NHP data to date; an NHP immunogenicity study is planned pre-dosing.
Market opportunity
Suppression is solved. A durable cure is not.
Nucleos(t)ide analogues suppress viral DNA but rarely clear HBsAg — functional cure on therapy occurs at roughly 1% per year. That leaves a large, diagnosed, reimbursed population waiting for a finite, curative regimen.
Two ways to win: CARG-201 is positioned both as an immunological combination partner to antiviral and antisense therapy, and as a monotherapy for patients who do not reach functional cure on those agents. Unlike ASO and siRNA agents, it restores the T-cell response behind spontaneous clearance rather than only lowering circulating antigen.
Why this time is different
Prior HBV immunotherapies shared four limitations. CARG-201 was designed against all four.
Two antigens, one construct
Single-antigen yeast- and vector-based vaccines produced no durable HBsAg decline in suppressed patients.
MHBs and HBc are co-expressed from one injection, broadening CD4+ and CD8+ epitope coverage.
Replicating RNA, sustained antigen
Non-replicating vectors deliver a fixed, fast-decaying dose, and anti-vector immunity constrains re-dosing.
VLV self-amplifies inside transduced cells — sustained expression from one dose, with no meaningful pre-existing immunity.
Intrinsic adjuvant breaks tolerance
Chronic antigen exposure exhausts HBV-specific T cells; antigen alone does not reverse it, and added adjuvants brought toxicity.
dsRNA intermediates trigger RIG-I → IFN-α/β in the same antigen-presenting cells — no exogenous adjuvant.
Restores immunity, not just lower antigen
ASO and siRNA agents reduce circulating HBsAg but do not rebuild HBV-specific immunity, leaving a rebound question.
Induces HBV-specific CD8+ T cells together with anti-HBs — the effectors that clear infected hepatocytes.
Pipeline
One platform, two disease areas.
CaroGen advances infectious-disease programs in-house. Oncology applications of AVIDIO™ are exclusively licensed to Viridion Therapeutics, an independent CaroGen spinout now raising its own Series A.
| Program | Indication | Discovery → Phase 2/3 | Status |
|---|---|---|---|
| CARG-201Replicating RNA immunotherapy | Chronic hepatitis B | IND authorized | |
| CARG-2020Locoregional immunotherapy | Recurrent ovarian cancer & solid tumors | Licensed to Viridion |
- Funded by ~$11.0M non-dilutive
NIH and DoD grants carried the program from discovery through IND-enabling work.
- FDA IND authorization
Clinical hold removed after additional nonclinical safety studies were submitted and reviewed.
- Phase 1/1b in HBV patients
3+3 dose escalation, single IM injection, in CHB patients on stable NUC therapy.
- Proof-of-concept data
The partnering inflection — followed by Phase 2/3 planning and combination work.
Clinical development
Phase 1/1b design — CARG-201-IN.
A dose-escalation study of a single intramuscular injection in non-cirrhotic CHB patients on NUC therapy, under IND 31717.
Study design
- 3+3 dose escalation, ~5 cohorts
- Sentinel dosing; cohort fills ≥48h later if no safety signal
- Single IM injection (prime first)
- Follow-up up to 6 months
- Serotype-switch boost considered if anti-VSV-G titers indicate
Who enrolls
- Adults 18–40, non-cirrhotic CHB
- Stable NUC regimen ≥6 months
- HBsAg 50–4,000 IU/mL; HBeAg +/–
- HBV DNA negative; ALT ≤ 2× ULN
- Excludes prior VSV-G-pseudotyped or CAR-T vector exposure
Endpoints
- Primary: safety and MTD on NUC therapy
- HBV antigen-specific T-cell response
- HBsAg / HBeAg seroconversion and titer
- Anti-HBs / anti-HBe antibody response
- ALT, HBV DNA and anti-VSV-G titers
CMC & manufacturing
Higher-titer supply to be manufactured as soon as possible.
IP & origins
Yale science, owned and developed by CaroGen.
U.S. Patent No. 12,577,585 (issued March 2026) covers both composition of matter and methods of use across infectious disease, with PCT coverage in the U.S., EU, Japan and China — protection estimated through 2040+.
Professor John Rose invented the VLV platform — the SFV replicase + VSV-G architecture at the core of CARG-201. All foundational patents trace to Yale.
Developed AVIDIO™ for infectious disease and generated all IND-enabling data. Holds U.S. Patent No. 12,577,585 — composition of matter and methods of use.
Exclusive AVIDIO™ oncology rights, as an independent spinout raising its own Series A. CaroGen retains full HBV and infectious-disease rights.
Exclusive worldwide Yale license since 2012; $30K annual maintenance royalty pre-commercial. Rose et al. PNAS (2014) 111:16866.
Leadership
Drug developers who have done this before.
200+ molecules · 50+ INDs · 15 NDAs · 30+ patents
30+ years in biopharma leadership. Formerly Vion Pharmaceuticals (Yale spin-off), Panacea, Genzyme and Genelabs. Co-inventor on the AVIDIO™ patent estate.
Principal investigator on the NIH and DoD grants funding CARG-201. Nine years on the Yale faculty; former Group Leader at VaxInnate.
38+ years in regulatory affairs; 40+ INDs filed. Approvals include ZOLINZA, Primacor and Omniscan. Secured the CARG-201 IND authorization.
20+ years in GMP biologics. Former Director at Protein Sciences (acquired by Sanofi). Oversees CARG-201 CMC and cGMP strategy.
Open role — appointment underway.
Open role — appointment underway.
Scientific founder & advisory board
Retired Professor and Director of the Program in Virology and Vaccine Development, Yale School of Medicine. Originator of the VLV platform.
Professor and Scientific Director, C.S. Mott Center for Human Development, Wayne State University. Former Yale professor.
Professor and Chair, Department of Immunology and Microbial Disease, Albany Medical College. Co-inventor of the CARG-201 prime-boost approach.
Professor, University of Connecticut. Bacterial pathogenesis, genomics and vaccines.
Professor, Department of Obstetrics and Gynecology, and Professor, Department of Oncology.
Associate Professor. Inflammation, cancer immunology and the tumor microenvironment.
Research collaborations
Governance
Board of Directors & advisors.
Board of Directors
Co-Founder of CaroGen and Viridion Therapeutics. 30+ years of biopharmaceutical leadership.
Co-Founder, President and CSO. Principal investigator on the NIH and DoD grants funding CARG-201.
Advisors
Biotech executive and entrepreneur; former CEO of CURE (Connecticut's bioscience cluster) and a long-standing leader in the state's life-sciences community.
Veteran anti-infectives and vaccines R&D leader with senior research roles across the pharmaceutical industry.
Work with us
Partners, investors and future colleagues.
CaroGen is advancing CARG-201 through Phase 1/1b and recruiting a permanent Chief Executive Officer to lead the next stage.
balmassian@carogencorp.com