Pregena is developing AAC-T (Activated Autologous Cell Therapy), an immunomodulatory cell therapy to improve IVF outcomes using the patient's own immune cells.
Evaluated in 4,215 patients across 28 independent clinical studies.
Clinical Data
Seven controlled clinical studies in RIF patients (3 or more prior failed embryo transfers): AAC-T (PBMC activated with hCG) versus control.
Pooled controlled studies · PBMC activated with hCG · p < 0.001
The Unmet Need
Infertility affects 1 in 6 people worldwide (World Health Organization). Despite continued advances in IVF, approximately two-thirds of embryo transfers fail to achieve clinical pregnancy. Recurrent Implantation Failure (RIF), commonly defined as 3 or more prior failed embryo transfers, affects up to 15% of IVF patients.
Successful embryo implantation depends on bi-directional maternal-fetal crosstalk during the window of implantation, involving maternal immune cell modulation, endometrial vascular and extracellular matrix remodeling, and trophoblast invasion.
The Therapy
An immunomodulatory cell therapy that uses the patient's own immune cells to support embryo implantation.
What it is: AAC-T uses autologous peripheral blood mononuclear cells (PBMCs) activated ex vivo with human chorionic gonadotropin (hCG) and administered via intrauterine infusion prior to embryo transfer. It was first published by Yoshioka et al. in 2006.
How it works: hCG is the embryo's earliest natural implantation signal. hCG-activated PBMCs initiate a coordinated cytokine and cellular response that supports the immunological cascade required for embryo implantation.
How it is delivered: AAC-T is autologous and is delivered through a four-step protocol within the patient's IVF cycle.
Mechanism of Action
AAC-T primes the uterine environment for embryo implantation by restoring the controlled inflammatory signaling shown to be deficient in RIF patients during the implantation window. In treated patients, Th17 and natural killer cell frequency rise and regulatory T cell frequency falls, restoring the inflammatory tone required for embryo recognition (Abdolmohammadi-Vahid et al., 2025, Reproductive Medicine and Biology).
Paracrine factors released by hCG-activated PBMCs support tissue and vascular remodeling at the endometrial implantation surface. In human trophoblast cell models, hCG-activated PBMCs increase MMP-2, MMP-9, and VEGF expression and decrease TIMP-1 and TIMP-2, supporting extracellular matrix remodeling and angiogenic signaling at the implantation site (Yu et al., 2015, PLOS ONE).
Peripheral blood mononuclear cells include the monocyte, T helper, regulatory T cell, and natural killer subsets that govern maternal-fetal tolerance, endometrial receptivity, and trophoblast invasion.
Human chorionic gonadotropin is the embryo's earliest natural implantation signal. It activates PBMCs and elicits a coordinated cytokine response that prepares the maternal immune environment for implantation.
The Process
AAC-T is delivered within the patient's IVF cycle.
Peripheral blood is collected by routine venipuncture during the standard IVF workflow
PBMCs are isolated and activated ex vivo with human chorionic gonadotropin
Activated cells are administered by intrauterine infusion prior to embryo transfer
Standard embryo transfer proceeds as normal
Patient Groups
Primary Indication
Commonly defined as 3 or more prior failed embryo transfers. This is the patient group evaluated in the controlled clinical studies of AAC-T.
Target Patient Group
Advanced maternal age is an identified target patient group for AAC-T.
Target Patient Group
Frozen embryo transfer cycles are an identified target patient group for AAC-T.
Key Publications
Journal of Reproductive Immunology. PBMC meta-analysis of eight studies. CPR RR 1.92, LBR RR 1.93 (I²=2%).
Scientific Reports (Nature). PBMC achieves Moderate GRADE for both CPR and LBR.
Journal of Reproductive Immunology. Seven studies, 1,173 patients. CPR OR 3.43, LBR OR 2.79.
Journal of Reproductive Immunology. Network meta-analysis of 21 studies, 2,917 patients: PBMC significantly improved clinical pregnancy versus control.
International Journal of Reproductive BioMedicine. Most current meta-analysis. RCT-only RR 2.12, I²=0%. Argues ESHRE guidelines outdated.
Journal of Assisted Reproduction and Genetics. RCT-only network meta-analysis of 25 studies, 3,035 patients: PBMC significantly improved clinical pregnancy versus control.
Human Reproduction. First clinical application. 41.2% vs 11.1% CPR in patients with 4+ failed transfers.
Journal of Reproductive Immunology. n=633. 4+ failures: 39.6% vs 14.3% CPR.
Journal of Reproductive Immunology. Double-blind randomized controlled trial. 42% vs 22% clinical pregnancy rate.
Immuno. Endometrial immune compartment study in 70 RIF patients.
Reproductive Medicine and Biology. Controlled clinical trial, miRNA regulation, 100 RIF patients.
Journal of Clinical Endocrinology & Metabolism. hCG activates monocytes through C-type lectin recognition.
Cell Communication and Signaling. Preclinical implantation-failure model: hCG-activated PBMCs increased implantation sites.
Kaohsiung Journal of Medical Sciences. miR-126-3p/PI3K/Akt/eNOS vascular signaling cascade.
Regulatory Pathway
AAC-T has a defined regulatory pathway as a Section 351 biologic. A clinical trial protocol and a cGMP-compliant manufacturing process have been developed in preparation for an Investigational New Drug (IND) application.
Team
Founder and Chairman of White Rhino Ventures, an impact-venture firm that develops, funds, and operates ventures addressing global challenges. More than a decade of capital markets experience leading investments across venture equity, private placements, and complex deal structuring. Track record of translating breakthrough science to traditional markets, leading institutional due diligence, and executing corporate turnarounds. Expertise in regulatory strategy, business development, and building high-performance teams from concept through commercialization.