Pregena is developing AAC-T (Activated Autologous Cell Therapy), a first-in-class immunomodulatory approach to improve IVF outcomes using the patient's own immune cells.
The Global Crisis
The World Health Organization estimates that 186 million people are affected by infertility globally. The global demand for baby (the number of babies desired but not yet conceived) is estimated at 130 million.
The driving force: later parenthood. The average age of first birth has risen to 31 in the US and continues climbing globally. Female fertility declines significantly after 35. By age 40, approximately 90% of a woman's ovarian reserve has been depleted, and the remaining oocytes have higher rates of chromosomal abnormalities.
This isn't a lifestyle choice problem. It's a demographic reality. As societies develop, birth ages rise, and the gap between when people want children and when biology cooperates continues to widen.
Demand for Baby
An estimated 130 million babies are desired worldwide each year, representing the global demand for baby. Of those born, 500,000 are now conceived through IVF, from 2.5 million cycles performed annually across thousands of clinics worldwide.
In developed nations, 2-3% of all births already rely on assisted reproductive technology, and that percentage is rising fast. In Denmark, it's over 10%. As the average age of first birth continues to climb, more couples will need help conceiving.
This is a structural shift, not a trend. The demand for effective fertility treatment is growing in lockstep with demographic change, creating an expanding market with a critical unmet need.
Reproductive Success Rates
Nearly two-thirds of IVF cycles fail. The average couple undergoes 5 cycles and spends $60,000 to $100,000+ before either succeeding or giving up entirely.
Over half of couples drop out of IVF before achieving pregnancy. Not because treatment couldn't eventually work, but because the emotional, physical, and financial toll of repeated failure is simply too high.
The bottleneck is implantation failure. Modern IVF has optimized egg retrieval, fertilization, and embryo culture. But when a genetically normal embryo is transferred to a prepared uterus, it still fails to implant the majority of the time.
The reason: the maternal immune system. Successful implantation requires a precisely orchestrated immune cascade, a shift from rejection to tolerance. When this cascade is disrupted, the endometrium rejects the embryo. No approved therapy exists to address this.
The Solution
A first-in-class immunomodulatory cell therapy that uses the patient's own immune cells to prepare the uterine environment for embryo implantation.
What it is: AAC-T is an autologous cell therapy. The patient's own peripheral blood mononuclear cells (PBMCs) are drawn from a standard blood sample, activated with human chorionic gonadotropin (hCG), and delivered to the uterine cavity before embryo transfer.
How it works: The activated immune cells reprogram the uterine environment from rejection to tolerance. They coordinate six biological pathways simultaneously: immune tolerance, endometrial receptivity, vascular remodeling, trophoblast invasion, trophoblast support, and progesterone enhancement, creating the conditions the embryo needs to implant.
Why it's different: Previous approaches tried to solve implantation with drugs. They all failed. AAC-T works with the body's own immune system, the same mechanism that enables natural pregnancy. It is autologous (no rejection risk), requires no immunosuppression, and integrates into existing IVF protocols with zero disruption.
Patient Groups
RIF · 3+ Failed Transfers
The most clinically validated population for AAC-T. These patients have transferred 3+ genetically normal embryos without successful implantation. Meta-analysis shows 2.12x clinical pregnancy rate in this group.
AMA · The Majority of IVF Cycles
Women over 35 represent the largest segment of IVF patients. Age-related immune dysregulation contributes to implantation failure beyond just egg quality. AAC-T addresses the endometrial immune environment that declines with age.
Cryo-FET · Growing Rapidly
Frozen embryo transfers now outnumber fresh cycles in many countries. Without the natural hormonal priming of a stimulated cycle, the endometrium may be less receptive. AAC-T prepares the immune environment for cryo-transferred embryos.
Mechanism of Action
hCG-primed PBMCs shift the local immune environment from rejection (Th1/Th17) to tolerance (Th2/Treg), producing a 3-fold increase in Th2 cells and a 4-fold increase in regulatory T cells. Measurable Th17/Treg ratio correction (0.814 → 0.559, p<0.0001) creates conditions favorable for semi-allogeneic embryo acceptance.
Activated cells secrete a coordinated cytokine cascade (IL-6, LIF, IL-1β) that promotes endometrial receptivity. Downregulation of estrogen receptor-α removes the molecular blockade on integrin αvβ3 expression, enabling embryo attachment. 182 dysregulated genes normalized in RNA-seq analysis.
VEGF and angiogenic factors secreted by primed PBMCs activate the miR-126-3p/PI3K/Akt/eNOS signaling cascade, enhancing uterine blood flow, spiral artery development, and new microvessel formation critical for supporting early implantation and placental formation.
Activated PBMCs release soluble factors that increase trophoblast invasion 2.8-fold (p<0.05) through upregulation of MMP-2, MMP-9, and VEGF while suppressing TIMP-1 and TIMP-2. Chemoattractant signaling guides the embryo to the implantation site via integrin-mediated pathways.
Growth factor secretion (HB-EGF, TGF-β, LIF) supports early trophoblast invasion and placental development. Conditioned media from activated PBMCs is sufficient to drive invasion without cell-to-cell contact, confirming a paracrine mechanism.
Th2 cytokines (IL-4, IL-10) produced by immune remodeling act on the corpus luteum to enhance progesterone production 2.5-fold (9.32 vs 3.80 ng/mL, p=0.00001). Progesterone maintains the endometrial lining through early pregnancy, representing a hormonal feedback axis from the immune cascade.
hCG-activated PBMCs trigger an immune cascade that shifts the uterine environment from rejection to tolerance. Th2/Treg cells increase 3-4x, endometrial receptivity genes normalize, and vascular remodeling enables embryo implantation. The result: a 2.12x improvement in clinical pregnancy rate across RCTs with zero heterogeneity.
The Process
AAC-T integrates seamlessly into existing IVF protocols with minimal disruption to the clinical workflow.
Standard peripheral blood collection from the patient
PBMCs isolated and primed with human chorionic gonadotropin for 48-72 hours
Activated cells delivered directly to the uterine cavity 2-3 days before transfer
Standard IVF embryo transfer into optimally prepared endometrium
Clinical Evidence
18.8% → 40.3%
2.12x relative improvement (Chow 2025, 6 RCTs)RR 1.93
~93% relative improvement2.12 to 3.57
p < 0.001 (meta-analyses)CPR = Clinical Pregnancy Rate · LBR = Live Birth Rate · OR = Odds Ratio · RR = Relative Risk
PBMC consistently ranked #1-3 for CPR across all network meta-analyses of intrauterine therapies for RIF.
AAC-T has more clinical data than any other therapy for improving IVF implantation: 80+ published studies, 9,000+ patients, 18 controlled trials, 16 meta-analyses, and a 2.12x improvement in clinical pregnancy rate with zero serious adverse events.
No competing approach comes close.
ESHRE noted insufficient evidence in 2023. Since then, 4 new meta-analyses confirm benefit. Chow 2025 explicitly argues the guidelines were "based on outdated systematic reviews." RCT-only evidence now shows RR 2.12 with zero heterogeneity.
Interactive Clinical Data
All 18 controlled clinical trials with patient-level data · 2,588 patients
Clinical pregnancy rates: control groups vs. AAC-T treatment groups.
Key Publications
Journal of Reproductive Immunology. Gold-standard PBMC meta-analysis. CPR RR 1.92, LBR RR 1.93 (I²=2%).
Scientific Reports (Nature). PBMC achieves Moderate GRADE for both CPR and LBR. Highest evidence quality among immunotherapies.
Journal of Reproductive Immunology. Protocol optimization: 48h culture = OR 5.13 vs 24h = OR 2.26.
Journal of Reproductive Immunology. NMA: PBMC ranked #2 of 6 therapies for CPR, essentially equivalent to PRP (OR 0.98).
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 NMA: PBMC one of only two therapies improving live birth.
Human Reproduction. First clinical application. 52.9% vs 15.4% CPR in RIF 5+ group.
American Journal of Reproductive Immunology. n=633. 4+ failures: 4.81× CPR improvement (P<0.01).
Journal of Reproductive Immunology. DB-RCT, Th17/Treg ratio 0.814→0.559, 42% vs 22% CPR.
Immuno. First endometrial tissue biomarker study, 70 RIF patients.
Reproductive Medicine and Biology. RCT, miRNA regulation, 100 RIF patients.
Journal of Clinical Endocrinology & Metabolism. Mannose receptor/NF-κB pathway discovery. Foundation for hCG-PBMC mechanism.
Journal of Reproductive Immunology. Th1→Th2/Treg characterization, 157 women. Immune shift quantification.
Cell Communication and Signaling. RNA-seq analysis, 869 genes analyzed, 182 normalized. Transcriptomic validation.
Kaohsiung Journal of Medical Sciences. miR-126-3p/PI3K/Akt/eNOS vascular cascade discovery.
Industry Investment
Top-tier venture capital firms have invested nearly a billion dollars trying to improve IVF outcomes. None succeeded. None used immunomodulatory cell therapy.
| Company | Capital Raised | Status | Patients Studied | Notes |
|---|---|---|---|---|
 Pregena |
Private | Active | 9,000+ | Industry-leading data, safety, and efficacy. 2.12x CPR, 0 SAEs, 25 patents. |
 |
$127M | Active | 40 | Phase 3 (Jan 2025). Only 40 patients studied. |
 |
$65M | Active | 0 | Phase 2 (May 2025). 0 published patients. Licensed ObsEva assets. |
 |
$228M | Failed | 91 | Wrong biology. Reverse merger 2018. |
 |
$384M | Failed | 1,700+ | Nolasiban. 7% improvement insufficient. NDA withdrawn. Wind-down 2024. |
 |
$52M | Failed | N/A | RESPONSE trial: no benefit vs placebo (BMJ 2019). |
| Total | $856M+ | Excludes Pregena (private) |
Clinical Trial Partnerships
Advancing through partnerships with leading reproductive medicine centers. An asset-light model that leverages existing clinical infrastructure and investigator expertise.
Evaluating 361 HCT/P pathway for minimally manipulated autologous cell product classification, which could significantly reduce regulatory timeline versus full BLA.
Leadership
Assembling world-class expertise across clinical development, reproductive immunology, and cell therapy manufacturing.
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.
Get in Touch
We are advancing AAC-T toward FDA approval through a U.S. Phase 2 clinical trial with 120 RIF patients and an 18-month readout. Partnering with leading reproductive medicine centers.