The Pre-clinical Science Behind ABS-201 for Endometriosis

Endometriosis is a chronic, hormone-driven inflammatory disease where endometrial-like tissue grows and forms self-sustaining lesions outside the uterus, which can cause significant pain, ovarian cysts, scar tissue, and infertility. The standard of care is largely palliative-managing symptoms rather than modifying the disease. Up to 33% of patients do not respond to hormonal treatment alone and many patients attempting to conceive require treatment adjustment or cessation to support pregnancy. 1-3

None of the FDA-approved treatments address the underlying disease pathway. 4 Endometriotic lesions actively perpetuate their own growth by producing local prolactin that promotes self-sustained expansion, inflammation, and pelvic pain. 5,6 Targeting this loop through prolactin receptor (PRLR) blockade could offer a non-sex hormonal therapeutic approach. To explore this approach, Absci conducted a pre-clinical study to evaluate ABS-201, an AI-designed, highly selective anti-PRLR antibody, as a potentially disease-modifying therapeutic for endometriosis.

• doi: 10.1186/s12905-023-02490-1

• doi: 10.1097/GCO.0000000000000983

• doi: 10.1093/humupd/dmaa033

• doi: 10.1016/j.fertnstert.2017.05.004

• doi: 10.3389/fendo.2020.594370

• doi: 10.1016/j.pharmthera.2023.108435

Endometriosis was established in mice by transplanting uterine tissue from the donor mice into the peritoneal cavity of recipient mice (homologous transplant), replicating the key features of human disease. Two weeks after lesion establishment, mice received one of four treatments over four weeks: an inactive control antibody (IgG1), ABS-201, or a gonadotropin-releasing hormone (GnRH) modulator used as a hormonal comparator.

Assessments and Analysis:

• Non-evoked pain: Assessed by measuring the spontaneous distance traveled, as a surrogate to pain measurement.

• Evoked pain: Assessed using Von Frey filament testing, standard method for assessing mechanical pain thresholds

• Inflammation: Assessed by measuring inflammatory cytokines in peritoneal fluid using a method called ELISA.

In a homologous transplant mouse model of endometriosis, ABS-201 treatment demonstrated significant reductions in both spontaneous and evoked pain behaviors, alongside significant suppression of key inflammatory cytokines in the peritoneal fluid.

For spontaneous (non-evoked) pain , mice treated with ABS-201 moved significantly more than untreated disease controls ( P =0.001, one-way ANOVA), a well-established indicator of reduced pelvic pain, 1 reaching levels comparable to a leading hormonal therapy used as a benchmark.

For touch-triggered (evoked) pain, untreated disease mice showed markedly heightened sensitivity compared to healthy controls. ABS-201-treated mice recovered significantly ( P =0.0003, one-way ANOVA), with far greater tolerance to touch, matching the hormonal comparator.

• doi: 10.1093/molehr/gaaf023

• doi: 10.1093/molehr/gaaf023

The team measured three key inflammatory cytokines TNFα, IL-1β, and CCL2, known to be elevated in endometriosis patients and are closely linked to lesion growth, immune cell recruitment, and pain signaling. These inflammatory cytokines were significantly reduced in mice treated with ABS-201 compared to untreated disease control (P<0.0001, one-way ANOVA).

In a preclinical endometriosis model, ABS-201 significantly reduced spontaneous and evoked pain and meaningfully suppressed the inflammatory signals driving disease progression-without altering the hormonal axis.

Absci won the Best Poster award for this study at the 2026 Society of Endometriosis and Uterine Disorders Congress