Precision Biologics to Present at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 1st, 2024

BETHESDA, Md., May 30, 2024 /PRNewswire/ -- Precision Biologics, Inc. reports that novel findings from its ongoing phase 2 clinical trial, combining NEO-201 with pembrolizumab for the treatment of patients resistant to prior checkpoint inhibitor therapy, will be presented in a poster at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting, McCormick Place Convention Center, Chicago, Illinois, USA, June 1(st), 2024.

Poster title: Reduction of circulating naïve Tregs and gMDSCs and low levels of soluble MICA are prognostic for efficacy of combined NEO-201 and pembrolizumab

Presentation of the poster in person will be made at the McCormick Place Convention Center in Chicago, Illinois, USA, on Saturday June 1(st), 2024, Hall A from 9am - 12pm, Session: Developmental Therapeutics-Immunotherapy, poster board #9, poster # 2530.

BACKGROUND:

    --  The employment of immune checkpoint inhibitors (ICIs), such as
        pembrolizumab (anti-PD-1 mAb), in cancer immunotherapy has been shown to
        enhance activity of the immune system against cancer cells.

    --  Although ICIs show efficacy and improved survival of certain cancer
        patients, the response rate of PD-1/PD-L1 blockade against solid tumors
        is around 20-30% in the first line setting and significantly lower in
        checkpoint refractory disease. One cause identified for this low
        response rate is the infiltration of the tumor microenvironment (TME) by
        immunosuppressive cells, such as regulatory T cells (Tregs) and
        granulocytic myeloid-derived suppressor cells (gMDSCs). The accumulation
        of these immunosuppressive cells in the TME impairs the antitumor
        immunity triggered by ICIs.

    --  A strategy to restore antitumor immunity and overcome tumor resistance
        to ICIs is to combine ICIs with anticancer drugs able to bind to and
        deplete Tregs and gMDSCs.

    --  NEO-201 is a humanized IgG1 monoclonal antibody that binds to Core 1
        and/or extended Core 1 O-glycans expressed by several human solid and
        blood tumors, as well as mature granulocytes, but it does not bind to
        most normal tissues and human immune cell subsets (B cells, CD4(+) T
        cells, CD8(+) T cells, NK cells, monocytes). Previous studies showed
        that NEO-201 can bind and mediate the killing of Tregs via CDC. Further
        studies presented at AACR in 2023 showed that NEO-201 can bind and
        mediate the killing of gMDSCs via ADCC.

    --  The ability of NEO-201 to mediate the killing of immunosuppressive cells
        served as the rationale for combination of NEO-201 with pembrolizumab in
        the ongoing phase II clinical trial (NCT03476681) for the treatment of
        patients with NSCLC, head and neck, cervical and endometrial cancers who
        were refractory to multiple lines of standard treatment, including ICIs.
    --  Preliminary findings from this ongoing clinical trial presented at the
        CRI-ENCI-AACR in September 2023 in Milan, Italy and at the SITC annual
        meeting in November 2023 in San Diego, CA, USA, revealed that, after
        combination treatment with NEO-201 and pembrolizumab some patients
        experienced durable stable disease (SD). Patients with durable SD (>84
        days) demonstrated a decreasing trend in circulating gMDSCs and Tregs.
        Conversely, patients with progressive disease (PD) exhibited an
        increasing trend of circulating gMDSCs and Tregs. This preliminary data
        suggests that elimination of circulating gMDSCs and Tregs mediated by
        NEO-201 may enable patients to overcome resistance to PD-1/PD-L1
        checkpoint inhibitors, in subjects for whom pembrolizumab is currently
        indicated and with solid tumors resistant to prior ICIs treatment.

STUDY PRESENTED AT ASCO 2024:

    --  NEO-201 uses Natural Killer (NK) cells as effector cells to mediate the
        killing of its target cells through ADCC. Several studies reported that
        cancer cells inhibit NK cell antitumor activity by releasing soluble
        factors into the bloodstream, such as soluble MHC class 1 chain-related
        protein A (MICA.) Elevated serum levels of soluble MICA (sMICA) have
        been correlated with impairment of NK cell activity, cancer progression
        and metastasis.

    --  This study reports that median serum levels of sMICA pre-treatment were
        33-fold higher in patients with PD compared to patients with SD and that
        levels of sMICA remained elevated in patients with PD and low in
        patients with SD at all time points post treatment.

    --  High levels of sMICA in patients with PD can impair NK cell activity.
        This impairment negatively impacts the NK cell mediated ADCC triggered
        by NEO-201 against cancer cells, Tregs and gMDSCs. Consequently, the
        effectiveness of NEO-201 and pembrolizumab treatment is reduced, leading
        to disease progression in these patients.

    --  Conversely, low levels of sMICA pre- and post-treatment do not hinder
        the antitumoral activity of NK cells. This allows NEO-201 to effectively
        mediate the killing of its target cells, including cancer cells, Tregs
        and gMDSCs, through ADCC. As a result, this phenomenon can lead to the
        durable stabilization of the disease.
    --  This study reports that low levels of sMICA, together with the reduction
        of both circulating Tregs and gMDSCs mediated by NEO-201, were
        associated with durable SD in cancer patients refractory to prior ICIs
        and that they could be favorable prognostic markers for clinical benefit
        following combination treatment with NEO-201 and pembrolizumab. Ongoing
        enrollment in this clinical trial will validate these findings in larger
        cohorts.

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SOURCE Precision Biologics