Investigational Drug Candidates

Clinical Development Compounds

Bosakitug (ATI-045): Investigational Humanized Anti-TSLP Monoclonal Antibody

Potential targets: Severe asthma, chronic rhinosinusitis with nasal polyps, atopic dermatitis, COPD.

Bosakitug is an investigational, novel, humanized anti-TSLP monoclonal antibody that specifically binds to human thymic stromal lymphopoietin (TSLP) with high affinity and long residence time, blocking its interaction with the receptor complex and disrupting signal transduction. TSLP is an epithelial cell-derived cytokine expressed in skin, gut, lungs, and thymus and exerts a profound influence on the polarization of dendritic cells to drive T helper (Th) 2 cytokine production. TSLP also directly promotes T-cell proliferation in response to T-cell receptor activation and Th2 cytokine production and supports B-cell expansion and differentiation.

This mechanism prevents a broad range of immune cells targeted by TSLP from releasing proinflammatory cytokines.

Due to its ability to block the interaction of TSLP with the receptor, bosakitug has the potential to treat a variety of atopic, immunologic and respiratory diseases.

ATI-2138: Investigational Oral Covalent ITK/JAK3 Inhibitor

Potential therapeutic targets: T cell-mediated autoimmune diseases.

ATI-2138 is an investigational oral covalent ITK/JAK3 inhibitor. ITK and JAK3 are important targets in immune regulation.

ITK inhibitors target the non-receptor tyrosine kinase, ITK, within the T-cell receptor (TCR) signaling pathway, thereby interfering with the development and effector function of immune system T cells. ITK is a key signaling kinase downstream of the TCR and as such, regulates IL17 and IFNγ expression. The potential combination effect of inhibiting T cell receptors (inhibiting T cell maturation and activation) and IL17 production means an ITK inhibitor may function as a “small molecule anti-IL17”, but with broader immunomodulatory activity.

JAK3 regulates key cytokines that signal through the common gamma chain receptor such as IL2, IL4, IL7, IL9, IL15 and IL21.

A dual ITK/JAK3 inhibitor could result in additive or synergistic anti-inflammatory activity that may be beneficial in a number of autoimmune and inflammatory diseases.

ATI-052: Investigational Humanized Bi-specific Anti-TSLP and Anti-IL4R Antibody

Potential targets: various respiratory and dermatology targets.

ATI-052 is an investigational humanized anti-TSLP and anti-IL4R bispecific antibody that blocks both the upstream TSLP receptor signal transduction and downstream interleukin-4 receptor (IL4R) activation thereby inhibiting this central proinflammatory pathway. ATI-052 utilizes the same TSLP as bosakitug but is engineered to bind more tightly to FcRn, potentially extending its half-life.

ATI-052 has the potential to treat a variety of atopic, immunologic and respiratory diseases.

Lepzacitinib (ATI-1777): Investigational Soft Topical JAK1/JAK3 Inhibitor

Potential therapeutic targets: atopic dermatitis; potentially other dermatologic conditions.

Soft JAK inhibitors (ATI-1777) are designed to be topically applied and active in the skin, but may be rapidly metabolized and inactivated when they enter the bloodstream, which may result in significantly reduced systemic exposure. These tissue-restricted properties may result in efficacy with potential minimization of systemic safety issues. The JAK family of kinases are a subgroup of non-receptor tyrosine kinases that are essential in transducing signals originating from cytokine receptors. JAK inhibitors are approved to treat inflammatory and autoimmune disorders.

We are currently seeking a global development and commercialization partner for this program (excluding Greater China).

Zunsemetinib (ATI-450): Investigational Oral MK2 Pathway Inhibitor

Potential therapeutic targets: metastatic breast cancer (MBC); pancreatic ductal adenocarcinoma (PDAC).

MBC: Phosphorylated MK2 is upregulated in primary tumors and metastatic bone lesions from MBC patients. MK2 is responsible for the production of a subset of critical pro-tumorigenic factors secreted by the stromal microenvironment to support tumor growth and metastasis. Additionally, MK2 drives both metastatic and chemotherapy induced bone loss in MBC patients through, at least in part, its role in RANKL biology and osteoclast production and activation. In preclinical studies, zunsemetinib has been demonstrated to impact murine models of MBC through inhibition of tumor growth and metastasis along with bone preservation.

PDAC: Phosphorylated MK2 is highly expressed in PDAC tissue and expression levels are directly associated with poor outcomes in patients with PDAC. The current first and second line standard of care for PDAC patients is FOLFIRINOX combination chemotherapy. Irinotecan and its metabolite, SN-38, are the main drivers of cancer cell apoptosis associated with FOLFIRINOX. The effectiveness of FOLFIRINOX is limited by pro-survival resistance mechanisms that are driven through SN-38 activation of the MK2 pathway and phosphorylation of two direct MK2 substrates, HSP-27 and Beclin-1. In both patient derived xenografts and in the autochthonous genetic KPPC model of PDAC in mice, zunsemetinib has demonstrated that it blocks phosphorylation and activation of HSP-27, induces tumor cell killing and enhances the efficacy of FIRINOX (a version of FOLFIRINOX used in murine models).