Novel bispecific oligonucleotide therapeutics for the treatment of chronic inflammation/allergy
DTI Inc.

Research and Development

Pioneering Microenvironmental Resolution in Immunology and Beyond

Dual Targets, Inc. (DTI) is a Tokyo-based private biotech company advancing a proprietary platform of first-in-class bispecific RNA oligonucleotides (BSOs). We aim to shift the treatment paradigm for chronic inflammatory, allergic, and autoimmune diseases by targeting the critical vascular prerequisite for chronicity: the specialized vascular gateways of the tissue microenvironment.

Beyond Cytokine Suppression: Modulating the Vascular & Tissue Microenvironment

Chronic inflammation causes progressive tissue destruction and severe clinical symptoms. Currently available treatments—including topical steroids, calcineurin inhibitors, PDE4/JAK inhibitors, and systemic biologics (e.g., TNF-a, IL-17, IL-23)—primarily focus on suppressing downstream cytokines (refs 1,2).
However, they do not disrupt the structural architecture that maintains chronic inflammation. Ectopic High Endothelial Venules (HEVs) develop in chronic lesions, acting as specialized vascular “gateways” that drive the continuous infiltration and accumulation of effector T cells, resident memory T cells (TRM), and plasmacytoid DCs (pDCs) into the tissue (refs: 3-7). When systemic therapies are paused, these vascular gateways remain active, probably leading to inevitable relapse and secondary loss of response (LOR) to systemic biologics.

The Dual Targets Platform: Simultaneous Spatial-Temporal Blockade

Our lead asset, DS-06, represents a breakthrough in targeted oligonucleotide therapy by blocking leukocyte trafficking at its origin. The synthesis of L-selectin ligands (PNAd) on HEVs—which allows immune cells to tether, roll, and home into inflamed skin—relies on a highly coordinated, step-by-step enzymatic cascade involving specific carbohydrate sulfotransferases (refs: 8,9).
Unlike conventional single-target approaches, DTI’s unique proprietary bispecific design is engineered to simultaneously bind and silence both CHST2 and CHST4 mRNAs in both time and space. This unprecedented “Simultaneous Spatial-Temporal Blockade” completely collapses the ligand synthesis pathway on endothelial cells, physically shutting down the pathogenic cellular supply line at the vascular gateway level.

“Pipeline-in-a-Product” for Dermatology

Topically applied DS-06 cream has shown effective penetration of artificial dermal membranes without triggering non-specific IFN/TLR signaling. By aiming to effectively block T cell and pDC migration at the HEV gateway, DS-06 holds the potential to offer a highly differentiated pipeline-in-a-product opportunity across four major indications (refs: 4-7):

  • Atopic Dermatitis (AD): Microenvironment Resolution for Refractory Lichenification
    Designed to act on stubborn, thickened plaques where standard topicals fail to resolve chronic leukocyte infiltration. Supported by in vivo models—where DS-06 demonstrated superior inflammation control compared to tacrolimus, robustly reducing HEV-like vessels and dermal infiltrating CD4+ T cells—this approach aims to fundamentally restore the local microenvironment.
  • Psoriasis: Relapse Prevention & LOR Booster
    Positioned as a potential proactive maintenance therapy post-biologic clearing. By blocking de novo HEV formation, it is hypothesized to prevent TRM reactivation and new immune cell influx, offering a promising pathway to true localized disease modification to prevent relapse.
  • Cutaneous Lupus Erythematosus (CLE): Systemic-Sparing Therapy
    A first-in-class topical concept engineered to selectively shut down pDC homing through the vascular endothelium, offering a potential powerful alternative to high-risk oral immunosuppressants for deep active lesions.
  • Bullous Pemphigoid: Steroid-Sparing Adjuvant
    Envisioned as a potent, non-steroidal topical adjuvant. It is hypothesized to provide critical efficacy to reduce fatal infection risks associated with systemic high-dose steroids by cutting off the vascular recruitment of eosinophils and T cells, with the goal of entirely avoiding the skin atrophy caused by super-potent topical steroids in vulnerable elderly populations.

Platform Expansion: From Immunology to Oncology

The potential of DTI’s proprietary bispecific oligonucleotide platform extends far beyond dermatology. The ability to execute a simultaneous spatial-temporal blockade of dual targets positions our platform to address one of the most highly sought-after frontiers in Oncology: Synthetic Lethality (ref 10).
Current approaches to synthetic lethality often rely on combination therapies, which are frequently hindered by mismatched pharmacokinetics and overlapping systemic toxicities. DTI’s single-molecule bispecific design overcomes these hurdles by perfectly synchronizing the knockdown of two redundant or compensatory survival pathways within the exact same tumor cell.
We are actively exploring the application of our bispecific RNA technology to induce targeted synthetic lethality. DTI is seeking strategic pharmaceutical partners to accelerate our lead asset toward the clinic, and to co-explore the vast potential of our bispecific platform across diverse oncology and immunology pipelines.

References:

  1. Bieber T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov. 2022 Jan;21(1):21-40.
  2. Yuan M, Lee J, Taylor M, Cho RJ, Cheng JB. Advancing Precision Medicine in Inflammatory Skin Disease. Am J Clin Dermatol. 2025 Nov;26(6):853-861.
  3. Streeter PR, Rouse BT, Butcher EC. Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes. J Cell Biol. 1988 Nov;107(5):1853-62.
  4. Blanchard L, Girard JP. High endothelial venules (HEVs) in immunity, inflammation and cancer. Angiogenesis. 2021 Nov;24(4):719-753.
  5. Budair FM, Nomura T, Hirata M, Kabashima K. PNAd-expressing vessels characterize the dermis of CD3+ T-cell-mediated cutaneous diseases. Clin Exp Immunol. 2024 Mar 12;216(1):80-88.
  6. Kogame T, Kabashima K, Egawa G. Putative Immunological Functions of Inducible Skin-Associated Lymphoid Tissue in the Context of Mucosa-Associated Lymphoid Tissue. Front Immunol. 2021 Aug 26;12:733484.
  7. Hashizume H, Horibe T, Yagi H, Seo N, Takigawa M. Compartmental imbalance and aberrant immune function of blood CD123+ (plasmacytoid) and CD11c+ (myeloid) dendritic cells in atopic dermatitis. J Immunol. 2005 Feb 15;174(4):2396-403.
  8. Yeh JC, Hiraoka N, Petryniak B, Nakayama J, Ellies LG, Rabuka D, Hindsgaul O, Marth JD, Lowe JB, Fukuda M. Novel sulfated lymphocyte homing receptors and their control by a Core1 extension beta 1,3-N-acetylglucosaminyltransferase. Cell. 2001 Jun 29;105(7):957-69.
  9. van Zante A, Rosen SD. Sulphated endothelial ligands for L-selectin in lymphocyte homing and inflammation. Biochem Soc Trans. 2003 Apr;31(2):313-7.
  10. Ueda K, Yamada Y, Tanaka H, Sato T, Sasaki J, Sakamoto S, Minomi K, Yamada H, Sugimoto M. A novel bispecific siRNA concept: Efficient dual knockdown of YAP1 and WWTR1 with a single guide strand. Mol Ther Nucleic Acids. 2025 Nov 10;36(4):102768.