Our Pipeline

While Duet is dedicated to moving our drugs into the clinic as quickly as possible, these decisions are driven by scientific results. All our development-stage programs are supported by years of rigorous research that clearly define the mechanism of therapeutic action and establish clear proof-of-principle that our drugs have the potential to significantly impact human health.

Candidate

Program/Indication

Discovery/Optimization

IND enabling

Phase 1

DUET-101

Solid Tumors

DUET-102

Glioblastoma

DUET-202

Solid Tumors & Hematological Malignancies

DUET-301

Solid Tumors & Hematological Malignancies

DUET-101

CpG-STAT3ASO for genitourinary and head & neck cancers

Mechanism of Action

DUET-101 consists of two functional elements:

An ASO-based inhibitor of STAT3 to release immunosuppression
A CpG oligonucleotide to target STAT3 inhibitor into tumor-resident myeloid cells, which then activates TLR9 to jump-start a T cell-mediated immune response

The CpG allows the bifunctional oligonucleotide to bind to scavenger receptors on the surface of the myeloid cells and B cells and be internalized into endosomes. The STAT3ASO molecule binds directly to the STAT3 mRNA, recruiting RNase H1 to degrade the STAT3 mRNA. The use of ASO permits other chemical modifications resulting in greater stability in human blood. This allows for systemic treatment of harder-to-reach solid tumors such as prostate or kidney cancers.

Rationale for genitourinary cancers

Genitourinary (GU) cancer is an umbrella term that is used to describe cancers of the male reproductive tract. These include:

Prostate cancer – prostate cancer typically affects men over 50 years old and is the second most common cancer in men. While there are multiple treatment options for early stages of prostate cancer, there are no curative treatments for patients with metastatic, hormone-independent tumors.
Bladder cancer – cancer of the bladder is the fourth most common cancer in men and typically impacts men over 55 years of age.
Kidney cancer – kidney cancer is one of the top 10 most common cancers diagnosed each year in the United States, which typically affect older men (64 is the average age of diagnosis).

While there are multiple treatment options for early stages of GU cancers, there are no curative treatments for patients with advanced, metastatic stages of these diseases. The role of STAT3 in promoting progression, metastatic spread, and tumor immune tolerance in these cancers is well established.

Rationale for head & neck cancers

Head and neck cancers are collectively known as squamous cell carcinomas (HNSCC) as they usually begin in the squamous cells, which line the mucosal surfaces of the mouth, throat, and voice box. HNSCC can begin in the sinuses, muscles or nerves of the head and neck, or salivary glands but these are relatively rare compared to squamous cell carcinomas. Heavy tobacco and alcohol use, particularly in combination, or chronic human papillomavirus (HPV) infections are significant risk factors for the development of HNSCC. The prognosis for patients with HPV-negative HNSCC is significantly worse than for patients with HPV-positive cancers with higher degree of recurrence after standard treatments such as surgery and radiation therapy.

Recent studies suggest that STAT3 plays important role especially in HPV-negative HNSCC progression and in resistance of these tumors to radiation therapy.

DUET-202

CpG-STAT3siRNA for B-cell non-Hodgkin lymphoma

Mechanism of Action

The mechanism of action for DUET-202 is similar to DUET-101 except the STAT3 inhibitor is an siRNA molecule rather than an ASO. The STAT3siRNA STAT3siRNA combines with the RISC complex and degrades STAT3 mRNA.. This allows for systemic treatment of harder-to-reach solid tumors such as prostate or kidney cancers. Furthermore, DUET-202 utilizes a lipid nanoparticle based delivery system to enhance delivery to target tissues.

Rationale for B-cell non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) is not a single disease but rather a set of dozens of different cancers that involve B or T lymphocytes. Duet is focused on diffuse large B-cell lymphoma (DLBCL) with only ~40% of 5-year overall survival even with combined chemo-immunotherapy, where more effective treatments are needed.

STAT3 is frequently upregulated in NHL and is associated with poor survival rates in patients with aggressive forms of lymphoma (e.g., DLBCL).

Duet is exploring opportunities of using DUET-01 in combination with immune checkpoint inhibitors (ICIs) for B-cell non-Hodgkin lymphoma.