Cullinan Oncology employs a modality-agnostic approach to develop targeted therapeutics, focusing on high-impact targets across various cancer and autoimmune diseases. Their research model emphasizes collaboration with academic and industry partners, which enhances the discovery of innovative therapies. The company has built a diversified pipeline that includes clinical-stage assets designed to inhibit key disease drivers or leverage the immune system to eliminate diseased cells. Their portfolio features a range of modalities, including T cell engagers and monoclonal antibodies, aimed at creating first- or best-in-class treatment options.

The company’s pipeline includes promising candidates such as CLN-978, a CD19xCD3 T cell engager for systemic lupus erythematosus and rheumatoid arthritis, and CLN-619, an anti-MICA/B antibody for pan-cancer applications. Additionally, they are exploring early-stage programs like T cell receptor-based constructs and novel protein degraders targeting immune regulation. Cullinan Oncology's rigorous development criteria ensure that only the most promising assets progress through clinical trials, ultimately aiming to deliver transformative therapeutics that prioritize patient benefit.

United States

Cullinan Oncology is advancing a growing portfolio of innovative, early-stage clinical therapeutic assets by capitalizing on the latest scientific breakthroughs. We combine a unique portfolio model with innovative sourcing techniques and drug development expertise to discover and advance candidates for potentially transformative oncology drugs.

Cancer

Hematologic Diseases

Lung Diseases

Lymphatic Diseases

Cullinan Oncology

Non-small cell lung carcinoma

Zipalertinib

Acute myeloid leukemia

Relapsed/refractory acute myeloid leukemia

CLN-049&nbsp;is a humanized bispecific antibody being developed for relapsed/refractory AML. CLN-049&nbsp;is designed to simultaneously bind to FLT3 on target leukemic cells and to CD3 on T cells, triggering the T cells to kill the targeted cancer cells via their intrinsic cytolytic mechanisms. Studies have shown that FLT3 is expressed by FACS staining on AML blasts in at least 75% of AML patients, regardless of an oncogenic driver mutation. The expression of FLT3 on the surface of leukemic blasts in most AML patients and its role as a known oncogenic driver make it an attractive therapeutic target for a T cell engager approach.
In preclinical studies, CLN-049&nbsp;led to potent FLT3-dependent killing of leukemic cells&nbsp;in vitro&nbsp;at a wide range of FLT3 expression levels on AML cells. Treatment with CLN-049, even at low doses, led to survival benefit in an AML xenograft model and complete elimination of leukemic blasts in various mouse models implanted with primary patient leukemic cells or AML cell lines.

CLN-049 (FLT3xCD3)

Solid tumor/s

CLN-619 is a humanized IgG1 monoclonal antibody that binds to MICA and MICB expressed on a wide variety of cancer cells. MICA/B are stress-induced ligands that are recognized by both cytotoxic innate and adaptive immune cells via their NKG2D receptor. To evade lysis by these immune cells, tumor cells shed MICA/B from their cell surface. CLN-619 promotes an antitumor response through multiple mechanisms of action, including prevention of the proteolytic release of MICA/B from cancer cells, antibody-dependent cell-mediated cytotoxicity, or ADCC, enhancement of MICA/B binding to NKG2D, and reduction of the inhibitory effect of shed MICA/B.
In preclinical studies, animals treated with CLN-619 as a monotherapy demonstrated significant inhibition of tumor growth and a dramatic reduction of serum levels of soluble MICA. Multiple studies evaluating serum samples from cancer patients have demonstrated that high serum levels of shed MICA correlate with a poor prognosis.

CLN-619 (MICA/B) +/- pembrolizumab

CLN-081 is an orally available, irreversible EGFR inhibitor that is designed to selectively target cells expressing mutant EGFR variants, including EGFR exon 20 insertion mutations, with relative sparing of cells expressing wild type EGFR. CLN-081 is currently in a Phase 1/2a dose escalation and expansion trial evaluating oral, twice-daily administration of various doses in patients with NSCLC harboring EGFRex20ins mutations who have had at least one prior treatment with platinum-based chemotherapy or another approved standard therapy. CLN-081 is being developed in Cullinan Pearl, a Cullinan subsidiary.

Blood cancer

Non-Hodgkin lymphoma

CLN-978 is a fully human, half-life extended, single-chain T cell-engaging trispecific antibody construct targeting CD19, CD3 and human serum albumin (HSA) for B cell malignancies.
CD19 is a clinically and commercially validated target in B-NHL via multiple modalities, including T cell antibodies (TCEs), CAR-T cells, and monoclonal antibodies.
CLN-978 contains two targeting domains comprised of single-chain variable fragments (scFv), one recognizing CD19 on malignant cells with high affinity and the other one recognizing CD3 on T cells.
CLN-978 resembles the BiTE format but, in addition, contains a single domain antibody (VHH) binding to HSA to increase the molecule’s serum half-life.
CLN-978 redirects and activates T cells—which are transiently tethered to target cells—to destroy cancer cells via T cell mediated cytotoxicity. This interaction is dependent on the presence of CD19 on target cells.

CLN-978 (CD19xCD3)

CLN-617 is a potential first-in-class cytokine therapy comprised of two potent and synergistic antitumor cytokines, IL-2 and IL-12, in a single molecule. The molecule is intended for intratumoral injection and employs collagen-binding and size-enhancing domains designed to retain the CLN-617 molecule inside the tumor and thereby enhance efficacy and reduce toxicity. While CLN-617 is injected and retained locally in the tumor, it directs a broad immune response that may help eradicate not only the injected tumor, but also attack distant tumor sites, as observed in preclinical studies. Preclinical studies have also demonstrated the potential for enhanced efficacy when CLN-617 is combined with checkpoint inhibitor therapy. Cullinan plans to evaluate CLN-617 in a Phase 1 clinical trial in patients with advanced solid tumors.

CLN-617 (IL-2 and IL-12) +/- pembrolizumab

Multiple myeloma

CLN-619 (MICA/B)

Autoimmune disease

Systemic lupus erythematosus

Sjögren’s Disease

CLN-978 is a novel, differentiated and highly potent CD19xCD3 bispecific T cell engager. CLN-978 triggers redirected lysis of CD19-expressing target cells in vitro and in vivo. CLN-978 is engineered to achieve very high affinity binding to CD19 to efficiently target B cells, including those with very low CD19 levels. Small in molecular size (65 kDa), CLN-978 contains two single-chain variable fragments, one binding with very high affinity to the CD19 target and the other binding to CD3 on T cells, and a single-domain antibody binding to human serum albumin to extend serum half-life. CLN-978 was developed by an internal Cullinan team and is a wholly owned asset. CLN-978 has the potential to offer a convenient, off-the-shelf, subcutaneously delivered therapeutic option for patients with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren’s disease.

Rheumatoid arthritis

CLN-418/HBM7008 is the only B7H4 x 4-1BB bispecific immune activator in clinical studies. Both B7H4 and 4-1BB have been targets of high interest and both have been evaluated clinically. Their distinct biology and mechanisms of action provide strong rationale to combine them as a bispecific antibody. B7H4 is an attractive tumor associated antigen (TAA) highly expressed on multiple tumor types, including triple negative breast cancer, ovarian cancer and lung cancer, while expression on normal tissue is low. A coinhibitory immune checkpoint with PD-L1 in the B7 family, B7H4 has minimal overlap with PD-L1 expression. Targeting B7H4 has the potential to address tumor types for which PD-L1-based immunotherapies have exhibited limited efficacy.
4-1BB is a key costimulatory molecule for both T- and NK-cell engagement and is being studied in multiple clinical programs. However, safety concerns such as hepatic toxicity remain despite the biological validation of the 4-1BB pathway. Conditional activation of 4-1BB in the tumor microenvironment that is dependent on B7H4 expression presents a novel approach to harness the potential of both targets. CLN-418/HBM7008, with strict TAA crosslinking dependent T cell activation, can potentially translate to better safety and a more favorable therapeutic window.

Cullinan Oncology

Company Details