Where Speed Meets Strategy

Multi-dose and single target dose regimen data in December; initiate Phase 2a expansion in early 2027

The OUTRACE trials are part of Cullinan’s comprehensive, global clinical development program for CLN-978, a novel, differentiated, and highly potent investigational CD19xCD3 bispecific T cell engager. CLN-978 is currently being studied in a Phase 1 clinical trial in Europe in patients with active, difficult-to-treat rheumatoid arthritis. 

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 people living with rheumatoid arthritis.  

Currently approved therapies can reduce symptoms of the disease and help protect the joints from damage. However, these therapies can result in chronic immune suppression, increasing infection and cancer risk, especially in elderly people with RA. Additionally, many patients stop responding or are not able to tolerate these treatments and remain with significant disease activity. The goal of our clinical trial is for patients to achieve low disease activity or even remission. 

Multi-dose and single target dose regimen data in December; initiate Phase 2a expansion in early 2027 in patients with SLE and in patients with lupus nephritis

The OUTRACE trials are part of Cullinan’s comprehensive, global clinical development program for CLN-978, a novel, differentiated, and highly potent investigational CD19xCD3 bispecific T cell engager. CLN-978 is currently being studied in a global Phase 1b clinical trial in patients with moderate to severe SLE.

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 people living with SLE.

Currently approved therapies can reduce the symptoms of SLE. However, these therapies result in chronic immune suppression, increasing infection and cancer risk. Additionally, many patients stop responding or are not able to tolerate these treatments and remain with significant disease activity. The goal of our clinical trial is for patients to achieve low disease activity or even remission.

Multi-dose and single target dose regimen data in December

The OUTRACE trials are part of Cullinan’s comprehensive, global clinical development program for CLN-978, a novel, differentiated, and highly potent investigational CD19xCD3 bispecific T cell engager. CLN-978 is currently being studied in a global Phase 1 clinical trial in patients with active, moderate to severe Sjögren’s disease. 

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 people living with Sjögren’s disease. 

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. 

Currently, there are no approved medicines that treat Sjögren’s disease, but there are therapies that address dryness and other symptoms. No approved treatment has been shown to comprehensively slow disease progression or treat all aspects of Sjögren’s disease.  

Global Phase 1/2 study in relapsing and refractory ITP and wAIHA underway

Velinotamig is an investigational BCMAxCD3 T cell engager designed to redirect cytotoxic T cells to target BCMA-expressing cells, including pathogenic, autoantibody-producing plasma cells. Velinotamig is engineered with high-affinity binding to BCMA and lower-affinity binding to CD3, with the goal of enhancing target cell depletion while minimizing non-specific T cell activation and associated cytokine-related toxicity. By targeting BCMA-expressing cells, velinotamig has the potential to address autoimmune diseases driven by pathogenic autoantibodies.

Cullinan is evaluating whether a defined-duration treatment regimen of velinotamig can provide sustained clinical benefit for patients with ITP and wAIHA, potentially reducing the burden of chronic treatment.

The global, open-label, multicenter Phase 1/2 study will evaluate the safety, tolerability, and preliminary clinical activity of velinotamig in adults with relapsing or refractory ITP and wAIHA. The study includes a Phase 1b multiple-ascending dose portion followed by a Phase 2a dose-expansion portion in separate ITP and wAIHA expansion groups.

ITP and wAIHA are serious, potentially life-threatening autoimmune blood disorders in which pathogenic autoantibodies contribute to the destruction of platelets and red blood cells, respectively.

Patients with ITP and wAIHA often experience significant disease burden, including debilitating fatigue and reduced quality of life, as well as severe disease manifestations such as bleeding in ITP and anemia in wAIHA. Despite available therapies, many patients experience persistent or relapsing disease, remain dependent on chronic treatment, or develop substantial adverse events from current therapies, underscoring the need for approaches that can deliver sustained disease control.

Multi-dose regimen data from the Genrix Bio Phase 1/2 study in SLE at ACR Convergence 2026 in November

Velinotamig is a BCMAxCD3 T cell engager designed to redirect cytotoxic T cells to target BCMA-expressing cells, including pathogenic, autoantibody-producing plasma cells. Velinotamig is engineered with high-affinity binding to BCMA and lower-affinity binding to CD3, with the goal of enhancing target cell depletion while minimizing non-specific T cell activation and associated cytokine-related toxicity. By targeting BCMA-expressing cells, velinotamig has the potential to address autoimmune diseases driven by pathogenic autoantibodies.

Initial clinical data from the ongoing Phase 1/2 study in patients with refractory moderate to severe SLE demonstrated encouraging activity, including complete renal responses in two patients with nephritis at the initial target dose, accompanied by rapid reductions in disease-related autoantibodies and improvements in other biomarkers.

Currently approved therapies can reduce the symptoms of SLE. However, these therapies result in chronic immune suppression, increasing infection and cancer risk. Additionally, many patients stop responding or are not able to tolerate these treatments and remain with significant disease activity.

U.S. FDA accepted NDA for treatment of relapsed EGFR ex20ins NSCLC; PDUFA target action date of February 27, 2027

REZILIENT1 is a pivotal Phase 2b trial assessing zipalertinib in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, with insertions at exon 20 (ex20ins) who have progressed after receiving prior systemic therapy, as well as in a separate cohort of patients progressing after prior treatment with a currently approved agent for ex20ins NSCLC.

Zipalertinib is an orally available next-generation investigational small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with ex20ins mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer.

In January 2022, zipalertinib received Breakthrough Therapy designation from the FDA. Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

Patients with NSCLC harboring EGFR ex20ins mutations have poorer outcomes than those with more common EGFR mutations, such as exon 19 deletions. While currently approved therapies for EGFR exon20ins-positive NSCLC have shown the ability to shrink tumors and delay disease progression, there remains a significant unmet need for oral therapies that are safer and more effective. 

Parallel cohort study ongoing

REZILIENT2 is a Phase 2 parallel cohort study sponsored by Taiho Oncology, assessing zipalertinib in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, with insertions at exon 20 (ex20ins) or other uncommon mutations. Cohorts of the study include those who have progressed after receiving standard platinum-based chemotherapy and prior treatment with an ex20ins agent for their advanced disease, a first-line cohort of patients who have not received prior treatment for advanced or metastatic disease, and patients with active brain metastases and/or leptomeningeal disease (LMD).

Zipalertinib is an orally available next-generation investigational small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with ex20ins mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer.

In January 2022, zipalertinib received Breakthrough Therapy designation from the FDA. Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

Patients with NSCLC harboring EGFR ex20ins mutations have poorer outcomes than those with more common EGFR mutations, such as exon 19 deletions. While currently approved therapies for EGFR exon20ins-positive NSCLC have shown the ability to shrink tumors and delay disease progression,  there remains a significant unmet need for oral therapies that are safer and more effective. 

Primary endpoint of PFS met at planned interim analysis with full results shared at IASLC 2026 WCLC; NDA submission initiated under FDA Real-Time Oncology Review, with submission completion expected by year-end 2026

REZILIENT3 is a global Phase 3 trial sponsored by Taiho Oncology, evaluating the combination of zipalertinib and chemotherapy as a potential first-line treatment for adults with previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC).

Zipalertinib is an orally available next-generation investigational small molecule designed to target activating mutations in epidermal growth factor receptor (EGFR). The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion (ex20ins) mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer.

In January 2022, zipalertinib received Breakthrough Therapy designation from the FDA. Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

Patients with NSCLC harboring EGFR ex20ins mutations have poorer outcomes than those with more common EGFR mutations, such as exon 19 deletions. While currently approved therapies for EGFR exon20ins-positive NSCLC have shown the ability to shrink tumors and delay disease progression, there remains a significant unmet need for oral therapies that are safer and more effective.

Potentially registrational Phase 2 study underway; Phase 1 dose escalation data update in December

CLN-049 is an investigational bispecific T cell engager designed to simultaneously bind the extracellular domain of FLT3 on acute myeloid leukemia (AML) cells and the CD3 epsilon T cell receptor subunit on T cells. FLT3 is a promising target as this mutation plays a key role in the proliferation of leukemic cells. FLT3 (wildtype or mutant) is detected on AML cells in more than 80% of patients.

CLN-049 is currently being investigated via intravenous administration.

CLN-049 has received Orphan Drug Designation and Fast Track Designation from the U.S. FDA for the treatment of relapsed/refractory AML. 

In some people, MDS can progress into AML. Currently approved treatments for MDS and AML can delay disease progression and in some cases lead to remission, particularly in patients with specific genetic profiles or who are eligible for intensive therapy. However, a significant unmet need remains for a broadly applicable and accessible therapy that produces high and durable response rates. Patients are typically diagnosed at an average age of 68 and have a five-year survival rate of 10% or less in the relapsed setting. Currently, the only potential curative therapy for AML is intensive chemotherapy with or without hematopoietic stem cell transplantation, which remains out of reach for older patients due to the high risk of therapy-related mortality.

Phase 1/2 study evaluating CLN-049 in combination with azacitidine and venetoclax to begin in Q4 2026

CLN-049 is an investigational bispecific T cell engager designed to simultaneously bind the extracellular domain of FLT3 on acute myeloid leukemia (AML) cells and the CD3 epsilon T cell receptor subunit on T cells. FLT3 is a promising target as this mutation plays a key role in the proliferation of leukemic cells. FLT3 (wildtype or mutant) is detected on AML cells in more than 80% of patients.

CLN-049 is currently being investigated via intravenous administration.

CLN-049 has received Orphan Drug Designation and Fast Track Designation from the U.S. FDA for the treatment of relapsed/refractory AML. 

In some people, MDS can progress into AML. Currently approved treatments for MDS and AML can delay disease progression and in some cases lead to remission, particularly in patients with specific genetic profiles or who are eligible for intensive therapy. However, a significant unmet need remains for a broadly applicable and accessible therapy that produces high and durable response rates. Patients are typically diagnosed at an average age of 68 and have a five-year survival rate of 10% or less in the relapsed setting. Currently, the only potential curative therapy for AML is intensive chemotherapy with or without hematopoietic stem cell transplantation, which remains out of reach for older patients due to the high risk of therapy-related mortality.

Phase 1 study ongoing

CLN-049 is an investigational bispecific T cell engager designed to simultaneously bind the extracellular domain of FLT3 on acute myeloid leukemia (AML) cells and the CD3 epsilon T cell receptor subunit on T cells. FLT3 is a promising target as this mutation plays a key role in the proliferation of leukemic cells. FLT3 (wildtype or mutant) is detected on AML cells in more than 80% of patients. CLN-049 is currently being investigated via intravenous administration. 

A significant unmet need remains for the eradication of measurable residual disease (MRD) that indicates relapse even when patients meet clinical criteria for complete remission. While no therapies are currently approved specifically for MRD in AML, some available treatments have demonstrated the ability to delay relapse and extend remission in select patient populations. Currently, the only potential curative therapy for AML is intensive chemotherapy with or without hematopoietic stem cell transplantation, which remains out of reach for older patients due to the high risk of therapy-related mortality.