Our

Programs

A diversified Pipeline

We are dedicated to advancing our pipeline to fulfill unmet needs of patients with cancer. We leverage our scientific excellence to create differentiated ideas, identify unique targets, and select the optimal modality to develop transformative therapeutics across cancer indications.

A Robust Pipeline Powered by Modality-Agnostic Targeted Oncology

Taking a modality-agnostic approach offers incredible freedom to develop the most effective cancer therapies. Our programs range from engineered therapeutic proteins to innovative monoclonal antibodies, as well as kinase inhibitors and protein degraders, designed to target both the tumor and tumor microenvironment.

Patients also need more tolerable cancer treatments. We employ strategies to improve tumor response, minimize toxicity, and allow more patient-friendly dosing.

A Diverse Disease Requires A Diverse Approach To Research and Development

Programs Underway

Zipalertinib (CLN-081/TAS6417)

Unmet Need
In the U.S., approximately 16% of non-small cell lung cancer (NSCLC) cases harbor epithelial growth factor receptor (EGFR) mutations, with insertions at exon 20 (EGFRex20ins) accounting for 12% of those mutations. Patients with EGFRex20ins mutations have poorer outcomes than those with more common EGFR mutations, such as exon 19 deletions. There remains a significant unmet need for therapies targeting EGFRex20ins mutations in NSCLC that are safer and more effective.

Mechanism Of Action
Zipalertinib (CLN-081/TAS6417) is a novel, orally bioavailable, irreversible EGFR inhibitor that, based on preclinical models, selectively and potently targets cells expressing EGFRex20ins mutations while relatively sparing cells expressing wild-type EGFR in order to avoid the toxicities associated with inhibition of wild-type EGFR. This was rationally designed with a distinct chemical scaffold to be highly selective for mutant vs wild-type EGFR, and to avoid inhibiting the closely related receptor human epidermal growth factor receptor 2 (HER2).

Asset Potential
In ongoing Phase 1/2a study, zipalertinib (CLN-081/TAS6417) demonstrated promising efficacy in heavily pretreated patients, including patients who progressed on treatment with EGFR tyrosine kinase inhibitors (TKIs), with favorable safety and tolerability profile. Results are encouraging in heavily pretreated patients, including those who progressed with other EGFR TKI. The safety profile is amenable for long-term treatment at doses <150mg BID. Zipalertinib (CLN-081/TAS6417) demonstrates the potential to become a new standard of care to treat NSCLC harboring EGFRex20ins mutations.

Development Plan

The ongoing partnership with Taiho Pharmaceuticals Co, Ltd in developing zipalertinib (CLN-081/TAS6417) allows us to broaden our development program for this asset
Zipalertinib (CLN-081/TAS6417) is being investigated in a Phase 2 study in EGFRex20ins NSCLC patients progressing after prior systemic therapy. The study will enroll patients at the 100 mg BID dose, and will also include a limited cohort of patients to evaluate safety and efficacy at 150 mg BID administered with food
In January of 2022, Cullinan Oncology announced that zipalertinib (CLN-081/TAS6417) received Breakthrough Therapy designation from the FDA

News

View More on Zipalertinib

CLN-619

Unmet Need
A hallmark of cancer is the ability to avoid destruction by immune cells. Cancer cells develop escape mechanisms that can render them invisible to the human immune system. This immune evasion enables unrestricted tumor growth and potential metastasis. There is a significant unmet need for treatments that can help overcome immune-evasion mechanisms employed by tumors.

Mechanism Of Action

Based on preclinical models, CLN-619 is a potential first-in-class MICA/MICB-directed IgG1 antibody that restores the MICA/ MICB-NKG2D axis to promote NK-mediated tumor cell lysis. MHC class I chain-related proteins A and B (MICA/MICB) are proteins found on the surface of stressed cells and serve as a warning flag to the organism that the cell is damaged, targeting the flagged cells for elimination by immune cells. Cell stressors that activate MICA/MICB include viral infection, genotoxic stress, and malignant transformation. MICA/MICB are minimally expressed on normal cells and are upregulated in most solid tumor types and hematologic malignancies.

In cancer patients, tumor cells can escape natural killer group 2 member (NKG2D)-mediated lysis by shedding MICA/MICB from the cell surface via proteases present in the tumor microenvironment. CLN-619 restores the MICA/MICB pathway to engage both innate and adaptive immune cells and exerts its effects through multiple mechanisms:

Prevention of MICA/MICB shedding and restoration of NKG2D engagement
Functional Fc mediates both antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP)
Enhancement of NKG2D receptor binding to MICA/MICB

CLN-619 treatment stabilizes MICA and MICB by preventing shedding and restoring immunosurveillance

Learn More About CLN-619's MOA

Asset Potential CLN-619 is the only MICA/MICB-directed antibody currently in clinical development and has the potential to be first-in-class. MICA/MICB are expressed in most cancer types, providing the opportunity to treat patients across multiple indications in solid and hematological malignancies. With MICA/MICB as an immune-activating signal, there is an opportunity to combine CLN-619 with:

Immunotherapies targeting distinct immune-activation pathways, such as checkpoint inhibitors, that reinvigorate the adaptive immune response.
A variety of standard of care therapies, like radiation and chemotherapy, that can enhance MICA/MICB expression.
Enhancers of NK cell activation and functions such as cytokines (IL-15) and IMiDs.

Development Plan

Cullinan Oncology licensed CLN-619 in 2020 from COI Pharmaceuticals and its subsidiary, PDI Therapeutics, for clinical development, and our strong collaboration continues. CLN-619 offers a potential novel approach for patients who failed to respond to other immu-notherapies like checkpoint inhibitors, thereby extending the therapeutic reach to a broader group of patients.
CLN-619 is currently being studied in a global Phase 1 dose-escalation clinical trial as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors.

CLN-049

Unmet Need
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults with 20,050 new cases expected in the US in 2022. AML is a rapidly growing cancer. Patients are typically diagnosed at an average age of 72 and have a 5-year survival rate of 10% or less in the relapsed setting. A significant unmet need remains for a broadly applicable and accessible therapy that produces high and durable response rates.

Mechanism Of Action
Based on preclinical models, CLN-049 is a novel T cell engaging bispecific antibody candidate designed to simultaneously bind the extracellular domain of FLT3 on AML cells and a CD3 receptor on T cells. This interaction redirects the patient’s effector T cells toward cancer cells and enables T cell-mediated cancer cell death. By binding the extracellular domain of FLT3, CLN-049 is capable of targeting AML cells independently of their FLT3 mutational status. CLN-049 was designed to have high affinity for FLT3 to also target AML cells with low overall levels of FLT3 expression. The silent Fc domain and CD3-targeting domains that are functionally monovalent aim to minimize non-specific T cell activation and reduce potential toxicity.

Learn More About CLN-049s MOA

Asset Potential
Currently, the only potential curative therapy for relapsed/refractory AML is intensive chemotherapy followed by hematopoietic stem cell transplantation which remains out of reach for most elderly patients due to the high risk of therapy-related mortality. FLT3 is a promising target being explored for AML immunotherapy as it is significantly upregulated in AML cells compared to normal cells, and is detectably expressed on AML cells in >80% of patients, including wild-type and mutant forms, while only minimally expressed in healthy cells and tissues. Both FLT3 and its mutant forms are oncogenic drivers, as they play a key role in promoting leukemic cell proliferation and survival, making FLT3 target loss and resulting drug resistance during CLN-049 therapy unlikely. FLT3 is expressed on leukemic stem cells as well as blast cells, which may increase response durability of potential therapeutics.

CLN-049 has the potential for an improved therapeutic index compared to other bispecific antibody therapies developed for AML due to its potency being largely independent of FLT3 expression level or mutational status. FLT3 expression is limited on normal myeloid-derived cells but upregulated on AML blasts. This will likely cause less cytokine release upon T cell activation than for targets like CD33 and CD123, which are frequently and highly expressed on normal myeloid cells. This allows for consistent dosing based on efficacy and safety profile.

CLN-049 has the potential to treat >80% of patients with AML due to its ability to recognize both mutant and wild type FLT3 with high affinity, offering the potential to treat AML regardless of FLT3 mutational status. This is a strong differentiator, as TKIs, which only target mutant FLT3, can treat only 20-30% of AML cases.

Development Plan

Cullinan Oncology acquired an exclusive license from the University of Tubingen/German Cancer Research Center (DKTK) and this collaboration continues to propel this asset forward.
CLN-049 is currently being studied in a Phase 1 trial in patients with relapsed/refractory AML or high-risk myelodysplastic syndrome (MDS), often a precursor to acute leukemia, for which the only curative therapy is transplant.

2022 AACR

2022 JITC

News

View More on CLN-049

CLN-418

CLN-978

Unmet Need
B-cell Non-Hodgkin’s lymphomas (B-NHL) are a diverse group of blood cancers that develop from B lymphocytes, a type of white blood cell. Despite significant advances for the treatment of some B-NHL subtypes, substantial unmet needs remain for effective treatments. Chemotherapy-containing regimens remain the frontline standard of care for many patients with B-NHL, but curative potential is only available for some patients with certain subtypes (e.g., DLBCL). CAR-T cell approaches are promising but challenges remain with toxicity and accessibility in the community setting, where the majority of B-NHL patients receive care.

Mechanism Of Action
Based on preclinical models, 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.

Asset Potential
CLN-978 is a novel, highly potent, half-life extended, potentially best-in-class CD19XCD3 T cell engager candidate that may provide an alternative to CD19 CAR-T cell therapies with a more convenient, off the shelf option. High-affinity binding of CLN-978 to CD19 allows for greater potency against tumor cells expressing low levels of CD19.

CLN-978 has the potential to become a treatment option for patients who have relapsed on other CD19-directed therapies due to reduced CD19 target expression. Preclinical evidence has demonstrated CLN-978’s high potency, extended half-life, and advantageous safety profile by subcutaneous delivery.

Development Plan
CLN-978 is a product of discovery efforts by the internal Cullinan Oncology team, led by Patrick Baeuerle, our Chief Scientific Officer. CLN-978 was designed for off-the-shelf functionality, unlike CAR-T cell therapies or other cellular engineering approaches. IND-enabling studies of CLN-978 are currently ongoing with an IND submission expected in the first half of 2023.

2022 AACR

CLN-617

Unmet Need
While checkpoint inhibitors have revolutionized immuno-oncology, only a minority of patients respond, often due to the tumor being "cold," which means it lacks an appreciable number of infiltrated, tumor-specific T cells. For several decades, preclinical researchers and clinical investigators have characterized the powerful role interleukin (IL)-2 and IL-12 play in stimulating the immune response to cancer and turning the tumor "hot." Previous attempts to administer IL-2 and IL-12 directly into the tumor have failed to improve efficacy due to leakage of drug from the injection site. Because of the systemic toxicities of both IL-2 and IL-12, delivery directly into the tumor is theoretically attractive as long as an effective retention strategy is leveraged.

Mechanism Of Action
Based on preclinical models, CLN-617 is a potential first-in-class cytokine therapy candidate uniquely combining two potent antitumor cytokines—IL-2 and IL-12—in a single molecule. The molecule is designed for intratumoral injection to enhance efficacy and reduce toxicity. It employs collagen-binding and size-enhancing domains to retain the CLN-617 molecule inside the tumor tissue after intratumoral injection to prevent leakage. While CLN-617 stays inside the injected tumor, it directs a broad immune response, like a vaccine, that helps to eradicate not only the injected tumor, but also attack distant tumor sites as observed in preclinical studies.

Asset Potential
CLN-617 is a potential first-in-class cytokine therapy candidate for intratumoral injection and is the first to combine IL-2 and IL-12 in a single molecule. CLN-617 is effectively retained in tumor tissue in preclinical animal models to avoid systemic toxicity. Local administration of CLN-617 promotes broad systemic immunosurveillance, potentially enabling the treatment of advanced disease, including mediating the regression of non-injected distal tumors and generating a memory of T cell responses to enhance long-term survival. Collagen is the major component of the tumor microenvironment; binding to collagen helps keep CLN-617 in the tumor.

CLN-617 has the potential to be a pan cancer therapy since collagen is expressed across all solid tumors. CLN-617 has the potential for efficacy as a monotherapy or in combination with checkpoint inhibitors. Preclinical studies show that CLN-617 can significantly impact the growth of non-injected tumors, and that combination with checkpoint inhibitors helps to completely eradicate distant tumors. These results encourage exploration of CLN-617 in combination with checkpoint inhibitors in clinical trials.

Development Plan

CLN-617 was discovered at Cullinan Oncology with tumor retention technology licensed from the MIT Dane Wittrup Lab whose innovative technologies propelled the characterization and development of CLN-617. Dr. Wittrup remains actively involved in the program.
IND-enabling studies of CLN-617 are currently ongoing with IND submission expected in the first half of 2023.

2021 Informa Connect AET Europe

Early Programs

TCR-Based Targeting Of A Senescence And Cancer-Related Protein pMHC Complex

HPK1 Targeting: Potential first-in-class protein degrader that acts as a negative regulator of T cells and TCR signaling

All of Cullinan's molecules are investigational; safety and efficacy have not been established; they have not been approved by any health authority.
Descriptions of asset MOAs are based on pre-clinical data.

A Robust And Diversified Pipeline

Our clinical programs span a range of indications and modalities.

Discover Our Pipeline

Harnessing Science for Patient Benefit

Our clinical trials are designed with clinically relevant endpoints and predefined benchmarks for success.

See Our Clinical Trials