Pipeline Test

We are a clinical-stage immunotherapy company targeting complementary mechanisms to fight cancer, including checkpoint inhibitors, immune activators, and tumor microenvironment conditioning agents.

Product Candidate

Target

Partner

Phase 1

Phase 2

Majority / Fully-owned pipeline

Product Candidate

Botensilimab +/- Balstilimab

Mechanism/Target:

Fc-enhanced CTLA-4 +/- PD-1

Phase 2

Non-MSI-H-colorectal cancer

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Balstilimab is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer. The effectiveness and safety of PD-1 inhibitors have established PD-1 as a fundamental target in immuno-oncology treatments.

Emerging data suggests that balstilimab may have a unique mechanism compared to other PD-1 therapies. It has demonstrated stronger efficacy preclinically against PD-L1 negative tumors than pembrolizumab, indicating a broader mechanism that aligns with its clinical effectiveness in both PD-L1 positive and negative cervical cancer.

Agenus is developing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations with external agents.

Agenus holds exclusive global rights to balstilimab, except for Greater China. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab in Greater China. For more information, visit Our Partnerships.

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Balstilimab is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer. The effectiveness and safety of PD-1 inhibitors have established PD-1 as a fundamental target in immuno-oncology treatments.

Emerging data suggests that balstilimab may have a unique mechanism compared to other PD-1 therapies. It has demonstrated stronger efficacy preclinically against PD-L1 negative tumors than pembrolizumab, indicating a broader mechanism that aligns with its clinical effectiveness in both PD-L1 positive and negative cervical cancer.

Agenus is developing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations with external agents.

Agenus holds exclusive global rights to balstilimab, except for Greater China. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab in Greater China. For more information, visit Our Partnerships.

Product Candidate

Botensilimab +/- Balstilimab

Mechanism/Target:

Fc-enhanced CTLA-4 +/- PD-1

Phase 2

PD-1 r/r melanoma

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Balstilimab is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer. The effectiveness and safety of PD-1 inhibitors have established PD-1 as a fundamental target in immuno-oncology treatments.

Emerging data suggests that balstilimab may have a unique mechanism compared to other PD-1 therapies. It has demonstrated stronger efficacy preclinically against PD-L1 negative tumors than pembrolizumab, indicating a broader mechanism that aligns with its clinical effectiveness in both PD-L1 positive and negative cervical cancer.

Agenus is developing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations with external agents.

Agenus holds exclusive global rights to balstilimab, except for Greater China. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab in Greater China. For more information, visit Our Partnerships.

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Balstilimab is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer. The effectiveness and safety of PD-1 inhibitors have established PD-1 as a fundamental target in immuno-oncology treatments.

Emerging data suggests that balstilimab may have a unique mechanism compared to other PD-1 therapies. It has demonstrated stronger efficacy preclinically against PD-L1 negative tumors than pembrolizumab, indicating a broader mechanism that aligns with its clinical effectiveness in both PD-L1 positive and negative cervical cancer.

Agenus is developing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations with external agents.

Agenus holds exclusive global rights to balstilimab, except for Greater China. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab in Greater China. For more information, visit Our Partnerships.

Product Candidate

Botensilimab + Chemotherapy

Mechanism/Target:

Fc-enhanced CTLA-4

Phase 2

Pancreatic cancer

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Product Candidate

Botensilimab +/- Balstilimab

Mechanism/Target:

Fc-enhanced CTLA-4 +/- PD-1

Phase 1

Solid tumors

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Balstilimab is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer. The effectiveness and safety of PD-1 inhibitors have established PD-1 as a fundamental target in immuno-oncology treatments.

Emerging data suggests that balstilimab may have a unique mechanism compared to other PD-1 therapies. It has demonstrated stronger efficacy preclinically against PD-L1 negative tumors than pembrolizumab, indicating a broader mechanism that aligns with its clinical effectiveness in both PD-L1 positive and negative cervical cancer.

Agenus is developing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations with external agents.

Agenus holds exclusive global rights to balstilimab, except for Greater China. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab in Greater China. For more information, visit Our Partnerships.

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Balstilimab is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer. The effectiveness and safety of PD-1 inhibitors have established PD-1 as a fundamental target in immuno-oncology treatments.

Emerging data suggests that balstilimab may have a unique mechanism compared to other PD-1 therapies. It has demonstrated stronger efficacy preclinically against PD-L1 negative tumors than pembrolizumab, indicating a broader mechanism that aligns with its clinical effectiveness in both PD-L1 positive and negative cervical cancer.

Agenus is developing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations with external agents.

Agenus holds exclusive global rights to balstilimab, except for Greater China. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab in Greater China. For more information, visit Our Partnerships.

Product Candidate

Balstilimab +/- Zalifrelimab

Mechanism/Target:

PD-1 +/- CTLA-4

Partner:

Phase 2

Cervical cancer

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Balstilimab is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer. The effectiveness and safety of PD-1 inhibitors have established PD-1 as a fundamental target in immuno-oncology treatments.

Emerging data suggests that balstilimab may have a unique mechanism compared to other PD-1 therapies. It has demonstrated stronger efficacy preclinically against PD-L1 negative tumors than pembrolizumab, indicating a broader mechanism that aligns with its clinical effectiveness in both PD-L1 positive and negative cervical cancer.

Agenus is developing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations with external agents.

Zalifrelimab

AGEN1884 (anti-CTLA-4)

Tumor cells suppress the immune system by using the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway, which limits T cell activation and memory T cell proliferation. Zalifrelimab blocks the interaction between CTLA-4 and its binding partners CD80 and CD86, promoting T cell activation and tumor-killing response. Clinical trials have shown its efficacy in multiple indications, including a Phase 2 study in cervical cancer where it demonstrated robust activity in combination with balstilimab.

Agenus holds exclusive global rights to balstilimab and zalifrelimab, excluding Greater China. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab and zalifrelimab in Greater China. For more information, visit Our Partnerships.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Balstilimab is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer. The effectiveness and safety of PD-1 inhibitors have established PD-1 as a fundamental target in immuno-oncology treatments.

Emerging data suggests that balstilimab may have a unique mechanism compared to other PD-1 therapies. It has demonstrated stronger efficacy preclinically against PD-L1 negative tumors than pembrolizumab, indicating a broader mechanism that aligns with its clinical effectiveness in both PD-L1 positive and negative cervical cancer.

Agenus is developing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations with external agents.

Zalifrelimab

AGEN1884 (anti-CTLA-4)

Tumor cells suppress the immune system by using the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway, which limits T cell activation and memory T cell proliferation. Zalifrelimab blocks the interaction between CTLA-4 and its binding partners CD80 and CD86, promoting T cell activation and tumor-killing response. Clinical trials have shown its efficacy in multiple indications, including a Phase 2 study in cervical cancer where it demonstrated robust activity in combination with balstilimab.

Agenus holds exclusive global rights to balstilimab and zalifrelimab, excluding Greater China. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab and zalifrelimab in Greater China. For more information, visit Our Partnerships.

Product Candidate

AGEN2373 + Botensilimab

Mechanism/Target:

CD137 + Fc-enhanced CTLA-4

Phase 1

PD-1 r/r melanoma

AGEN2373

(anti-CD137 agonist)

Conditionally active antibody designed to activate T and NK cells while mitigating liver toxicities common to the CD137 target class

CD137 (4-1BB) is an activating receptor expressed on T and NK cells. Upon binding to CD137, AGEN2373 is designed to stimulate the growth and activation of cytotoxic T and NK cells, triggering a lasting memory response to cancer. AGEN2373 binds to a unique epitope designed to achieve this response specifically within the tumor microenvironment. This selective binding is designed to avoid serious side effects associated with CD137 activation in the liver that have been reported by competitor molecules.

AGEN2373 has demonstrated preliminary clinical activity and has been well tolerated by patients without signs of liver toxicity.

Gilead has an exclusive option to license AGEN2373. For more information, visit Our Partnerships.

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

AGEN2373

(anti-CD137 agonist)

Conditionally active antibody designed to activate T and NK cells while mitigating liver toxicities common to the CD137 target class

CD137 (4-1BB) is an activating receptor expressed on T and NK cells. Upon binding to CD137, AGEN2373 is designed to stimulate the growth and activation of cytotoxic T and NK cells, triggering a lasting memory response to cancer. AGEN2373 binds to a unique epitope designed to achieve this response specifically within the tumor microenvironment. This selective binding is designed to avoid serious side effects associated with CD137 activation in the liver that have been reported by competitor molecules.

AGEN2373 has demonstrated preliminary clinical activity and has been well tolerated by patients without signs of liver toxicity.

Gilead has an exclusive option to license AGEN2373. For more information, visit Our Partnerships.

Botensilimab

AGEN1181 (Fc-enhanced anti-CTLA-4)

Novel innate and adaptive immune activator with broad activity across hot and cold cancers

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to inhibit immune response, but botensilimab, a CTLA-4 antibody with modified Fc region, engages with activating receptors on immune cells to promote a more effective response. Botensilimab activates existing T cells, eliminates regulatory T cells, primes and expands new T cells, and establishes memory cells for durable immunity. Botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers.

Agenus is conducting phase 2 trials with botensilimab in melanoma, MSS colorectal cancer (with balstilimab), and pancreatic cancer (with chemotherapy).

Agenus holds exclusive global rights to botensilimab.

Product Candidate

AGEN2373

Mechanism/Target:

CD137

Partner:

Phase 1

Solid tumors

AGEN2373

(anti-CD137 agonist)

Conditionally active antibody designed to activate T and NK cells while mitigating liver toxicities common to the CD137 target class

CD137 (4-1BB) is an activating receptor expressed on T and NK cells. Upon binding to CD137, AGEN2373 is designed to stimulate the growth and activation of cytotoxic T and NK cells, triggering a lasting memory response to cancer. AGEN2373 binds to a unique epitope designed to achieve this response specifically within the tumor microenvironment. This selective binding is designed to avoid serious side effects associated with CD137 activation in the liver that have been reported by competitor molecules.

AGEN2373 has demonstrated preliminary clinical activity and has been well tolerated by patients without signs of liver toxicity.

Gilead has an exclusive option to license AGEN2373. For more information, visit Our Partnerships.

AGEN2373

(anti-CD137 agonist)

Conditionally active antibody designed to activate T and NK cells while mitigating liver toxicities common to the CD137 target class

CD137 (4-1BB) is an activating receptor expressed on T and NK cells. Upon binding to CD137, AGEN2373 is designed to stimulate the growth and activation of cytotoxic T and NK cells, triggering a lasting memory response to cancer. AGEN2373 binds to a unique epitope designed to achieve this response specifically within the tumor microenvironment. This selective binding is designed to avoid serious side effects associated with CD137 activation in the liver that have been reported by competitor molecules.

AGEN2373 has demonstrated preliminary clinical activity and has been well tolerated by patients without signs of liver toxicity.

Gilead has an exclusive option to license AGEN2373. For more information, visit Our Partnerships.

Product Candidate

AGEN1571 +/- Balstilimab +/- Botensilimab

Mechanism/Target:

ILT2 +/- PD-1 +/- CTLA-4

Phase 1

Solid tumors

AGEN1571

(anti-ILT-2)

Promotes adaptive and innate immune responses to overcome immunotherapy resistance

Immunoglobulin-like transcript 2 (ILT2, also known as LILRB1) is an immunosuppressive receptor prominently expressed on resting macrophages, monocytes, and dendritic cells (DCs), with variable expression on T cells, B cells, NK cells, and NKT cells in the tumor microenvironment. High ILT2 expression has been associated with poor prognosis in several cancers, and ILT2 activation has been reported to impair cytotoxic activity of NK and effector T cells, attenuate B cell function, inhibit antigen-presentation by dendritic cells, and promote the immunosuppressive activity of myeloid cells.

AGEN1571 is an ILT-2 antagonist antibody designed to promote antitumor immunity and overcome resistance to checkpoint blockade by reversing ILT2-mediated immunosuppression and promoting activation of NK, NKT, T cells, and myeloid cells. AGEN1571 demonstrates superior functional activity compared to a clinical-stage competitor with greater immune cell activation and ability to reprogram myeloid cells to a pro-inflammatory state.

Agenus controls worldwide rights to AGEN1571.

AGEN1571

(anti-ILT-2)

Promotes adaptive and innate immune responses to overcome immunotherapy resistance

Immunoglobulin-like transcript 2 (ILT2, also known as LILRB1) is an immunosuppressive receptor prominently expressed on resting macrophages, monocytes, and dendritic cells (DCs), with variable expression on T cells, B cells, NK cells, and NKT cells in the tumor microenvironment. High ILT2 expression has been associated with poor prognosis in several cancers, and ILT2 activation has been reported to impair cytotoxic activity of NK and effector T cells, attenuate B cell function, inhibit antigen-presentation by dendritic cells, and promote the immunosuppressive activity of myeloid cells.

AGEN1571 is an ILT-2 antagonist antibody designed to promote antitumor immunity and overcome resistance to checkpoint blockade by reversing ILT2-mediated immunosuppression and promoting activation of NK, NKT, T cells, and myeloid cells. AGEN1571 demonstrates superior functional activity compared to a clinical-stage competitor with greater immune cell activation and ability to reprogram myeloid cells to a pro-inflammatory state.

Agenus controls worldwide rights to AGEN1571.

Partner-Directed Pipeline

Product Candidate

MK-4830

Mechanism/Target:

ILT4

Partner:

Phase 2

Neoadjuvant Ovarian

ILT4

(anti-ILT4 antagonist)

Catalyzes reprogramming of tumor-associated macrophages, relieving myelosuppression and enhancing T cell function

Immunoglobulin-like transcript 4 (ILT4, also known as LILRB2) is an immunosuppressive receptor commonly expressed by many myeloid lineages, including monocytes, macrophages, granulocytes, and dendritic cells. In the tumor microenvironment, ILT4 is expressed by myeloid-derived suppressor cells (MDSCs), which suppress T-cell activation, proliferation, and effector responses. MK-4830 is a first-in-class ILT-4 antibody designed to abrogate PD-1 resistance by reprogramming myeloid cells into a proinflammatory state and enhancing the anti-tumor T cell response.

In a first-in-human study (NCT03564691) in advanced solid tumors, the combination of MK-4830 with pembrolizumab (PD-1) resulted in a 24% response rate, with multiple responses observed in patients progressing on prior PD-1 therapy and all responses maintained for at least 6 months. A Phase II study of MK-4830 in combination with pembrolizumab and chemotherapy with or without bevacizumab in neoadjuvant ovarian is ongoing.

Merck has an exclusive worldwide license to MK-4830. For more information, visit Our Partnerships.

ILT4

(anti-ILT4 antagonist)

Catalyzes reprogramming of tumor-associated macrophages, relieving myelosuppression and enhancing T cell function

Immunoglobulin-like transcript 4 (ILT4, also known as LILRB2) is an immunosuppressive receptor commonly expressed by many myeloid lineages, including monocytes, macrophages, granulocytes, and dendritic cells. In the tumor microenvironment, ILT4 is expressed by myeloid-derived suppressor cells (MDSCs), which suppress T-cell activation, proliferation, and effector responses. MK-4830 is a first-in-class ILT-4 antibody designed to abrogate PD-1 resistance by reprogramming myeloid cells into a proinflammatory state and enhancing the anti-tumor T cell response.

In a first-in-human study (NCT03564691) in advanced solid tumors, the combination of MK-4830 with pembrolizumab (PD-1) resulted in a 24% response rate, with multiple responses observed in patients progressing on prior PD-1 therapy and all responses maintained for at least 6 months. A Phase II study of MK-4830 in combination with pembrolizumab and chemotherapy with or without bevacizumab in neoadjuvant ovarian is ongoing.

Merck has an exclusive worldwide license to MK-4830. For more information, visit Our Partnerships.

Product Candidate

INCAGN2390

Mechanism/Target:

TIM-3

Partner:

Phase 1

PD-1 r/r melanoma, SCCHN, endometrial cancer

INCAGN2390

(anti-TIM-3 antagonist)

Targeting T Cell Exhaustion and Dysfunction

T-cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint receptor expressed on the surface of cytotoxic T cells, regulatory T cells (Tregs), monocytes and natural killer (NK) cells. Increasing expression of TIM-3 on cytotoxic T cells and NK cells are associated with immune cell exhaustion and infection. In addition, Tregs expressing TIM-3 show enhanced immunosuppressive function, and TIM-3 signaling can suppress the immune function of monocytes. INCAGN2390 is designed to potently block TIM-3 to reinvigorate T and NK cells and reduce immunosuppression by Tregs.

Incyte has an exclusive worldwide license to INCAGN2390, and is developing a unique triple combination of INCAGN2390 with INCAGN2385 (LAG-3) and PD-1 in melanoma and squamous cell carcinoma of the head and neck (SCCHN). For more information, visit Our Partnerships.

INCAGN2390

(anti-TIM-3 antagonist)

Targeting T Cell Exhaustion and Dysfunction

T-cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint receptor expressed on the surface of cytotoxic T cells, regulatory T cells (Tregs), monocytes and natural killer (NK) cells. Increasing expression of TIM-3 on cytotoxic T cells and NK cells are associated with immune cell exhaustion and infection. In addition, Tregs expressing TIM-3 show enhanced immunosuppressive function, and TIM-3 signaling can suppress the immune function of monocytes. INCAGN2390 is designed to potently block TIM-3 to reinvigorate T and NK cells and reduce immunosuppression by Tregs.

Incyte has an exclusive worldwide license to INCAGN2390, and is developing a unique triple combination of INCAGN2390 with INCAGN2385 (LAG-3) and PD-1 in melanoma and squamous cell carcinoma of the head and neck (SCCHN). For more information, visit Our Partnerships.

Product Candidate

INCAGN2385

Mechanism/Target:

LAG-3

Partner:

Phase 1

PD-1 r/r melanoma, SCCHN, endometrial cancer

INCAGN2385

(anti-LAG-3 antagonist)

Addressing T Cell Exhaustion and Suppression

Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint receptor expressed on the surface of both activated cytotoxic T cells and regulatory T cells (Tregs). The presence and activity of LAG-3 steadily increases with exposure to tumor antigen, leading to T cell exhaustion. Tregs expressing LAG-3 also gather at tumor sites and show potent suppression of cytotoxic T cells. INCAGN2385 is designed to potently block LAG-3, to enable T cells to regain their cytotoxic function and abrogate immunosuppression by Tregs.

Incyte has an exclusive worldwide license to INCAGN2385, and is developing a unique triple combination of INCAGN2385 with INCAGN2390 (TIM-3) and PD-1 in melanoma and squamous cell carcinoma of the head and neck (SCCHN). For more information, visit Our Partnerships.

INCAGN2385

(anti-LAG-3 antagonist)

Addressing T Cell Exhaustion and Suppression

Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint receptor expressed on the surface of both activated cytotoxic T cells and regulatory T cells (Tregs). The presence and activity of LAG-3 steadily increases with exposure to tumor antigen, leading to T cell exhaustion. Tregs expressing LAG-3 also gather at tumor sites and show potent suppression of cytotoxic T cells. INCAGN2385 is designed to potently block LAG-3, to enable T cells to regain their cytotoxic function and abrogate immunosuppression by Tregs.

Incyte has an exclusive worldwide license to INCAGN2385, and is developing a unique triple combination of INCAGN2385 with INCAGN2390 (TIM-3) and PD-1 in melanoma and squamous cell carcinoma of the head and neck (SCCHN). For more information, visit Our Partnerships.

Product Candidate

BMS-986442 + Nivolumab + Chemotherapy

Mechanism/Target:

TIGIT (bispecific)

Partner:

Phase 1

NSCLC and solid tumors

BMS-986442

AGEN1777 (TIGIT bispecific)

Fc-enhanced anti-TIGIT bispecific which targets a second major inhibitory receptor expressed on T and NK cells to improve anti-tumor activity

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is expressed on tumor-infiltrating cytotoxic T cells, helper T cells, regulatory T cells and NK cells across multiple cancers, contributing to local suppression of immune-surveillance. BMS-986442 is a first-in-class bispecific anti-TIGIT antibody engineered with an enhanced Fc region for improved T and NK cell activation. BMS-986442 blocks the activity of TIGIT as well as a second major inhibitory receptor expressed on T and NK cells to improve anti-tumor immunity. In preclinical studies, this approach has shown single-agent activity in tumor models where anti-PD-1 or first-generation anti-TIGIT monospecific antibodies alone are ineffective.

BMS has an exclusive worldwide license to BMS-986442 and intends to develop in high priority tumor indications including non-small cell lung cancer. For more information, visit Our Partnerships.

BMS-986442

AGEN1777 (TIGIT bispecific)

Fc-enhanced anti-TIGIT bispecific which targets a second major inhibitory receptor expressed on T and NK cells to improve anti-tumor activity

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is expressed on tumor-infiltrating cytotoxic T cells, helper T cells, regulatory T cells and NK cells across multiple cancers, contributing to local suppression of immune-surveillance. BMS-986442 is a first-in-class bispecific anti-TIGIT antibody engineered with an enhanced Fc region for improved T and NK cell activation. BMS-986442 blocks the activity of TIGIT as well as a second major inhibitory receptor expressed on T and NK cells to improve anti-tumor immunity. In preclinical studies, this approach has shown single-agent activity in tumor models where anti-PD-1 or first-generation anti-TIGIT monospecific antibodies alone are ineffective.

BMS has an exclusive worldwide license to BMS-986442 and intends to develop in high priority tumor indications including non-small cell lung cancer. For more information, visit Our Partnerships.

Product Candidate

UGN-301

Mechanism/Target:

CTLA-4 + RTGel™

Partner:

Phase 1

NMIBC

UGN-301 + RTGel™

Zalifrelimab (anti-CTLA-4)

Tumor cells suppress the immune system by using the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway, which limits T cell activation and memory T cell proliferation. Zalifrelimab blocks the interaction between CTLA-4 and its binding partners CD80 and CD86, promoting T cell activation and tumor-killing response. Clinical trials have shown its efficacy in multiple indications, including a Phase 2 study in cervical cancer where it demonstrated robust activity in combination with balstilimab.

Urogen has an exclusive license to develop and commercialize zalifrelimab formulated for intravesical delivery utilizing its proprietary RTGel™ technology (UGN-301) for the treatment of urinary tract cancers. For more information, visit Our Partnerships.

UGN-301 + RTGel™

Zalifrelimab (anti-CTLA-4)

Tumor cells suppress the immune system by using the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway, which limits T cell activation and memory T cell proliferation. Zalifrelimab blocks the interaction between CTLA-4 and its binding partners CD80 and CD86, promoting T cell activation and tumor-killing response. Clinical trials have shown its efficacy in multiple indications, including a Phase 2 study in cervical cancer where it demonstrated robust activity in combination with balstilimab.

Urogen has an exclusive license to develop and commercialize zalifrelimab formulated for intravesical delivery utilizing its proprietary RTGel™ technology (UGN-301) for the treatment of urinary tract cancers. For more information, visit Our Partnerships.

Clinical Collaborations

Product Candidate

CR6086 + Balstilimab

Mechanism/Target:

EP4 + PD-1

Partner:

Phase 1

Non-MSI-H-colorectal cancer

CR6086 + Balstilimab

Rottapharm Biotech is conducting a clinical trial combining balstilimab (PD-1 antagonist) with CR6086 (EP4 antagonist) in patients with pMMR-MSS colorectal cancer. CR6086 is expected to inhibit the immune suppressive role of prostaglandins in the tumor microenvironment, improving immunogenicity and responsiveness to immunotherapy. The Phase 1/2 study commenced in 2021.

CR6086 + Balstilimab

Rottapharm Biotech is conducting a clinical trial combining balstilimab (PD-1 antagonist) with CR6086 (EP4 antagonist) in patients with pMMR-MSS colorectal cancer. CR6086 is expected to inhibit the immune suppressive role of prostaglandins in the tumor microenvironment, improving immunogenicity and responsiveness to immunotherapy. The Phase 1/2 study commenced in 2021.

Product Candidate

NLM001 + Zalifrelimab

Mechanism/Target:

Hedgehog + CTLA-4

Partner:

Phase 2

Pancreatic cancer

NLM001 + Zalifrelimab

Nelum is conducting a clinical trial combining zalifrelimab (CTLA-4 antagonist) with NLM-001 (hedgehog inhibitor) and chemotherapy in patients with advanced pancreatic cancer. NLM-001 in combination with chemotherapy is anticipated to condition the tumor microenvironment to improve T cell infiltration, activation, and responsiveness to immunotherapy. The Phase 1/2 study commenced in 2021.

NLM001 + Zalifrelimab

Nelum is conducting a clinical trial combining zalifrelimab (CTLA-4 antagonist) with NLM-001 (hedgehog inhibitor) and chemotherapy in patients with advanced pancreatic cancer. NLM-001 in combination with chemotherapy is anticipated to condition the tumor microenvironment to improve T cell infiltration, activation, and responsiveness to immunotherapy. The Phase 1/2 study commenced in 2021.

Product Candidate

OBT076 + Balstilimab

Mechanism/Target:

CD205 + PD-1

Partner:

Phase 2

Solid tumors

OBT076 + Balstilimab

Oxford BioTherapeutics is conducting a clinical trial combining balstilimab with OBT076 (CD205-targeting antibody-drug conjugate) in patients with solid tumors, including lung, gastric, and ovarian cancer. OBT076 is expected to deplete CD205+ cancer cells, and immuno-suppressive cells within the tumor microenvironment, leading to T cell activation and increased response to immunotherapy.

OBT076 + Balstilimab

Oxford BioTherapeutics is conducting a clinical trial combining balstilimab with OBT076 (CD205-targeting antibody-drug conjugate) in patients with solid tumors, including lung, gastric, and ovarian cancer. OBT076 is expected to deplete CD205+ cancer cells, and immuno-suppressive cells within the tumor microenvironment, leading to T cell activation and increased response to immunotherapy.