Pipeline

We are a clinical-stage immunotherapy company targeting multiple 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

Balstilimab +/- Zalifrelimab

Mechanism/Target:

PD-1 +/- CTLA-4

Partner:

Phase 2

Cervical (2nd line)

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Programmed death receptor-1 (PD-1) is a negative regulator of the immune system that dampens a T-cell’s ability to kill cancer. Balstilimab is designed to block the PD-1 protein in order to reinvigorate exhausted T cells and restore their cytotoxic function. The broad activity and strong safety profile of PD-1 inhibitors have made this a foundational target in the immuno-oncology treatment landscape.

Emerging clinical and preclinical data supports that balstilimab may have a differentiated mechanism from its commercial counterparts. Balstilimab has also shown superior killing of PD-L1 negative tumors compared to other anti PD-1 therapies, including pembrolizumab, suggesting a broader mechanism consistent with balstilimab’s clinical activity in both PD-L1 positive and negative cervical cancer.

Agenus is advancing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations of therapeutic candidates.

Zalifrelimab

AGEN1884 (anti-CTLA-4)

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Zalifrelimab acts to empower the immune system by blocking the interaction between CTLA-4 and its binding partners CD80 and CD86, encouraging T cells to remain active and continue their tumor-killing response. It has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.

Zalifrelimab has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.


Agenus controls worldwide rights to balstilimab and zalifrelimab, except for Greater China and certain South America rights. 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

Programmed death receptor-1 (PD-1) is a negative regulator of the immune system that dampens a T-cell’s ability to kill cancer. Balstilimab is designed to block the PD-1 protein in order to reinvigorate exhausted T cells and restore their cytotoxic function. The broad activity and strong safety profile of PD-1 inhibitors have made this a foundational target in the immuno-oncology treatment landscape.

Emerging clinical and preclinical data supports that balstilimab may have a differentiated mechanism from its commercial counterparts. Balstilimab has also shown superior killing of PD-L1 negative tumors compared to other anti PD-1 therapies, including pembrolizumab, suggesting a broader mechanism consistent with balstilimab’s clinical activity in both PD-L1 positive and negative cervical cancer.

Agenus is advancing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations of therapeutic candidates.

Zalifrelimab

AGEN1884 (anti-CTLA-4)

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Zalifrelimab acts to empower the immune system by blocking the interaction between CTLA-4 and its binding partners CD80 and CD86, encouraging T cells to remain active and continue their tumor-killing response. It has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.

Zalifrelimab has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.


Agenus controls worldwide rights to balstilimab and zalifrelimab, except for Greater China and certain South America rights. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab and zalifrelimab in Greater China. For more information, visit Our Partnerships.

Product Candidate

Balstilimab +/- Zalifrelimab

Mechanism/Target:

PD-1 +/- CTLA-4

Partner:

Phase 2

Cervical (2nd line)

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Programmed death receptor-1 (PD-1) is a negative regulator of the immune system that dampens a T-cell’s ability to kill cancer. Balstilimab is designed to block the PD-1 protein in order to reinvigorate exhausted T cells and restore their cytotoxic function. The broad activity and strong safety profile of PD-1 inhibitors have made this a foundational target in the immuno-oncology treatment landscape.

Emerging clinical and preclinical data supports that balstilimab may have a differentiated mechanism from its commercial counterparts. Balstilimab has also shown superior killing of PD-L1 negative tumors compared to other anti PD-1 therapies, including pembrolizumab, suggesting a broader mechanism consistent with balstilimab’s clinical activity in both PD-L1 positive and negative cervical cancer.

Agenus is advancing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations of therapeutic candidates.

Zalifrelimab

AGEN1884 (anti-CTLA-4)

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Zalifrelimab acts to empower the immune system by blocking the interaction between CTLA-4 and its binding partners CD80 and CD86, encouraging T cells to remain active and continue their tumor-killing response. It has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.

Zalifrelimab has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.


Agenus controls worldwide rights to balstilimab and zalifrelimab, except for Greater China and certain South America rights. 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

Programmed death receptor-1 (PD-1) is a negative regulator of the immune system that dampens a T-cell’s ability to kill cancer. Balstilimab is designed to block the PD-1 protein in order to reinvigorate exhausted T cells and restore their cytotoxic function. The broad activity and strong safety profile of PD-1 inhibitors have made this a foundational target in the immuno-oncology treatment landscape.

Emerging clinical and preclinical data supports that balstilimab may have a differentiated mechanism from its commercial counterparts. Balstilimab has also shown superior killing of PD-L1 negative tumors compared to other anti PD-1 therapies, including pembrolizumab, suggesting a broader mechanism consistent with balstilimab’s clinical activity in both PD-L1 positive and negative cervical cancer.

Agenus is advancing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations of therapeutic candidates.

Zalifrelimab

AGEN1884 (anti-CTLA-4)

Tumor cells use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Zalifrelimab acts to empower the immune system by blocking the interaction between CTLA-4 and its binding partners CD80 and CD86, encouraging T cells to remain active and continue their tumor-killing response. It has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.

Zalifrelimab has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.


Agenus controls worldwide rights to balstilimab and zalifrelimab, except for Greater China and certain South America rights. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab and zalifrelimab in Greater China. For more information, visit Our Partnerships.

Product Candidate

Botensilimab +/- Balstilimab

Mechanism/Target:

Fc-enhanced CTLA-4 + PD-1

Phase 1

MSS-colorectal

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 suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Botensilimab is a CTLA-4 antibody with modifications in the Fc region that increase engagement with activating receptors on immune cells to promote a more effective immune response against cancer. Botensilimab empowers the immune system by activating existing T cells, priming and expanding new T cells, eliminating immunosuppressive regulatory T cells, and establishing memory cells for durable immunity.

Botensilimab is designed for efficacy and tolerability advantages over first generation immunotherapies:

  • Extend the curative benefits of I-O to cold tumors that do not respond to approved immunotherapies
    • As presented at ESMO GI 2022, botensilimab demonstrated unprecedented activity in combination with balstilimab in MSS colorectal cancer, with a 24% response rate and 73% disease control rate in heavily pre-treated patients with a median of 4 prior lines of therapy
    • As presented at SITC 2021, botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers
  • Expand clinical benefit in hot tumors such as melanoma, where CTLA-4 is approved, but results in clinical benefit in only a third of patients and long term survival in less than a quarter of patients
    • Responses have been observed across both hot and cold cancers in patients who express a biomarker associated with poor outcomes to first-generation CTLA-4
  • Improve tolerability by reducing or eliminating side effects that cause treatment discontinuation
    • Notably, no hypophysitis, carditis, or neurologic toxicities have been observed.

Agenus is initiating randomized phase 2 studies with botensilimab in melanoma, MSS colorectal cancer (combination with balstilimab), and pancreatic cancer (combination with chemotherapy).

Agenus controls worldwide rights to botensilimab.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Programmed death receptor-1 (PD-1) is a negative regulator of the immune system that dampens a T-cell’s ability to kill cancer. Balstilimab is designed to block the PD-1 protein in order to reinvigorate exhausted T cells and restore their cytotoxic function. The broad activity and strong safety profile of PD-1 inhibitors have made this a foundational target in the immuno-oncology treatment landscape.

Emerging clinical and preclinical data supports that balstilimab may have a differentiated mechanism from its commercial counterparts. Balstilimab has also shown superior killing of PD-L1 negative tumors compared to other anti PD-1 therapies, including pembrolizumab, suggesting a broader mechanism consistent with balstilimab’s clinical activity in both PD-L1 positive and negative cervical cancer.

Agenus is advancing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations of therapeutic candidates.

Agenus controls worldwide rights to balstilimab, except for Greater China and certain South America rights. 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 suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Botensilimab is a CTLA-4 antibody with modifications in the Fc region that increase engagement with activating receptors on immune cells to promote a more effective immune response against cancer. Botensilimab empowers the immune system by activating existing T cells, priming and expanding new T cells, eliminating immunosuppressive regulatory T cells, and establishing memory cells for durable immunity.

Botensilimab is designed for efficacy and tolerability advantages over first generation immunotherapies:

  • Extend the curative benefits of I-O to cold tumors that do not respond to approved immunotherapies
    • As presented at ESMO GI 2022, botensilimab demonstrated unprecedented activity in combination with balstilimab in MSS colorectal cancer, with a 24% response rate and 73% disease control rate in heavily pre-treated patients with a median of 4 prior lines of therapy
    • As presented at SITC 2021, botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers
  • Expand clinical benefit in hot tumors such as melanoma, where CTLA-4 is approved, but results in clinical benefit in only a third of patients and long term survival in less than a quarter of patients
    • Responses have been observed across both hot and cold cancers in patients who express a biomarker associated with poor outcomes to first-generation CTLA-4
  • Improve tolerability by reducing or eliminating side effects that cause treatment discontinuation
    • Notably, no hypophysitis, carditis, or neurologic toxicities have been observed.

Agenus is initiating randomized phase 2 studies with botensilimab in melanoma, MSS colorectal cancer (combination with balstilimab), and pancreatic cancer (combination with chemotherapy).

Agenus controls worldwide rights to botensilimab.

Balstilimab

AGEN2034 (anti-PD-1)

Validated backbone therapy to enable novel combinations

Programmed death receptor-1 (PD-1) is a negative regulator of the immune system that dampens a T-cell’s ability to kill cancer. Balstilimab is designed to block the PD-1 protein in order to reinvigorate exhausted T cells and restore their cytotoxic function. The broad activity and strong safety profile of PD-1 inhibitors have made this a foundational target in the immuno-oncology treatment landscape.

Emerging clinical and preclinical data supports that balstilimab may have a differentiated mechanism from its commercial counterparts. Balstilimab has also shown superior killing of PD-L1 negative tumors compared to other anti PD-1 therapies, including pembrolizumab, suggesting a broader mechanism consistent with balstilimab’s clinical activity in both PD-L1 positive and negative cervical cancer.

Agenus is advancing balstilimab as a backbone agent for combination trials within its portfolio, as well as supplying drug to collaborators to enable novel combinations of therapeutic candidates.

Agenus controls worldwide rights to balstilimab, except for Greater China and certain South America rights. Betta Pharmaceuticals has an exclusive license to develop and commercialize balstilimab in Greater China. For more information, visit Our Partnerships.

Product Candidate

Botensilimab

Mechanism/Target:

Fc-enhanced CTLA-4

Phase 1

PD-1 r/r melanoma, Pancreatic (w/chemo)

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 suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Botensilimab is a CTLA-4 antibody with modifications in the Fc region that increase engagement with activating receptors on immune cells to promote a more effective immune response against cancer. Botensilimab empowers the immune system by activating existing T cells, priming and expanding new T cells, eliminating immunosuppressive regulatory T cells, and establishing memory cells for durable immunity.

Botensilimab is designed to have important efficacy and tolerability advantages over first generation immunotherapies:

  • Extend the curative benefits of I-O to cold tumors that do not respond to approved immunotherapies
    • As presented at ESMO GI 2022, botensilimab demonstrated unprecedented activity in combination with balstilimab in MSS colorectal cancer, with a 24% response rate and 73% disease control rate in heavily pre-treated patients with a median of 4 prior lines of therapy
    • As presented at SITC 2021, botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers
  • Expand clinical benefit in hot tumors such as melanoma, where CTLA-4 is approved, but results in clinical benefit in only a third of patients and long term survival in less than a quarter of patients
    • Responses have been observed across both hot and cold cancers in patients who express a biomarker associated with poor outcomes to first-generation CTLA-4
  • Improve tolerability by reducing or eliminating side effects that cause treatment discontinuation
    • Notably, no hypophysitis, carditis, or neurologic toxicities have been observed.

Agenus is initiating randomized phase 2 studies with botensilimab in melanoma, MSS colorectal cancer (combination with balstilimab), and pancreatic cancer (combination with chemotherapy).

Agenus controls worldwide 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 suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Botensilimab is a CTLA-4 antibody with modifications in the Fc region that increase engagement with activating receptors on immune cells to promote a more effective immune response against cancer. Botensilimab empowers the immune system by activating existing T cells, priming and expanding new T cells, eliminating immunosuppressive regulatory T cells, and establishing memory cells for durable immunity.

Botensilimab is designed to have important efficacy and tolerability advantages over first generation immunotherapies:

  • Extend the curative benefits of I-O to cold tumors that do not respond to approved immunotherapies
    • As presented at ESMO GI 2022, botensilimab demonstrated unprecedented activity in combination with balstilimab in MSS colorectal cancer, with a 24% response rate and 73% disease control rate in heavily pre-treated patients with a median of 4 prior lines of therapy
    • As presented at SITC 2021, botensilimab is the first CTLA-4 inhibitor to demonstrate clinical responses across 9 cold and treatment-resistant cancers
  • Expand clinical benefit in hot tumors such as melanoma, where CTLA-4 is approved, but results in clinical benefit in only a third of patients and long term survival in less than a quarter of patients
    • Responses have been observed across both hot and cold cancers in patients who express a biomarker associated with poor outcomes to first-generation CTLA-4
  • Improve tolerability by reducing or eliminating side effects that cause treatment discontinuation
    • Notably, no hypophysitis, carditis, or neurologic toxicities have been observed.

Agenus is initiating randomized phase 2 studies with botensilimab in melanoma, MSS colorectal cancer (combination with balstilimab), and pancreatic cancer (combination with chemotherapy).

Agenus controls worldwide rights to botensilimab.

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 suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Botensilimab is a CTLA-4 antibody with modifications in the Fc region that increase engagement with activating receptors on immune cells to promote a more effective immune response against cancer. Botensilimab empowers the immune system by activating existing T cells, priming and expanding new T cells, eliminating immunosuppressive regulatory T cells, and establishing memory cells for durable immunity.

Agenus controls worldwide 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 suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Botensilimab is a CTLA-4 antibody with modifications in the Fc region that increase engagement with activating receptors on immune cells to promote a more effective immune response against cancer. Botensilimab empowers the immune system by activating existing T cells, priming and expanding new T cells, eliminating immunosuppressive regulatory T cells, and establishing memory cells for durable immunity.

Agenus controls worldwide 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

Mechanism/Target:

ILT2

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.

Product Candidate

AGEN1423

Mechanism/Target:

CD73 / TGFβ trap

Phase 1

Solid tumors

AGEN1423

(anti-CD73 / TGFβ trap)

Bifunctional antibody targeting two dominant pathways that suppress the immune response to cancer

CD73 is involved in the production of adenosine, a molecule that can limit function of various immune cells, while TGFβ signaling in the tumor microenvironment creates a barrier to immune cell infiltration. AGEN1423 is uniquely designed to improve anti-tumor immunity in two ways: (1) neutralizing adenosine (via CD73 blockade) to increase immune cell function, and (2) promoting their increased infiltration (via TGFβ blockade) into the tumor.

Agenus controls worldwide rights to AGEN1423.

AGEN1423

(anti-CD73 / TGFβ trap)

Bifunctional antibody targeting two dominant pathways that suppress the immune response to cancer

CD73 is involved in the production of adenosine, a molecule that can limit function of various immune cells, while TGFβ signaling in the tumor microenvironment creates a barrier to immune cell infiltration. AGEN1423 is uniquely designed to improve anti-tumor immunity in two ways: (1) neutralizing adenosine (via CD73 blockade) to increase immune cell function, and (2) promoting their increased infiltration (via TGFβ blockade) into the tumor.

Agenus controls worldwide rights to AGEN1423.

Partner-Directed Pipeline

Product Candidate

MK-4830

Mechanism/Target:

ILT4

Partner:

Phase 2

NSCLC, ES-SCLC, EC, melanoma, CRC, RCC

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. Multiple Phase II studies are underway, including studies in melanoma, ovarian, lung, esophageal, colorectal, renal cancers.

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. Multiple Phase II studies are underway, including studies in melanoma, ovarian, lung, esophageal, colorectal, renal cancers.

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

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

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

INCAGN1876

Mechanism/Target:

GITR

Partner:

Phase 1

SCCHN

INCAGN1876

(anti-GITR agonist)

Energizes the T cell response to antigen

Glucocorticoid-induced TNFR-related protein (GITR) is an activating receptor on the surface of T cells and other immune cells. INCAGN1876 is designed to selectively bind and activate GITR on immune cells. On T cells, GITR activation enhances cell reproduction and the generation of cancer-killing activity. GITR activation can also block the suppressive abilities of regulatory T cells, further enhancing cytotoxic T cell function.

Incyte has an exclusive worldwide license to INCAGN1876, and is developing in combination in squamous cell carcinoma of the head and neck (SCCHN). For more information, visit Our Partnerships.

INCAGN1876

(anti-GITR agonist)

Energizes the T cell response to antigen

Glucocorticoid-induced TNFR-related protein (GITR) is an activating receptor on the surface of T cells and other immune cells. INCAGN1876 is designed to selectively bind and activate GITR on immune cells. On T cells, GITR activation enhances cell reproduction and the generation of cancer-killing activity. GITR activation can also block the suppressive abilities of regulatory T cells, further enhancing cytotoxic T cell function.

Incyte has an exclusive worldwide license to INCAGN1876, and is developing in combination in squamous cell carcinoma of the head and neck (SCCHN). For more information, visit Our Partnerships.

Product Candidate

INCAGN1949

Mechanism/Target:

OX40

Partner:

Phase 1

Pancreatic cancer

INCAGN1949

(anti-OX40 agonist)

Activates and amplifies T cell stimulation

OX40 is a receptor expressed on the surface of activated cytotoxic T cells and regulatory T cells. INCAGN1949 is designed to selectively bind and activate OX40, in order to amplify T cell responses and create a tumor microenvironment more favorable to the antitumor immune response. On T cells, OX40 activation increases the number and activity of cytotoxic T cells. OX40 activation can also block the suppressive abilities of regulatory T cells, further enhancing cytotoxic T cell function.

Incyte has an exclusive worldwide license to INCAGN1949. For more information, visit Our Partnerships.

INCAGN1949

(anti-OX40 agonist)

Activates and amplifies T cell stimulation

OX40 is a receptor expressed on the surface of activated cytotoxic T cells and regulatory T cells. INCAGN1949 is designed to selectively bind and activate OX40, in order to amplify T cell responses and create a tumor microenvironment more favorable to the antitumor immune response. On T cells, OX40 activation increases the number and activity of cytotoxic T cells. OX40 activation can also block the suppressive abilities of regulatory T cells, further enhancing cytotoxic T cell function.

Incyte has an exclusive worldwide license to INCAGN1949. For more information, visit Our Partnerships.

Product Candidate

BMS-986442

Mechanism/Target:

TIGIT (bispecific)

Partner:

Phase 1

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 use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Zalifrelimab acts to empower the immune system by blocking the interaction between CTLA-4 and its binding partners CD80 and CD86, encouraging T cells to remain active and continue their tumor-killing response. It has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.

Zalifrelimab has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study 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 use the cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathway to suppress initiation of an immune response, decreasing T cell activation and the ability to proliferate into memory T cells. Zalifrelimab acts to empower the immune system by blocking the interaction between CTLA-4 and its binding partners CD80 and CD86, encouraging T cells to remain active and continue their tumor-killing response. It has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study in combination with balstilimab.

Zalifrelimab has demonstrated clinical efficacy in multiple indications, including robust activity in a late-stage (Phase 2) cervical cancer study 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

MSS-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.