Immunohistochemistry Antibody Validation Report for Anti-Cdk2 Antibody (STJ92197)
Characterization of the anti-CTLA-4 antibody AGEN1884...
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0.01 0.1 1 10 0 5000 10000 15000 20000 Fc g RIIIA-V158 Antibody concentration ( μ g/mL) MFI 0.01 0.1 1 10 0 1000 2000 3000 4000 Fc g RIIIA-F158 Antibody concentration ( μ g/mL) MFI Isotype.G1 + Isotype.G4 Nivolumab + Isotype.G1 AGEN1884 + Isotype.G4 AGEN1884 + Nivolumab Isotype.G1 + Isotype.G4 Pembrolizumab + Isotype.G1 AGEN1884 + Isotype.G4 AGEN1884 + Pembrolizumab Isotype.G1 + Isotype.G4 anti-LAG-3 + Isotype.G1 AGEN1884 + Isotype.G4 AGEN1884 + anti-LAG-3 Isotype.G1 + Isotype.G4 anti-CD137 + Isotype.G1 AGEN1884 + Isotype.G4 AGEN1884 + anti-CD137 0 20 40 60 80 IL-2 Secretion Fold change Characterization of the anti-CTLA-4 antibody AGEN1884, including toxicology and pharmacology assessments in non-human primates Randi B. Gombos 1 , Breelyn A. Wilky 2 , Ana Gonzalez 1 , Mariana Manrique 1 , Dhan Chand 1 , David Savitsky 1 , Benjamin Morin 1 , Ekaterina Breous-Nystrom 1 , Christopher Dupont 1 , Rebecca A. Ward 1 , Cornelia Mundt 1 , Benjamin Duckless 1 , Hao Tang 1 , Mark A. Findeis 1 , Andrea Schuster 1 , Jeremy D. Waight 1 , Dennis Underwood 1 , Christopher Clarke 1 , Gerd Ritter 3 , Taha Merghoub 4 , David Schaer 4 , Jedd Wolchok 4 , Marc van Dijk 1 , Jennifer S. Buell 1 , Jean-Marie Cuillerot 1 , Robert Stein 1 , Elise E. Drouin 1 and Nicholas S. Wilson 1 Author Disclosures Randi B. Gombos, Ana Gonzalez, Mariana Manrique, Dhan Chand, David Savitsky, Benjamin Morin, Ekaterina Breous- Nystrom, Christopher Dupont, Rebecca A. Ward, Cornelia Mundt, Benjamin Duckless, Hao Tang, Mark A. Findeis, Andrea Schuster, Jeremy D. Waight, Dennis Underwood, Christopher Clarke, Marc van Dijk, Jennifer S. Buell, Jean-Marie Cuillerot, Robert Stein, Elise E. Drouin and Nicholas S. Wilson: Agenus Inc. and subsidiaries thereof: Current or former employment and stock ownership. Breelyn Wilky, David Schaer, Jedd Wolchok, Taha Merghoub and Gerd Ritter: No competing interests declared. • AGEN1884 cooperates with antibodies targeting the PD-1 pathway and other immuno-modulatory co- inhibitory and co-stimulatory pathways to promote T cell responsiveness • In combination with anti-PD-1, AGEN1884 also promoted a PD proliferative response in circulating T cells in vivo • By virtue of its human IgG1 Fc region, AGEN1884 demonstrated selective depletion of CTLA-4-expressing intratumoral Treg cells and increased potency at enhancing IL-2 production in vitro • At maximal doses, AGEN1884 and the IgG2 variant demonstrated similar enhancement of vaccine-specific antibody responses in non-human primates • Phase 1 clinical trial (NCT02694822) evaluating AGEN1884 in patients with advanced solid tumors has demonstrated acceptable safety profile at 0.1, 0.3, 1.0 and 3.0mg/kg dose levels SUMMARY 1 Current or former employee of Agenus Inc., Lexington, MA, or subsidiary thereof; 2 School of Medicine at the University of Miami, Miami, FL 3 The Ludwig Institute for Cancer Research, New York, NY; 4 Memorial Sloan Kettering Cancer Center, New York, NY References 1. Tykodi, SS. OncoTargets and Therapy. 2014; 4:1349-1359. 2. Buchbinder, EI and Desai, A. Am J Clin Oncol. 2016; 39:98-106. 3. Mo A. et al. Vaccine. 2011; 29:8530-8541. 4. Kreiter S. et al. Nature. 2015; 520:692-696. 5. Wilky BA. et al. J Clin Oncol. 2017; 15_suppl: 3075-3075 Poster: #P325 SITC Annual Meeting Washington, DC, USA • November 9-12, 2017 ABSTRACT CTLA-4: A MASTER REGULATOR OF THE IMMUNE SYNAPSE Cynomolgus monkeys (n=6 per group) were administered 10 mg/kg of A) AGEN1884 or B) an IgG2 Fc variant via IV administration with a Hepatitis B vaccine on days 1 and 29. Duplicate samples were analyzed for anti-HBsAg-specific IgG serum titers. AGEN1884 (IGG1) IS MORE POTENT THAN AN IGG2 OR FC SILENT VARIANT AT ENHANCING T CELL RESPONSIVENESS Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important negative regulator of T cell function. Together with CD28, these receptors exemplify a co-inhibitory and co-stimulatory signaling axis that dynamically sculpts the interaction of antigen-specific T cells with antigen presenting cells (APCs). Preclinical studies have demonstrated that anti-CTLA-4 antibodies can enhance tumor-specific immunity through a variety of mechanisms including: i) blockade of CD80 or CD86 binding to CTLA-4; ii) preventing CTLA-4-expressing regulatory T cells from physically removing CD80 and CD86 from the surface of APCs; and iii) selective elimination of CTLA-4-expressing intratumoral regulatory T cells by an Fcγ receptor-dependent mechanism. Here we describe the pharmacological and toxicological characterization of a novel human IgG1 anti-CTLA-4 antagonist antibody, AGEN1884. AGEN1884 potently enhanced T cell responsiveness in vitro, and combined effectively with other immunomodulatory antibodies targeting co-inhibitory and co-stimulatory receptors on T cells. AGEN1884 was well-tolerated in non-human primates and was confirmed to modulate cellular and humoral immune responses to co-administered reporter vaccines. In addition to the activity of AGEN1884 as a monotherapy, a memory T cell proliferative response was observed in peripheral blood of animals when co- administered with an anti-PD-1 antibody. Finally, we provide a comparison of the in vitro and in vivo functional properties of an IgG2 variant of AGEN1884, revealing important antibody isotype differences that may have an impact on the design of optimal dosing regimens in patients. Taken together, the pharmacologic properties of AGEN1884 support its clinical investigation as both a single therapeutic agent and in combination therapies.. Kinetics of Expression AGEN1884 ENGAGES FC GAMMA RECEPTORS AND HAS THE POTENTIAL TO MEDIATE ADCC TOWARD ACTIVATED REGULATORY T CELLS A) Human PBMCs were stimulated with the superantigen staphylococcal enterotoxin A (SEA) in the presence of AGEN1884 alone, or in combination with other immunomodulatory antibodies. Enhanced cytokine production (example: IL-2) was measured in the culture supernatant at day 4. B) Human PBMCs were incubated with AGEN1884 (10 μg/ml) alone or in combination with a panel of antagonist or agonist antibodies (10 μg/ml). T cell IL-2 production was measured. Nivolumab and pembrolizumab were commercially sourced, whereas anti-LAG-3, anti-CD137 and AGEN2034 (anti-PD-1) were generated in-house. AGEN1884 COOPERATES WITH OTHER IMMUNOMODULATORY ANTIBODIES TO ENHANCE T CELL RESPONSIVENESS A) A-C) Binding of increasing doses of AGEN1884 or an IgG2 Fc variant to A) rJurkat-huFcγRIIA-H131 + , B) rCHO-huFcγRIIIA- V158 + , and C) rCHO-huFcγRIIIA-F158 + engineered cell lines. The mean fluorescence intensity (MFI) was determined based on binding of an anti-F(ab’)2-PE labeled secondary F(ab’)2 fragment to AGEN1884 (black squares) compared to the IgG2 variant (white squares) are shown. D-E) Primary effector T cells or regulatory T cells were activated with anti-CD3/CD28 beads for 7 days. After stimulation, CTLA- 4 and Foxp3 expression were confirmed by flow cytometry. D) CTLA-4 high target CD3 + FoxP3 + T cells or E) CTLA-4 + target CD3 + FoxP3 - T cells were co-cultured with primary NK cells at an effector:target ratio of 5:1 in the presence of increasing concentrations of AGEN1884. Cell-specific lysis was assessed as a percentage of CD3+ target cells that stained positive for the non-viable cell marker 7-aminoactinomycin D when assessed using flow cytometry. As a control, cells were incubated with 10 μg/mL of an IgG2 variant. Data were analyzed using a Student’s t-test for each dose of AGEN1884 compared to the isotype. Significant differences depicted were p<0.05 (*). B) Antagonist Agonist aPD-1 aPD-1 aLAG-3 aCD137 CTLA-4 D) Activated Regulatory T Cells Isotype control (10 μ g/mL) AGEN1884 (0.3 μ g/mL) AGEN1884 (1.1 μ g/ml) AGEN1884 (3.3 μ g/mL) AGEN1884 (10 μ g/mL) IgG2 variant (10 μ g/mL) 0 10 20 30 Target cell lysis (%) CTLA-4 E) Activated Effector T Cells Isotype control (10 μ g/mL) AGEN1884 (0.3 μ g/mL) AGEN1884 (1.1 μ g/ml) AGEN1884 (3.3 μ g/mL) AGEN1884 (10 μ g/mL) IgG2 variant (10 μ g/mL) 0 10 20 30 Target cell lysis (%) * * * Nivolumab or Nivolumab plus AGEN1884 A) Cynomolgus monkeys were administered nivolumab alone (3 mg/kg) or in combination with AGEN1884 (10mg/kg). PBMCs were isolated pre and post antibody administration. PBMCs were thawed and surface stained with T cell lineage markers and a viability dye, followed by permeabilization and staining for a cellular marker of proliferation (Ki67). Cells were analyzed using flow cytometry. B) Representative histograms and dot plots from an individual animal administered nivolumab alone. C) Representative histograms and dot plots from an individual animal administered nivolumab together with AGEN1884. A) Example: Dosing regimen Single dose of: AGEN1884 COOPERATES WITH PD-1 BLOCKADE TO ENHANCE PROLIFERATION OF CENTRAL MEMORY T CELLS IN NON-HUMAN PRIMATES + T cell proliferation assessed in PBMCs using Ki67 B) Nivolumab C) Nivolumab plus AGEN1884 Central Effector Naïve Central Effector Naïve Pre-dose Day 3 Pre-dose Day 3 0.3% 0.3% 3% 14% 2% 2% Ki67 SSC-A SSC-A Ki67 0.3% 0.2% 1% 7% 3% 1% Central Memory Effector Memory Naïve T cells CD95 CD28 CD95 CD28 CD8+ T cells CD4+ T cells Naïve T cells Central Memory Effector Memory Ki67 Ki67 3% CD8+ T cells CD4+ T cells Pre-dose Day 3 0.3% 0.4% 2% 4% 3% 1% SSC-A SSC-A 0.8% 0.8% 3% 4% 2% Central Memory Effector Memory Naïve T cells Pre-dose Day 3 Central Effector Central Effector Naïve CD95 CD28 Naïve CD95 CD28 Central Effector APC Superantigen MHC CD80/CD86 CTLA-4 AGEN1884 in combination TCR Signal 1 CD28 Signal 2 IL2 gene T cell Primary T Cell Assay Days -7 15 29 43 59 69 0 500,000 1,000,000 1,500,000 2,000,000 Anti-HBsAg IgG (U/mL) Control IgG2 variant Days -7 15 29 43 59 69 0 500,000 1,000,000 1,500,000 2,000,000 Anti-HBsAg IgG (U/mL) Control AGEN1884 Antibody + Hepatitis B vaccine IMMUNE RESPONSES IN NON-HUMAN PRIMATES TO REPORTER VACCINES CO- ADMINISTERED WITH AGEN1884 OR AN IGG2 FC VARIANT 1 10 100 1000 0 5 10 15 20 Antibody concentration (µg/ml) IL-2 Secretion Fold change IgG2 variant Isotype (IgG2) AGEN1884 Isotype (IgG1) PRELIMINARY CLINICAL DATA REVEAL SIGNS OF CLINICAL ACTIVITY WITH COMPLETE RESPONSE OF ANGIOSARCOMA AFTER TREATMENT WITH AGEN1884 In Phase 1 clinical trials (NCT02694822), early clinical data observations of one confirmed complete response (July 21, 2017) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Patient 189-002 was a 62-year-old female being treated for angiosarcoma of nose and cheeks with 0.1mg/kg of AGEN1884 (n=5 in cohort). At week 33, a 92% reduction of target lesion was observed (Wilky BA. et al. Poster presented at: 53 rd Annual Meeting of the American Society of Clinical Oncology; 2017 June 2-6; Chicago, IL) Isotype.G1 + Isotype.G4 AGEN2034 + Isotype.G1 AGEN1884 + Isotype.G4 AGEN1884 + AGEN2034 0 20 40 60 IL-2 Secretion Fold change aPD-1 A) B) Human PBMCs were stimulated with a sub-maximal concentration of the SEA superantigen (100 ng/mL) and increasing doses of AGEN1884, an IgG2 variant, an N297A variant or isotype controls. Representative data indicate the mean ± SEM of multiple replicates in each treatment group. 0.1 1 10 0 1000 2000 3000 4000 5000 Fc g RIIA-H131 Antibody concentration ( μ g/mL) MFI AGEN1884 IgG2 variant A) B) C) Acknowledgments The licensed antibodies AGEN1884, the IgG2 variant thereof, and AGEN2034 were originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. These antibodies are partnered with Recepta Biopharma S.A. for certain South American rights. We wish to thank the subjects, as well as the investigators and their teams, who participated in this study. 0.1 1 10 100 1000 0 20 40 60 80 Antibody concentration (µg/ml) IL-2 Secretion Fold change Isotype N297A variant IgG2 variant AGEN1884 Donor 1 Donor 2 1.2% 2.6% 2.3% Ki67 CD4 + T cells Day -7 Day 3 Day 10 2.9% 2.2% 2.3% 1.5% 3.3% 3.2% 2.6% 2.3% 0.8% Day 18 Day 22 Day 14 CD8 + T cells Day -7 Day 3 Day 10 CD4 + T cells 2.1% 15.3% 8.9% CD8 + T cells Ki67 16.5% 12.5% 4.78% 2.38% 17.7% 7.2% 13.7% Day 14 Day 18 3.1% 7.6% Day 22 Naïve T cells Central Memory Effector Memory
Transcript of Characterization of the anti-CTLA-4 antibody AGEN1884...
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Characterization of the anti-CTLA-4 antibody AGEN1884, including toxicology and pharmacology assessments in non-human primates Randi B. Gombos1, Breelyn A. Wilky2, Ana Gonzalez1, Mariana Manrique1, Dhan Chand1, David Savitsky1, Benjamin Morin1, Ekaterina Breous-Nystrom1, Christopher Dupont1, Rebecca A. Ward1, Cornelia Mundt1, Benjamin Duckless1, Hao Tang1, Mark A. Findeis1, Andrea Schuster1, Jeremy D. Waight1, Dennis Underwood1, Christopher Clarke1, Gerd Ritter3, Taha Merghoub4, David Schaer4, Jedd Wolchok4, Marc van Dijk1, Jennifer S. Buell1, Jean-Marie Cuillerot1, Robert Stein1, Elise E. Drouin1 and Nicholas S. Wilson1
Author DisclosuresRandi B. Gombos, Ana Gonzalez, Mariana Manrique, Dhan Chand, David Savitsky, Benjamin Morin, Ekaterina Breous-Nystrom, Christopher Dupont, Rebecca A. Ward, Cornelia Mundt, Benjamin Duckless, Hao Tang, Mark A. Findeis, Andrea Schuster, Jeremy D. Waight, Dennis Underwood, Christopher Clarke, Marc van Dijk, Jennifer S. Buell, Jean-Marie Cuillerot, Robert Stein, Elise E. Drouin and Nicholas S. Wilson: Agenus Inc. and subsidiaries thereof: Current or former employment and stock ownership. Breelyn Wilky, David Schaer, Jedd Wolchok, Taha Merghouband Gerd Ritter: No competing interests declared.
• AGEN1884 cooperates with antibodies targeting the PD-1 pathway and other immuno-modulatory co-inhibitory and co-stimulatory pathways to promote T cell responsiveness
• In combination with anti-PD-1, AGEN1884 also promoted a PD proliferative response in circulating T cells in vivo
• By virtue of its human IgG1 Fc region, AGEN1884 demonstrated selective depletion of CTLA-4-expressing intratumoral Treg cells and increased potency at enhancing IL-2 production in vitro
• At maximal doses, AGEN1884 and the IgG2 variant demonstrated similar enhancement of vaccine-specific antibody responses in non-human primates
• Phase 1 clinical trial (NCT02694822) evaluating AGEN1884 in patients with advanced solid tumors has demonstrated acceptable safety profile at 0.1, 0.3, 1.0 and 3.0mg/kg dose levels
SUMMARY
1Current or former employee of Agenus Inc., Lexington, MA, or subsidiary thereof; 2School of Medicine at the University of Miami, Miami, FL 3The Ludwig Institute for Cancer Research, New York, NY; 4Memorial Sloan Kettering Cancer Center, New York, NY
References1. Tykodi, SS. OncoTargets and Therapy. 2014; 4:1349-1359. 2. Buchbinder, EI and Desai, A. Am J Clin Oncol. 2016; 39:98-106.3. Mo A. et al. Vaccine. 2011; 29:8530-8541.4. Kreiter S. et al. Nature. 2015; 520:692-696.5. Wilky BA. et al. J Clin Oncol. 2017; 15_suppl: 3075-3075
Poster: #P325SITC Annual MeetingWashington, DC, USA • November 9-12, 2017
ABSTRACT
CTLA-4: A MASTER REGULATOR OF THE IMMUNE SYNAPSE
Cynomolgus monkeys (n=6 per group) were administered 10 mg/kg of A) AGEN1884 or B) an IgG2 Fc variant via IV administration with aHepatitis B vaccine on days 1 and 29. Duplicate samples were analyzed for anti-HBsAg-specific IgG serum titers.
AGEN1884 (IGG1) IS MORE POTENT THAN AN IGG2 OR FC SILENT VARIANTAT ENHANCING T CELL RESPONSIVENESS
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important negative regulator of T cell function. Together withCD28, these receptors exemplify a co-inhibitory and co-stimulatory signaling axis that dynamically sculpts theinteraction of antigen-specific T cells with antigen presenting cells (APCs). Preclinical studies havedemonstrated that anti-CTLA-4 antibodies can enhance tumor-specific immunity through a variety ofmechanisms including: i) blockade of CD80 or CD86 binding to CTLA-4; ii) preventing CTLA-4-expressingregulatory T cells from physically removing CD80 and CD86 from the surface of APCs; and iii) selectiveelimination of CTLA-4-expressing intratumoral regulatory T cells by an Fcγ receptor-dependent mechanism.Here we describe the pharmacological and toxicological characterization of a novel human IgG1 anti-CTLA-4antagonist antibody, AGEN1884. AGEN1884 potently enhanced T cell responsiveness in vitro, and combinedeffectively with other immunomodulatory antibodies targeting co-inhibitory and co-stimulatory receptors on Tcells. AGEN1884 was well-tolerated in non-human primates and was confirmed to modulate cellular andhumoral immune responses to co-administered reporter vaccines. In addition to the activity of AGEN1884 as amonotherapy, a memory T cell proliferative response was observed in peripheral blood of animals when co-administered with an anti-PD-1 antibody. Finally, we provide a comparison of the in vitro and in vivo functionalproperties of an IgG2 variant of AGEN1884, revealing important antibody isotype differences that may have animpact on the design of optimal dosing regimens in patients. Taken together, the pharmacologic properties ofAGEN1884 support its clinical investigation as both a single therapeutic agent and in combination therapies..
Kinetics of Expression
AGEN1884 ENGAGES FC GAMMA RECEPTORS AND HAS THE POTENTIALTO MEDIATE ADCC TOWARD ACTIVATED REGULATORY T CELLS
A) Human PBMCs were stimulated with the superantigenstaphylococcal enterotoxin A (SEA) in the presence ofAGEN1884 alone, or in combination with otherimmunomodulatory antibodies. Enhanced cytokineproduction (example: IL-2) was measured in the culturesupernatant at day 4.B) Human PBMCs were incubated with AGEN1884 (10µg/ml) alone or in combination with a panel of antagonist oragonist antibodies (10 µg/ml). T cell IL-2 production wasmeasured. Nivolumab and pembrolizumab werecommercially sourced, whereas anti-LAG-3, anti-CD137 andAGEN2034 (anti-PD-1) were generated in-house.
AGEN1884 COOPERATES WITH OTHER IMMUNOMODULATORYANTIBODIES TO ENHANCE T CELL RESPONSIVENESS
A)
A-C) Binding of increasing doses of AGEN1884 or an IgG2 Fc variant to A) rJurkat-huFcγRIIA-H131+, B) rCHO-huFcγRIIIA-V158+, and C) rCHO-huFcγRIIIA-F158+ engineered cell lines. The mean fluorescence intensity (MFI) was determined based onbinding of an anti-F(ab’)2-PE labeled secondary F(ab’)2 fragment to AGEN1884 (black squares) compared to the IgG2 variant(white squares) are shown.D-E) Primary effector T cells or regulatory T cells were activated with anti-CD3/CD28 beads for 7 days. After stimulation, CTLA-4 and Foxp3 expression were confirmed by flow cytometry. D) CTLA-4high target CD3+FoxP3+ T cells or E) CTLA-4+ targetCD3+FoxP3- T cells were co-cultured with primary NK cells at an effector:target ratio of 5:1 in the presence of increasingconcentrations of AGEN1884. Cell-specific lysis was assessed as a percentage of CD3+ target cells that stained positive for thenon-viable cell marker 7-aminoactinomycin D when assessed using flow cytometry. As a control, cells were incubated with 10µg/mL of an IgG2 variant. Data were analyzed using a Student’s t-test for each dose of AGEN1884 compared to the isotype.Significant differences depicted were p<0.05 (*).
B) Antagonist AgonistaPD-1 aPD-1 aLAG-3 aCD137
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A) Cynomolgus monkeys were administered nivolumab alone (3 mg/kg) or in combination with AGEN1884 (10mg/kg). PBMCs wereisolated pre and post antibody administration. PBMCs were thawed and surface stained with T cell lineage markers and a viability dye,followed by permeabilization and staining for a cellular marker of proliferation (Ki67). Cells were analyzed using flow cytometry.B) Representative histograms and dot plots from an individual animal administered nivolumab alone.C) Representative histograms and dot plots from an individual animal administered nivolumab together with AGEN1884.
A) Example: Dosing regimenSingle dose of:
AGEN1884 COOPERATES WITH PD-1 BLOCKADE TO ENHANCEPROLIFERATION OF CENTRAL MEMORY T CELLS IN NON-HUMAN PRIMATES
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IMMUNE RESPONSES IN NON-HUMAN PRIMATES TO REPORTER VACCINES CO-ADMINISTERED WITH AGEN1884 OR AN IGG2 FC VARIANT
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PRELIMINARY CLINICAL DATA REVEAL SIGNS OF CLINICAL ACTIVITY WITHCOMPLETE RESPONSE OF ANGIOSARCOMA AFTER TREATMENT WITH AGEN1884
In Phase 1 clinical trials (NCT02694822), early clinical data observations of one confirmed complete response (July 21, 2017) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Patient 189-002 was a 62-year-old female being treated for angiosarcoma of nose and cheeks with 0.1mg/kg of AGEN1884 (n=5 in cohort). At week 33, a 92% reduction of target lesion was observed (Wilky BA. et al. Poster presented at: 53rd
Annual Meeting of the American Society of Clinical Oncology; 2017 June 2-6; Chicago, IL)
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Human PBMCs were stimulated with a sub-maximal concentration of the SEA superantigen (100 ng/mL) and increasing doses ofAGEN1884, an IgG2 variant, an N297A variant or isotype controls. Representative data indicate the mean ± SEM of multiple replicates ineach treatment group.
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A G E N 1 8 8 4Ig G 2 v a r ia n t
A) B) C)
AcknowledgmentsThe licensed antibodies AGEN1884, the IgG2 variant thereof, and AGEN2034 were originally developed under a Collaborative Research and Development Agreement between Ludwig Cancer Research, 4-Antibody AG (now Agenus Switzerland Inc.) and Recepta Biopharma S.A. These antibodies are partnered with ReceptaBiopharma S.A. for certain South American rights. We wish to thank the subjects, as well as the investigators and their teams, who participated in this study.
0 .1 1 1 0 1 0 0 1 0 0 00
2 0
4 0
6 0
8 0
A n t ib o d y c o n c e n tra t io n (µ g /m l)
IL-2
Sec
reti
on
Fo
ld c
ha
ng
e
Is o ty p e
N 2 9 7 A v a r ia n t
Ig G 2 v a r ia n t
A G E N 1 8 8 4
Donor 1 Donor 2
1.2% 2.6%2.3%
Ki67
CD4+
T cells
Day -7 Day 3 Day 10
2.9%2.2%2.3%
1.5% 3.3% 3.2% 2.6% 2.3%0.8%
Day 18 Day 22Day 14
CD8+
T cells
Day -7 Day 3 Day 10CD4+
T cells2.1% 15.3%8.9%
CD8+
T cells
Ki67
16.5%12.5%4.78%2.38% 17.7%
7.2% 13.7%
Day 14 Day 18
3.1%
7.6%
Day 22
Naïve T cells
CentralMemory
EffectorMemory
