AGEN1777 / Agenus - LARVOL DELTA

A Study of BMS-986442 With Nivolumab With or Without Chemotherapy in Solid Tumors and Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=36 | Terminated | Sponsor: Bristol-Myers Squibb | N=225 ➔ 36 | Active, not recruiting ➔ Terminated; Business objectives have changed

Combination therapy • Enrollment change • Metastases • Trial termination • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Study Investigating AGEN1777 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | Trial completion date: Sep 2025 ➔ Apr 2024

Combination therapy • Metastases • Trial completion • Trial completion date • Oncology • Solid Tumor

BMS ditches TIGIT, walking away from $200M bet on Agenus bispecific (FierceBiotech) - "Bristol Myers Squibb is axing another big bet from the Caforio era, terminating a deal for Agenus’ TIGIT bispecific antibody three years after paying $200 million to buy into the program...Agenus granted BMS an exclusive license to AGEN1777, which binds TIGIT and CD96 on T cells, in 2021 in return for $200 million upfront. BMS paid $20 million when the first patient received AGEN1777 in phase 1 later that year and handed Agenus a $25 million milestone in relation to the start of a phase 2 study in January 2024. Now, BMS has decided AGEN1777 is no longer part of its plans...Agenus plans to explore further development of the candidate, including by considering combinations with its other assets and may look for a new partner for the program."

Licensing / partnership • Pipeline update • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastroesophageal Cancer • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

A Study of BMS-986442 With Nivolumab With or Without Chemotherapy in Solid Tumors and Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=225 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Nov 2026 ➔ Jul 2024 | Trial primary completion date: Nov 2026 ➔ Jul 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Ligand Reports First Quarter 2024 Financial Results (Businesswire) - "On May 7, Ligand announced a $100 million royalty financing agreement with Agenus, Inc. Under the terms of the agreement, in exchange for an initial $75 million payment, Ligand will receive 18.75% of the royalties and 31.875% of the future milestones on six Agenus-partnered oncology programs including BMS-986442 (Bristol Myers Squibb), AGEN2373 (Gilead Sciences), INCAGN2385 and INCAGN2390 (Incyte), MK-4830 (Merck), and UGN-301 (UroGen Pharma)."

Financing • Licensing / partnership • Oncology

A Study of BMS-986442 With Nivolumab With or Without Chemotherapy in Solid Tumors and Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=225 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Study Investigating AGEN1777 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=4 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | N=75 ➔ 4

Combination therapy • Enrollment change • Metastases • Oncology • Solid Tumor

BMS-986442 (AGEN1777), a novel TIGIT/CD96 bispecific antibody, demonstrates superior monotherapy and combination activity versus conventional anti-TIGIT antibodies in preclinical models (AACR 2024) - P1/2 | "In primary human in vitro assays, BMS-986442 potently enhanced T cell responsiveness and activation compared with conventional anti-TIGIT mAbs alone and in combination with anti-PD-1 (nivolumab). Lastly, BMS-986442 promoted superior NK cell activation in tumor co-culture assays.In conclusion, BMS-986442 demonstrated a differentiated FcγR-dependent mechanism-of-action to enhance innate and adaptive immune responses compared with anti-TIGIT or anti-CD96 mAbs. BMS-986442 is currently advancing in phase I clinical studies in patients with advanced solid cancers (NCT05543629)."

IO biomarker • Monotherapy • Preclinical • Oncology • Solid Tumor • CD40 • CD8 • CD83 • CD86 • CD96 • TIGIT

Agenus Announces Preclinical Data on BMS-986442 (AGEN1777) at AACR 2024 (Businesswire) - "Agenus...announced that the first preclinical data from BMS-986442 (AGEN1777) will be presented in an oral presentation at the upcoming AACR Meeting....In non-clinical assays, BMS-986442 demonstrated superior immune activation both as monotherapy and in combination with PD-(L)1 blockade compared to conventional TIGIT antibodies."

Preclinical • Oncology

Agenus to Receive $25 Million Milestone Payment from Bristol Myers Squibb for TIGIT-CD96 Bispecific Program (Businesswire) - "Agenus...announced it has triggered the second development milestone payment under its global licensing agreement with Bristol Myers Squibb for BMS-986442, an Fc-enhanced bispecific TIGIT antibody. Agenus will receive a $25 million cash payment from Bristol Myers Squibb with the dosing of the first patient in the phase 2 dose expansion portion of the ongoing CA115-001 clinical trial of BMS-986442....The agreement also includes up to $1.32 billion in additional development, regulatory and commercial milestones plus tiered double-digit to mid-teens royalties."

Financing • Trial status • Non Small Cell Lung Cancer • Solid Tumor

A Study of BMS-986442 With Nivolumab With or Without Chemotherapy in Solid Tumors and Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=225 | Recruiting | Sponsor: Bristol-Myers Squibb | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Metastases • Phase classification • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Agenus Reports Third Quarter 2023 Results (Businesswire) - "Bristol Myers Squibb's BMS-986442, originally developed by Agenus and known as AGEN1777, is a bispecific antagonist targeting both TIGIT and CD96....Currently, a phase 2 dose expansion study is underway, assessing BMS-986442 in combination with nivolumab, with or without chemotherapy. The screening for this phase commenced on October 13, 2023, and dosing of the first phase 2 patient is scheduled for November, which will result in a milestone payment for Agenus."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of BMS-986442 With Nivolumab With or Without Chemotherapy in Solid Tumors and Non-small Cell Lung Cancer (clinicaltrials.gov) - P1b/2 | N=225 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Study Investigating AGEN1777 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=75 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Oncology • Solid Tumor

"@ScotsKnight2 @AstraZeneca @ultragenyx Big pharmas #TIGIT deals! EOS-448 @GSK → $ITOS $2B AGEN1777 @ScienceAtBMS → $AGEN $1.56B Ociperlimab @Novartis → $BGNE $1B AB308 @GileadSciences → $RCUS $700M Etiqilimab @MereoBioPharma $MREO owns 100%: no value on current MC" (@ej23ny)

TIGIT

"$BMY hedging its bets here. I think the bispecific is $AGEN AGEN1777 (Tigit x undisclosed target) $AZN" (@JacobPlieth)

TIGIT

A Study Investigating AGEN1777 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=75; Recruiting; Sponsor: Agenus Inc.; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Oncology • Solid Tumor

Agenus to Receive $20M Milestone Payment from Bristol Myers Squibb with Dosing of First Patient with its TIGIT Bispecific Antibody (GlobeNewswire) - "Agenus Inc...announced it has triggered the first development milestone payment under its global licensing agreement with Bristol Myers Squibb for AGEN1777, an Fc-enhanced bispecific anti-TIGIT antibody. Agenus will receive a $20 million cash payment with the dosing of the first patient...The first patient was treated at Providence Cancer Institute by Dr. Rachel Sanborn....The global license agreement with Bristol Myers Squibb included a $200 million upfront payment paid in July 2021, and up to $1.36 billion in development, regulatory and commercial milestones in addition to tiered double-digit royalties on net product sales."

Commercial • Trial status • Oncology • Solid Tumor

A Study Investigating AGEN1777 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=75; Not yet recruiting; Sponsor: Agenus Inc.

Clinical • Combination therapy • New P1 trial • Oncology • Solid Tumor

Agenus Corporate Update and Second Quarter 2021 Financial Report (GlobeNewswire) - “AGEN1181 rapidly advancing in the clinic; data to be presented in 2H 2021…Phase 1 trial of AGENT-797 in hematologic cancers dose cohorts completed with data readouts planned in the second half of 2021…FDA cleared Investigational New Drug (IND) application; Phase 1 dosing with AGEN1777 alone and in combination with an anti-PD-1 in advanced solid tumors planned to begin this quarter…Results from a Phase 2 trial of balstilimab plus zalifrelimab combination in recurrent or metastatic cervical cancer to be presented in a Mini Oral Session at the European Society for Medical Oncology (ESMO) Congress 2021 on September 19 from 11:35 – 11:40am ET.”

Clinical data • New P1 trial • P1 data • P2 data • Cervical Cancer • Gynecologic Cancers • Hematological Malignancies • Oncology • Solid Tumor

"💼 MedNess BUSSINESS Onco-News 📌 @OncoSec & @Merck to conduct a Ph3 Study, KEYNOTE-C87, of TAVO™ + KEYTRUDA® for Late-Stage #MetastaticMelanoma 📌 @Agenus_Bio Closes $200M Upfront @bmsnews Collaboration and Announces @US_FDA Acceptance of IND for AGEN1777" (@Medness8)

Oncology • Solid Tumor

Agenus Closes $200M Upfront BMS Collaboration and Announces FDA Acceptance of IND for Partnered Anti-TIGIT Bispecific Antibody, AGEN1777 (GlobeNewswire) - "Agenus Inc...announced the closing of its global exclusive license with Bristol Myers Squibb for Agenus’ proprietary bispecific antibody program, AGEN1777, and the U.S. Food and Drug Administration (FDA) clearance of an Investigational New Drug (IND) application for this therapy...Bristol Myers Squibb intends to advance the research and development of AGEN1777 in immuno-oncology for high priority tumor indications including non-small cell lung cancer...Phase 1 dosing for AGEN1777 is expected to begin during the third quarter of 2021....Under the terms of the agreement with Bristol Myers Squibb, Agenus receives a $200 million upfront payment in connection with the closing."

IND • Licensing / partnership • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

"$AGEN Agenus Closes $200M Upfront BMS Collaboration and Announces FDA Acceptance of IND for Partnered Anti-TIGIT Bispecific Antibody, AGEN1777 https://t.co/Bwtr7FgPfw" (@stock_titan)

FDA event • TIGIT

BMS to pay up to $1.56bn for Agenus’ bispecific antibody programme (PharmaTimes) - "BMS will pay Agenus $200m upfront and up to $1.36bn in development, regulatory and commercial milestones as well as tiered double-digit royalties on net product sales as part of the agreement...In return, BMS will become solely responsible for the development and subsequent commercialisation of AGEN1777 and any related products globally....Agenus is planning to file an investigational new drug application (IND) for AGEN1777 with the US Food and Drug Administration (FDA) in the second quarter of the year."

Licensing / partnership • Oncology

Agenus and Bristol Myers Squibb Announce Exclusive Global License for Agenus’ Anti-TIGIT Bispecific Antibody Program (GlobeNewswire) - "Bristol-Myers Squibb Company...and Agenus Inc...announced that they have entered into a definitive agreement under which Bristol Myers Squibb will be granted a global exclusive license to Agenus’ proprietary bispecific antibody program, AGEN1777, that blocks TIGIT and a second undisclosed target...Under the agreement, Bristol Myers Squibb will become solely responsible for the development and any subsequent commercialization of AGEN1777 and its related products worldwide. Agenus will receive a $200 million upfront payment and up to $1.36 billion in development, regulatory and commercial milestones in addition to tiered double-digit royalties on net product sales...Agenus expects to file an Investigational New Drug ('IND') application for the development of AGEN1777 with the U.S. Food and Drug Administration in the second quarter of 2021."

IND • Licensing / partnership • Oncology