CD96

Preclinical findings demonstrate superior pharmacological activity, offering a differentiated mechanism-of-action to enhance anti-tumor immunity in advanced solid cancers LEXINGTON, Mass.--(BUSINESS WIRE)-- Agenus Inc. (“Agenus”) (Nasdaq: AGEN), a leader in discovering and developing novel immunological agents to treat various cancers, today announced that the first preclinical data from BMS-986442 (AGEN1777) will be presented in an oral presentation at the upcoming AACR Meeting, to be held April 5 – 10, 2024 in San Diego, CA. 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. This novel, Fc-enhanced, bispecific antibody is differentiated from conventional TIGIT monoclonal antibodies by optimally targeting two critical immune checkpoint receptors in the same pathway, TIGIT and CD96. BMS-986442 (AGEN1777) leverages Agenus’ proprietary Fc-engineering platform to harness novel mechanisms of action that extend beyond the capabilities of conventional anti-TIGIT therapy. This innovative strategy could represent a promising approach to overcome the limitations of current anti-TIGIT therapies. “Immune checkpoint blockade has emerged as a powerful strategy in enhancing anti-tumor immunity. However, conventional TIGIT antibodies have faced limitations with monotherapy activity in clinical settings,” said Dhan Chand, Ph.D., Vice President of Research. “BMS-986442 has the potential to address these challenges through Fc modification and the targeting of complementary pathways.” Presentation Details: Abstract Title: BMS-986442 (AGEN1777), a novel TIGIT/CD96 bispecific antibody, demonstrates superior monotherapy and combination activity versus conventional anti-TIGIT antibodies in preclinical models Abstract Number: 3915 Presenting Author: Dhan Chand Session: Immune Targets and Therapies Presentation Session Date and Time: Monday April 8, 2024, 2:30 p.m. – 4:30 p.m. PST Data presented at the conference will be available to view in the publications section of the Agenus website ( ) following the AACR Meeting. About BMS-986442 (AGEN1777) BMS-986442 (AGEN1777) is being developed in partnership between Agenus and Bristol Myers Squibb. The TIGIT and CD96 bispecific antibody is currently being investigated for the treatment of multiple solid tumors in clinical studies in combination with nivolumab and/or chemotherapy. TIGIT is expressed on T cells and NK cells, sharing ligands with the CD96 receptor, and generating co-stimulatory or co-inhibitory signals. Co-inhibition of TIGIT and CD96 is intended to restore effector cell function by blocking the inhibitory immune checkpoint signaling pathway. About Agenus Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The company’s mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus is headquartered in Lexington, MA. For more information, visit or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. Forward Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding a partnered BMS-986442 program, expected timelines, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.

GSK CEO Emma Walmsley sees particular potential to outperform in specialty oncology. GSK is moving to ease worries about the looming loss of exclusivity on its HIV blockbuster, setting out plans to launch at least 12 major products and deliver more than 38 billion pounds sterling ($48 billion) in risk-adjusted sales by 2031. The company expects dolutegravir, which brought in (PDF) 5.4 billion pounds last year, to lose exclusivity in the U.S. and the EU from 2028 to 2030. With the HIV drug accounting for almost 20% of sales in 2023, the prospect of generic rivals turning a major product into a footnote in GSK’s earnings is a source of concern for investors as they evaluate how the company will look at the end of the decade. GSK used its fourth-quarter results to try to allay those concerns. Talking on GSK’s results call with investors, CEO Emma Walmsley set out a “planned set of near-term new product launches, each with peak year sales potential of 2 billion pounds or more,” that will soften the impact of the loss of exclusivity. The road map includes more than 4 billion in peak sales linked to both depemokimab, the long-acting anti-IL-5 treatment GSK is studying in asthma, and pneumococcal vaccines acquired in the $3.3 billion takeover of Affinivax. GSK tipped mRNA seasonal flu and combination sales to top out above 3 billion pounds and the cough candidate acquired in the $2 billion Bellus buyout to hit 2.5 billion pounds. GSK is predicting more than 38 billion pounds in 2031 sales. Walmsley said GSK recognizes “there is development risk” and, “by definition, not everything will come through.” But, equally, the forecast is risk-adjusted and, as such, “there’s significant potential for upside with successful development outcomes,” the CEO said.  Walmsley sees particular potential to outperform in specialty oncology, “reflecting the development risk and the upside returns.” The cancer side of the schedule features new opportunities for Jemperli, GSK’s PD-1 drug, and antibodies that target the CD226 axis. GSK has invested in all three CD226 checkpoints, namely TIGIT, CD96 and PVRIG, and believes the gamble may be rewarded with 2 billion pounds in peak sales. Tony Wood, Ph.D., chief scientific officer at GSK, told investors that data on the CD226 axis will “begin to mature” toward the end of the year and will support conversations about “exploring our combinations with TIGIT in particular.” Lung and head and neck cancer are among the indications on GSK’s hit list.

The clinical trial for NTX1088 has progressed to include a new combination arm with KEYTRUDA® and expanded to 5 global sites, including 2 Israeli sites JERUSALEM, Dec. 26, 2023 /PRNewswire/ -- Nectin Therapeutics Ltd., (Nectin), a biotechnology company developing novel targeted immunotherapies that address resistance to approved immune oncology treatments, announced today that it has progressed its Phase 1 clinical trial of NTX1088 to include a combination therapy arm with the immune-oncology drug KEYTRUDA® (pembrolizumab), MSD's anti-PD-1 therapy, and expanded the trial to four additional global sites to include Sheba Medical Center, Hadassah Medical Center, Ochsner Health, and City of Hope along with flagship site, MD Anderson Cancer Center. NTX1088 is Nectin's First-in-Class lead candidate – a highly potent monoclonal antibody directed against PVR (CD155), a transmembrane protein expressed on cancer cells and associated with resistance to PD1 and PDL1 immune checkpoint inhibitors. PVR blockade by NTX1088 is the first and only therapeutic approach aimed at restoring the antitumor immune activity of DNAM1 (CD226). DNAM1 is a cell surface glycoprotein, central to the function of T and NK cells, that is degraded by PVR on tumor cells. Restoring the expression and activation of DNAM1 by blocking PVR results in increased antitumor activity from T and NK cells. PVR blockade by NTX1088 further stimulates an antitumor immune response by preventing the suppressing signaling of several immune checkpoint receptors, including TIGIT and CD96. NTX1088 is currently being clinically evaluated as a monotherapy and in combination with KEYTRUDA® (pembrolizumab). "We are very pleased to treat Israeli patients as part of NTX1088's clinical trial," said Dr. Raanan Berger, Director of the Cancer Center at the Sheba Medical Center. "We are impressed by the pre-clinical data and the novel mechanism of action of PVR blockade and are looking forward to collaborating with Nectin Therapeutics to evaluate the impact of this first-in-class therapy for cancer patients." "Nectin's innovative pipeline holds a therapeutic promise for patients with hard-to-treat cancers. This transformational potential is proudly driven by dedicated research efforts in Israel, making it very compelling for Nectin to establish trial sites close to home," said Dr. Keren Paz, Chief Development Officer of Nectin Therapeutics. "We are encouraged by the rapid progress of our NTX1088 clinical program and are excited to expand it globally." About NTX1088 NTX1088 is a first-in-class monoclonal antibody directed against a key immune checkpoint, PVR (CD155), currently in a Phase I clinical trial. NTX1088 blocks the interaction between PVR and DNAM1(CD226), a transmembrane molecule, involved in the activation of anti-cancer T and NK cells. By preventing internalization and degradation of DNAM1, NTX1088 leads to restoration of DNAM1 expression on the surface of immune cells, resulting in robust antitumor activity. NTX1088 also blocks PVR interactions with its other ligands, such as TIGIT and CD96, preventing their immune inhibitory signaling. NTX1088 demonstrates superior antitumor activity compared to approved and investigational immune checkpoint inhibitors in preclinical models and had a favorable safety profile in non-human primates. NTX1088 is currently being clinically evaluated as a monotherapy and in combination with KEYTRUDA® (pembrolizumab). About Nectin Therapeutics Nectin Therapeutics is a clinical stage biotechnology company devoted to transforming the lives of cancer patients by leveraging unique insights into the nectin pathways to develop the next generation of immune oncology (IO) therapies. The company's differentiated therapies have the potential to set new standards for efficacy and patient response rates across various difficult-to-treat cancers. Nectin's technology addresses major escape mechanisms of current IO therapies through a diverse pipeline of novel monoclonal antibodies and antibody-drug-conjugates (ADC). It has a world-class scientific and management team with deep experience in oncology drug development and a successful track record in building biotechnology companies and developing innovative therapies. Nectin Therapeutics is a venture-backed, privately held company, funded by aMoon Fund, Peregrine Ventures, IBF, Integra Holdings, the Myeloma Investment Fund (MIF), and the Cancer Focus Fund. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Media Relations Rebecca Ash Gova10 for Nectin Therapeutics rebecca@gova10.com +972-52-663-5075 SOURCE Nectin Therapeutics