TGF-β x LRRC32

Swiss-based Roche announced it is buying UK-based Tusk Therapeutics in a deal that could hit $758 million (U.S.). Swiss-based Roche announced it is buying UK-based Tusk Therapeutics in a deal that could hit $758 million (U.S.). Under the terms of the acquisition, Roche is paying $81 million upfront with another possible $677 million in various milestone payments. This is another deal in the immuno-oncology area. Tusk focuses on developing therapeutic antibodies to treat cancer. It currently has two lead programs, CD25 and CD38. The focus is on T regulatory cells (Tregs). Jonathan Gardner, writing for Vantage, says, “The UK group’s focus on trendy T regulatory cells (Tregs) in immuno-oncology certainly did not hurt its case, as the biopharma world casts around for ways to magnify the benefit of PD-(L)1 agents like Roche’s Tecentriq. The rationale is that by turning off the immunosuppressive effects of Tregs, PD-(L)1 agents will work even better.” Both CD25 and CD37 are the targets of the company’s two programs, both in Phase I clinical studies. It is believed that Tregs target both CD25 and CD37. CD38 is the target of Johnson & Johnson ’ s Darzalex, where it inhibits growth of CD38-positive multiple myeloma cells. Tusk hopes to develop its compound in solid tumors. “We are delighted that Roche will further develop this novel antibody and drive the development ahead,” said Luc Dochez , Tusk’s chief executive officer, in a statement. “The remaining portfolio of our immune-oncology targets will be further developed by Black Belt Therapeutics , a newly formed company spun out of Tusk Therapeutics.” Tusk was founded in 2014 by Droia Oncology Ventures . It is built on the work of Sergio Quezada, professor in the Research Department of Haematology at the University College London (UCL) Cancer Institute in London. The company has strategic partnerships and licensing deals with Cancer Research Technology, Cancer Research UK ’ s commercial arm and UCL. Gardner writes, “In acquiring Tusk, Roche became the first big pharma to complete a Treg deal focused on oncology. Lilly ’s license of NKTR-358, a Treg stimulator, is focused on stimulating Tregs to fight lupus, while Novartis ’s deal with Parvus is related to Treg downregulation of beta cell-destroying immune cells in type 1 diabetes.” In late-August, AbbVie exercised its exclusive license option to develop and commercialize Belgium-based Argenx ’s ARGX-115. The compound is an antibody that targets novel immuno-oncology target glycoprotein A repetitions predominant (GARP). ARGX-115 is currently in preclinical studies. The compound binds specifically to GARP, which is key in regulating production and release of active transforming growth factor beta (TGF-beta). The companies believe the compound can selectively limit the immunosuppressive activity of activated regulatory T-cells. This results in stimulating the immune system to attack cancer cells. The compound was discovered under Argenx’s Innovative Access Program with the de Duve Institute at the Catholique University of Louvain and WELBIO. It was then licensed under a research and option deal in 2013. And in July, BioLineRx , based in Tel Aviv, Israel, and Merck & Co. , based in Kenilworth, New Jersey, announced they are expanding their immuno-oncology collaboration. The collaboration revolves around the combination of BioLineRx’s BL-8040 in combination with Merck’s Keytruda (pembrolizumab), an anti-PD-1 therapy, in patients with metastatic pancreatic cancer. This is currently in a Phase IIa clinical trial. Under the expansion agreement, they will investigate a triple combination looking at the safety, tolerability and efficacy of BL-8040, Keytruda and chemotherapy. In earlier work presented at ASCO 2018 Gastrointestinal Cancers Symposium in January, BL-8040 as a monotherapy was found to be safe and well tolerated and increased infiltration of T-cells into the tumor in metastatic pancreatic cancer patients. It also caused an increase in the number of total immune cells in the peripheral blood, while peripheral blood regulatory T-cells (Tregs), which can slow anti-tumor immune response, decreased. Topline data for the combination is expected to be released in the second half of this year.

Chicago-based AbbVie has exercised its exclusive license option to develop and commercialize Belgium-based Argenx’s ARGX-115. The compound is an antibody that targets novel immuno-oncology target glycoprotein A repetitions predominant (GARP). Chicago-based AbbVie has exercised its exclusive license option to develop and commercialize Belgium-based Argenx ’s ARGX-115. The compound is an antibody that targets novel immuno-oncology target glycoprotein A repetitions predominant (GARP). The original deal was inked in April 2016. With today’s announcement, AbbVie picks up a worldwide, exclusive license to develop and commercialize ARGX-115-based products. Argenx is eligible for various milestone payments up to $625 million in addition to tiered royalties on any commercial products. Argenx also has the rights to co-promote any ARGX-115-based products in Europe and the Swiss Economic Area. “We are very excited by AbbVie’s decision to exercise its option to license and develop ARGX-115, given its compelling track record in oncology,” said Tim Van Hauwermeiren, Argenx’s chief executive officer, in a statement. “We are proud of the work that this milestone represents for Argenx—both in efficiently advancing a premier Innovative Access Program candidate to clinical development and in facilitating wider recognition of the important research out of the de Duve Institute/Catholique University of Louvain around this first-in-class target.” ARGX-115 is currently in preclinical studies. The compound binds specifically to GARP, which is key in regulating production and release of active transforming growth factor beta (TGF-beta). The companies believe the compound can selectively limit the immunosuppressive activity of activated regulatory T-cells (Tregs). This results in stimulating the immune system to attack cancer cells. The compound was discovered under Argenx’s Innovative Access Program with the de Duve Institute/Université Catholique de Louvain and WELBIO . It was then licensed under a research and option deal in 2013. Hauwermeiren went on to say, “Our Innovative Access Program remains a strategic priority for us, capitalizing on the combined strengths of the Argenx antibody platform and the deep disease biology expertise at research institutions. We continue to seek out cutting-edge research and targets while advancing our current collaborations, all with the potential to broaden our pipeline and demonstrate our discipline as a strategic partner.” Pharmaphorum notes, “AbbVie is lagging behind rivals in the field of cancer immunotherapy. While Bristol-Myers Squibb and Merck & Co . have been marketing PD-1 checkpoint inhibitors for several years, AbbVie’s PD-1 drug is only in early trials. AbbVie also has an anti-CD40 antibody in early stage development for solid tumors.” Eli Lilly is also working in the area of TGF-beta inhibition. Its galunisertib is in Phase II/III trials for hepatocellular carcinoma. “Immuno-oncology is one of AbbVie’s key focus areas in our mission to discover and develop medicines that drive transformational improvements in cancer treatment,” said Tom Hudson, AbbVie’s vice president, Oncology Early Discovery and Development, in a statement. “Our collaboration with Argenx over the past two years has been productive, and we look forward to continue working together to fuel scientific progress for patients.” According to Reuters, after the announcement, Argenx shares climbed by more than 6 percent in early trading. “After listing on the stock market in 2014, Argenx’s share price has increased tenfold and it joined Belgium’s blue-chip index Bel20 earlier this year.”

April 21, 2016 By Alex Keown , BioSpace.com Breaking News Staff NORTH CHICAGO, Ill. – AbbVie struck a deal with Belgium-based drugmaker argenx worth up to $685 million on a preclinical immuno-oncology drug targeting GARP, a protein believed to contribute to immuno-suppressive effects of T-cells. AbbVie will pay argenx $40 million upfront for the development and commercialization ARGX-115. Argenx will also be eligible to receive $20 million in additional milestone payments. The remaining hundreds of millions of dollars that are possible parts of the deal would come to argenx based on pre-determined milestones as well as tiered, up to double-digit royalties on net sales upon commercialization, the companies announced this morning. Tim van Hauwermeiren , chief executive officer of argenx, said in a statement his company believes ARGX-115 has the potential to advance immuno-oncology by selectively targeting tumor immune escape pathways. “The ability to modulate the body’s own immune system to fight cancer is one of the most promising scientific advancements over the past decade,” said Anil Singhal , vice president of early oncology development at AbbVie. “We believe that the ARGX-115 program is a unique opportunity to explore the potential to block certain immune-suppressive pathways that allow cancers to grow.” GARP is a protein present on the surface of regulatory T lymphocyte, also referred to as Tregs, which inhibit immune responses in order to prevent unwanted auto-immune disorders. But in patients suffering from cancer, Tregs play a negative role by suppressing immune responses needed to destroy cancer cells. GARP allows Tregs to execute their immunosuppressive action by triggering the production of an inhibitory messenger, a cytokine known as “TGF-beta,” according to data provided by argenx. In addition to the ARGX-115 program, and upon reaching a predetermined preclinical stage milestone, AbbVie will fund further GARP-related research by argenx for an initial period of two years. AbbVie will have the right to license additional therapeutic programs emerging from this research, for which argenx could receive associated milestone and royalty payments. Immunotherapy is one of the areas of cancer research many companies, such as AstraZeneca , Genentech , Clovis Oncology , Kite Pharmaceuticals and more, are focusing on for cancer treatments. Immunotherapy is a treatment approach that focuses on harnessing the body’s own immune system to fight cancer cells. Scientists are using various approaches to trigger immune system responses, including the use of checkpoint inhibitors The deal will also grant argenx the right to co-promote ARGX-115-based products in the European Union and Swiss Economic Area and combine the product with its own future immuno-oncology programs. Should AbbVie not exercise its option to license ARGX-115, argenx retains the right to pursue development of ARGX-115 alone, the two companies said. Not only is AbbVie furthering its immunotherapy position with the argenx collaboration, but the company also struck a five-year agreement with the University of Chicago to improve the pace of discovery and advance medical research in oncology. Both organizations will initially work together to advance research in several areas of oncology, which include breast, lung, prostate, colorectal and hematological cancer, AbbVie announced this week.