PARPBP

Drugs that interfere with a way tumors repair damage to their DNA have become valuable tools for treating certain cancers. Some big pharmaceutical companies are developing drugs that improve on this approach, and Merck KGaA is getting its contender by striking a deal with Jiangsu Hengrui Pharmaceuticals. Per deal terms announced Monday, Merck KGaA will pay Hengrui €160 million (about $169 million) up front for global rights, except China, to HRS-1167, a small molecule belonging to a class of drugs called PARP inhibitors. Milestone payments could bring China-based Hengrui up to €1.4 billion ($1.48 billion). PARP enzymes are key to DNA damage response, a mechanism for fixing the damage resulting from the rapid proliferation of cells characteristic of cancer progression. By targeting and blocking these enzymes, PARP inhibitors prevent those repairs, which in turn leads to cell death. Lynparza from AstraZeneca and GSK’s Zejula blazed the trail for PARP inhibitors. Those commercialized drugs broadly address PARP enzymes to treat ovarian cancer, fallopian tube cancer, and primary peritoneal cancer. Hengrui’s drug is a “next-generation” PARP inhibitor designed to be a more potent and selective blocker of the PARP1 enzyme. In Monday’s announcement, Merck KGaA said specifically targeting the PARP1 enzyme offers the opportunity to expand PARP inhibition in both established and new indications. The company points to Phase 1 data showing encouraging signs of clinical activity and patient benefit as a monotherapy. Merck KGaA also noted that compared with first-generation PARP inhibitors, HRS-1167 offers greater potential for use in combination with chemotherapy as well as novel cancer drugs. Hengrui’s drug is joining a Merck KGaA pipeline that includes programs addressing other targets in the DNA damage response cascade, such as ATR, ATM, and DNA-PK. Gilead Sciences entered the chase for a selective PARP1 inhibitor earlier this year with the acquisition of privately held Xinthera and its preclinical PARP1-targeting small molecules. AstraZeneca is further ahead with AZD5305, a PARP1-blocking drug currently in Phase 2 testing as part of combinations that include Enhertu and datopotamab deruxtecan, two antibody drug conjugates (ADC) from its partnership with Daiichi Sankyo. Merck KGaA’s Hengrui deal could also yield an ADC. The agreement grants the German company the option to license global rights, excluding China, to SHR-A1904. This Hengrui ADC addresses Claudin-18.2, a protein abundant in gastric, pancreatic, and esophageal cancers. Merck KGaA said the Hengrui asset is complementary to its own ADC portfolio, which uses different technologies to link the drug payload to the targeting antibody. Merck KGaA’s ADC M9140 is in early-stage clinical development in metastatic colorectal cancer. “This partnership with Hengrui fully aligns with both our external innovation ambition and our oncology research and development strategy by diversifying our robust internal pipeline in our focus areas of DNA damage response inhibition and antibody-drug conjugates,” Danny Bar-Zohar, global head of research & development and chief medical officer for Merck KGaA’s healthcare business, said in a prepared statement. “The synergies of these assets with our portfolio offer broad potential for development and the opportunity to advance more therapeutic options for patients with difficult-to-treat cancers.”

LIANYUNGANG, China, Oct. 30, 2023 /PRNewswire/ -- Jiangsu Hengrui Pharmaceuticals Co., Ltd ("Hengrui Pharma"), a global pharmaceutical company focused on scientific and technological innovation, today announced a licensing agreement with Merck KGaA, Darmstadt, Germany, a leading science and technology company, for its next-generation potent and selective PARP1 (poly (ADP-ribose) polymerase 1) inhibitor, HRS-1167. This is Hengrui's first strategic collaboration with a global pharmaceutical company. The agreement includes an option to an exclusive license for its innovative Claudin-18.2 antibody drug conjugate (ADC) SHR-A1904. "Given the high unmet need in oncology, we are excited to work closely with Merck KGaA, Darmstadt, Germany, to bring Hengrui's innovations to cancer patients worldwide," said Frank Jiang, board member and Chief Strategy Officer of Hengrui Pharma. "Partnering with Merck KGaA, Darmstadt, Germany, on our PARP franchise is an important milestone on Hengrui's globalization journey. We look forward to advancing our molecules rapidly through development and reaching patients in need." Under the terms of the agreement, Merck KGaA, Darmstadt, Germany, will provide Hengrui Pharma with an upfront payment of €160 million. Hengrui Pharma will receive payments for technology transfer as well as an option exercise for the Claudin-18.2 ADC for up to €90 million. Upon the achievement of certain development, regulatory and commercial milestones, Hengrui is eligible to receive royalty payments on net sales of such products by Merck KGaA, Darmstadt, Germany. Potential payments may total up to €1.4 billion with up to double-digit royalty payments. "This partnership with Hengrui fully aligns with both our external innovation ambition and our oncology research and development strategy by diversifying our robust internal pipeline in our focus areas of DNA damage response inhibition and antibody-drug conjugates," said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business of Merck KGaA, Darmstadt, Germany. "The synergies of these assets with our portfolio offer broad potential for development and the opportunity to advance more therapeutic options for patients with difficult-to-treat cancers. We look forward to leveraging the significant expertise of Hengrui and our strong collaboration ahead." Merck KGaA, Darmstadt, Germany, will receive exclusive rights to develop, manufacture and commercialize HRS-1167 worldwide, outside of mainland China, an exclusive option to develop, manufacture and commercialize SHR-A1904 worldwide, outside of mainland China, and an option to co-promote HRS-1167 and SHR-A1904 in mainland China. About HRS-1167 and SHR-A1904 HRS-1167 is a selective, highly active and orally available PARP1 small molecule inhibitor internally developed by Hengrui with intellectual property rights, which belongs to the second generation of PARP inhibitors. Poly (ADP-ribose) polymerase (PARP) is key in DNA repair pathways. Compared to first-generation PARP inhibitors, HRS-1167 has higher selectivity and affinity for PARP1 and induces DNA trapping. HRS-1167 is currently in early clinical development (Phase 1) and has the potential to be used as a monotherapy and as part of a combination therapy for treating a wider range of patients. SHR-A1904 is an antibody drug conjugate (ADC) targeting Claudin 18.2, internally developed by Hengrui with intellectual property rights. It binds to the target antigen on the surface of tumor cells, allowing the drug to be endocytosed by cells and releasing a small-molecule toxin to kill tumor cells. The product is currently in clinical Phase 1 trials in China, U.S. and Australia. Currently, no Claudin 18.2 targeting ADC product has received marketing authorization. About Hengrui Pharma Hengrui Pharma is an innovative global pharmaceutical company focused on unmet clinical needs, with a strong track record of scientific and technological innovation. Since its first innovative drug approval in 2011, Hengrui Pharma has invested more than 33 billion yuan in R&D and set up 14 R&D centers in Lianyungang, Shanghai, the U.S. and Europe. It has 8 major manufacturing sites and a global R&D team of more than 5,000 professionals. Hengrui Pharma has independently established a number of leading technology platforms such as its ADC platform, proteolysis targeting chimera (PROTAC), molecular gels, bi/multi-specific antibodies, and AI molecular design, which provide a strong foundation for innovative R&D. Hengrui strives for continued innovation and collaboration with global partners to serve a healthy China and benefit patients around the world. Media Contact: Su Zhang su.zhang.sz1@hengrui.com SOURCE Jiangsu Hengrui Pharmaceuticals Co., Ltd

Pictured: Gilead sign in front of building/courtesy of Tada Images/Shutterstock Tuesday, a Delaware jury ruled in favor of Gilead Sciences, finding that the company’s HIV prevention medicines Truvada (emtricitabine/tenofovir disoproxil fumarate) and Descovy (emtricitabine/tenofovir alafenamide) do not infringe on U.S. government patents and that the patents themselves are invalid in the first place. Three patent claims were at the core of the lawsuit. Jurors overwhelmingly took Gilead’s side and found that the government failed to provide enough evidence showing that patients or physicians violated these patent protections by using Truvada or Descovy for pre-exposure prophylaxis (PrEP) for HIV. Meanwhile, the jury found that Gilead had been able to show “clear and convincing evidence” that all three patent claims were invalid. Truvada is a combination of two inhibitors of the HIV-1 reverse transcriptase enzyme. It prevents the virus from integrating its genetic material into its host and replicating inside the patient’s body. The drug was first approved in 2004 for the treatment of HIV-1 and then again in July 2012 for use as PrEP. Like Truvada, Descovy combines two HIV reverse transcriptase inhibitors and works via a similar mechanistic pathway. It was first approved in 2016 for HIV treatment and won another regulatory nod in October 2019 for prevention. A month later, in November 2019, the Trump administration, through the Department of Human and Health Services (HHS), sued Gilead over these PrEP approvals. The government alleged that the drug regimen that Truvada and Descovy use was first invented and proposed for prophylaxis by CDC researchers in the early 2000s. “Gilead has received billions of dollars in revenue from HIV prevention regimens invented by HHS researchers and patented by the United States,” said Jody Hunt, the Department of Justice’s assistant attorney general for the civil division in a 2019 statement. Cancer, Inflammatory Disease Deal Also on Tuesday, Gilead announced it was acquiring private San Diego biotech XinThera but declined to disclose the deal’s financial details. The buyout will give Gilead rights to XinThera’s small molecule inhibitors targeting the PARP1 protein for oncology indications and the MK2 protein for inflammatory diseases. Both PARP1 and MK2 programs have candidates that could enter clinical trials later this year and could also be leveraged to address other conditions, with the potential for combination treatments with other molecules in Gilead’s portfolio. XinThera’s highly selective PARP1 inhibitors bypass the hematological toxicities typically seen with first-generation dual PARP1/2 inhibitors. This could potentially enable combo treatments with DNA-damaging agents such as Gilead’s own Trodelvy (sacituzumab govitecan-hziy), which delivers a toxic payload into cancer cells to induce cell death. Trodelvy was first approved in 2020 for metastatic triple-negative breast cancer. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.