ARO-HSD

GSK is looking for hints of causality in Mendelian genetics—or patterns in biological inheritance—that cause significant disease early in life.\n Following GSK’s deal-heavy end to 2024, Chief Scientific Officer Tony Wood, Ph.D., doesn’t expect the trend to let up in the new year, zeroing in on partnerships that can expand knowledge about genetic factors driving disease. And, while Wood said the pharma still isn’t interested in joining the overcrowded obesity landscape, GSK is considering ways to build past the GLP-1 space.  GSK started this year’s J.P. Morgan Healthcare Conference by acquiring precision biotech IDRx, including its phase 3-ready gastrointestinal cancer candidate, for $1 billion.“Obviously, we have a growing interest in in rectal, colorectal and GI cancers,” Wood told Fierce Biotech on Monday at the conference, adding that IDRx has all the characteristics he and Chief Commercial Officer Luke Miels look for in business deals.“It\'s got an interesting clinical profile that could be accelerated,” Wood said. “That profile is anchored in something you can explain from the early characteristics of the molecule and strategically aligned with our growing interests in solid tumors associated with the GI tract.”The deal follows a string of partnerships penned over the last few months, including a $35 million upfront Alzheimer’s pact with Danish biotech Muna Therapeutics, a deal involving Rgenta’s RNA-targeting discovery platform, an antibody-drug conjugate deal with Duality, a $45 million upfront Relation-ship for fibrotic diseases and osteoarthritis, and a multi-target neurodegenerative pact with Vesalius Therapeutics.And Wood doesn’t expect the deals to slow down anytime soon. But what does the London-based Big Pharma look for in potential partners? The most optimal deals are “all about target finding” and “matching targets to patients,” Wood said.GSK has invested heavily in large-scale data sets for genetics, Wood explained, adding that the focus was a priority for former GSK CSO Hal Barron, M.D., who headed over to Altos Labs in 2022.Leveraging those deals and data, GSK hunts for signs of causality in Mendelian genetics—or patterns in biological inheritance—that cause significant disease early in life.The partnerships help the Big Pharma piece together what kind of impact particular pathways or forms of pharmacology can have, Wood said, providing GSK-4532990 in alcoholic liver disease (ALD) as a prime example.Back in 2021, GSK picked up the investigational siRNA oligonucleotide via a partnership with Arrowhead. The candidate targets HSD17B13, a gene that is involved in lipid metabolism and is mainly expressed in the liver.In a phase 1 study, the asset demonstrated a “durable reduction in HSD17B13 expression and reductions in key marker of liver injury,” according to a Dec. 17 event (PDF) about GSK’s early pipeline.Human studies show that naturally occurring gene variants protect against both alcohol-related and nonalcohol-related liver disease, GSK said, cutting risk by about 30% to 50% for carriers compared to those without.“This is one of the strongest levels of genetic validation we’ve seen for any target,” the Big Pharma said. “And, reassuringly, this protective effect is maintained even in the case of continued alcohol consumption.” “So, we\'ve got this lovely example of the genetics line up, [and] the targets line up in the cells that are showing the disease,” Wood told Fierce.That gives GSK confidence in the candidate, with a pair of phase 2 studies assessing the siRNA’s efficacy in both metabolic dysfunction-associated steatohepatitis patients with advanced fibrosis and patients with ALD.The program is emblematic of GSK’s plans for obesity—that is to say, Wood still doesn’t intend on moving directly into the heavily populated landscape, but that doesn’t mean the company isn’t touching obesity-related conditions.“It\'s very crowded, and I\'ve got an enormously exciting portfolio in front of me already,” Wood said, adding that he’s instead eyeing the later stages of diseases driven by inflammation.The Big Pharma is considering what comes after GLP-1s and what could be used with GLP-1s across lung, liver and kidney indications, he explained.“We\'re deliberately targeting mechanisms that are going to be at that more fibrotic end of the spectrum,” Wood said. “A lot of our thinking in that area is really about what remaining risk persists after you\'ve dealt with the problems of weight reduction.” 

Elsie Biotechnologies今天宣布，继2023年7月宣布的研究合作取得成功之后，GSK已对Elsie的发现平台行使非独家许可的选择权，以探索该平台的功能。这将允许GSK在其寡核苷酸药物发现研究中采用Elsie的发现平台和P（V）化学技术。 Elsie Biotechnologies致力于通过整合药物发现、开发和递送环节来发挥寡核苷酸疗法的全部潜力，以提升治疗效果、降低毒性、并优化递送过程。Elsie公司的发现平台是一项超高通量的专有工艺，可以对寡核苷酸分子的化学空间进行全面评估。通过将其专有的编码技术应用于寡核苷酸治疗候选药物，研究人员可以评估所有可能的核苷酸序列或化学修饰模式，以增加活性、降低毒性和改善递送。此外，Elsie还应用其专有的P（V）化学技术，包括一套新型试剂和工艺，以完全合成控制的方式来合成多种寡核苷酸疗法。 根据协议条款，Elsie将收到GSK的许可付款，并可根据具体目标获得额外的开发和商业里程碑。GSK活跃于寡核苷酸领域，其在2022年12月与Wave Life Sciences达成1.7亿美元合作，以使用该公司的寡核苷酸平台，该平台提供编辑、剪接和沉默形式的三种RNA靶向模式。此外，GSK与Ionis Pharmaceuticals合作的反义寡核苷酸药物bepirovirsen目前正在进行两项3期试验，作为乙型肝炎病毒感染的潜在“功能性治愈”药物，该药物于本周获得美国FDA的快速通道资格。GSK还与Arrowhead Pharmaceuticals合作开发GSK4532990，该药物正处于2期开发阶段，用于治疗脂肪性肝炎。 参考资料： [1] GSK Exercises Option to License Elsie Biotechnologies’ Discovery Platform to Find and Develop Novel Oligonucleotides. Retrieved February 14, 2024 from https://www.businesswire.com/news/home/20240213991639/en/GSK-Exercises-Option-to-License-Elsie-Biotechnologies%E2%80%99-Discovery-Platform-to-Find-and-Develop-Novel-Oligonucleotides [2] GSK still has a crush on oligonucleotides, sealing the deal with Elsie. Retrieved February 14, 2024 from https://www.fiercebiotech.com/biotech/gsk-still-has-crush-oligonucleotides-seals-deal-elsie 内容来源于网络，如有侵权，请联系删除。