Patisiran sodium

NewLimit’s lead asset uses lipid nanoparticles to deliver mRNA to liver cells that codes for transcription factors known to make hepatocytes look—and act—younger.\n Anti-aging biotech NewLimit plans to push a liver-rejuvenating mRNA medicine into the clinic with the aid of a $130 million series B fundraising round.The round was led by Kleiner Perkins alongside new investors Nat Friedman/Daniel Gross, Khosla Ventures and Human Capital, the company announced in a May 6 release.The preclinical company’s lead asset uses lipid nanoparticles to deliver mRNA to liver cells that codes for transcription factors known to make hepatocytes look—and act—younger, NewLimit co-founder and President Jacob Kimmel, Ph.D., told Fierce Biotech in an interview.“Old and young cells use different genes,” Kimmel said, “and then, more importantly, old cells have a loss of function that occurs in the cell types that we\'re going after.” In the liver, for example, older cells aren’t as good at processing alcohol and caffeine as younger cells, Kimmel added.The company’s first target is alcohol-related liver disease, Kimmel said, with plans to enter the clinic in the next few years. But, just like GLP-1s before them, NewLimit hopes to use early indications as a stepping stone to broader and broader patient populations. “We\'ve really been inspired by GLP-1s, medicines that started in a group of diabetic patients that later expanded through obesity and later to a number of other indications as well,” Kimmel said. “Following an approval in alcoholic liver disease, if we are so lucky, we would then hope to expand to earlier stage liver disease patients for multiple etiologies, and eventually to treating patients who have metabolic syndrome.” Kimmel said the company is developing intravenous drugs with the goal of dosing every three weeks at the shortest, similar to Alnylam’s small interfering RNA drug Onpattro (patisiran).“You can dose that medicine every three weeks, and this is something where it\'s both demonstrated to be safe and effective and commercially viable,” Kimmel said. “We see that as sort of the minimum bar, and we think we\'ve got some early evidence today that we\'re on track.”NewLimit’s science builds on discoveries in epigenetic reprogramming, the idea that tweaks to how genes are expressed can make cells behave differently or even switch cell types entirely. For example, Shinya Yamanaka, Ph.D., won a Nobel Prize in 2012 for demonstrating that mouse skin cells could be induced to turn into stem cells, at which point they could then develop into many other possible cell types.NewLimit was founded in 2022 with the goal of making medicines that reprogram old cells to extend patients’ health spans, a term that has been growing in popularity. Last month, Flagship Pioneering debuted a preemptive medicine biotech called Etiome with $50 million in financing and a goal of “increasing our health spans, not just our lifespans,” company CEO Avak Kahvejian, Ph.D., told Fierce.

When CRISPR pioneer Feng Zhang met with investors to discuss his new drug delivery technology over dinner in the summer of 2021, it didn’t take long to pitch the idea. By the time the appetizers arrived , the investors were sold. But getting the technology to work well enough to test in humans will take longer, and in the meantime, Zhang’s company, Aera Therapeutics , is turning to an older delivery technology for some of its first programs, Endpoints News has learned. The Cambridge, MA-based company initially focused on developing novel protein nanoparticles that promised to deliver CRISPR gene editing therapies into parts of the body that lipid nanoparticles have had a hard time reaching, such as the brain, kidney and muscles. But now Aera is turning to lipid nanoparticles for at least one of its programs. Aera has developed lipid nanoparticles, or LNPs, that target T cells of the immune system. It hopes to create CAR-T cell therapies that quell autoimmune diseases via a simple blood infusion. The so-called in vivo cell therapy approach could reduce the complexity and expense of commercial therapies that require removing a patient’s cells from their body and editing them in the lab, a process known as ex vivo cell therapy. Developing in vivo cell therapies for autoimmune disease, cancer and genetic blood diseases like sickle cell is quickly becoming one of the most competitive parts of the cell and gene therapy field. Only a few companies have begun testing in vivo cell therapies in the clinic, but well over a dozen have declared their intentions to join the race. Aera is undaunted. “We understand it’s very competitive. But at the same time, it’s not solved,” Aera CEO Akin Akinc told Endpoints News . “No one’s really that far ahead,” he added. “In the autoimmune space, there’s probably going to be a lot of winners.” Akinc said that the addition of LNPs doesn’t mean that the company’s work on protein nanoparticles has been harder or slower than expected, though he noted that Aera’s protein nanoparticle therapies are “probably going to be a little bit further off than some of the nearer term applications with LNPs.” “This was going to be a platform build,” Akinc said. “I think the investors, I think all of us, knew that was going to take time.” Aera started working on LNPs about a year and a half ago, according to Akinc. And in some ways, the shift isn’t a total surprise. Akinc helped develop the LNPs used in Onpattro, the first gene-silencing RNAi therapy made by Alnylam Pharmaceuticals, and the first product using fatty bubbles to safely deliver genetic medicines to the human body. LNP scientists are in high demand, but they’re easier to find than experts in protein nanoparticles, a technology that has barely begun to emerge from academic labs. Since both lipid and protein nanoparticles are manufactured synthetically — as opposed to viral vectors, which are grown in cells — Aera has recruited many LNP scientists to its company, and it’s been natural for them to switch between the two platforms, he said. When infused into the bloodstream, LNPs tend to get soaked up by the liver. Figuring out how to redirect them to bone marrow or immune cells, and at doses that can be safely administered and affordably manufactured, is no small feat. Most companies, including Aera, are reluctant to say exactly how they’re doing it. “I can’t give you all the secrets,” Akinc said. “But philosophically, we felt that it didn’t make sense to take standard LNPs for the liver and simply slap on a targeting ligand, right?” Instead, Aera scientists re-engineered the nanoparticle to avoid the liver and then added a targeting molecule — Akinc won’t say what kind — to direct them to T cells. While other companies have begun to share promising results in mice and monkeys, it’s too soon to know if these will hold up when tested in people. The work was disclosed this week in an abstract for the upcoming American Society of Gene & Cell Therapy meeting in New Orleans. Akinc said it’s Aera’s first presentation at a scientific conference. Akinc described the LNP therapy for autoimmune disease as one of several discovery-stage programs at the company. Aera hasn’t named a lead program, disclosed its other programs, or said when it expects to start the first clinical trial. And Akinc emphasized that its work on protein nanoparticles continues. “We’re aiming those at taking big swings at really tough problems that have been difficult to solve with LNPs and viral vectors,” such as delivery of mRNA-based therapies to the brain, he said. And he doesn’t want to use the protein nanoparticles for things that can be done with LNPs. “That’s why we didn’t say let’s do T cell targeting with [protein nanoparticles] because we think we could do that with LNPs,” he said.