University of California San Diego

Ionis Pharmaceuticals is looking to extend the reach of Tryngolza (olezarsen) beyond its initial approval for an ultra-rare genetic lipid disorder, as new Phase III trial data suggest its drug could become the first treatment option for a much larger patient group. On Tuesday, the company reported that an 80-mg monthly dose of the RNA-targeted medicine lowered fasting triglyceride levels by 72% in the CORE study and 55% in the CORE2 study, compared to placebo, in patients with severe hypertriglyceridaemia (sHTG). A 50-mg dose produced placebo-adjusted reductions of 63% and 49%, respectively. Both studies, which together enrolled a total of 1063 participants, required patients to remain on standard lipid-lowering therapy throughout the trial period.The trials also met their secondary endpoint, showing a substantial decline in acute pancreatitis events. Across both trials, pooled data indicated that Tryngolza reduced such events by 85% versus placebo over 12 months, the first therapy to do so, according to Sam Tsimikas, Ionis' head of global cardiovascular development"Despite current standard of care and lifestyle changes, people with sHTG — who could have triglyceride levels reaching into the thousands — remain vulnerable to unpredictable and life-threatening acute pancreatitis attacks," Tsimikas said. Participants were randomised to receive Tryngolza or placebo every four weeks via subcutaneous injection for a year. Adverse events were generally mild, with injection site reactions being the most common side effect. Year-end filing Ionis intends to file a supplemental new drug application with the FDA by year-end, with detailed trial data slated for presentation at an upcoming medical conference. The readout could position Ionis to expand beyond the narrow market it entered last December, when the FDA approved Tryngolza for familial chylomicronaemia syndrome (FCS), a rare subtype of sHTG. While FCS represents only about 3000 US patients, sHTG affects some 3 million people in the country, including more than a million who are considered high risk. In an interview with FirstWord last year, CEO Brett Monia said that "having first-mover advantage just solidifies our leadership in this space," as the company looks to tackle other forms of sHTG. For more, see – ViewPoints: Though Tryngolza faces modest FCS market, nod offers foot in door to larger opportunity.

Welcome to another edition of Endpoints Weekly, and happy Labor Day weekend! I’ve returned from vacation and am ready to help you get your weekend started. Let’s get into the headlines. We had a lot of news out of Washington, DC this week, including growing turmoil at the CDC, where the Trump administration pushed out Director Susan Monarez just a few weeks after she was confirmed by the Senate. Reports indicated that HHS Secretary Robert F. Kennedy Jr. pressured Monarez to change the agency’s guidance on Covid-19 vaccines. Read more below on all the updates from the nation’s capital. Elsewhere, we had a story from Jared Whitlock this week about how Scripps is shaking up its business model to reduce its dependence on government funding. Novartis also made a deal with the inventor of Eisai and Biogen’s Alzheimer’s drug Leqembi, while Merck outlined the strategy for its $5 billion HIV business. And biotech correspondent Kyle LaHucik took a look at the emerging MC4R landscape. Have a great holiday weekend! — Max Gelman Susan Monarez was pushed out of her role as CDC director, weeks after being confirmed. While the exact reason wasn’t immediately clear, lawyers saying they represent Monarez initially claimed in a social media post that she had not officially been fired and would not resign, Endpoints’ Alexis Kramer and Max Bayer wrote . The Washington Post, which first reported the news, said Monarez had refused to resign after pressure to change vaccine policy. HHS announced in a social media post that Monarez is no longer CDC director, and said Secretary Robert F. Kennedy Jr. “has full confidence in his team.” Other CDC leaders have resigned, according to the Post and other media reports, including CDC chief medical officer Debra Houry and National Center for Immunization and Respiratory Diseases Director Demetre Daskalakis. The Post reported that HHS Deputy Secretary Jim O’Neill has been tapped as acting CDC leader. 💰A decade ago, Scripps Research’s financial model looked much different. The nonprofit once got 70% of its funding from government grants. Now that share is 30%, Jared Whitlock reported this week. The organization is pushing discoveries into clinical trials and launching a fund backed by private investors. The reinvention has left Scripps better positioned than other research institutes to withstand recent science funding cuts — and it’s attracting attention from other research institutions looking for ways to shore up their finances. “We as nonprofits need to start thinking more broadly about how we fund and grow our impact than simply relying on federal funding and philanthropy,” Scripps CEO Peter Schultz said in an interview. Read more about Scripps’ model here. 🔬 A growing number of drugmakers is focusing on the melanocortin 4 receptor, or MC4R, one of the most genetically validated pathways in weight control. Superluminal Medicines, Deep Apple Therapeutics and Congruence Therapeutics are all planning to move MC4R-targeting drugs into the clinic next year. Rhythm CEO Alastair Garfield said MC4R is part of a system “designed to be able to control your hunger, your energy expenditure and your body weight.” While it could have implications in weight loss, Pfizer appears to be going for a different outcome. The pharma giant quietly launched a Phase 1 study on the US clinical trials registry last month to treat older adults with unintended weight loss and/or people at risk of malnutrition, according to the database. Check out Kyle LaHucik’s story for the details. 🤝 Novartis is teaming up with BioArctic to help solve the mysteries of the blood-brain barrier. The arrangement will pair BioArctic’s BBB technology with an in-house antibody from Novartis to create a new drug. The deal is worth $30 million upfront and up to $772 million in biobucks, and Novartis has an option for a global license. Much still remains unclear about the partnership, since neither company said which disease they’re going to tackle. But the program will be aimed at one drug target in CNS and neurological disorders. BioArctic, a Swedish biotech that invented Leqembi, has also teamed up with Eisai and Bristol Myers Squibb on BBB pacts in the last 18 months. Merck has taken several steps to position its HIV business as a potential plug for its upcoming Keytruda-sized hole in revenue in recent weeks. CEO Rob Davis said the company’s HIV portfolio could amount to a $5 billion opportunity, and researchers are preparing a Phase 3 program for a once-monthly PrEP tablet. Some analysts, however, remain skeptical that Merck can compete with more established presences in the field, such as Gilead and ViiV. Keytruda, the best-selling drug in the world, recorded sales of $29.5 billion last year, and it’s expected to surpass $30 billion in 2025. The drug’s patent expires in 2028. Kyle LaHucik has more you can read here .

A decade ago, 70% of Scripps Research’s funding came from government grants. But that share is now 30%, after Scripps reinvented its financial model to reduce its dependence on Washington. The shift has left Scripps better positioned than many other research institutes to withstand the billions of dollars in science funding cuts from the Trump administration. Scripps, which has nearly $1.3 billion in assets, offers a different financial model for biomedical research. It’s pushing discoveries into clinical trials, and launching a fund backed by private investors, a much more expansive role compared to research institutes that typically stick to early-stage drug discovery. As a result, Scripps has attracted attention from peers that are searching for ways to shore up their own finances. But even with less reliance on federal funding, the intent isn’t to replace it entirely, nor bolster the administration’s view that less money should flow to biomedical institutes. In an interview with Endpoints News , Scripps CEO Peter Schultz said that Scripps’ strategy is rather to extend government dollars that underpin its discoveries and translational work. “We as nonprofits need to start thinking more broadly about how we fund and grow our impact than simply relying on federal funding and philanthropy,” Schultz said. Scripps has helped to hatch well-known medicines like blockbuster Humira. It’s widely known for its work on cancer, heart conditions and HIV. In 2017, Nature Index ranked it first worldwide in the impact and quality of its science, beating out research centers at places like MIT and Stanford University. When Schultz was appointed as the CEO of Scripps in 2015, he had to contend with the institute running a $16 million operating loss. Scripps had been operating in the red the four previous years as well. Pharmaceutical companies at the time had become pickier with licensing deals, and NIH funding was fickle. In response, Scripps remade itself to push discoveries further into drug development. It shuttles promising ideas to Calibr, its commercialization arm that leads clinical trials. By doing more of the heavy lifting, Scripps has secured more favorable milestone payments and royalties. That came with higher risks, too — while Scripps can fetch higher payments, a more pricey clinical trial could flop. In 2023, Scripps recorded $112 million in operating income, according to its latest financial report. It received about 42% of its $641 million in revenue from government grants. Schultz said the figure has fallen further to about 30%. The rest of its funding comes from a mix of pharmaceutical partnerships, royalty and licensing revenues, and philanthropy. In the past two years, it has licensed a tuberculosis drug candidate to the Gates Medical Research Institute, licensed its experimental long-acting HIV drug to Gilead, and expanded a partnership with AbbVie. Schultz said such sources can offer more flexible, unrestricted capital. That flexibility, he said, has allowed Scripps to diversify revenue and take new approaches. It’s now working on a dedicated regenerative medicine fund that will support drug programs through early clinical testing, using money from private investors rather than pharma or philanthropy. Even with the financial makeover, Scripps is still hurting from Trump administration cuts that wiped out $6 million in funding this year for its part in the All of Us Research Program, a nationwide consortium to build one of the largest, most diverse health datasets. In addition, Scripps lost $3.5 million in funding to develop drugs against viruses with high pandemic potential, as part of the administration’s pullback of $11.4 billion in pandemic funding. Scripps could face additional cuts, depending on the outcome of court battles over the Trump administration’s plan to slash billions in payments to universities for research overhead, also known as indirect costs. Others are taking note of Scripps’ approach. Schultz said a leader from another biomedical institution recently visited Scripps to study its structure. “You guys are 10 years ahead of us,” Schultz recalled the official telling him. Scripps feeds translational revenues back into its discovery engine. But some see danger in biomedical institutes drifting too far away from fundamental discovery. “It really is the responsibility of academic centers to pursue basic science,”  said Keith Yamamoto, the former vice chancellor for science policy and strategy at UCSF. Yamamoto said the model might work for Scripps, but he doubts it’s widely applicable. Many institutions lack the infrastructure, financing or leadership experienced in both academia and industry. The tension, in part, reflects a struggle in biomedical research: the so-called “valley of death,” in which promising early-stage research languishes. Scripps’ strategy is one approach, but it’s not the only option. Yamamoto pointed to a potential alternative idea modeled on the Department of Energy’s loan guarantee fund, which helped finance companies like Tesla. In medicine, a similar vehicle could back high-risk, high-reward projects, especially for rare diseases, where private investment has lagged.