East China Normal University

A little-known Chinese biotech startup has zipped ahead of US companies in one of the gene editing field’s most competitive races. YolTech Therapeutics announced Monday that it started a clinical trial of an experimental CRISPR therapy for transfusion-dependent beta thalassemia, a genetic blood disease. But rather than removing a patient’s cells and editing them in the lab, as companies in the US have already done, the Shanghai-based biotech plans to edit the cells directly in the bone marrow with a simple transfusion. The trial is the first public disclosure globally of so-called in vivo editing therapy for a blood disease. It’s a potentially cheaper, easier and safer alternative to Casgevy, the sole commercial gene editing treatment made by CRISPR Therapeutics and Vertex in Boston. Several US drugmakers, including well-funded startups and public companies, are working on in vivo therapies for sickle cell disease. Many believe that an in vivo therapy is the only way to make treatments broadly available for beta thalassemia and sickle cell disease — which can be treated with the same approach. But designing lipid nanoparticles that can reach stem cells of the bone marrow is challenging, and YolTech’s announcement that it found a solution ready for clinical testing came as a surprise. YolTech’s beta thalassemia drug is its fourth gene editing therapy to enter clinical studies in a little over a year. Until now, its programs have mimicked ones pioneered by American companies, and the 80-person biotech hasn’t attracted much attention since it was founded in 2021. But that’s starting to change. YolTech, which raised a $32 million Series A in December 2023, has moved at lightning speed with a fraction of the funding of other gene editing companies. CEO and co-founder Yuxuan Wu told Endpoints News on Tuesday that he is “looking for some potential collaborators in the United States and Europe” and took meetings with several pharma companies at the JP Morgan Healthcare Conference in San Francisco this month. If the startup is successful, it will build upon the recent trend of biotech investors and pharma companies turning to China as a source of new drugs . So far, the biggest investments have centered around cancer and obesity drugs. But YolTech wants to prove that Chinese companies can compete in cutting-edge fields like gene editing, too. “We don’t want to just stop at being considered a Chinese company. Hopefully, we will be a global company as well,” Zi Jun Emma Wang, YolTech’s chief technology officer and co-founder, told Endpoints. “It doesn’t matter where the science originates from. Good science should be good science.” Wu cut his teeth on CRISPR a decade ago as a postdoc in Dan Bauer’s lab at Harvard and Boston Children’s Hospital, where he researched editing for blood diseases. Bauer himself was a colleague and former trainee of Boston Children’s hematologist Stuart Orkin, whose work using gene editing to boost fetal hemoglobin would become the trick employed in Casgevy. Wu continued his work on CRISPR when he opened his own lab at East China Normal University in Shanghai in 2018. He also co-founded BRL Medicine, a Shanghai startup making its own CRISPR-edited cell therapies for beta thalassemia and sickle cell. It was a tough time to be a gene editor in the country. The same year, Chinese scientist He Jiankui had announced the birth of babies whose genes were edited as embryos. The swift global condemnation put a damper on gene editing research in China and stalled BRL’s work, because hospitals didn’t want anything to do with CRISPR. Over the next few years, Wu increasingly began to view cell-based therapies as too complex and expensive for China, an idea that’s only solidified since Casgevy’s approval in the US in 2023. The treatment is an onerous process: Doctors first harvest a patient’s bone marrow cells and ship them to a lab where they are altered with CRISPR. Before the edited cells are reinfused, the patient receives chemotherapy to clear out the old diseased cells. Casgevy costs $2.2 million per patient in the US, and that doesn’t include a lengthy hospital stay. Roughly a year after its launch, CRISPR Therapeutics said that 50 patients have had their cells collected. In 2021, Wu co-founded YolTech to develop in vivo therapies as an alternative. That summer, Intellia Therapeutics reported the first glimpse of promising data from therapies that used lipid nanoparticles to deliver CRISPR into the liver to treat transthyretin amyloidosis. YolTech soon began working on its own therapy for that disease, as well as two other liver-targeted programs. All three are now in early-stage clinical studies. Wang and Wu said that the in vivo program for beta thalassemia (which is more common in China than sickle cell disease) has always been a focus for YolTech, but the company kept quiet about its progress until November, when scientists from YolTech and East China Normal University published a preprint on bioRxiv describing how an in vivo therapy could boost fetal hemoglobin in mice. Wang said that the nanoparticles described in the preprint are “from a couple years ago,” noting that essentially every aspect of the therapy has been optimized since then. The experimental drug, dubbed YOLT-204, uses lipid nanoparticles designed to target hematopoietic stem cells of the bone marrow to shuttle mRNA molecules encoding the company’s own base editors. Those CRISPR tools will make a single letter change to a gene that controls production of fetal hemoglobin, boosting levels of that oxygen-ferrying protein. Crucially, the new nanoparticles are decorated with a molecule that homes in on bone marrow cells, although the company isn’t disclosing details of the key ingredient yet. “We screened thousands of formulations,” Wang said. “I would not claim that we solved the problem, but we have a good candidate to test in the clinic.”

Multidrug-resistant bacterial infections that cannot be treated by any known antibiotics pose a serious global threat. A research team has now introduced a method for the development of novel antibiotics to fight resistant pathogens. The drugs are based on protein building blocks with fluorous lipid chains. Multidrug-resistant bacterial infections that cannot be treated by any known antibiotics pose a serious global threat. In the journal Angewandte Chemie, a Chinese research team has now introduced a method for the development of novel antibiotics to fight resistant pathogens. The drugs are based on protein building blocks with fluorous lipid chains. Antibiotics are often prescribed far too readily. In many countries they are distributed without prescriptions and administered in factory farming: prophylactically to prevent infections and enhance performance. As a result, resistance is on the rise -- increasingly against reserve antibiotics as well. The development of innovative alternatives is essential. It is possible to learn some lessons from the microbes themselves. Lipoproteins, small protein molecules with fatty acid chains, are widely used by bacteria in their battles against microbial competitors. A number of lipoproteins have already been approved for use as drugs. The common factors among the active lipoproteins include a positive charge and an amphiphilic structure, meaning they have segments that repel fat and others that repel water. This allows them to bind to bacterial membranes and pierce through them to the interior. A team led by Yiyun Cheng at East China Normal University in Shanghai aims to amplify this effect by replacing hydrogen atoms in the lipid chain with fluorine atoms. These make the lipid chain simultaneously water-repellant (hydrophobic) and fat-repellant (lipophobic). Their particularly low surface energy strengthens their binding to cell membranes while their lipophobicity disrupts the cohesion of the membrane. The team synthesized a spectrum (substance library) of fluorous lipopeptides from fluorinated hydrocarbons and peptide chains. To link the two pieces, they used the amino acid cysteine, which binds them together via a disulfide bridge. The researchers screened the molecules by testing their activity against methicillin-resistant Staphylococcus aureus (MRSA), a widespread, highly dangerous strain of bacteria that is resistant to nearly all antibiotics. The most effective compound they found was "R6F," a fluorous lipopeptide made of six arginine units and a lipid chain made of eight carbon and thirteen fluorine atoms. To increase biocompatibility, the R6F was enclosed within phospholipid nanoparticles. In mouse models, R6F nanoparticles were shown to be very effective against sepsis and chronic wound infections by MRSA. No toxic side effects were observed. The nanoparticles seem to attack the bacteria in several ways: they inhibit the synthesis of important cell-wall components, promoting collapse of the walls; they also pierce the cell membrane and destabilize it; disrupt the respiratory chain and metabolism; and increase oxidative stress while simultaneously disrupting the antioxidant defense system of the bacteria. In combination, these effects kill the bacteria -- other bacteria as well as MRSA. No resistance appears to develop. These insights provide starting points for the development of highly efficient fluorous peptide drugs to treat multi-drug resistant bacteria.

TUSTIN, Calif.--( BUSINESS WIRE )--LIBERTY Dental Plan, a leading benefits administrator founded in 2002 by dentists and health industry professionals which currently administers dental benefits in all 50 states, today announced the appointment of Jian Yu as Chief Financial Officer and Chief Actuarial Officer. Effective Dec. 28, 2023, she will succeed Mary Anne Jones, who has served as LIBERTY’s Interim Chief Financial Officer since June 2023. Yu brings to LIBERTY a wealth of financial and actuarial executive leadership experience from her more than 25-year career in the healthcare industry, along with extensive experience in strategic planning, risk management, actuarial pricing, healthcare trend management, and advanced analytics. “Jian is a proven leader and strategist whose financial acumen and integrity deliver results, and we are thrilled to have her join the LIBERTY executive leadership team,” said Marti Lolli, President and Chief Executive Officer of LIBERTY. “Jian joins LIBERTY at a pivotal time as we continue on a historical growth trajectory,” Lolli continued. “I am confident that Jian’s deep financial expertise, long-standing relationships within the industry, and forward-thinking business leadership will successfully propel us forward as we continue to grow exponentially. On behalf of LIBERTY, I also want to extend my sincere gratitude to Mary Anne Jones, who has served as our Interim Chief Financial Officer during our search. We wish her the best as she transitions to full-time retirement after an impressive career of leading healthcare companies to achieve financial success.” “I am honored to join LIBERTY at this pivotal time in the company’s history,” said Yu. “I look forward to joining the experienced leadership team and working together to drive LIBERTY’s successful growth in the dental plan marketplace.” Prior to joining LIBERTY, Yu was Senior Vice President and Chief Actuary at Priority Health, and served in senior leadership roles at Milliman and WellCare Health Plans. She most recently served as Vice President, Associate Chief Actuary for Markets outside California at Kaiser Permanente. Yu received her master’s degree from the University of Wisconsin—Madison, and a bachelor’s degree in mathematics from East China Normal University in Shanghai. ABOUT LIBERTY LIBERTY is a dental benefits administrator founded by dentists and health industry professionals in 2002. LIBERTY currently administers dental benefits in all 50 states, including on behalf of over six million Medicaid, Medicare Advantage, commercial, and exchange members. A high-touch approach to member and provider engagement, along with innovations to improve the quality and cost-effectiveness of dental care delivery, has propelled the company’s growth. Welsh, Carson, Anderson & Stowe , is a majority investor in LIBERTY. Elevance Health , a customer since 2010, is a minority investor. Learn more at www.LIBERTYDentalPlan.com . Follow us on LinkedIn .