ReCode Therapeutics, Inc.

The global race to develop in vivo CAR-T therapies that could replace onerous cell therapies with simpler, safer infusions continues to heat up, and now a Chinese biotech startup has quietly begun clinical tests of its treatments. In an exclusive interview with Endpoints News , Starna Therapeutics said it’s seen complete elimination of circulating B cells — the cells that can run amok in autoimmune disease and blood cancer — following a single infusion of its treatment in a small, undisclosed number of lupus patients and a single non-Hodgkin lymphoma patient. Those preliminary results have not been presented or published, but the Suzhou-based company said the early glimpses of potential efficacy led it to raise $44 million in Series B funding co-led by LYFE Capital, Lilly Asia Ventures and Hillhouse. Additional investors included Sherpa Healthcare Partners, Primavera Capital Group and Source Code Capital. “Based on our flow cytometry data, there’s zero B cells per microliter in the blood within 72 hours after our first dose,” said Elliott Sun, chief business officer at Starna. “We closed this round of financing very quickly based on this observation.” The fundraising is the latest in a string of fevered investments in in vivo CAR-T therapies that promise to eliminate the need to engineer cells outside the body. Dozens of startups are working in the field, with new ones launching or pivoting to join the fray seemingly every month. They are drawn by the curative potential and the allure of a quick payout. Just this year, AbbVie , AstraZeneca , Bristol Myers Squibb and Gilead Sciences have all acquired in vivo CAR-T startups with little to no clinical data. So far, Starna has only tested its therapy in investigator-initiated studies (IITs) — a cheaper, faster and less formal way to test cell and gene therapies in China without waiting for clearance from national drug regulators. It’s an increasingly popular tactic among in vivo CAR-T developers, including ones based in Europe and the US. In the company’s ongoing ITTs, which began in July, a bone marrow biopsy from a lupus patient and a lymph node biopsy from a non-Hodgkin lymphoma patient showed “very good B cell depletion” after multiple infusions of Starna’s therapy, without the need for the chemotherapy pretreatment that accompanies traditional CAR-T therapies, Sun said. The therapies caused “super mild cytokine release” but otherwise seemed safe, he added. The company isn’t disclosing the exact dose, but Sun said it was below 0.1 mg/kg, potentially creating a “wide therapeutic window” to test higher doses. Going forward, Starna will likely focus on autoimmune disease, and it plans to treat six lupus patients by the end of the year, according to Sun. The new funding should help the company begin Phase 1 studies in China and the US next year, pending approval from regulators. Starna was co-founded in 2021 by mRNA therapeutics developer Rongkuan (Frank) Hu, lipid nanoparticle scientist Qiang Cheng and organic chemist Xueliang (Fisher) Yu. All three trained as postdoctoral researchers at UT Southwestern Medical Center in Dallas — Cheng and Yu together, and Hu before them. Hu, the startup’s CEO, helped make the first mRNA Covid-19 vaccine commercialized in China while at CSPC Pharmaceutical Group in Shanghai. Cheng, who now runs a lab at Peking University, was part of the team that worked on the selective organ-targeting nanoparticle technology that became the basis for the UT Southwestern spinout ReCode Therapeutics. And Yu, who is Starna’s head of chemistry, worked at ReCode for a year. Starna originally had broad goals to develop lipid nanoparticles, or LNPs, that could deliver mRNA medicines to parts of the body beyond the liver. To do that, Starna and Cheng’s lab built a library of more than 3,000 ionizable lipids, one of the key ingredients that hold an LNP together and can shift its affinity toward different cells. That effort led to LNPs that could target the central nervous system, lung, kidney, muscle and spleen, the company said. But over the past two years, Starna has narrowed its focus and is now “dedicated to the in vivo CAR-T program,” Hu told Endpoints. The company’s in vivo CAR-T program uses an LNP targeting the spleen, a major site of immune cells. It also sticks full antibodies on the nanoparticle surface to target killer T cells. And if any of the nanoparticles get sucked up by liver cells — as they tend to do — a microRNA binding site inside the mRNA acts as a kill switch to prevent production of the therapy in the liver. Starna is planning to test at least three versions of its in vivo CAR-T therapies in separate IITs. The study that is already underway uses linear mRNA to engineer T cells to target CD19. By the end of the year, Starna will begin testing a “dual-CAR” approach that targets both CD19 and BCMA. And by early next year, the startup plans to advance an in vivo CAR-T therapy based on circular RNA . That’s a next-generation version of the genetic molecule that several Western companies, like Orbital Therapeutics , which Bristol Myers Squibb acquired for $1.5 billion earlier this month, have raised hundreds of millions of dollars to develop. “People believe circular mRNA has better durability, longer expression,” Sun said. But the company’s preclinical studies surprisingly found that linear mRNA “can provide better potency” with “very rapid killing compared to a circular platform,” he said. Starna is “continuing to optimize the circular platform,” he added. The roughly 60-person startup previously raised a $24 million Series A funding in 2022 and developed several other therapies before pivoting to in vivo CAR-T. Its deprioritized programs include: an mRNA vaccine for RSV ready for clinical testing; an mRNA cancer vaccine for glioblastoma that’s in an IIT; and past efforts to develop mRNA therapies for multiple lung diseases.

The FDA’s own website notes that mifepristone is safe and was approved more than 20 years ago \"based on a thorough and comprehensive review of the scientific evidence.”\n A group of 53 biotech leaders is expressing support for mifepristone in a letter to the FDA, urging the agency not to impose new restrictions on its use as an abortion medication and slamming a \"fatally flawed\" report fueling recent scrutiny.The June 30 letter was shared as a comment to a citizen petition in support of mifepristone submitted to the FDA on Feb. 4 by the American College of Obstetricians and Gynecologists, the Society of Family Planning and the Society for Maternal-Fetal Medicine.The lead signatory of the letter is Grace Colón, Ph.D., the CEO and co-founder of cardiopulmonary startup Inaya Therapeutics. Other notable signatures come from Recode Therapeutics CEO Shehnaaz Suliman, M.D.; Sena Therapeutics Executive Chair Julia Owens, Ph.D.; Nkarta CEO Paul Hastings; and Alnylam\'s founding CEO John Maraganore, Ph.D.The letter centers on an April article from the Ethics and Public Policy Center (EPPC), an anti-abortion conservative think tank, claiming mifepristone is harmful to women. The group declares that 1 in 10 women taking mifepristone experience a serious adverse event and that the pill has a failure rate of at least 5.26%, requiring many patients to attempt abortion multiple times. The think tank has not yet provided a data set to back up the claims.FDA Commissioner Martin Makary, M.D., announced plans to review the safety of the abortion pill in June after pressure from Sen. Josh Hawley, R-Mo., based on the EPPC report.“The EPPC report is fundamentally, fatally flawed,” the biotech leaders wrote in their letter. “It was not reviewed in the standard scientific vetting process. To date, the dataset has not been made available to researchers in the field.”The authors also declared the report is riddled with methodological flaws, like counting emergency room visits as serious adverse events, “contradicting FDA guidance and exaggerating the number of adverse events associated with mifepristone.” Mifepristone is a highly studied medication, with more than 100 peer-reviewed studies demonstrating its safety and efficacy, the biotech leaders wrote. Risks are similar to that of commonly prescribed antibiotics and over-the-counter NSAIDs. The FDA’s own website notes that mifepristone is safe and was approved “more than 20 years ago based on a thorough and comprehensive review of the scientific evidence.”“The FDA has never relied on publications with such unreliable methodologies,” the authors wrote about the EPPC document. “We urge the FDA to continue its tradition of following rigorous scientific evaluations as the sole basis for determining the ongoing safety and effectiveness of approved medicines.”Allowing unreliable information would \"pave the way for any political or interest group to undermine well-grounded FDA decisions with baseless claims,\" the biotech executives and investors said. \"The resulting regulatory uncertainty could destabilize the drug approval process, chill drug development and innovation and compromise patient health.\"Makary’s June announcement almost immediately sparked another citizen petition, this one from the states of Massachusetts, New York, New Jersey and California, which echoed the earlier petition in calling on the agency to remove the mifepristone Risk Evaluation and Mitigation Strategy (REMS) program and not place any new restrictions on access to the pill. The REMS program limits who can prescribe mifepristone and under what circumstances.

Plus, news about Novartis, Signify Bio, Ocugen, Dynavax and ViGeneron: Cullinan Therapeutics gets rights to T cell engager developed in China: The company made a deal with Chongqing-based Genrix Bio for velinotamig, a BCMAxCD3 bispecific T cell engager. It’s paying $20 million upfront and up to $692 million in milestones for the rights outside of Greater China. “We believe T cell engagers represent the next wave of innovation in autoimmune diseases,” Cullinan CEO Nadim Ahmed said in a release. Once a Genrix-run Phase 1 trial in China wraps up, Cullinan will handle further development of the asset in autoimmune diseases. — Jaimy Lee Kardigan acquires another drug: The cardiology startup , which unveiled with $300 million in January, acquired the rights to ataciguat, a spokesperson told Endpoints News . The drug was developed by Sanofi and the Mayo Clinic and had been licensed by Rancho Santa Fe Bio . The once-daily oral drug is a guanylate cyclase activator. Kardigan has now taken it into a Phase 3 trial in moderate calcific aortic valve stenosis. The spokesperson said the company hopes ataciguat can delay the need for valve replacement surgery. The biotech also licensed a mid-stage Ionis drug earlier this year. It has “multiple late-stage candidates,” per the spokesperson. — Kyle LaHucik Novartis’ 100-week data for kidney disease drug: The Swiss drugmaker’s APRIL targeting monoclonal antibody, dubbed zigakibart, achieved an average 60% reduction in proteinuria at 100 weeks in a Phase 1/2 trial in people with IgA nephropathy, according to results presented this week at the European Renal Association’s annual meeting in Vienna. Zigakibart is being evaluated in the Phase 3 BEYOND study, which is measuring the primary endpoint of change in proteinuria at 40 weeks. — Ayisha Sharma Signify Bio launches with $15M: The company counts several well-known biotech entrepreneurs as its leaders, including Taysha Gene Therapies founder RA Session II and ReCode Therapeutics co-founder Daniel Siegwart. It’s also being financed by blue-chip backers like Eli Lilly and the Gates Foundation Strategic Investment Fund. Signify is developing what it calls in situ protein therapeutics from research out of Siegwart’s lab at the UT Southwestern Medical Center. — Jaimy Lee Ocugen inks gene therapy deal with unnamed company: Ocugen is getting $11 million in upfront and near-term milestone payments, plus $150 million in sales milestones, for the rights to OCU400 in South Korea. It’s developing OCU400 to treat retinitis pigmentosa. — Jaimy Lee Dynavax responds to Glass Lewis claims: The company continues to push back against putting Deep Track Capital executives on its board. — Jaimy Lee ViGeneron’s name change: Its new name is VeonGen Therapeutics, and it’s working on gene therapies for patients with Stargardt disease and a form of retinitis pigmentosa. — Jaimy Lee