Hyperoxaluria, Primary

MB-111 is a potential first-in-class in vivo ultracompact CRISPR therapy for Familial Chylomicronemia Syndrome and Severe Hypertriglyceridemia Dr. Brown brings deep expertise in nucleic acid drug development as Mammoth advances its lead program, MB-111, to IND-enabling stage and continues to build a leading company in genetic medicines BRISBANE, CA, USA I May 05, 2025 I Mammoth Biosciences, Inc. , a biotechnology company harnessing its proprietary next-generation CRISPR gene editing platform to create potential one-time curative therapies, today announced the nomination of its first clinical development candidate, MB-111, and the appointment of biotechnology industry veteran, Bob D. Brown, Ph.D., to its Board of Directors. MB-111 utilizes CasPhi — an ultracompact CRISPR in vivo gene editing system that is less than half the size of first-generation, Cas9-based systems — encapsulated in a lipid nanoparticle for delivery to the liver after IV administration. Share MB-111 utilizes CasPhi — an ultracompact CRISPR in vivo gene editing system that is less than half the size of first-generation, Cas9-based systems — encapsulated in a lipid nanoparticle for delivery to the liver after IV administration. MB-111 has the potential to be a first-in-class, one-time treatment for patients with very high triglycerides including familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG). MB-111 is designed to permanently disrupt the expression of the APOC3 gene in the liver, and thus to reduce expression of ApoC-III protein. ApoC-III is a critical driver of lipid metabolism and disrupting its production has been shown to reduce plasma triglycerides in patients with pathologically elevated levels, including those with FCS and SHTG. These patients suffer from recurrent episodes of acute pancreatitis, leading to frequent hospitalizations, as well as an increased risk of cardiovascular disease. Mammoth Biosciences is on track to initiate IND-enabling studies this year. “The nomination of our lead program as a development candidate is a major milestone for Mammoth and the gene editing field, as well as the first proof point of the therapeutic potential of our novel ultracompact CRISPR systems and gene editing technologies,” said Trevor Martin, Ph.D., co-founder and Chief Executive Officer of Mammoth Biosciences. “The preclinical data on MB-111 is compelling, and we’re excited about its potential to be a first-in-class genetic cure for debilitating diseases such as FCS and SHTG. We believe Dr. Brown’s extensive drug discovery and development experience, and track record of building leading companies in siRNA and antisense oligonucleotide therapeutics across rare and chronic diseases will be invaluable to our goal of increasing the number of patients who can derive benefit from Mammoth Biosciences’ genetic medicines.” Dr. Bob D. Brown brings over 30 years of experience in multidisciplinary biotechnology research and drug development, including in the US and ex-US jurisdictions. Most recently, Dr. Brown served as Chief Scientific Officer and Executive Vice President of R&D at Dicerna Pharmaceuticals, an RNAi-focused therapeutics company that was acquired by Novo Nordisk. At Novo, he served as President and Head of the Dicerna Transformation Research Unit and SVP. During his time at Dicerna, he led the discovery and early clinical development of numerous genetic medicines, including nedosiran for the treatment of primary hyperoxaluria, RG6346 for the treatment of chronic hepatitis B, belcesiran for the treatment of alpha-1 antitrypsin deficiency, and several other drug candidates now in the clinical development pipelines of large pharmaceutical companies. Prior to Dicerna, Dr. Brown held various positions at Genta, a clinical-stage antisense oligonucleotide therapeutics company, most recently as its Vice President of Research and Technology. Previously, he was a co-founder and Vice President of R&D of Oasis Biosciences, which was acquired by Gen-Probe. Dr. Brown is an inventor or co-inventor of more than 85 issued US patents, and earned a Ph.D. in molecular biology from the University of California, Berkeley and B.S. degrees in chemistry and biology from the University of Washington, Seattle. “I’m honored to join Mammoth Biosciences at such a pivotal moment, as CRISPR technology stands ready to transform healthcare and redefine the future of medicine,” said Dr. Brown. “I look forward to working with the exceptional Mammoth Biosciences team to harness the power of their groundbreaking platform to tackle some of the most pressing medical challenges and improve patients’ lives. Drawing on my experiences in drug discovery and clinical development, I aim to help advance Mammoth Biosciences’ ultracompact CRISPR gene editing therapies—starting with MB-111—toward clinical application.” About Mammoth Biosciences Mammoth Biosciences is a biotechnology company focused on leveraging its proprietary ultracompact CRISPR systems to develop potential long-term curative therapies for patients with life-threatening and debilitating diseases. Founded by CRISPR pioneer and Nobel laureate Jennifer Doudna and Trevor Martin, Janice Chen, and Lucas Harrington, the company’s ultracompact systems are designed to be more specific and enable in vivo gene editing in difficult to reach tissues utilizing both nuclease applications and new editing modalities beyond double stranded breaks, including base editing, reverse transcriptase editing, and epigenetic editing. The company is building out its wholly owned pipeline of potential in vivo gene editing therapeutics and capabilities and has partnerships with leading pharmaceutical and biotechnology companies to broaden the reach of its innovative and proprietary technology platform. Mammoth Biosciences’ deep science and industry experience, along with a robust and differentiated intellectual property portfolio, have enabled the company to further its mission to transform the lives of patients and deliver on the promise of CRISPR technologies. SOURCE: Mammoth Biosciences

SHANGHAI, April 28, 2025 /PRNewswire/ -- YolTech Therapeutics Co.,Ltd, a clinical-stage in vivo gene editing company committed to pioneering the next generation of precision genetic medicines, announced promising interim clinical data from an investigator-initiated trial (IIT) of YOLT-101 (NCT06458010), and the data has been published on medRxiv. YOLT-101 is an investigational in vivo base editing therapy for the treatment of heterozygous familial hypercholesterolemia (HeFH). Clinical data demonstrate that YOLT-101 can safely and effectively reduce low-density lipoprotein cholesterol (LDL-C) levels in HeFH patients with a single administration. As a next-generation gene-editing therapy, YOLT-101 represents a breakthrough in lipid-lowering treatment – moving beyond daily pills and regular injections, and opening a new era of "one-time treatment for lifelong LDL-C reduction." YOLT-101 is a next-generation in vivo base-editing therapeutic independently developed by YolTech. It features the novel, proprietary adenine base editor, YolBE—specifically hpABE5—which consists of nCas9 and a newly discovered deaminase derived from Hafnia paralvei. For delivery, it utilizes a new lipid nanoparticle (LNP) formulation. Unlike traditional CRISPR/Cas9 systems that rely on inducing DNA double-strand breaks (DSBs), hpABE5 enables precise single-base editing without generating DSBs, thereby significantly reducing the risks of chromosomal abnormalities and off-target effects. Extensive preclinical studies have demonstrated its excellent genome editing safety profile. The in vivo base-editing therapy is delivered via intravenous infusion and selectively internalized by hepatocytes, where it induces a precise nucleotide conversion within the PCSK9 gene. This targeted edit disrupts PCSK9 protein expression, leading to enhanced uptake of LDL-C by LDL receptor on hepatocyte surfaces and finally resulting in a marked reduction in plasma LDL-C levels. Study Design of the IIT This is an open-label clinical trial conducted in patients with HeFH. The primary objective is to evaluate the safety and tolerability of YOLT-101, while also aiming to explore preliminary efficacy and pharmacodynamics. As of March 15, 2025, a total of 6 subjects have been enrolled: 1 in the 0.2 mg/kg cohort, 2 in the 0.4 mg/kg cohort, and 3 in the 0.6 mg/kg cohort. All subjects have completed at least 24 weeks of safety follow-up, with the longest reaching 36 weeks. Safety and Tolerability YOLT-101 has shown good safety and tolerability. As of March 15, 2025, no serious adverse events (SAEs), dose-limiting toxicity (DLT) events, or Grade ≥3 adverse events (according to CTCAE v5.0) were observed in any dose group. All enrolled subjects are under follow-up as scheduled. The most common treatment-related adverse event was transient infusion-related reactions (5/6, 83.3%), with a manifestation of fever that resolved within 24 hours. Mild elevations in liver enzymes (3/6, 50.0%) were reported, which emerged on Day 4-7 following administration and rapidly alleviated usually after 7 days. All these patients did not show any relevant symptoms, and their plasma bilirubin levels (important indices for liver function) remained within normal limits throughout. No clinically significant changes were observed in other laboratory parameters. Efficacy and Pharmacodynamics LDL-C levels demonstrated a dose-dependent reduction following administration. Baseline LDL-C was 4.9 ± 0.6 mmol/L. In the 0.4 mg/kg and 0.6 mg/kg cohorts, sustained reductions in LDL-C were observed as early as Week 1 post-administration, reaching a maximal effect by Week 4. In the 0.6 mg/kg group, mean LDL-C level decreased by around 50% through the last follow-up with acquired data compared to baseline. The subject with the greatest response showed an LDL-C level of approximately 1 mmol/L (maximal percent change from baseline over 74%), and the efficacy has sustained for over 6 months following single-dose infusion. Pharmacodynamic data showed consistent trends, with plasma PCSK9 protein levels decreasing by over 70% from baseline starting at Week 4 in the 0.6 mg/kg group (maximal individual reduction reached 87%). Notably, all enrolled subjects in this study were HeFH patients. PCSK9-targeting therapies typically show reduced efficacy in this population compared to with general hypercholesterolemic population. This suggests that YOLT-101 may demonstrate even greater lipid-lowering potential in the general hypercholesterolemic population. In summary, YOLT-101 exhibits favorable safety and tolerability in HeFH patients, with adverse events being mild and transient. Both pharmacodynamic (PCSK9) and efficacy (LDL-C) outcomes in the 0.4 mg/kg and 0.6 mg/kg groups showed durable, dose-dependent reductions. These results support the potential of YOLT-101 to achieve "single-dose, lifelong lipid lowering." "We are dedicated to revolutionizing traditional approaches to cardiovascular disease through next-generation base editing technology and groundbreaking single-dose treatment," said Dr. Yuxuan Wu, co-founder and CEO of YolTech Therapeutics. " Patients with heterozygous familial hypercholesterolemia (HeFH) suffer from a lifelong, genetically driven impairment in LDL-C metabolism, resulting in markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. This population is at exceptionally high risk for premature atherosclerotic cardiovascular diseases. Current lipid-lowering therapies rely heavily on long-term, continuous administration. However, once treatment is discontinued, LDL-C levels rebound. These regimens are frequently hindered by poor patient adherence and drug intolerance—highlighting a critical unmet need for more durable, patient-friendly therapeutic solutions. Current clinical data of YOLT-101 demonstrates a single YOLT-101 administration can lead to significant and durable reductions in LDL-C levels. By precisely editing key genes regulating LDL-C levels in the liver, YOLT-101 has the potential to be a transformative 'one-time treatment, lifelong cure' therapy. We look forward to further confirming its safety and efficacy in larger-scale clinical studies and conferring benefits to patients worldwide." About Familial Hypercholesterolemia (FH) Familial hypercholesterolemia (FH) is caused by mutations in LDL metabolism-related genes (LDLR, APOB, PCSK9). As a result, patients with FH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). The global prevalence of FH is 1:200-1:250, affecting a total of ~34 million people worldwide. Current FH management strategies include lifestyle modifications, lipid-lowering medications, lipoprotein apheresis, and liver transplantation. The standard of treatment involves pharmacotherapy, with most patients receiving a triple regimen of statins, ezetimibe, and PCSK9 inhibitors. However, current therapies have significant limitations including suboptimal efficacy, intolerable side effects, and poor long-term adherence. These challenges underscore the urgent need for novel, durable therapies to address the lifelong treatment burden of FH. About YolTech YolTech Therapeutics is a clinical-stage in vivo gene editing company committed to pioneering the next generation of precision genetic medicines. Our approach combines innovative gene editing technologies with an advanced lipid nanoparticle (LNP) delivery system, creating a versatile platform designed to address a wide range of serious diseases. Central to our mission is the development of internal capabilities, including end-to-end manufacturing, to ensure the highest standards of quality and scalability. Our lead candidate, targeting ATTR, marks a significant milestone as China's first LNP-mediated in vivo gene editing therapy to enter clinical development. With promising early clinical outcomes, YolTech is also advancing therapies for familial hypercholesterolemia (FH) and primary hyperoxaluria type 1 (PH1). As a company dedicated to transforming the treatment landscape, YolTech continues to push the boundaries of what is possible in gene editing. For more information, please visit: SOURCE YolTech Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Isomorphic Labs, a young company whose artificial intelligence technology for drug research has already landed partnerships with big pharmaceutical companies, unveiled $600 million in new financing this week as it looks to advance its own drug pipeline. London-based Isomorphic is an autonomous subsidiary of Alphabet. It came from DeepMind, a different Alphabet subsidiary that uses machine learning to solve problems. Isomorphic was formed in 2021 to build on the success of DeepMind’s AlphaFold, a technology that successfully predicted how a protein would fold based on its amino acid sequence. The company is led by founder and CEO Demis Hassabis, who also co-founded and leads DeepMind. Early last year, Isomorphic revealed two partners: Eli Lilly and Novartis. Both alliances, which span the discovery of small molecules for multiple undisclosed targets, came with upfront cash and the potential for milestone payments. Sponsored Post Tackling Rising Drug Costs and Growing Popularity of GLP-1’s See how Quantum Health is providing the steps to help their members tackle the cost of specialty medications and other drugs. By Quantum Health and MedCity News Isomorphic says its AI drug design engine has foundational AI models capable of working across multiple therapeutic areas and drug modalities. The company is not yet disclosing the targets or therapeutic areas of its internal research. But as an example of its capabilities, Isomorphic points to AlphaFold 3, which was released by the company and DeepMind last year. This technology can predict the structure and interactions of all of life’s molecules. Isomorphic said the new financing, its first external round, was led by Thrive Capital and included participation from GV and follow-on capital from earlier investor Alphabet. In addition to supporting its AI drug design engine, the capital will also help Isomorphic advance internal programs to the clinic. Isomorphic’s large financing comes amid investment headwinds. Capital raised by biotech companies in the first quarter of this year comes out to about $13 billion, analysts at William Blair said in a research note. That’s well below the $25.7 billion raised in the first quarter of 2024 and it’s also below the $18.8 billion quarterly average last year. Though 2024 started strong, the firm notes that biotech funding has declined sequentially for four consecutive quarters. Here’s a recap of other recent financings as the first quarter came to a close: presented by Health Tech The 5 Best Software to Buy for Managing a Spa Franchise Choosing the right software translates directly into better client management, operational efficiency and growth for your spa franchise. Discover which tool is best for your business. By Meevo —AIRNA raised $155 million to advance to Phase 1/2 testing with AIR-001, a potential treatment for alpha-1 antitrypsin deficiency. Venrock Healthcare Capital Partners led the Series B round, which was co-led by Forbion Growth. Here’s more about AIRNA’s RNA-editing therapy for AATD, which puts it in competition with Korro Bio and Wave Life Sciences, both in early clinical development with RNA-editing therapies for the rare liver protein deficiency. —Character Biosciences pulled in $93 million to reach the clinic with two internally discovered complement inhibitors, each in development for different stages of the dry form of age-related macular degeneration. The Series B financing was co-led by aMoon and Luma Group, both new investors in the startup. Character, a spinout of Clover Health, closed an $18 million Series A financing in 2022. —Epicrispr Biotechnologies raised $68 million as it prepares for Phase 1 testing of EPI-321, an epigenetic therapy that addresses the underlying cause of facioscapulohumeral muscular dystrophy (FSHD). The South San Francisco-based biotech’s therapies come from Gene Expression Modulation System, a technology that enables precise and durable control of gene expression. Epicrispr presented preclinical data for the FSHD therapy last fall during the European Society of Cell and Gene Therapy annual meeting. —Tempero Bio closed $70 million in funding to support TMP-301 for substance use disorders. The Oakland based company plans to advance the drug candidate two Phase 2 tests, one in alcohol use disorder and the other in cocaine use. 8VC led Tempero’s Series B financing. —Hillstar Bio launched with $67 million to support the development of immunotherapies for autoimmune diseases. The Boston-based startup says its therapies selectively deplete pathogenic cells while preserving healthy ones. The company’s lead program targets TRBV9-positive T cells; a clinical trial is planned for 2026 with an initial focus on axial spondyloarthritis and potentially other immune and inflammatory disorders. —Flagship Pioneering revealed its latest AI startup, Lila Sciences. While Lila’s technology allows it to process large amounts of data and make predictions, and the company says its technology also helps scientists design and conduct new experiments, generating hypotheses and testing them in real-world environments. Lila isn’t developing its own drugs. Rather, it’s looking to strike up partnerships with other companies aiming to leverage the technology for applications ranging from drug R&D, carbon capture, and sustainable agriculture. While Flagship startups typically launch with $50 million from the startup creator, Lila is backed by $200 million in committed seed financing from a syndicate that includes General Catalyst, March Capital, and a subsidiary of the Abu Dhabi Investment Authority, among others. —Augustine Therapeutics closed €78 million (about $85 million) for drugs that block the enzyme HDAC6 to treat neuromuscular, neurodegenerative, and cardio-metabolic diseases. The Leuven, Belgium-based company will apply the new capital to Phase 1/2 testing of lead program AGT-100216, an experimental treatment for rare neuromuscular disorder Charcot-Marie Tooth disease. Novo Holdings and Jeito Capital co-led Augustine’s Series A financing. —Osivax raised €10 million to continue development of OVX836, a broad-spectrum influenza vaccine candidate that has reached Phase 2b testing. The financing, which Lyon, France-based Osivax described as the first close of a Series B financing, added new investor Meiji Seika Pharma Co. —Montara Therapeutics’ expanded its seed round by $20 million as the company advances its lead epilepsy program to the preclinical research that could support an investigational new drug application (IND). San Francisco-based Montara develops “BrainOnly” drugs, therapies that selectively target the central nervous system while blocking harmful peripheral effects. With the expanded financing, the round now totals $28 million. —Ampersand Biomedicines revealed $65 million in financing to bring programs in immuno-oncology and immuno-inflammation into IND-enabling studies. The Flagship Pioneering-founded startup develops biologic drugs from a platform technology that identifies “addresses,” markers found on disease-driving targets but not on healthy cells. Eli Lilly joined Flagship in Ampersand’s Series B round, which comes two years after the drug discovery biotech’s launch. —Arbor Biotechnologies raised $73.9 million to finance Phase 1/2 testing of its gene therapy for primary hyperoxaluria type 1, a rare enzyme deficiency. In vivo editing by the Arbor gene therapy, ABO-101, is intended to knock down expression of the HAO1 gene that drives the disease. Arch Venture Partners and TCGX led the Series C round for Cambridge-based Arbor, whose last financing was a $215 million Series B round in 2021. —RegCell announced its relocation from Japan to Emeryville, California, as it progresses toward the clinic with an experimental regulatory T cell (Treg) treatment for autoimmune disease. The technology of RegCell generates epigenetically reprogrammed, antigen specific Tregs intended to restore immune tolerance. The company is financially backed by $8.5 million in seed financing and up to $37.3 million in non-dilutive funding from The Japan Agency for Medical Research and Development. —Cambridge, U.K.-based Maxion Therapeutics revealed £58 million (about $72 million) in financing to reach human testing with MAX001, a potential treatment for a spectrum of inflammatory diseases such as atopic dermatitis and inflammatory bowel disease. The company’s drugs combine knottins, a type of protein, with antibodies. These “KnotBodies” are intended to modulate ion channels and G protein-coupled receptors. General Catalyst led Maxion’s Series A financing. —Latigo Biotherapeutics closed $150 million in financing for its non-opioid pain drug pipeline. Latigo is in Phase 2 testing with lead program LTG-001, a blocker of a sodium channel called NaV1.8. That’s the same target as Vertex Pharmaceuticals’ recently approved non-opioid pain drug, Journavx. Blue Owl Capital led Latigo’s Series B round. —Curevo Vaccine closed $110 million to continue clinical development of amezosvatein, an experimental shingles vaccine. In addition to extending the Phase 2 program to an additional 640 participants, the company aims to finalize dose selection for the planned Phase 3 study. Seattle-based Curevo also said Moncef Slaoui, the former GSK vaccine executive and chief scientific advisor to Operation Warp Speed, has been named chair of the company’s board of directors. Medixci led Curevo’s Series B financing. —Insilico Medicine, a company that employs generative AI to drug discovery and development, raised $110 million for its pipeline and technology. Its most advanced drug candidate is rentosertib (formerly ISM001-055), a small molecule in mid-stage clinical development for idiopathic pulmonary fibrosis. A private equity fund of Value Partners Group led Insilico’s Series E financing. —Vivace Therapeutics raised $35 million to advance a potentially first-in-class drug that addresses the Hippo pathway. Lead Vivace drug VT3989 blocks TEAD proteins in this pathway, which contribute to cancer when dysregulated. VT3989 is being readied for Phase 3 testing in mesothelioma. RA Capital Management led the San Mateo, California-based biotech’s Series D financing. —Callio Therapeutics emerged with $187 million for its new twist on antibody drug conjugates (ADC) for cancer. Currently available ADCs carry a single drug payload. Callio, which splits its operations between Seattle and Singapore, is developing multi-payload ADCs. Frazier Life Sciences led Callio’s Series A financing, which it will use to achieve clinical proof of concept for a dual payload ADC targeting the cancer protein HER2. The target of a second Callio program is undisclosed. —Garuda Therapeutics raised $50 million to support its R&D of off-the-shelf hematopoietic stem cell therapies for potential applications in a range of blood disorders. Investors in the Series A-1 round include OribiMed, Northpond Ventures, Cormorant Asset Management, and Japanese pharma company Kyowa Kirin. —Cancer biotech Eikon Therapeutics closed $350 million in financing to support a pipeline that includes lead program EIK1001, which is in Phase 3 testing in advanced melanoma. This drug is a small molecule that activates TLR7/8 receptors to spark an immune response against cancer. —Bambusa Therapeutics, startup developing bispecific antibodies applications in immunology and inflammation, said its Series A financing raised about $90 million. Lead program BBT001 is being readied for Phase 1 testing in dermatological conditions. New investor RA Capital Management led the Boston-based biotech’s financing. —Abcuro raised $200 million to support ulviprubart, a drug in Phase 2/3 testing for inclusion body myositis, an autoimmune disease in which T cells chronically attack muscle tissue. The drug is an antibody that blocks a target called KLRG1. New Enterprise Associates led the Newton, Massachusetts-based biotech’s Series C financing. —Newleos Therapeutics unveiled clinical-stage neuropsychiatric drug candidates licensed from Roche and backed by $93.5 million in funding. Lead Newleos program NTX-1955 target the GABA A receptor subunit gamma 1 as a potential treatment for anxiety. Newleos plans to advance this small molecule to proof-of-concept clinical testing in generalized anxiety disorder. Goldman Sachs Alternatives led Newleos’s Series A financing.