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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. 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Single infusion of VERVE-102 led to dose-dependent decreases in blood PCSK9 and LDL-C, with mean reduction in LDL-C of 53% and a maximum reduction of 69% observed in the 0.6 mg/kg dose cohort VERVE-102 was well-tolerated with no treatment-related serious adverse events and no clinically significant changes in ALT or platelets observed at any dose level among 14 participants VERVE-102 utilizes a proprietary GalNAc-LNP which has demonstrated a potentially best-in-class safety profile In the second half of 2025, Verve expects to report final Heart-2 dose escalation data, dose the first patient in a Phase 2 clinical trial for VERVE-102, and receive a decision from Eli Lilly and Company for the PCSK9 opt-in Company to host conference call and webcast today, Monday, April 14, 2025, at 8 a.m. ET BOSTON, April 14, 2025 (GLOBE NEWSWIRE) -- Verve Therapeutics, a clinical-stage company developing a new class of genetic medicines for cardiovascular disease, today announced positive initial data from the Heart-2 Phase 1b clinical trial of VERVE-102. The Heart-2 Phase 1b clinical trial is evaluating patients with heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD), two populations that require deep and durable reductions of low-density lipoprotein cholesterol (LDL-C) levels in the blood. Among 14 participants across three dose levels, VERVE-102 was well-tolerated, with no treatment-related serious adverse events (SAEs) and no clinically significant laboratory abnormalities observed. A single infusion of VERVE-102 led to dose-dependent decreases in blood PCSK9 protein levels and LDL-C, with a mean reduction in blood LDL-C of 53% and a maximum LDL-C reduction of 69% observed among four participants in the 0.6 mg/kg dose cohort. “These initial Heart-2 data are promising with respect to both safety and efficacy and suggest the potential for a new era of cardiovascular disease treatment where a single dose might lead to lifelong control of LDL-C,” said Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at Harvard Medical School and Founding Chairman, TIMI Study Group, Brigham and Women’s Hospital. “Despite existing treatments to lower LDL-C, atherosclerotic cardiovascular disease (ASCVD) remains the most frequent cause of death worldwide. The reduction of ASCVD risk depends on both the magnitude of LDL-C reduction as well as the duration. With existing treatments, approximately half of patients discontinue their prescribed lipid lowering therapy within one year, resulting in poor real-world control of LDL-C. VERVE-102 holds great promise to transform the care of ASCVD and move that care from daily pills or intermittent injections over decades to a one dose future for sustained LDL-C lowering.” VERVE-102 VERVE-102 is a novel, in vivo, investigational base editing medicine designed to be a single-course treatment that permanently turns off the PCSK9 gene in the liver and durably reduces disease-driving LDL-C. VERVE-102 consists of an adenine base editor and a guide RNA (gRNA) targeting the PCSK9 gene. Both are encapsulated in a lipid nanoparticle (LNP) and administered as a single intravenous infusion over two to four hours. VERVE-102 uses Verve’s proprietary GalNAc-LNP delivery technology, which is designed to allow the LNP to access liver cells using either the low-density lipoprotein receptor (LDLR) or the asialoglycoprotein receptor (ASGPR). Heart-2 Clinical Trial Design The Heart-2 clinical trial is an open-label Phase 1b clinical trial designed to evaluate the safety and tolerability of VERVE-102 administration in adult patients with HeFH and/or premature CAD who require additional lowering of LDL-C. The trial is a single-ascending dose study and endpoints include pharmacokinetics and changes in blood LDL-C and PCSK9 protein levels. HeFH is diagnosed based on high LDL-C levels, a personal or family history of ASCVD, physical exam features, and/or mutations identified in certain genes. Premature CAD is defined as evidence of CAD (heart attack, coronary revascularization procedure, or coronary atherosclerosis on imaging) occurring in men ≤ 55 years old or women ≤ 65 years old. The Heart-2 clinical trial is expected to include four dose cohorts, each comprised of three to nine participants with HeFH and/or premature CAD. Initial data reported today are from 14 participants across the first three cohorts (weight-based cohorts of 0.3 mg/kg, 0.45 mg/kg, and 0.6 mg/kg) with at least 28 days of follow-up for each participant as of a data cutoff date of March 13, 2025. Heart-2 Safety and Tolerability VERVE-102 has been well-tolerated, with no treatment-related SAEs, no dose-limiting toxicities, and no cardiovascular events observed. Across all 14 participants, there was one infusion related reaction (Grade 2) which involved transient symptoms that resolved with acetaminophen. No clinically significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, or platelets were observed at any dose level. There were no dose-dependent trends in any of these laboratory measurements. Heart-2 Efficacy Analysis Following a single infusion of VERVE-102, dose-dependent reductions in two pharmacodynamic (PD) measures were observed: blood LDL-C and PCSK9 protein levels. Of note, in this patient population, LDL-C is a validated surrogate endpoint for clinical benefit accepted by the U.S. Food and Drug Administration (FDA) and other regulatory agencies. Mean blood LDL-C and PCSK9 protein reductions from baseline, using a time-averaged percent change from day 28 through the last available follow-up, were as follows: Cohort 1; 0.3 mg/kg (n=4): LDL-C reduction was 21% and PCSK9 reduction was 46%. Cohort 2; 0.45 mg/kg (n=6): LDL-C reduction was 41% and PCSK9 reduction was 53%. Cohort 3; 0.6 mg/kg (n=4): LDL-C reduction was 53% and PCSK9 reduction was 60%. Among the 14 participants, a maximum LDL-C reduction of 69% was achieved in a participant in the 0.6 mg/kg cohort. For LNP-delivered in vivo gene editing medicines, total RNA dose administered is emerging as a key driver of PD. As such, Verve also evaluated the Heart-2 PD data by total RNA dose. The analysis includes the 14 participants in the Heart-2 clinical trial grouped into three ranges of total RNA dose administered: < 25 mg (n=4), 25 – < 50 mg (n=7), and 50 – < 60 mg (n=3). Mean LDL-C reductions from baseline, using a time-averaged percent change from day 28 through the last available follow-up, were as follows: Across all 14 participants, VERVE-102 demonstrated a strong dose-dependent response between the amount of total RNA administered and LDL-C reductions. Three participants received a total RNA dose between 50 and 60 mg, with an average dose received of 55 mg of total RNA. In this dose group, VERVE-102 demonstrated a time-averaged LDL-C mean reduction of 59%. Each of the three participants who received a dose ≥ 50 mg achieved a > 50% time-averaged reduction of LDL-C from baseline. “Verve was founded seven years ago with a vision of one treatment dose potentially leading to a lifetime of LDL-C lowering. The data presented today suggest that this game-changing, one dose future is possible,” said Sekar Kathiresan, M.D., co-founder and chief executive officer of Verve Therapeutics. “We are pleased by the safety VERVE-102 has demonstrated so far, and our proprietary GalNAc-LNP delivery technology is showing a potentially best-in-class safety profile. The initial efficacy data suggest that VERVE-102 has the potential to match or exceed the LDL-C reduction provided by currently available PCSK9-targeting therapies. Among participants who received a dose greater than 50 mg total RNA, we observed a mean LDL-C reduction of 59% and a maximum LDL-C reduction of 69%. Furthermore, VERVE-101 has continued to show excellent durability for the base editing mechanism out to nearly two years, with follow-up ongoing.” Dr. Kathiresan continued, “In sum, VERVE-102 has the potential to solve the urgent need for enduring efficacy in patients living with HeFH or ASCVD. We are incredibly grateful to the patients and healthcare professionals who believe in our mission and participate in our clinical trials. Together, we are striving to revolutionize cardiovascular disease treatment and deliver a one dose future.” Next Steps The Heart-2 clinical trial is enrolling participants in the fourth dose cohort of 0.7 mg/kg in the United Kingdom, Canada, Israel, Australia, and New Zealand. As of April 7, 2025, Verve has dosed two participants in this cohort. The early laboratory and clinical safety profile is in line with the first three cohorts. Verve expects to announce the final data from the dose escalation portion of the Heart-2 clinical trial, including durability data, in the second half of 2025. Verve plans to dose the first patient in the Phase 2 clinical trial of VERVE-102 in the second half of 2025, subject to regulatory clearance. With the recent clearance by the U.S. FDA of the investigational new drug (IND) application for VERVE-102, Verve expects to enroll patients at U.S. trial sites in the Phase 2 clinical trial. Verve expects its current capital position to be sufficient to fund its operations into mid-2027, which includes the completion of the Phase 2 clinical trial. Under the PCSK9 program collaboration agreement with Verve, Eli Lilly and Company (Lilly) holds the right to opt-in to share worldwide development expenses (33% contributed by Lilly) and to jointly commercialize and share profits and expenses related to commercialization in the U.S. on a 50/50 basis. Verve retains control of the development and commercialization of all collaboration products in the U.S., and Verve holds all product rights outside the U.S. Verve expects to deliver the opt-in package for the PCSK9 program and receive a decision from Lilly in the second half of 2025. Conference Call Information Verve will host a conference call and webcast today, Monday, April 14, 2025, at 8 a.m. ET to review the initial Heart-2 clinical data. The conference call can be accessed via this link: https://register-conf.media-server.com/register/BI2d0a1d3cccc6461f95e6d7f836157a60. A live webcast will also be available under Events in the Investors section of the company’s website at https://ir.vervetx.com/events. The archived webcast will be available on the company’s website beginning approximately two hours after the event. About Verve Therapeutics Verve Therapeutics, Inc. (Nasdaq: VERV) is a clinical-stage company developing a new class of genetic medicines for cardiovascular disease with the potential to transform treatment from chronic therapies to single-course gene editing medicines. The company’s lead programs – VERVE-102, VERVE-201, and VERVE-301 – target the three cholesterol drivers of atherosclerosis: LDL-C, remnant cholesterol, and Lp(a). VERVE-102 is designed to permanently turn off the PCSK9 gene in the liver and is being developed initially for heterozygous familial hypercholesterolemia (HeFH) and ultimately to treat patients with established atherosclerotic cardiovascular disease (ASCVD) who continue to be impacted by high LDL-C levels. VERVE-201 is designed to permanently turn off the ANGPTL3 gene in the liver and is initially being developed for refractory hypercholesterolemia, where patients still have high LDL-C despite treatment with maximally tolerated standard of care therapies, and homozygous familial hypercholesterolemia (HoFH). VERVE-301 is designed to permanently turn off the LPA gene to reduce Lp(a) levels. Lp(a) is a genetically validated, independent risk factor for ASCVD, ischemic stroke, thrombosis, and aortic stenosis. For more information, please visit www.VerveTx.com. Cautionary Note Regarding Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the company’s ongoing Heart-2 clinical trial; the timing and availability of data for the Heart-2 trial and timing for initiation of the Phase 2 clinical trial for VERVE-102; the timing for delivery of the opt-in package and of Lilly’s decision for the PCSK9 program; the potential advantages and therapeutic potential of VERVE-102 and the period over which the company believes that its cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses. All statements, other than statements of historical facts, contained in this press release, including statements regarding the company’s strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the company’s limited operating history; the company’s ability to timely submit and receive approvals of regulatory applications for its product candidates; advance its product candidates in clinical trials; initiate, enroll and complete its ongoing and future clinical trials on the timeline expected or at all; correctly estimate the potential patient population and/or market for the company’s product candidates; replicate in clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of VERVE-101, VERVE-102, and VERVE-201; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the company’s most recent filings with the Securities and Exchange Commission and in other filings that the company makes with the Securities and Exchange Commission in the future. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof and should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company’s views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so. Investor Contact Jen Robinson Verve Therapeutics, Inc. jrobinson@vervetx.com Media Contact Ashlea Kosikowski 1AB ashlea@1abmedia.com

Verve Therapeutics’ CEO Sekar Kathiresa. Credit: Boston Globe via Getty Images. Verve Therapeutics saw its stock surge by more than 26% when markets opened today (14 April) after the company announced early-stage clinical data for its Eli Lilly-partnered experimental gene editing therapy VERVE-102. The company reported encouraging safety and efficacy from the Phase Ib Heart-2 trial (NCT06164730), which is testing the one-time treatment in patients with heterozygous familial hypercholesterolaemia (HeFH) and/or premature coronary artery disease (CAD). Patients with these disorders are at high risk of cardiovascular events due to elevated low-density lipoprotein cholesterol (LDL-C) levels. VERVE-102 uses a CRISPR base-editing system to permanently deactivate the PCSK9 gene in liver cells. This increases the number of LDL receptors and lowers LDL-C levels. In April 2024, Verve halted enrolment into its Heart-1 trial (NCT05398029) investigating VERVE-101 – another gene editing therapy targeting PCSK9 – after a patient experienced elevated liver enzyme levels and low platelet levels. The adverse effects were linked to the lipid nanoparticle delivery system used to deliver the genetic payload. Among the 13 patients enrolled, six were dosed at 0.45 mg/kg, with the sixth patient showing abnormal lab results within four days of treatment. Verve announced that it would prioritise the development of VERVE-102 following these safety issues. Against this backdrop, the latest VERVE-102 data appears to signal progress. No treatment-related serious adverse events or clinically significant laboratory abnormalities were noted in the Heart-2 trial. Key safety markers, including liver enzymes and platelet counts, remained within normal limits across all dose levels. In the highest dose group of 0.6 mg/kg, the therapy achieved a mean reduction in LDL-C of 53%, with one participant reaching a maximum reduction of 69%. The trial enrolled 14 participants who received a single infusion of VERVE-102 across three escalating dose cohorts. Verve’s CEO Sekar Kathiresa said: “The initial efficacy data suggest that VERVE-102 has the potential to match or exceed the LDL-C reduction provided by currently available PCSK9-targeting therapies.” Among these PCSK9-targeting therapies is Novartis’s Leqvio (inclisiran), Amgen’s Repatha (evolocumab), and Regeneron’s Praluent (alirocumab). However, none of these therapies offer the single-dose approach that Verve is putting forward. “Verve was founded seven years ago with a vision of one treatment dose potentially leading to a lifetime of LDL-C lowering. The data presented today suggest that this game-changing, one dose future is possible,” added Kathiresa in the 14 April announcement. The PCSK9 programme is being developed under a collaboration with Eli Lilly, which holds an option to co-develop and co-commercialise VERVE-102 in the US. If exercised, Lilly would contribute 33% of global development costs and equally share US profits and expenses. According to Verve, a decision from Lilly is expected in H2 2025. The US-based biotech now plans to initiate a Phase II trial in H2 2025. The Phase Ib study accrued patients in the UK, Canada, Israel, Australia and New Zealand, and Verve now plans to start enrolling patients at US sites following US Food and Drug Administration (FDA) approval of Verve’s investigational new drug (IND) application. Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic You have a right to withdraw your consent at any time, by clicking here . We may still continue to send you service-related and other non-promotional communications. For more information relating to our privacy practices, we invite you to review our privacy policy .