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SHANGHAI, Sept. 4, 2024 /PRNewswire/ -- YolTech Therapeutics, a clinical-stage in vivo gene editing company, announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) to YOLT-203 for the treatment of primary hyperoxaluria type 1 (PH1) in September. Earlier that month, YOLT-203 received Rare Pediatric Disease Designation (RPDD) from the FDA. After reviewing YolTech's submission, the FDA determined that the therapy is not only appropriate for primary hyperoxaluria type 1 (PH1), but also applicable to the broader category of primary hyperoxaluria (PH). As a result, the designations were granted for PH, reflecting the expanded scope of the therapy's potential impact. These dual designations underscore the transformative potential of YOLT-203 to address this rare and life-threatening genetic disorder. About Primary Hyperoxaluria and PH1 Primary hyperoxaluria (PH) is a rare autosomal recessive genetic disorder in which excessive oxalate production in the liver causes kidney stone formation, progressive renal damage, and systemic oxalosis. The most common subtype of PH, primary hyperoxaluria type 1 (PH1), results from dysfunction of alanine-glyoxylate aminotransferase (AGT) due to mutations in the AGXT gene. In the absence of intervention, most patients progress to end-stage renal disease (ESRD), requiring intensive hemodialysis and often a dual liver-kidney transplant to correct the metabolic defect and address organ failure. About YOLT-203 YOLT-203 is an innovative investigational in vivo gene editing therapy designated to provide a one-time, potentially curative treatment for primary hyperoxaluria type 1 (PH1). YOLT-203 permanently reduces excessive oxalate production in PH1 by deactivating the HAO1 gene through YolTech's proprietary YolCas12™ system, a novel CRISPR/Cas enzyme identified through the High-Throughput Evolution Platform (HEPDONE®). YOLT-203 is administered through intravenous infusion of liver-targeted lipid nanoparticles (LNPs) encapsulating YolCas12 mRNA and a guide RNA (gRNA) targeting the HAO1 gene. YOLT-203 also represents a historic milestone as the first in vivo gene editing therapy to enter clinical trial globally for a pediatric rare disease. Clinical Development and Early Results The investigator-initiated clinical study of YOLT-203 began on August 5, 2024, with the first adult patient dosed, followed by the first pediatric patient on August 20, 2024. Early data from preclinical and initial clinical studies have demonstrated promising reductions of over 90% in blood oxalate levels, with no dose-limiting toxicities (DLTs) or severe adverse events (SAEs) leading to treatment interruptions observed to date. Significance of FDA Designations The Rare Pediatric Disease Designation (RPDD) program encourages the development of new drugs and biologics for rare pediatric conditions. This designation makes YolTech eligible to receive a priority review voucher (PRV) upon potential FDA approval of YOLT-203. Similarly, the Orphan Drug Designation (ODD) program provides benefits including tax credits, exemption from certain FDA fees, and seven years of market exclusivity upon regulatory approval. About YolTech Therapeutics 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, visit: or follow YolTech on LinkedIn: YolTech Therapeutics. Contacts Colin LIN Business Development & Investor Relations [email protected] +86 180 2100 7750 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

SHANGHAI, Aug. 22, 2024 /PRNewswire/ -- YolTech Therapeutics, a pioneering clinical-stage gene editing company dedicated to delivering lifelong cures, today announced a major milestone: the first patient has been dosed with YOLT-203, the company's cutting-edge in vivo genome editing candidate. This marks the commencement of an Investigator-Initiated Trial (IIT) and represents a global first in the application of in vivo gene editing therapies for Primary Hyperoxaluria Type 1 (PH1). YOLT-203 is designed as a single-dose, potentially curative therapy, harnessing the power of YolTech's proprietary YolCas12™ editor. This trial sets a new standard in the field, pushing the boundaries of what gene editing can achieve in treating life-threatening genetic diseases. Primary hyperoxaluria is a genetic disorder associated with hepatic oxalate overproduction, leading to increased renal oxalate excretion. PH1 as the most commonly diagnosed subtype, is a childhood-onset autosomal recessive disease form caused by AGXT gene mutations and absence or dysfunction of alanine-glyoxylate aminotransferase. Most patients ultimately progress to renal failure and require intensive hemodialysis as a bridge to a dual liver/kidney transplant to resolve the metabolic defect in the liver and replace the terminally damaged kidneys. YOLT-203, independently developed by YolTech, is powered by YolTech's proprietary YolCas12™ editor, a novel CRISPR/Cas gene editing tool developed through YolTech's metagenomics discovery and protein engineering platform named HEPDONE® (High-Throughput Evolution Platform for Discovery and Optimization of Novel Editors) system. YolCas12™ has demonstrated significantly high gene editing activity in both prokaryotic and eukaryotic systems and has been proven to achieve high-efficiency in vivo editing via LNP-mRNA delivery in mice and non-human primates. YoLT-203 is utilizing YolCas12™ editor to target HAO1 gene, significantly preventing pathogenic protein expression in pre-clinical study, promising to provide effective treatment options for PH1 child and adult patients. The clinical study of YOLT-203, initiated by investigators, is a single-arm, open-label, dose-escalation clinical trial, aiming to evaluate the safety and tolerability of YOLT-203 in the Chinese population with PH1. 7 subjects are estimated to be enrolled. The first adult subject received the dose on 5th Aug 2024 and the first child patient were treated on 20th Aug 2024. This trial represents a pioneering effort as the first global clinical trial of an in vivo gene editing therapy targeting PH1. "PH1 is a devastating disease that can lead to life-threatening kidney damage and systemic complications," said Dr. Yuxuan Wu, Founder and CEO of YolTech. "As the first in vivo gene editing therapy for PH1, YOLT-203, using our proprietary YolCas12™ editor, has the potential to transform treatment options for patients suffering from this debilitating disease. We believe YOLT-203 is expected to bring significant clinical benefits to both children and adults affected by this condition, and we look forward to sharing and reporting more data from this program in the future." YolTech remains committed to progressing the clinical development of YOLT-203 and working closely with regulatory authorities, healthcare professionals, and patient advocacy groups to further the advancement of gene editing therapies. **About YOLT-203** YOLT-203 is an innovative in vivo gene editing therapy designed using YolTech's proprietary YolCas12™ system, a novel CRISPR/Cas tool developed through the High-Throughput Evolution Platform (HEPDONE®). This therapy is encapsulated within lipid nanoparticles (LNPs) that facilitate targeted delivery to the liver, where it addresses the underlying genetic mutations responsible for primary hyperoxaluria type 1 (PH1). Upon intravenous administration, the LNPs are recognized and internalized by liver cells. Once inside, the YolCas12™ editor protein, guided by the corresponding guide RNA (gRNA), targets and corrects mutations in the AGXT gene, aiming to reduce harmful oxalate levels in the blood, thereby offering a potential one-time, curative treatment for PH1. **About YOLT-203-101 Study** The YOLT-203-101 trial is a single-arm, open-label, single-dose, dose-escalation clinical study designed to evaluate the safety and tolerability of YOLT-203 in Chinese patients diagnosed with primary hyperoxaluria type 1 (PH1). The study will also preliminarily assess the impact of a single administration of YOLT-203 on plasma oxalate levels, a critical biomarker of therapeutic efficacy in PH1. The trial's dose-escalation phase will involve three dose groups, employing an accelerated titration approach to escalate doses from the starting level to the highest planned dose. Following the one-year main study, participants will enter a long-term follow-up period of fifteen years to monitor the sustained effects and safety of the treatment. **About YolTech** YolTech Therapeutics is a pioneering gene editing company dedicated to developing medicines delivering lifelong cures with serious diseases. YolTech has built a leading high-throughput evolution platform and innovative LNP delivery system. It possesses strong capabilities in novel Cas and base editor discovery and exceptional in-house LNP production capacity for GMP manufacturing, with independent intellectual property rights and core patent protection globally. YolTech's lead pipeline, YOLT-201, became the first LNP-mediated in vivo gene editing drug in China to enter registered clinical development in 2024. The company is also advancing gene editing therapies for familial hypercholesterolemia (FH) and primary hyperoxaluria type 1 (PH1) with promising early clinical results. For more information on the YOLT-203-101 trial, please visit: or follow YolTech on LinkedIn Contacts Colin LIN Business Development & Investor Relations [email protected] +86 180 2100 7750 SOURCE YolTech Therapeutics

The initial response to de novo subcutaneous (SC) BION-1301 treatment in Cohort 2 is highly consistent with Cohort 1 across both mechanistic biomarkers and proteinuria reductionsBION-1301 is well-tolerated, with no serious adverse events (SAEs) and no treatment discontinuations due to adverse events (AEs) in patients with IgAN across Cohorts 1 and 2BION-1301 continues to demonstrate rapid and sustained reductions in mechanistic biomarkers, including IgA and Gd-IgA1 levels, in patients with IgAN across Cohorts 1 and 2In Cohort 1, BION-1301 demonstrated mean proteinuria reductions of 30.4% at 12 weeks of treatment, 48.8% at 24 weeks of treatment and 66.9% at 52 weeks of treatment, as well as 67.4% in four patients at 76 weeks of treatment and 71.0% in two patients at 100 weeks of treatmentIn Cohort 2, de novo SC BION-1301 treatment resulted in mean proteinuria reductions of 28.7% in 15 patients at 12 weeks of treatment and 53.8% in nine patients at 24 weeks of treatmentCHK-336, a potent LDHA inhibitor with liver-targeted tissue distribution, demonstrated preclinical efficacy in PH1 and PH2 mouse models of primary hyperoxaluria (PH), and the potential for benefit in non-genetic hyperoxalurias caused by oxalate overproduction was also described.Chinook to host investor conference call, webcast and in-person event today at 6:30 pm EDT with Dr. Sreedhar A. Mandayam, Professor of Nephrology at the University of Texas MD Anderson Cancer Center and Baylor College of Medicine, and Laura Kooienga, MD, practicing nephrologist and director of research at Colorado Kidney Care SEATTLE, Nov. 04, 2022 (GLOBE NEWSWIRE) -- Chinook Therapeutics, Inc. (Nasdaq: KDNY), a biopharmaceutical company focused on the discovery, development and commercialization of precision medicines for kidney diseases, announced two posters on the BION-1301 and CHK-336 programs being presented today at ASN Kidney Week 2022 being held virtually and live in Orlando, Florida. An oral presentation and additional poster on Chinook’s collaboration with Evotec will also be presented at ASN Kidney Week 2022 later this afternoon and tomorrow. “The strong data we presented today at ASN Kidney Week from the ongoing phase 1/2 study of BION-1301 continue to demonstrate its disease-modifying potential in patients with IgAN,” said Eric Dobmeier, president and chief executive officer of Chinook Therapeutics. “We are pleased to see that the mechanistic biomarker and proteinuria reductions observed to date in patients receiving subcutaneous BION-1301 in Cohort 2 are highly consistent with those observed in Cohort 1. These data reinforce our confidence in the dose and schedule we have selected to take forward in the phase 3 trial of BION-1301 for patients with IgAN that we plan to initiate next year.” FR-PO659 – Updated Interim Results of a Phase 1/2 Study of BION-1301 in Patients with IgA Nephropathy BION-1301 is a novel anti-APRIL monoclonal antibody currently in phase 2 clinical development for patients with IgAN. Blocking APRIL is a potentially disease-modifying approach to treating IgAN by reducing circulating levels of galactose-deficient IgA1 (Gd-IgA1). Updated data from Cohort 1 and initial data from Cohort 2 were presented from Part 3 of the ongoing phase 1/2 multi-center trial (see www.clinicaltrials.gov, identifier NCT03945318) evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical responses of open-label BION-1301 treatment in patients with IgAN. Key highlights from the presentation include the following: Patients in Cohort 1 initially received a 450mg intravenous (IV) dose of BION-1301 every two weeks. After at least 24 weeks of IV dosing, patients in Cohort 1 transitioned to a 600 mg SC dose every two weeks for a total treatment duration of up to two years. Cohort 1 enrolled 10 patients, of which eight patients remain on treatment. All eight patients have transitioned from IV to SC administration, with a mean SC treatment duration of 40 weeks. Patients in Cohort 2 are receiving a SC dose of 600 mg of BION-1301 every two weeks for a total treatment duration of up to two years. Cohort 2 has enrolled 24 of the planned 30 patients. Mean treatment duration was 17 weeks, with time on treatment ranging from two to 30 weeks. Baseline 24-hour Urine Protein Excretion (g/day) The median baseline 24-hour urine protein excretion for patients enrolled in Cohort 1 was 1.2 g/day, with a range of 0.7 – 6.5 g/day, and the median baseline 24-hour urine protein excretion for patients enrolled in Cohort 2 was 1.0 g/day, with a range of 0.6 – 2.7 g/day. Cohorts 1 and 2 both represent a population of patients with IgAN at high risk of kidney disease progression. Safety and Tolerability As of the October 13, 2022 data cutoff, BION-1301 has been well-tolerated, with no serious adverse events or treatment discontinuations due to adverse events. Of all 34 patients enrolled in both Cohorts 1 and 2: Eight patients experienced mild (Grade 1 or 2) treatment-related AEs, including three patients with fatigue and three patients with injection site reactions.Seventeen patients experienced mild (Grade 1 or 2) infections, of which only one Grade 1 infection was assessed as treatment-related. Pharmacokinetics (PK) The PK profile demonstrated low inter-individual variability in BION-1301 serum concentrations and consistent trough concentrations following IV and SC administrations. To date, no anti-drug antibodies have been observed in patients. Mechanistic Biomarkers BION-1301’s effects on mechanistic biomarkers were highly consistent between Cohorts 1 and 2.In Cohort 1, reductions in IgA and Gd-IgA1 were maintained beyond 52 weeks of treatment. Reductions in IgM, and to a lesser extent IgG, were also observed (see figures below). Reductions in free APRIL confirm durable target neutralization sustained through one year.In Cohort 2, SC BION-1301 treatment resulted in rapid and sustained reductions in IgA and Gd-IgA1, IgM, and to a lesser extent IgG, through 24 weeks of treatment, consistent with Cohort 1 (see figures below). 24-hour UPCR In Cohort 1, BION-1301 demonstrated mean reductions in 24-hour urine protein creatinine ratio (UPCR) of 30.4% in seven patients at 12 weeks of treatment, 48.8% in all eight patients at 24 weeks of treatment, 66.9% in all eight patients at 52 weeks of treatment, 67.4% in four patients at 76 weeks of treatment and 71.0% in two patients at 100 weeks of treatment (see figure below). Clinically meaningful reductions in UPCR from baseline were seen in patients with IgAN across a wide range of baseline proteinuria levels by Week 12.UPCR continued to decline through one year, and reductions were maintained through two years, providing evidence of sustained efficacy.Among patients with available data at Week 52, seven of eight patients demonstrated a greater than 50% mean reduction in 24-hour UPCR from baseline at Week 52 In Cohort 2, BION-1301 demonstrated mean reductions in 24-hour UPCR of 28.7% in 15 patients at 12 weeks of treatment and 53.8% in 9 patients at 24 weeks of treatment, highly consistent with reductions observed at the same timepoints in Cohort 1 (see figure below). FR-PO334 – Preclinical Efficacy of CHK-336: A First in Class, Liver-Targeted, Small Molecule Inhibitor of Lactate Dehydrogenase for the Treatment of Primary Hyperoxalurias (PH) CHK-336 is a potent LDHA inhibitor with liver-targeted tissue distribution that is efficacious in PH1 and PH2 mouse models and has potential benefit in non-genetic hyperoxalurias caused by oxalate overproduction. CHK-336 demonstrates potent inhibition of LDHA in enzyme assays (IC50 = 0.2-0.3 nM) and primary hepatocyte assays across multiple species (IC50 = 52-165 nM). CHK-336 also demonstrates tight LDHA binding with a very slow off-rate (hours to days). CHK-336 exhibits a liver-targeted tissue distribution profile in mice, rats and monkey with high liver concentrations and low extra-hepatic tissue exposures. Since LDHA catalyzes the final step of oxalate production from glycolate, in vivo conversion of a 13C2-glycolate stable isotope tracer to 13C2-oxalate was dose-dependently blocked by CHK-336, demonstrating target engagement. Human PK predictions suggest CHK-336 has the potential to be a low, once-daily oral dose therapeutic in humans. CHK-336 was dosed orally, once-daily for seven days in male Agxt KO mice, a PH1 mouse model, and urinary oxalate concentrations were compared to a vehicle control group. Low, oral, once-daily doses of CHK-336 significantly and dose-dependently reduced urinary oxalate; the majority of treated mice reached the normal range observed in wild-type mice. CHK-336 also had a more rapid onset of action and comparable magnitude of urinary oxalate reduction compared to a GO-targeting siRNA. CHK-336 was dosed orally, once-daily for seven days at 25 mg/kg in male Grhpr KO mice, a PH2 mouse model, and significantly reduced urinary oxalate concentrations compared to the vehicle control group. Increased urinary oxalate and altered hepatic expression of genes involved in oxalate synthesis were observed in obese, hypertensive and diabetic rats compared to controls. This supports the potential therapeutic benefit of CHK-336 in non-genetic oxalate nephropathies associated with increased endogenous production of oxalate. The human safety and PK profiles of CHK-336 are currently under investigation in a phase 1 healthy volunteer SAD/MAD study (see www.clinicaltrials.gov, identifier NCT05367661) and data is expected to be presented in the first half of 2023. Administration of the 13C2-glycolate stable isotope tracer has been incorporated into the phase 1 study to assess LDHA target engagement in humans. FR-OR60 – A Multi-Omics Approach to IgA Nephropathy Characterization in the NURTuRE Cohort Enables Precision-Based Treatment Approaches An overview of the multi-omics analysis of the NURTuRE IgAN patient cohort will be delivered today as an oral presentation during the Glomerular Diseases: From Bench to Bedside session at 4:30 – 6:00 pm EDT in W414 at the Orange County Convention Center, West Building. SA-PO1011 – Unsupervised Characterization of the NURTuRE Cohort Reveals Gene Expression and Tissue Remodeling Dynamics along a Synthetic CKD Progression Axis An overview of the unsupervised characterization of the QUOD and NURTuRE patient cohorts will be delivered in collaboration with Evotec tomorrow (Saturday, November 5th) as a poster presentation at 10:00 am – 12:00 pm EDT in the Exhibit Hall of the Orange County Convention Center, West Building. Once published by ASN, all four presentations can be found in the Scientific Publications section of Chinook’s website. Live Conference Call and WebcastChinook will host a live conference call, webcast and in-person event today at 6:30 pm EDT to discuss presentations at the ASN Kidney Week 2022 and provide program updates. Members of the Chinook executive team will be joined by Dr. Sreedhar A. Mandayam, Professor of Nephrology at the University of Texas MD Anderson Cancer Center and Baylor College of Medicine and Laura Kooienga, MD, practicing nephrologist and director of research at Colorado Kidney Care. Conference Call and Webcast DetailsTo access the call, please dial (800) 715-9871 (domestic) or (646) 307-1963 (international) and provide the Conference ID 7505851 to the operator. To access the live webcast and subsequent archived recording of this and other company presentations, please visit the Investors section of Chinook’s website. The archived webcast will remain available for replay on Chinook’s website for 90 days. About Chinook Therapeutics, Inc.Chinook Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing precision medicines for kidney diseases. Chinook’s product candidates are being investigated in rare, severe chronic kidney disorders with opportunities for well-defined clinical pathways. Chinook’s lead program is atrasentan, a phase 3 endothelin receptor antagonist for the treatment of IgA nephropathy and other proteinuric glomerular diseases. BION-1301, an anti-APRIL monoclonal antibody, is being evaluated in a phase 1/2 trial for IgA nephropathy. CHK-336, an oral small molecule LDHA inhibitor for the treatment of hyperoxalurias, is being evaluated in a phase 1 healthy volunteer trial. In addition, Chinook is advancing research programs for other rare, severe chronic kidney diseases. Chinook is building its pipeline by leveraging insights in kidney single cell RNA sequencing, human-derived organoids and new translational models, to discover and develop therapeutics with differentiating mechanisms of action against key kidney disease pathways. To learn more, visit www.chinooktx.com. Cautionary Note on Forward-Looking StatementsCertain of the statements made in this press release are forward looking, including those relating to Chinook’s business, future operations, advancement of its product candidates and product pipeline, clinical development of its product candidates, including expectations regarding cash forecasts and timing of initiation and results of clinical trials, and regulatory submissions, including the timing of the results of our phase 3 ALIGN trial and phase 2 AFFINITY trial of atrasentan and submission for potential accelerated approval. In some cases, you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, including initiation of clinical trials of our existing product candidates or those developed as part of the Evotec collaboration, whether results of early clinical trials or preclinical studies will be indicative of the results of future trials, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that may be more advanced or have greater resources than we do, our ability to obtain and adequately protect intellectual property rights for our product candidates and the effects of COVID-19 on our clinical programs and business operations. Many of these risks are described in greater detail in our filings with the SEC. Any forward-looking statements in this press release speak only as of the date of this press release. Chinook assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. Photos accompanying this announcement are available at https://www.globenewswire.com/NewsRoom/AttachmentNg/fbb54cd0-dcc3-41b8-b0ce-d710809948cc https://www.globenewswire.com/NewsRoom/AttachmentNg/442ff21d-799f-4e1a-b6f2-6524611243bb