Abstract
Aim: Zerlasiran is an N-acetylgalactosamine-conjugated small interfering RNA that targets lipoprotein(a), a risk factor for atherosclerosis and calcific aortic stenosis. Zerlasiran has not been studied in Japanese participants previously.
Method: This was an open-label, single-dose trial that enrolled 18 adult participants with lipoprotein(a) levels ≥ 70 nmol/L at a single site in Japan to evaluate subcutaneous doses of zerlasiran (30 mg, 100 mg, and 300 mg) in three ascending-dose cohorts. The participants were monitored for 150 days post-dose to assess the systemic pharmacokinetics, pharmacodynamics (lipoprotein (a) and lipid biomarkers), and safety.
Results: Following dosing, median Tmax was reached at 5 hours with plasma concentrations gradually declining to undetectable levels by 36 hours, with t1/2 approximately 4 hours. Both Cmax and AUC0-inf increased in a dose-dependent manner. The maximum median (interquartile range [IQR]) percent reduction in lipoprotein (a) in the 30 mg, 100 mg, and 300 mg cohorts were -72.8% (-79.7%, -67.1%), 88.8% (-89.5%, -84.7%), and -97.8% (-98.6, -96.9%), respectively, between days 30 and 60, with a sustained effect observed at 150 days at all dose levels. All adverse events were mild and self-limiting.
Conclusion: Zerlasiran was well tolerated with no significant safety findings observed at any dose level. A typical pharmacokinetic profile expected of an N-acetylgalactosamine-conjugated small interfering RNA, coupled with a potent and sustained reduction in lipoprotein(a), was observed in Japanese participants. No adverse effects on either the liver or kidney function were observed.
Keywords: Lipoprotein(a), Zerlasiran, Pharmacokinetics, Safety, Small interfering RNA
See editorial vol. 33: 1135-1136
Introduction
Atherosclerotic cardiovascular disease (ASCVD) is the second leading cause of morbidity and mortality in Japan, despite significant advances in risk prevention 1) . Modulating low-density lipoprotein cholesterol (LDL-C) levels remains a cornerstone in preventing ASCVD events, and the expansion of potent treatment options over the past decade means that strict LDL-C control is achievable, although a significant residual risk remains. Elevated lipoprotein(a) [Lp(a)] is increasingly recognized as an independent, direct, and causal risk factor for ASCVD and calcific aortic stenosis. The threshold for an increased ASCVD risk is traditionally defined as Lp(a) ≥ 30 mg/dL (~70 nmol/L), which is observed in approximately 20% of the Japanese population 2 , 3) . However, contemporary data suggest that the lifetime risk of ASCVD increases continuously, starting at an even lower threshold than previously thought 4 , 5) , thus providing further evidence that Lp(a) is an important contributor to residual cardiovascular risk. Extensive epidemiological studies and Mendelian randomization analyses involving different ethnic groups have consistently supported a strong, causal, and continuous association between Lp(a) concentration and cardiovascular outcomes 4 , 5) . These studies have shown that a genetically determined doubling of Lp(a) levels results in a 22% increased risk of myocardial infarction (MI), consistent with a causal relationship between lifelong elevation in Lp(a) levels and MI risk 6) . Even when adjusting for other lipids and established risk factors, the risk of coronary artery disease increases continuously from ~Lp(a) ＞30 mg/dL 7) . Conversely, large-scale population data suggest that low levels of Lp(a) are not detrimental to human health, but are strongly associated with a lower risk of ASCVD 8) . Lp(a) is a low-density lipoprotein-like particle composed of a single apolipoprotein B100 (apoB) molecule linked to a single apolipoprotein A (apo[a]). It is the major carrier of oxidized phospholipids, which, in turn, exert potent proatherogenic and proinflammatory effects, accounting for a significant proportion of the cardiovascular risk attributable to Lp(a) 4 , 5) . Apo(a) synthesis is a dominant and rate-limiting component in the hepatic synthesis of Lp(a), which is encoded by the LPA gene. The levels of Lp(a) are predominantly genetically determined, remain stable throughout adulthood, and are unaffected by lifestyle changes. The currently approved anti-lipid treatments have a limited effect on lowering Lp(a).
Zerlasiran is a tri-antennary N-acetylgalactosamine (GalNAc)-conjugated, 19-mer double-stranded small interfering RNA (siRNA) that targets LPA mRNA. The GalNAc residues of zerlasiran bind specifically to the asialoglycoprotein receptor, which is predominantly expressed on hepatocytes, thereby ensuring highly targeted delivery to these cells. Following binding and receptor-mediated cellular uptake by endocytosis, LPA mRNA is degraded via RNA interference by the antisense strand of the siRNA. Through its highly specific silencing of LPA in hepatocytes, zerlasiran is designed to reduce the apo(a) concentration, thereby reducing the circulating Lp(a) levels. In previous phase 1 and 2 studies (NCT04606602, NCT05537571) conducted in predominantly Caucasian populations, zerlasiran was well tolerated, with no clinically concerning adverse reactions. A potent and durable lowering effect of Lp(a) at clinically relevant doses was observed, which allows for infrequent dosing in the clinic 9 - 11) . As zerlasiran has not been administered to Japanese participants previously, the objective of this study was to characterize its effects in adult Japanese participants with elevated Lp(a), but without a history of clinically overt ASCVD.
Aim
This study aimed to determine the pharmacokinetics (PK), pharmacodynamics (PD), and safety of zerlasiran following single subcutaneous (SC) doses of zerlasiran 30, 100, and 300 mg in Japanese participants with Lp(a) ≥ 70 nmol/L.
Methods
Study Design
This was an open-label, single-ascending dose study conducted between May 10, 2024 and February 12, 2025, at the Medical Corporation Heishinkai OPHAC hospital in Osaka, Japan. Three dose cohorts were planned to evaluate single doses of zerlasiran sequentially, starting from 30 mg, followed by 100 mg, and then 300 mg. The dose range was selected based on data from the completed first-in-human study, which investigated single doses of zerlasiran up to 600 mg and multiple doses up to 450mg 9) . The three doses were predicted to provide a clinically relevant range for a thorough investigation of the safety and PK-PD relationship of zerlasiran in Japanese participants. A safety review committee, consisting of the investigator and the sponsor’s medical representative, evaluated a minimum of four participants who completed at least seven days of post-dose safety assessment to confirm dose escalation decisions. An optional cohort to study a single dose of zerlasiran (450 mg) was not activated by the sponsor. Potential participants were invited to participate in an optional pre-screening visit for Lp(a) measurements, as this is not routinely measured in this population globally, including in Japan.
This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, and the protocol was approved by the Institutional Review Board of Medical Corporation Heishinkai on April 19, 2024. The study was registered with the Japan Registry of Clinical Trials (jRCT2051240068, June 18, 2024), and all patients provided their written informed consent.
Participants
For the main study, the key inclusion criteria were males and females of Japanese heritage, aged 20 to 70 years, with a body mass index between 18 and 32 32kg/m2 and a serum Lp(a) concentration ≥ 70 nmol/L. The key exclusion criteria were a history of clinically overt ASCVD, type 1 diabetes mellitus, or poorly controlled type 2 diabetes mellitus (glycated hemoglobin ≥ 86 mmol/mol), estimated GFR ＜60 mL/min/1.73 m2, moderate or severe liver cirrhosis, or any unstable medical condition. Participants were not permitted to take concomitant medications for the treatment of hyperlipidemia unless they had been on a stable dose for ≥ 8 weeks before screening and had no plans to alter therapy during the study. There were no formal criteria restricting attendance for the pre-screening visit, as the key aim was to enrich the screening of the main study with potential participants who have Lp(a) ≥ 70 nmol/L.
Interventions
The participants received a single dose of zerlasiran 30, 100, or 300 mg SC at a single injection site in the abdomen, with a maximum volume of 1.5mL per injection. Following an overnight stay, they were reviewed at outpatient visits at 3, 8, 15, 30, 60, 90, and 150 days post dose. Systemic PK was evaluated by serial blood samples at the following timepoints: pre-dose, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, and 36 hours to fully characterize the time course for the plasma concentration of zerlasiran. PK samples were analyzed using liquid chromatography with tandem mass spectrometry with an internally validated range of zerlasiran plasma concentration between 10.0 and 1000 ng/mL (Medpace Bioanalytical Laboratories, Cincinnati, United States). Safety assessments included serial measurements of vital signs, a 12-lead electrocardiogram, safety laboratory tests (hematology and biochemistry), physical examinations, and adverse events data collection. Local tolerability assessments were performed as structured evaluations for up to 8 days post-dose to carefully assess any injection site reactions. The Lp(a) levels were measured at pre-screening using a standard of care turbidimetric immunoassay, which reported levels as mass measurements in mg/dL (BM8060 JEOL Ltd., Japan). From the screening visit onwards, Lp(a) was measured at every visit using a particle-enhanced turbidimetric assay on a Roche c502 autoanalyzer, which reported levels as molar measurements in nmol/L and is relatively insensitive to apo(a) particle size variations (Medpace Bioanalytical Laboratories, Cincinnati, United States). Eligibility based on Lp(a) ≥ 70 nmol/L was confirmed at the formal screening visit using the Roche c502 assay (nmol/L). Pre-screening Lp(a) values reported in mg/dL were used solely to enrich the screening pool and were not used for eligibility or baseline. No unit conversion was applied when confirming eligibility. Liver safety was monitored using prespecified thresholds (Alanine aminotransferase or Aspartate aminotransferase ≥ 3 × upper limit of the Normal [ULN]; Alkaline phosphatase ≥ 2 × ULN; total bilirubin ≥ 2 × ULN; or international normalized ratio ＞1.5 if Alanine aminotransferase ≥ 3 × ULN) with prospective safety review committee oversight; renal safety was monitored descriptively using serial measurements of creatinine and eGFR.
Study Endpoints
The primary endpoints were the evaluation of the maximum plasma concentration (Cmax), time of the maximum plasma concentration (Tmax), apparent plasma terminal elimination half-life (t1/2), and exposure parameters by area under the plasma concentration–time curve (AUC). The secondary endpoints were safety and tolerability assessments of adverse events and changes in Lp(a), LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides, and apoB.
Statistical Analyses
A formal sample size calculation was not performed for the primary endpoints of this study. The number of participants was selected based on experience with the first-in-human trial, which adequately characterized the zerlasiran PK-PD relationship.
All continuous data were summarized using descriptive statistics. Baseline was defined as the last measurement prior to the first dose of study drug. The PK populations included all participants who received a dose of zerlasiran and had evaluable PK data, defined as at least three measurable post-dose concentrations. The plasma concentrations were summarized by dose level and listed for the PK population. Individual and mean plasma concentrations were plotted by dose level on linear and semi-log scales, respectively, against actual and nominal sampling times. The safety and PD populations included all participants who received a dose of zerlasiran. All adverse events were coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MeDRA) version 27.1. Biomarker data for the PD population were summarized using descriptive statistics and graphically using median plots of the Lp(a) values, change from baseline, and the percent change from baseline.
Results
Patients
A total of 363 participants attended the pre-screening visits, and the median (IQR) Lp(a) level was 11.0 (5.9, 23.7) mg/dL. The observed Lp(a) frequency distribution in this group is similar to that of a recently published Japanese population-based study ( Fig.1 ) 12) . The participant disposition is shown in Fig.2 . A total of 18 patients of Japanese heritage were enrolled in this study, with six participants in each of the three dose level cohorts. All treated participants completed their per-protocol study visits and were included in the full analysis. The mean (SD) age of the participants was 49.6 (11.7), and the range was similar across all cohorts ( Table 1 ) . Overall, 50% of the participants were women. However, the 300 mg cohort enrolled all women, resulting in a lower mean weight for this cohort (71.3 kg, 60.0 kg, and 56.2 kg for the 30 mg, 100 mg, and 300 mg cohorts, respectively). Despite this, the body mass index was similar between the cohorts, with the mean body mass index ranging from 21.74 kg/m2 to 24.56 kg/m2. Four participants had a history of hyperlipidemia, and one participant reported a history of type 2 diabetes mellitus, but none of the participants had clinically overt ASCVD. The overall median (IQR) Lp(a) level was 106 (95.70, 180.20) nmol/L and the mean (SD) LDL-C level was 120 (25.7) mg/dL.
Fig.1. Lipoprotein(a) frequency distribution in pre-screening.
A histogram showing the lipoprotein(a) frequency distribution in participants who attended the study prescreening visit. Values illustrated on the X-axis represent the central value of each bin. A total of 362 lipoprotein(a) results were available from 363 individuals who attended pre-screening.
Fig.2. Trial participant flow chart.
Trial participant flowchart showing participant disposition in this phase 1 study.
Table 1. Baseline Characteristics.
| Characteristics | Dose groups | ||
|---|---|---|---|
| 30mg (N = 6) | 100mg (N = 6) | 300mg (N = 6) | |
| Demographics | |||
| Age, mean (SD) years | 48.5 (12.6) | 50.7 (15.4) | 49.5 (7.97) |
| Female, n (%) | 1 (16.7) | 2 (33.3) | 6 (100) |
| Individuals of childbearing potential (%) | 1 (16.7) | 1 (16.7) | 4 (66.7) |
| Weight, mean (SD) Kg | 71.3 (10.0) | 60.0 (12.6) | 56.2 (6.68) |
| Body mass index, mean (SD) kg/m2 | 24.6 (3.0) | 21.7 (3.5) | 22.9 (2.8) |
| Participants of Japanese heritage n (%) | 6 (100) | 6 (100) | 6 (100) |
| Past Medical History | |||
| Dyslipidemia | 1 (16.7) | 1 (16.7) | 2 (33.3) |
| Hypertension | 1 (16.7) | 1 (16.7) | 0 (0) |
| Type 2 diabetes | 1 (16.7) | 0 (0) | 0 (0) |
| Concomitant Lipid-lowering Medications | |||
| Statins | 0 (0) | 1 (16.7) | 1 (16.7) |
| Eicosapentaenoic acid ethyl ester | 0 (0) | 0 (0) | 1 (16.7) |
| Omega-3-acid ethyl ester | 0 (0) | 1 (16.7) | 0 (0) |
| Ursodeoxycholic acid | 1 (16.7) | 0 (0) | 0 (0) |
| Laboratory parameters | |||
| Lipoprotein(a), median (IQR), nmol/L | 112 (100,180) | 127 (91.1, 165) | 103 (98.5, 183) |
| Total cholesterol, mean (SD), mg/dL | 214 (6.65) | 203 (39.7) | 194 (35.0) |
| LDL-C, mean (SD), mg/dL | 131 (14.1) | 123 (33.5) | 108 (24.5) |
| HDL-C, mean (SD), mg/dL | 57.3 (16.1) | 58.0 (9.53) | 63.3 (9.05) |
| Triglycerides, median (IQR), mg/dL | 141 (42.8) | 91.7 (31.4) | 78.0 (37.3) |
| Apolipoprotein B, mean (SD), md/dL | 101 (12.7) | 87.3 (20.6) | 76.2 (16.8) |
| C-Reactive protein (median, IQR), mg/L | 0.35 (0.14, 1.8) | 0.30 (0.2, 0.5) | 035 (0.05, 2.0) |
Pharmacokinetics
Zerlasiran was readily absorbed following a single SC administration, with the median Tmax reached at 5.0 h in all cohorts. There was a dose-dependent increase in Cmax and AUC0-last; the geometric mean (CV%) Cmax values were 93(48.1), 453(46.1), and 2180 (31.7) ng/mL, and the geometric mean (CV%) AUC0-last values were 838(25.0), 5190(29.7), and 23100(25.1) h × ng/mL in the 30-, 100-, and 300-mg cohorts, respectively. The mean zerlasiran concentration gradually declined from the peak. The median (range) t1/2 values were 4.08 (3.22–6.38), 3.64 (2.42–5.09), and 3.60 (2.49–4.72) h in the 30-, 100-, and 300-mg cohorts, respectively. Zerlasiran was undetectable in plasma samples at 36 h post-dose across all doses. The concentration–time profiles are shown in Fig.3 .
Fig.3. Mean (SD) plasma zerlasiran concentration-time profiles by dose level on linear and semi-logarithmic scales.
Mean (SD) plasma zerlasiran concentration-time profiles by dose level on linear and semi-logarithmic scales.
Pharmacodynamics
Following a single dose of zerlasiran, Lp(a) concentration decreased in a dose-dependent manner, reaching a nadir between days 30 and 60 in all doses. The maximum median (IQR) changes from baseline in lipoprotein concentration were -84.0 (-121, -74.0), -109 (-147, -74.7), -100.7 (-169, -97.1) nmol/L for the 30 mg, 100 mg, 300 mg cohorts respectively ( Fig.4a ) . This corresponded to a maximal median percentage change of − 72.8% (− 79.7%, − 67.1%), − 88.8% (− 89.5%, − 84.7%), and − 97.8% (− 98.6, − 96.9%) for the 30 mg, 100 mg, and 300 mg cohorts, respectively ( Fig.4b ) . In all cohorts, the duration of response persisted until the end of the study follow-up; 150 days after the administration of zerlasiran: the median (IQR) percent reduction from baseline in serum Lp(a) molar concentration was − 33.4% (− 44.8%, − 10.2%), − 42.6% (− 49.1%, − 36.7%),and − 88.6% (− 93.3%, − 82.3%) for the 30 mg, 100 mg, and 300 mg cohorts, respectively. The maximum mean (SD) percent reductions in LDL-C and apoB concentrations were ‑14.3% (SD 12.4%) at Day 30 in Cohort 3 and ‑16.0% (SD 16.3%) at Day 60 in Cohort 1, respectively. There were no clinically meaningful changes in HDL-C, total cholesterol, or triglycerides concentrations during the study.
Fig.4a. Change in the median (interquartile range) Lipoprotein(a) concentrations from baseline.
Change in the median (interquartile range) Lipoprotein(a) concentrations from baseline according to dose group.
Fig.4b. Percentage change in the median (interquartile range) lipoprotein(a) concentrations from baseline.
Percentage change in the median (interquartile range) lipoprotein(a) concentrations from baseline according to the dose group.
Safety
All treatment emergent adverse events (TEAEs) are shown in Table 2 . Overall, 17 participants (94.4%) experienced 23 TEAEs, all of which were graded by the investigator as mild in severity per the Common Terminology Criteria for Adverse Events, version 5.0. There were no serious adverse events or adverse events that led to study discontinuation. Mild injection site reactions occurred in 17 patients, with onset occurring at 12–24 hours, and all except one resolved by day 8 post dose. There were no liver events, and there were no clinically meaningful changes in renal parameters, CRP, glucose, vital signs, or on electrocardiography.
Table 2. Treatment Emergent Adverse Events.
| 30mg (N =6) | 100mg (N =6) | 300mg (N =6) | |
|---|---|---|---|
| Any TEAE, N (e) | 5 (5) | 6 (9) | 6 (9) |
| TEAE by preferred term | |||
| Headache | 0 (0) | 2 (2) | 1 (1) |
| Injection site reaction | 5 (5) | 6 (6) | 6 (6) |
| Nasopharyngitis | 0 (0) | 0 (0) | 1 (1) |
| Muscle injury | 0 (0) | 0 (0) | 1 (1) |
| Pain | 0 (0) | 1 (1) | 0 (0) |
| Serious adverse events | 0 (0) | 0 (0) | 0 (0) |
| TEAE leading to discontinuation | 0 (0) | 0 (0) | 0 (0) |
| TEAE leading to death | 0 (0) | 0 (0) | 0 (0) |
| Liver adverse events | 0 (0) | 0 (0) | 0 (0) |
| Renal adverse events | 0 (0) | 0 (0) | 0 (0) |
| QTcF prolongation | 0 (0) | 0 (0) | 0 (0) |
TEAE = treatment emergent adverse events; N = number of participants; e = number of events
Discussion
This open-label Phase 1 study characterized the PK, PD, safety, and tolerability profiles of zerlasiran at three dose levels (30, 100, and 300 mg) in Japanese participants with Lp(a) ≥ 70 nmol/L. These results demonstrated that zerlasiran was rapidly absorbed, well-tolerated, safe, and elicited substantial and durable Lp(a) reduction. This adds to the data from previous phase 1 and 2 studies in predominantly Caucasian populations, where a similar consistent PK-PD profile of a GalNAc-conjugated siRNA was seen 9 - 11) .
Following SC administration of zerlasiran, peak concentration was achieved approximately 5 h post-dose in all cohorts, with increases in Cmax and AUC in a dose-dependent manner comparable to that reported in the first-in-human study of zerlasiran (APOLLO, NCT04606602) 9) . Although a direct comparison of the results between studies should be interpreted with caution, it is notable that the mean Cmax and AUC0-last observed in this study were 1.84- and 1.66-fold and 2.32- and 1.80-fold higher, respectively, than those observed in APOLLO at the 100 mg and 300 mg doses. Since the main metabolic pathway of siRNA is by endogenous human RNAses, it is extremely unlikely that genetic polymorphisms of drug-metabolizing enzymes and drug transporters that are crucial for the metabolism of small molecular entities are involved 13) . The observed differences in PK parameters in the 100 mg and 300 mg cohorts could potentially be explained by differences in body weight between Japanese and non-Japanese participants. In this study, the mean weight of the participants in the 100 mg and 300 mg cohorts were 60.3 and 56.8 kg, respectively. By contrast, the mean weight of participants in the 100 and 300 mg cohorts for APOLLO were 88.5 and 83.6 kg, respectively. Despite the higher systemic exposure, safety and tolerability were favorable, with only mild adverse events noted. Importantly, injection-site reactions were mild and transient, and no liver or renal events were observed. The immunogenicity of zerlasiran was not tested in this single-dose study. However, zerlasiran is chemically modified and chemically synthesized; therefore, the risk is likely to be low, in keeping with other approved GalNAc-siRNA molecules 13) .
Consistent with previous findings, a single dose of zerlasiran administered to Japanese participants also showed a potent and durable effect on the Lp(a) levels. As the lipoprotein(a) inclusion criteria for this study differed from those in the APOLLO study (≥ 70 vs. 150 nmol/L), any direct comparison between the two populations should be made cautiously. In the current study, zerlasiran 300 mg led to a maximum median (IQR) percentage reduction in lipoprotein(a) of − 97.8% (− 98.6, − 96.9%) observed between days 30 and 60 and − 88.6% (− 93.3%, − 82.3%) at day 150 after a single dose. In the APOLLO study, the maximum median (IQR) percentage reduction in lipoprotein(a) for the 300 mg dose was −96% ( −98%, −89%) at days 30 and 60 and 71% (− 87%, − 48%) at day 150. These results suggest that the same infrequent dosing regimen of zerlasiran could be used for Japanese and non-Japanese participants in later-phase clinical trials. This observation is in line with several other GalNAc-conjugated siRNA molecules that have not required dose adjustment for use in the Japanese population, regardless of the target or specific chemical makeup of the molecule itself 14 - 18) . Although the incidence of ASCVD is lower in Japan than in Western countries, a recently published prospective cohort study in Japan showed that Lp(a) levels ≥ 30 mg/dL were associated with an increased risk of coronary artery disease. This association remained statistically significant even after adjustment for total cholesterol levels and lipid-lowering therapy use as confounding factors. These findings indicate that elevated Lp(a) is an important cardiovascular risk factor in the Japanese population, and that Japanese individuals may also benefit from Lp(a)-lowering therapies 12) .
Conclusion
Following a single dose of zerlasiran (30, 100, or 300 mg) in Japanese participants with elevated Lp(a) levels, the PK profile was as expected for SC-administered GalNAc siRNA and it was consistent with prior clinical studies. There were substantial and sustained decreases in the Lp(a) levels over 150 days at all dose levels. Zerlasiran was well tolerated, and no significant safety findings were observed at any dose level. These results support the further clinical development of zerlasiran in Japanese participants.
Acknowledgement
Silence Therapeutics PLC: Gareth Rees (Clinical Operations), Nick Allison (Biometrics) and Pooja Patel (Clinical Safety and Pharmacovigilance)
Medpace Inc: Ritsuko Cardona (Clinical Trials Manager), Hiromichi Takeuchi (Clinical Trials Manager), Boon Min Poh (Clinical Trials Manager), Jisin Yang (Medical Monitor), Mazeda Begum (Data Manager), Shunji Irino (Clinical Research Associate), Satoshi Sugihara (Regulatory), Mavis Teo (Project Coordinator), Etsunori Yuasa (Project Coordinator), Shuming Yang (Bioanalytical Chemistry)
Medical Corporation Heishinkai: Kumiko Hiraoka (Clinical Research Coordinator), Nanase Miyasato (Clinical Research Coordinator)
Source of Funding
This trial was funded by Silence Therapeutics PLC.
Conflict of Interest
Silence Therapeutics sponsored this study. Drs Henry Fok, David Rider and Curtis Rambaran are employees of and hold stock options in Silence Therapeutics. Dr Mariko Harada-Shiba has stock holdings or options of Liid Pharma; and has received honoraria from Amgen, MEDPACE, Novartis, Protosera, BML, Ultragenyx and Recordati Rare Diseases. Dr Yasuko Owada have no conflict of interest to disclose.
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