Silence Therapeutics Announces Positive Data from GEMINI Phase 1 Study of SLN124 in Healthy Volunteers
- Data shownSLN124,an siRNA which targets TMPRSS6, Washingtonis onand effective in reducing plasma iron levelsand had a long duration of action
- Data ssupport oIn progress phase 1 sstudy of SLN124 in patients with thalassemia and myelodysplastic syndrome (MDS)
- First clinical data from the owner of Silence MRNA GOLDâ¢ Platform– two more clinical data readingsplanned this year
May 19, 2021
LONDON, Silence Therapeutics plc AIM: SLN and Nasdaq: SLN (“Silence” or “the Company”), a leader in the discovery, development and delivery of new therapeutics based on short interfering ribonucleic acid (siRNA) for treating diseases of medical need, today announced positive foreground data from the GEMINI Phase 1 study of its wholly-owned product candidate, SLN124, in healthy volunteers. SLN124, a siRNA that targets TMPRSS6, is under development for the treatment of iron deficiency anemia, thalassemia and myelodysplastic syndrome (MDS).
The GEMINI phase 1, randomized, double-blind, placebo-controlled, single-dose escalating study evaluated the safety and tolerability of SLN124 (doses of 1.0, 3.0 and 4.5 mg / kg ) in 24 healthy volunteers (18 active and 6 placebo). Pharmacokinetic parameters and pharmacodynamic biomarkers of iron metabolism were also measured to assess iron reduction.
Initial study data showed that all doses of SLN124 were generally well tolerated, with no serious or severe treatment-emergent adverse events (TEEs) or TEEs leading to withdrawal. TEEs did not appear to be dose dependent and the majority were mild, including transient injection site reactions that resolved without intervention.
Notably, an approximately four-fold increase in mean hepcidin and a 50% reduction in plasma iron levels were also observed after a single dose of SLN124. The effects on hepcidin and iron appear to be dose dependent and were still observed at the end of the 8 week study at all doses, indicating a sustained and long duration of action.
These clinical data support preclinical results which demonstrated that SLN124 effectively improves red blood cell production and reduces anemia by increasing levels of hepcidin – a key natural regulator of iron balance and distribution in the body. . The company plans to measure red blood cell production and the effects on anemia in the ongoing GEMINI II Phase 1 study of SLN124 in people with thalassemia and MDS, who, unlike healthy volunteers, have levels significantly elevated iron.
Mark Rothera, President and CEO of Silence Therapeutics, mentionned: “These data represent the first clinical data of our MRNA GOLD â¢ platform and underline the promising potential of our technology for deliver precision medicines. We’re waiting impatiently at additional data in patients anticipated at a time of our wholly-owned clinical programs Later this year–the GEMINI II study on SLN124 for iron deficiency anemia conditions and the APOLLO study on SLN360 for cardiovascular disease due to high lipoprotein (a).“
Giles Campion, MD, EVP, Chief Medical Officer and Head of Research & Development of Silence Therapeutics, said: “Today’s results confirm the strong preclinical profile of SLN124 in humans – we have observed excellent security, robust gene voiced knockdown throughuntil aapproximate n Four–multiplication by average hepcidin with a 50% reduction of serum iron levels anda lasting effect whichlatested throughout the study.We are encouraged by this data in healthy volunteers and the opportunity for SLN124 to potentially tackle iron–loading anemia conditions such as thalassemia and MDS.“
John Porter, MARYLAND, Professor and Consultant in Hematology, Red Blood Cell Disorders Unit, University College London and Uuniversity of VSOllege LOndon Hhospitals, commented: “Despite the progress of our understanding thalassemia and MDS, there is no treatment specifically targeting the underlying mechanisms of these conditions as a means of improving the degree of anemia.There is a major unmet need for therapy that can provide safe and continuous monitoring of iron balance. and distribution as a means of improve the efficiency of red blood cell production. I am encouraged by the data from the SLN124 study in healthy volunteers and look forward to further clinical testing. “
Silence plans to present the full data from the GEMINI Phase 1 study of SLN124 in healthy volunteers at an appropriate scientific meeting later this year. In addition, the Company plans to report data from the single-dose escalating portion of the ongoing GEMINI II Phase 1 study of SLN124 in people with thalassemia and MDS in the second half of this year. SLN124 has the orphan drug designation for both conditions and the rare pediatric disease designation for beta thalassemia.
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About thalassemia and myelodysplastic syndrome (MDS)
Thalassemia and MDS are two rare conditions that prevent a person from making enough healthy red blood cells. Low levels of healthy red blood cells, known as anemia, cause less oxygen to different parts of the body. This can cause symptoms such as excessive fatigue and weakness. It can also lead to other serious health problems, such as heart disease. People with thalassemia or MDS can also store too much iron in their body, which leads to a phenomenon called “iron overload”, which damages organs such as the heart and liver.
Both conditions are usually treated with regular blood transfusions, which adds to the problem of iron overload. Iron chelation therapy removes excess iron from the body with the help of special drugs. While it helps reduce the amount of iron in the blood in people with thalassemia or MDS, it does not treat the underlying cause of the disease or prevent it from progressing. There is therefore a need for therapies which directly address the biological factors of the disease.
SLN124 is gene silencing therapy – therapy that is designed to temporarily block the message of a specific gene that would otherwise trigger an adverse reaction. In this case, SLN124 aims to temporarily “ silence ” TMPRSS6, a gene that stops the liver from making a special hormone that controls iron levels in the body – hepcidin. As hepcidin increases, it is hoped that the iron levels in the blood will decrease, which in turn could allow the production of healthier red blood cells, thus improving anemia. In preclinical studies, SLN124 has shown positive effects in improving red blood cell levels and reducing harmful iron levels.
SLN124 is currently being studied in the GEMINI clinical trial program. GEMINI II is a phase 1 study to investigate the effects of SLN124 in people with thalassemia or myelodysplastic syndrome (MDS), whose bodies produce fewer healthy red blood cells than normal and who may store too much iron in their body. body. For more information on the GEMINI II study, please Click here.
About Silence Therapeutics
Silence Therapeutics is developing a new generation of drugs by harnessing the body’s natural RNA interference mechanism, or RNAi, to inhibit the expression of specific target genes believed to play a role in the pathology of diseases with significant unmet need. Silence’s proprietary mRNAi GOLD â¢ platform can be used to create siRNAs (short interfering RNAs) that precisely target and reduce disease-associated genes in the liver, representing a substantial opportunity. Silence’s wholly owned product candidates include SLN360 designed to address the high and widespread unmet medical needs in reducing cardiovascular risk in people born with high levels of lipoprotein (a) and SLN124 designed to treat conditions. Iron deficiency anemia. Silence also maintains ongoing research and development collaborations with AstraZeneca, Mallinckrodt Pharmaceuticals and Takeda, among others. For more information, please visit https://www.silence-therapeutics.com/.
Certain statements made in this announcement are forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995 and other securities laws, including with respect to the clinical and business prospects of the company and the timing planned data reports from the company’s clinical studies. testing. These forward-looking statements are not historical facts but rather are based on the Company’s current expectations, estimates and projections regarding its industry; his beliefs; and assumptions. Words such as âanticipatesâ, âexpectsâ, âintendsâ, âplansâ, âbelievesâ, âseeksâ, âestimatesâ and similar expressions are intended to identify forward-looking statements. These statements are not guarantees of future performance and are subject to risks, uncertainties and other known and unknown factors, some of which are beyond the control of the Company, are difficult to predict and could cause actual results to differ. substantially from those expressed or anticipated. in forward-looking statements, including the risks identified in the company’s latest admission document and its amended annual report on Form 20-F filed with the United States Securities and Exchange Commission on April 29, 2021. The company puts caution holders of securities and potential security holders not to place undue reliance on these forward-looking statements, which reflect the views of the Company only as of the date of this announcement. The forward-looking statements made in this announcement relate only to events on the date on which the statements are made. The Company will assume no obligation to publicly post any revisions or updates to such forward-looking statements to reflect unforeseen events, circumstances or events occurring after the date of such announcement, unless the law or any appropriate regulatory authority l ‘required.