SNA-125 / Sienna - LARVOL DELTA

In vivo gene editing of Angiotensinogen in hepatocytes safely and potently reduces blood pressure in preclinical models (AHA 2025) - "CTX340 treatment results in a robust gene edit of AGT in primary human hepatocytes, SHRs, and NHPs, leading to sustained reductions in circulating AGT levels. Blood pressure reductions were observed only in the SHR model, consistent with elevated AGT's role in disease physiology. CTX340 was well tolerated in both SHR and NHPs, and repeat dosing supports the potential for safe and titratable AGT lowering."

Late-breaking abstract • Preclinical • Cardiovascular • Hypertension • AGT

Effectiveness of Salt Tablets in Inpatient Hyponatremia Improves with Higher Doses (KIDNEY WEEK 2025) - "For each case, we excluded treatment-days when NaCl tab administration occurred concomitantly or within +/- 24 hrs of additional treatment with either an IV NaCl-containing infusion/bolus (excluding drug vehicle) or oral tolvaptan, Na bicarbonate or Na phosphate...Results After excluding 47 patients due to concomitant therapy, 30 were included (mean age 72, 67% women, 90% white, mean baseline sNa 125 mEq/L)...High doses (i.e., 3 - 4 g tid/qid) were well tolerated, only 1 patient experienced mild nausea. Conclusion The effectiveness of NaCl tab for the treatment of inpatient hypoNa is greater when higher doses are used."

Clinical • Cardiovascular • Fibrosis • Heart Failure • Hepatology • Immunology

The Urine Calcium/Creatinine Ratio and Uricemia during Hyponatremia of Different Origins: Clinical Implications. (PubMed, J Clin Med) - "Patients with chronic hyponatremia due to SIADH usually have a high UCa/UCr ratio (>0.15). This is also observed in hyponatremia secondary to polydipsia. Patients with thiazide-induced hyponatremia usually have low UCa/UCr levels and this is the case even among those with a biochemistry similar to that in SIADH (uric acid < 4 mg/dL)."

Journal • Cardiovascular • Heart Failure • Osteoporosis • Rheumatology

[VIRTUAL] A LOWER THRESHOLD OF PERIOPERATIVE SODIUM CHANGES IS ASSOCIATED WITH NEUROLOGIC COMPLICATIONS POST LIVER TRANSPLANT (AASLD 2020) - "In bivariate analysis, patients in the NC group more commonly had grade 3 or 4 hepatic encephalopathy (HE) pre-LT, SNa125, in addition to ensuring better control of ΔSNa <6, may have a beneficial impact in decreasing risk of NCs post LT."

Cardiovascular • CNS Disorders • Epilepsy • Heart Failure • Hepatic Encephalopathy • Hepatology • Transplantation

Clinical experience of the efficacy and safety of low dose tolvaptan therapy in a UK tertiary oncology setting. (PubMed, J Clin Endocrinol Metab) - "In the largest series to date, although low-dose tolvaptan was demonstrated to be effective in correcting hyponatraemia due to SIAD in cancer patients, a significant proportion experienced over-rapid correction. Concurrent administration of demeclocycline and/or fluid restriction must be avoided due to the increased risk of over-rapid correction."

Clinical • Journal • Oncology

Sienna Biopharmaceuticals reports fourth quarter and full year 2017 financial results (GlobeNewswire) - “...SNA-125 for the treatment of atopic dermatitis and associated pruritus; Phase 1/2 proof-of-concept TLRs expected in the fourth quarter of 2018.”

P1/2 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

SNA-125: Initiation of P1/2 POC study for atopic dermatitis in H1 2018 (Creabilis) - Corporate Presentation: Data from P1/2 POC study for atopic dermatitis in H2 2018; Initiation of P2a POC study for atopic dermatitis in H2 2019

New P1/2 trial • New P2a trial • P1/2 data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

SNA-125: Patent protection related to compound in US until 2030 and EU until 2026 (Sienna Biopharmaceuticals) - Corporate Presentation: Patent term extension in US until 2035 and EU until 2031

Patent • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Sienna Biopharmaceuticals announces first patient dosed in proof-of-concept trial of topical by design JAK inhibitor SNA-125 for atopic dermatitis (GlobeNewswire) - “Sienna Biopharmaceuticals, Inc…announced that the first patient has been dosed in the Company’s Phase 1/2 proof-of concept clinical trial of topical product candidate SNA-125 in the treatment of atopic dermatitis and the associated pruritus, or itch….Results from this trial, which we expect to report in the fourth quarter of 2018.”

P1/2 data • Trial status • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation

Sienna Biopharmaceuticals to cease operations (San Fernando Valley Business Journal) - "Sienna Biopharmaceuticals Inc. will cease operations by the end of the week...according to a filing Wednesday with the Securities and Exchange Commission....There were no bids for Sienna’s other drugs, including flagship topicals SNA-120 for psoriasis and SNA-125 for atopic dermatitis."

Commercial

Sienna Biopharmaceuticals reports fourth quarter and full year 2018 financial results (GlobeNewswire) - "Sienna intends to initiate a Phase 2 study with a more optimal cream formulation of SNA-125 first in atopic dermatitis, subject to securing sufficient capital to complete the trial."

New P2 trial

Sienna Biopharmaceuticals announces its topical, non-steroidal TrkA inhibitor SNA-120 (0.05%) demonstrated significant impact on psoriasis in phase 2b study and plans to initiate phase 3 psoriasis trials in second half of 2019 (GlobeNewswire) - P1/2, N=30; "In this study, SNA-125 was well tolerated and showed no safety signals in both healthy subjects and patients with atopic dermatitis, with no serious adverse events reported. The most common treatment-related adverse events were pain and pruritus....The Company plans to initiate a Phase 2 study with SNA-125 in atopic dermatitis in the second half of 2019."

New P2 trial