Li9S3N (LSN) is investigated as a new lithium ion conductor and barrier coating between an electrolyte and Li metal anode in all solid state lithium ion batteries. LSN is an intriguing material since it has a 3-dimensional conduction channel, high lithium content, and is expected to be stable against lithium metal. The conductivity of LSN is measured with impedance spectroscopy as 8.3 × 10-7 S cm-1 at room temperature with an activation energy of 0.52 eV. Cyclic voltammetry (CV) scans showed reversible Li plating and striping. First principles calculations of stability, nudged elastic band (NEB) calculations, and ab initio molecular dynamics (AIMD) simulations support these experimental results. Substitution as a means to enhance conductivity is also investigated. First-principles calculations predict that divalent cation substituents displace a lithium from a tetrahedral site along the migration pathway, and reduce the migration energy for the lithium ions in the vicinity of the substituent. A percolating path with low migration energies (∼0.3 eV) can be formed throughout the crystal structure at a concentration of Li8.5M0.25S3N (M = Ca2+, Zn2+, or Mg2+), resulting in predicted conductivities as high as σ300 K = 2.3 mS cm-1 at this concentration. However, the enhanced conductivity comes at the expense of relatively large substitution energy. Halide substitution, such as Cl on a S site (in Kröger-Vink notation), has a relatively low energy cost, but only provides a modest improvement in conductivity.

Sodium-ion batteries are emerging as candidates for large-scale energy storage due to their low cost and the wide variety of cathode materials available. As battery size and adoption in critical applications increases, safety concerns are resurfacing due to the inherent flammability of organic electrolytes currently in use in both lithium and sodium battery chemistries. Development of solid-state batteries with ionic electrolytes eliminates this concern, while also allowing novel device architectures and potentially improving cycle life. Here we report the computation-assisted discovery and synthesis of a high-performance solid-state electrolyte material: Na10SnP2S12, with room temperature ionic conductivity of 0.4 mS cm(-1) rivalling the conductivity of the best sodium sulfide solid electrolytes to date. We also computationally investigate the variants of this compound where tin is substituted by germanium or silicon and find that the latter may achieve even higher conductivity.

Objective

To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM).

Methods

Participants (aged 36-85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV infusions every 4 weeks). The co-primary outcome measures were 6-minute walk distance (6MWD) and safety.

Results

Between November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24-104 in all treatment groups. Overall, 91.0% (n = 142) of participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg, and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [n = 34 of 55], respectively). The most frequently reported AEs in the pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively).

Conclusion

Extended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint.

Clinical trial registration

Clinicaltrials.gov identifier NCT02573467.

Classification of evidence

This study provides Class IV evidence that for patients with sIBM, long-term treatment with bimagrumab was safe, well-tolerated, and did not provide meaningful functional benefit. The study is rated Class IV because of the open-label design of extension treatment period 2.