Mission Phases Research Articles

Organizational affective commitment effects on militaries’ well-being during a deployment: A study of a peacekeeping mission

ABSTRACT Based on the Conservation of Resources Theory, this longitudinal study analyzes the contribution of organizational affective commitment during the preparation phase of a peacekeeping mission (T1) to explain the well-being of soldiers during that mission (T2). A sample of 409 Brazilian army participants in the MINUSTAH (United Nations Stabilization Mission in Haiti) was used in two waves – preparation of the troops in Brazil, and their deployment in Haitian territory. The data analysis was performed using structural equation modeling. The results supported organizational affective commitment during the preparation phase (T1) positively predicting the general well-being (perception of health and general satisfaction with life) of these soldiers during the deployment phase (T2). The workplace well-being (i.e. work engagement) of these peacekeepers was also found to mediate this relationship. Theoretical and practical implications are discussed, and limitations and suggestions for future research are presented.

Mission ORCA: Orbit Refinement for Collision Avoidance

Forecasting of collisions between resident space objects (RSOs) is becoming critical for the future exploitation of near-Earth space. A constellation of 28 spacecrafts (plus in-orbit spares) in sun synchronous orbits is proposed as a solution for improving the current space situational awareness capabilities. Each satellite uses an optical payload to track target RSOs, with the satellite's position precisely determined. Multiple pictures of the RSO are taken, and the spacecraft attitude used to calculate the target's position relative to the spacecraft. The target's orbit is then determined from the movement of the target through the field of view over time. The system outputs orbit state vectors of the tracked object, allowing precise orbit characterisation and collision forecasting to be delivered. The constellation's design allows high temporal resolution, so reliable information can be supplied to end-users. The paper shows the results of the system design of a demonstration mission meant to verify the feasibility of the concept, performed by a team of students of Cranfield University. The exercise addresses all the aspects of the preliminary design, including the definition of the mission and system requirements, the selection of the overall mission architecture, operations, and mission phases. A cap on the overall cost allows for the realisation of the platform within a university budget. The outline of the design includes not only the selection and sizing of all the subsystems and payload but also suggests a new strategy for deploying the constellation if the demonstration mission is successful. The utilisation of high TRL and COTS components, as well as mass, power, and link budgets, demonstrate the feasibility of the overall mission concept.

Design and Analysis of Direct Abort Orbits in the Earth-Moon Transfer Phase of Crewed Lunar Exploration Missions

A direct abort orbit design method is presented for direct abort missions in the Earth-Moon transfer phase of crewed lunar exploration missions. First, according to the demand of an emergency rescue in the Earth-Moon transfer phase, two direct abort orbit schemes are introduced. Then, a serial orbit design method is proposed for a high-fidelity direct abort orbit. An analytical model is established for the calculation of initial values, and the optimization design is performed in the high-fidelity orbit model to determine a single-impulse abort orbit. A hybrid optimization design process is proposed to generate a two-impulse abort orbit. The results of simulation examples verify the validity and feasibility of the proposed direct abort orbit design method. Finally, extensive simulations are carried out to analyze the characteristics of abort impulse and abort return time and reveal the general rules of direct abort orbits. The research conclusions can provide a reference for the design of emergency rescue schemes in future crewed lunar exploration missions.

Application of Probabilistic Set-Based Design Exploration on the Energy Management of a Hybrid-Electric Aircraft

The energy management strategy of a hybrid-electric aircraft is coupled with the design of the propulsion system itself. A new design space exploration methodology based on Set-Based Design is introduced to analyse the effects of different strategies on the fuel consumption, NOx and take-off mass. Probabilities are used to evaluate and discard areas of the design space not capable of satisfying the constraints and requirements, saving computational time corresponding to an average of 75%. The study is carried on a 50-seater regional turboprop with a parallel hybrid-electric architecture. The strategies are modelled as piecewise linear functions of the degree of hybridisation and are applied to different mission phases to explore how the strategy complexity and the number of hybridised segments can influence the behaviour of the system. The results indicate that the complexity of the parametrisation does not affect the trade-off between fuel consumption and NOx emissions. On the contrary, a significant trade-off is identified on which phases are hybridised. That is, the least fuel consumption is obtained only by hybridising the longest mission phase, while less NOx emissions are generated if more phases are hybridised. Finally, the maximum take-off mass was investigated as a parameter, and the impact to the trade-off between the objectives was analysed. Three energy management strategies were suggested from these findings, which achieved a reduction to the fuel consumption of up to 10% and a reduction to NOx emissions of up to 15%.

PicSat’s Enduring Legacy. Probing the Flight of a Small Astronomical Satellite

Observation of planetary transits and other cutting-edge scientific missions can take advantage of affordable nanosatellites to probe interesting stellar targets. PicSat, a CubeSat dedicated to observing the Beta Pictoris star system, was designed to provide high-precision star pointing, a critical requirement for planetary transit detection. PicSat’s Attitude Determination and Control System, responsible for delivering high-accuracy spacecraft pointing, requires dedicated development based on dynamic simulators. This paper presents a dynamic attitude and orbit propagation simulator for CubeSats in low Earth orbit, as well as for its de-tumbling mode. Validation has been performed through PicSat’s in-flight data. High-precision dynamic models have been obtained for both attitude and orbit. Such models are well suited to the different mission phases, from spacecraft design to data exploitation. It is, therefore, a crucial tool to minimize the chance of failure of both the platform and the payload, especially in satellites such as PicSat, whose pointing depends on both. PicSat left an enduring legacy: its platform data allow us to obtain flight models that will be valuable for future missions.

The LISA DFACS: Model Predictive Control design for the test mass release phase

This paper presents a Model Predictive Control (MPC) design for the test mass release phase of the LISA space mission. LISA is a gravitational wave observatory consisting of a triangular constellation of three spacecraft. The gravitational waves are detected by measuring the relative distance between free falling test masses by means of a laser interferometer. Each test mass is a cubic body located inside an electrostatic suspension that is initially locked by a clamp mechanism. Once the plungers are retracted, the test masses are released with high initial offsets and velocities. To detect the gravitational waves, each test mass must be accurately positioned at the cage centre and its attitude must be aligned with the local cage frame. However, the low actuation authority of the electrostatic suspension along with the critical initial conditions, make the attitude and translation control a difficult task. MPC is a suitable technique for this application because it can systematically account for command saturations, state constraints and can provide optimal (or sub-optimal) control inputs by solving an optimization problem online. In this paper, an MPC controller is designed and validated by means of Monte Carlo simulations, achieving satisfactory results.

Analysis of terrestrial water storage changes in the Shaan-Gan-Ning Region using GPS and GRACE/GFO

Both the Global Positioning System (GPS) and Gravity Recovery and Climate Experiment (GRACE)/GRACE Follow-On (GFO) provide effective tools to infer surface mass changes. In this paper, we combined GPS, GRACE/GFO spherical harmonic (SH) solutions and GRACE/GFO mascon solutions to analyze the total surface mass changes and terrestrial water storage (TWS) changes in the Shaan-Gan-Ning Region (SGNR) over the period from December 2010 to February 2021. To improve the reliability of GPS inversion results, an improved regularization Laplace matrix and monthly optimal regularization parameter estimation strategy were employed to solve the ill-posed problem. The results show that the improved Laplace matrix can suppress the edge effects better than that of the traditional Laplace matrix, and the correlation coefficient and standard deviation (STD) between the original signal and inversion results from the traditional and improved Laplace matrix are 0.84 and 0.88, and 17.49 mm and 15.16 mm, respectively. The spatial distributions of annual amplitudes and time series changes for total surface mass changes derived from GPS agree well with GRACE/GFO SH solutions and mascon solutions, and the correlation coefficients of total surface mass change time series between GPS and GRACE/GFO SH solutions, GPS and GRACE/GFO mascon solutions are 0.80 and 0.77. However, the obvious differences still exist in local regions. In addition, the seasonal characteristics, increasing and decreasing rate of TWS change time series derived from GPS, GRACE/GFO SH and mascon solutions agree well with the Global Land Data Assimilation System (GLDAS) hydrological model in the studied area, and generally consistent with the precipitation data. Meanwhile, TWS changes derived from GPS and GRACE mascon solutions in the SGNR are more reliable than those of GRACE SH solutions over the period from January 2016 to June 2017 (the final operation phase of the GRACE mission).

Powered-descent landing GNC system design and flight results for Tianwen-1 mission

The powered-descent landing (PDL) phase of the Tianwen-1 mission began with composite backshell—parachute (CBP) separation and ended with landing-rover touchdown. The main tasks of this phase were to reduce the velocity of the lander, perform the avoidance maneuver, and guarantee a soft touchdown. The PDL phase overcame many challenges: performing the divert maneuver to avoid collision with the CBP while simultaneously avoiding large-scale hazards; slowing the descent from approximately 95 to 0 m/s; performing the precise hazard-avoidance maneuver; and placing the lander gently and safely on the surface of Mars. The architecture and algorithms of the guidance, navigation, and control system for the PDL phase were designed; its execution resulted in Tianwen-1’s successful touchdown in the morning of 15 May 2021. Consequently, the Tianwen-1 mission achieved a historic autonomous landing with simultaneous hazard and CBP avoidance.

A Robust Post-Grasping Control Design for Robotic Testbed Demonstration of Space Debris Disposal

In this article, a ground-based floating platform setup that emulates the zero-gravity spacecraft's motion on the ground is utilized for an active debris removal mission scenario. There are various phases in an active debris removal mission, which could be listed as close-range rendezvous, attitude coordination in case of tumbling target, grasping of the debris spacecraft, and the post grasping (debris removal phase). This article focuses on the post-grasping phase of the debris removal mission, with the assumption that the floating platform has grabbed (grasped) a debris of unknown mass and mass distribution, which adds to the modeling uncertainty of the newly unified platform (floating platform+debris). In sequel of the debris grasping, the floating platform needs to follow the desired path to move the debris to a desired secure location. This post-grasping scenario introduces multiple challenges rising from various parametric uncertainties in the robot's dynamics rising from nonlinearities, inaccuracy in estimating its inertia, discretization of thruster inputs using PWMs, and external disturbances. Also, since the robot maneuvers and operates in eminently constrained environments, the controller must ensure impeccable accuracy. The state-of-the-art controllers ensuring a constrained control of space robots with parametric uncertainties use a strict barrier Lyapunov function (BLF), which demands the initial conditions of the states to be within a specified bound, which is impractical in many scenarios. Hence, we propose a robust time-varying BLF controller for space robots, which tackles uncertainties and external disturbances while avoiding strict initial conditions for the constrained states. The controller's stability is validated using a Lyapunov-like method, and its performance is verified using a simulated Slider model.

New analytical results on the study of aircraft performance with velocity dependent forces

Most aeronautical accidents happen during takeoff and landing. The main objective when studying those phases of the flight mission is to answer a seemingly simple questions: can the airplane safely takeoff and land on the stipulated runway dimensions with the intended weight? The main objective of the present paper is to obtain new analytical answer to those questions, for fixed wing airplanes. To our present knowledge such a solution, with the degree of generalisation proposed here, is new in the literature. Regarding previous studies, first a new power unit traction equation is employed to explicitly consider the influence of air density, angular velocity and diameter of the propeller. Then a new method for calculating the maximum weight is proposed. Next, the use of breaks is modeled and analysed and an equation to calculate the static gliding wind velocity is proposed. Finally, a toolbox created to perform the calculations is described. A thorough analysis of the influence of the airplane design parameters on the behavior of the motion equations is made, with special attention to the use of brakes. Numerical results are successfully compared with experimental data from two models of a commercial airplane, the Cessna 172 Skyhawk models N and S, and four UAV prototypes. The methodology employed uses simple laws of classical mechanics allied to basic calculus and is easy to understand by first year students of physics, engineering or mathematics.

Cooperation of unmanned systems for agricultural applications: A case study in a vineyard

Fully-autonomous vehicles, both aerial and ground, could provide great benefits in the Agriculture 4.0 framework when operating within cooperative architectures, thanks to their ability to tackle difficult tasks, particularly within complex irregular and unstructured scenarios such as vineyards on sloped terrains. A decentralised multi-phase approach has been proposed as an alternative to more common cooperative schemes. When perennial crops are considered, it is advantageous to build a simplified geometrical (and georeferenced) crops model, which can be identified by using 3D point clouds acquired during a-priori explorative missions by unmanned aerial vehicles. This model can be used to plan the tasks to be performed within the crops by the in-field aerial and ground drones. In this companion paper, the proposed strategy is applied to a specific case study involving a vineyard on a sloped terrain, located in the Barolo region in Piedmont, Italy. Ad-hoc technologies and guidance, navigation and control algorithms were designed and implemented. The main objectives were to improve the autonomous driving capabilities of the drones involved and to automate the process of retrieving low-complexity maps from the data collected with preliminary remote sensing missions to make them available for the autonomous navigation by a quadrotor and an unmanned 4-wheel steering ground vehicle within the vine rows. Preliminary results highlight the benefits achievable by exploiting the tailored technologies selected and applied to improve each of the analysed mission phases.

The ESA MIPAS/Envisat level2-v8 dataset: 10 years of measurements retrieved with ORM v8.22

Abstract. The observations acquired during the full mission of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument, aboard the European Space Agency Environmental Satellite (Envisat), have been analysed with version 8.22 of the Optimised Retrieval Model (ORM), originally developed as the scientific prototype of the ESA level-2 processor for MIPAS observations. The results of the analyses have been included into the MIPAS level-2 version 8 (level2-v8) database containing atmospheric fields of pressure, temperature, and volume mixing ratio (VMR) of MIPAS main targets H2O, O3, HNO3, CH4, N2O, and NO2, along with the minor gases CFC-11, ClONO2, N2O5, CFC-12, COF2, CCl4, CF4, HCFC-22, C2H2, CH3Cl, COCl2, C2H6, OCS, and HDO. The database covers all the measurements acquired by MIPAS in the nominal measurement mode of the full resolution (FR) part of the mission (from July 2002 to March 2004) and all the observation modes of the optimised resolution (OR) part (from January 2005 to April 2012). The number of species included in the MIPAS level2-v8 dataset makes it of particular importance for the studies of stratospheric chemistry. The database is considered by ESA the final release of the MIPAS level-2 products. The ORM algorithm is operated at the vertical grid coincident to the tangent altitudes of the observations or to a subset of them, spanning (in the nominal mode) the altitude range from 6 to 68 km in the FR phase and from 6 to 70 km in the OR period. In the latitude domain, FR profiles are spaced by about 4.7∘, while the OR profiles are spaced by about 3.7∘. For each retrieved species, the auxiliary data and the retrieval choices are described. Each product is characterised in terms of the retrieval error, spatial resolution, and “useful” vertical range in both phases of the MIPAS mission. These depend on the characteristics of the measurements (spectral and vertical resolution of the measurements), the retrieval choices (number of spectral points included in the analyses, number of altitudes included in the vertical retrieval grid), and the information content of the measurements for each trace species. For temperature, water vapour, ozone, and nitric acid, the number of degrees of freedom is significantly larger in the OR phase than in the FR one, mainly due to the finer vertical measurement grid. In the FR phase, some trace species are characterised by a smaller retrieval error with respect to the OR phase, mainly due to the larger number of spectral points used in the analyses, along with the reduced vertical resolution. The way of handling possible caveats (negative VMR, vertical grid representation) is discussed. The quality of the retrieved profiles is assessed through four criteria, two providing information on the successful convergence of the retrieval iterations, one on the capability of the retrieval to reproduce the measurements, and one on the presence of outliers. An easy way to identify and filter the problematic profiles with the information contained in the output files is provided. MIPAS level2-v8 data are available to the scientific community through the ESA portal (https://doi.org/10.5270/EN1-c8hgqx4).

Failure behavior analysis of phased-mission systems considering functional and physical isolation effects

Phased-Mission Systems (PMS) are widely applied in aerospace, telecommunication and intelligent systems for multiple, consecutive and non-overlapping phases of missions. The phase-dependent stresses and system structure cause some difficulties to the reliability analysis of PMSs. In this paper, we analyze the physical isolation effects on the degradation speeds and across-phase damage accumulations of failure mechanisms. And, some corresponding reliability and unreliability formulas are derived. Besides, a hierarchical Binary Decision Diagram (BDD)-based modeling method is proposed for incorporating functional and physical isolation effects into BDD models, and the analytical method with phase algebras is introduced for studying the failure behavior of PMS with functional dependence. In the case study, we evaluate the collision avoidance system of a fixed-wing unmanned aerial vehicle as an example to demonstrate the proposed modeling and analysis method. Results show that the physical isolation effects have significant influences on the degradations of components, which deserves detailed analysis for a more practical and realistic PMS’s failure behavior.

Mass and Shape Determination of (101955) Bennu Using Differenced Data from Multiple OSIRIS-REx Mission Phases

Abstract The Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission collected a sample from the rubble-pile asteroid (101955) Bennu for return to Earth. For the successful Touch And Go sample acquisition maneuver, the shape and mass of the asteroid needed to be known precisely. Here we use a combination of radiometric, image landmark, and laser altimetry data to determine Bennu’s mass, shape, and orientation simultaneously and to verify existing models thereof. Our shape determination consists of estimating a scale factor and three frame rotation angles that apply to both the global digital terrain model (GDTM) and the landmark coordinates. We use a data type called image constraints, where we take the difference of the observation of the same landmark in images taken at two different times. We analyze data from two phases of the OSIRIS-REx mission, Orbital B and Recon B, and show that interphase image constraints greatly reduce interdependencies between estimated parameters for mass, GDTM scale, and biases on the altimetry data. This results in an improved solution for the mass and shape relative to considering a single mission phase. We find Bennu’s gravitational parameter GM to be 4.89256 ± 0.00035 m3 s−2, and we find a scale factor of 1.000896 ± 0.00036 for the altimetry-based GDTM. Using the scaled volume, this results in a bulk density of 1191.57 ± 1.74 kg m−3 , which is within the uncertainties of previous analyses but more precise.

Optimal Information Filtering for Robust Aerocapture Trajectory Generation and Guidance

Entry flight is a critical mission phase of planetary aeroassist problems. During atmospheric flight, aleatory-epistemic uncertainty and environmental factors reduce the accuracy of predicted future states for precision targeting. This problem has been approached historically with closed-loop guidance rooted in certainty equivalence. This property separates estimation and control problems, allowing each to be considered independently. In other concept studies, an observer model is neglected altogether in favor of assuming perfect state knowledge. However, a flight system will inevitably have imprecise state information and variability in its underlying dynamics and measurement models. Systemic uncertainty is a fundamental limitation of existing entry guidance approaches. This work seeks to overcome these challenges by posing aerocapture as a robust optimization problem. The cost objective of the maneuver is reformulated to account for uncertainty in atmospheric structure, vehicle performance parameters, and state estimation accuracy using an observer-based consider filter. An expected value performance cost is developed from anticipated measurement conditioning effects. A rapid solution methodology is illustrated using explicit integration strategies with a parameterized control structure. Results for a Mars aerocapture concept study show improvement in the postcapture orbit accuracy with low computational overhead.

Asteroid Diameters and Albedos from NEOWISE Reactivation Mission Years Six and Seven

Abstract We present diameters and albedos computed for the near-Earth and main belt asteroids (MBAs) observed by the Near-Earth Object Wide-field Infrared Survey Explorer (NEOWISE) spacecraft during the sixth and seventh years of its Reactivation mission. These diameters and albedos are calculated from fitting thermal models to NEOWISE observations of 199 near-Earth objects (NEOs) and 5851 MBAs detected during the sixth year of the survey and 175 NEOs and 5861 MBAs from the seventh year. Comparisons of the NEO diameters derived from Reactivation data with those derived from the WISE cryogenic mission data show a ∼30% relative uncertainty. This larger uncertainty compared to data from the cryogenic mission is due to the need to assume a beaming parameter for the fits to the shorter-wavelength data that the Reactivation mission is limited to. We also present an analysis of the orbital parameters of the MBAs that have been discovered by NEOWISE during Reactivation, finding that these objects tend to be on orbits that result in their perihelia being far from the ecliptic, and thus missed by other surveys. To date, the NEOWISE Reactivation survey has provided thermal fits of 1415 unique NEOs. Including the mission phases before spacecraft hibernation increases the count of unique NEOs characterized to 1845 from WISE’s launch to the present.

Science and exploration of the moon enabled by surface telerobotics

Tele-operated rovers have been a feature of space exploration for decades. Ground control teams that operate these rovers generally comprise a robot operations team supported by science and robot engineering groups. But, in the future, astronauts will also remotely operate rovers. Several studies have proposed that astronauts should be able to control rovers from orbiting spacecraft such as the Deep Space Gateway (DSG). This concept of operations offers several benefits to human exploration. Firstly, it will enable astronauts to expand their sphere of influence beyond the confines of a spacecraft. Secondly, it will enable astronauts to safely perform surface work via an avatar. Thirdly, it will reduce the expenditure of life support consumables, and fourthly, it will spare astronauts from spending time on radiation-ravaged planetary surfaces. But integrating tele-operated rovers into human space exploration raises important questions. What system configurations are effective? Which modes of operation and control are most appropriate? When is it appropriate to rely (or not) on tele-operated rovers? The proposed research sought to answer the first two of these questions. It was designed to simulate three mission phases: pre-mission planning, site survey, and surface asset deployment. The study employed a derived terrain model located in the Lunares hab facility (located in Pila, Poland). Operators drove a Turtle rover through task sequences to survey sites while avoiding hazards/obstacles. This study simulated remote rover operations that assessed crew workload, crew situation awareness, robot asset acquisition, task sequence success, system issues, and rover performance. This study demonstrated basic competence in teleoperated rover driving, but more work must be conducted to produce a system that can behave reliably over many weeks and/or kilometers. Results indicated interactive monitoring is an effective strategy for crew-centric surface telerobotics. Safeguarded driving using this mode of operation enabled participants to perform each task successfully – success being measured by the metric of completing assigned tasks and completing the course. Participants maintained good situational awareness (SA) with low effort using interactive visualization of the rover state. From post-test debriefs it was determined participants maintained a high level of SA during operations and that the activity employed via the operator interface was a contributing factor to achieving these high levels. Since the test sessions were designed to be increasingly difficult in terms of task complexity it was expected that SA would decrease and task loading would increase across tasks and the data confirms this was the case.

Preliminary study of rescue systems for Mars landing

Entry, descent and landing (EDL) is probably the most difficult and risky phase of a human mission to Mars. Whatever the EDL systems for Mars, the qualification might be very difficult, very expensive and the risks could still be very high, especially for the first missions. Risks could nevertheless be mitigated if backup options existed during the final phase of EDL. If an important problem is encountered during the last minutes of the descent and if the velocity is lower than Mach 3, a possible option is to use an ejection seat, an individual parachute and small thrusters, which could be attached to the seat of the astronaut. The total mass of such a rescue system would be of the order of 230 kg, which does not include the mass of the astronaut. In the event of an emergency landing, the astronaut will still have to reach a safe haven quickly to survive because of his limited life support system autonomy. An automatic rover can be sent to rescue the astronaut and increase the maximum rescuing distance. A probabilistic risk assessment has been performed. Provided that the autonomy of the life support system is 8 h and that there is no insurmountable obstacle, it is shown that the probability of reachability is 0.9 at 50 km from the safe haven.

Rapid Interpretation of Temporal–Spatial Unmanned Aerial Vehicle (UAV) Operational Data – RITSUD: Aiding UAV Operators With Visualizations of Patterns-of-Life Activities

To accomplish their missions, the operators of military unmanned aerial vehicles (UAVs) aggregate and process information from multiple sources under time constraints, while experiencing partial sensory deprivation. We aimed to design, develop, and evaluate the need for designated information aids in the form of visualizations of spatial and temporal patterns-of-life for specific operational mission phases. In an evaluation conducted to assess the usefulness of the proposed visualizations, experienced UAV operators from two nations were presented with five scenarios in a narrative format. Each scenario contained one information-aid visualization for a specific mission phase. Participants had to interpret each mission phase and rate the information aid. Results showed that, in general, most operators favored the aids, but their appreciation of specific aids depended on the mission phase. There were also statistically significant differences between the nations. The results emphasize the potential for equipping UAV operators with information aids in the form of visualizations of spatial and temporal patterns-of-life. Moreover, the findings underline the need for more rigorous analyses of operators’ missions, as the need for specific visualizations was shown to vary with mission phase, and some visualizations were found to be more widely useful than others.

POS0695 KZR-616, A SELECTIVE IMMUNOPROTEASOME INHIBITOR FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM THE COMPLETED DOSE ESCALATION PHASE 1B PORTION OF THE MISSION STUDY

Background:KZR-616 is a first-in-class selective inhibitor of the immunoproteasome, which is active in >15 autoimmune disease models, including murine models of systemic lupus erythematosus (SLE)/lupus nephritis (LN).1,2,3 Selective inhibition of the immunoproteasome modulates both innate and adaptive immune effector cells, resulting in reduced inflammatory T helper cell subsets (Th1 and Th17), increased regulatory T cells, and decreased plasma cells and autoantibodies. KZR-616 was well tolerated in two healthy volunteer studies of 100 subjects receiving up to 75 mg subcutaneously (SC). Target levels of immunoproteasome inhibition were observed at doses ≥30 mg.3,4 KZR-616 is currently in Phase 2 studies for several autoimmune indications, including the ongoing Phase 2 portion of the MISSION Study (KZR-616-002; NCT0339013) in patients with LN.Objectives:Results of the completed MISSION Phase 1b dose escalation portion of the study are reported.Methods:In the open-label, multicenter, dose escalation Phase 1b portion, SLE patients (per SLICC Classification Criteria) with SLEDAI ≥4 despite stable background immunosuppressant, anti-malarial, and/or corticosteroid therapy were administered weekly KZR-616 subcutaneously at doses of 45 mg (cohort 1), 60 mg (cohort 2), 60 mg following step-up doses of 30 mg and 45 mg (cohort 2a), 60 mg following a step-up dose of 30 mg (cohorts 2b, 2c) or 75 mg following a step-up dose of 30 mg (cohort 3) for 13 weeks with follow-up through Week 25 (W25); a lyophilized formulation was used for cohorts 2b, 2c and 3. The disease activity measures assessed were: SLEDAI-2K, Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), 28 tender and swollen joint counts, Physician and Patient Global Assessments, and Patient Assessment of Pain. Safety and tolerability were assessed in the safety population (patients receiving at least one dose of KZR-616).Results:The Phase 1b portion of MISSION enrolled 47 SLE patients, including 2 patients with active proliferative LN. The most common treatment-emergent adverse events (TEAE) were injection site reactions, which were mostly mild. Infections occurred at a low rate, and there were no reports of peripheral neuropathy, prolonged hematologic AEs, or clinically significant laboratory abnormalities. No discontinuations were observed in cohorts 2b and 2c; no serious AEs were reported in cohort 3 and TEAEs were consistent with those reported in earlier cohorts. Mean values of all measures of disease activity improved in evaluable patients who completed the 13-week treatment period, and improvements were generally maintained at W25. All patients with elevated anti-double-stranded DNA antibody (anti-dsDNA) levels at baseline (n=7) had a reduction in levels with 3 of 7 experiencing a >50% reduction in their levels. Two of two patients with active proliferative LN had a >50% reduction in UPCR and experienced reductions in SLEDAI-2K scores as well as anti-dsDNA levels. Exposure to KZR-616, similar to that reported in healthy volunteers, was dose-proportional across doses, and no accumulation was observed.Conclusion:KZR-616 SC, once weekly for 13 weeks up to 75 mg, appears to be safe and well-tolerated in patients with active SLE on stable background therapy in the MISSION Phase 1b. At doses ≥45mg, efficacy was noted, including improvements in proteinuria in two of two patients with LN and serologic improvement in all 7 patients with quantifiable levels of anti-dsDNA antibodies at baseline. KZR-616 60 mg SC weekly for 24 weeks is currently being evaluated in the MISSION Phase 2 in patients with LN. Based on the results of MISSION, inhibition of the immunoproteasome with KZR-616 represents a novel strategy to treat autoimmune diseases.