We present results from an extensive follow-up campaign of the tidal disruption event (TDE) ASASSN-15oi spanning δt ∼ 10–3000 days, offering an unprecedented window into the multiwavelength properties of a TDE during its first ≈8 yr of evolution. ASASSN-15oi is one of the few TDEs with strong detections at X-ray, optical/UV, and radio wavelengths and it also featured two delayed radio flares at δt ∼ 180 days and δt ∼ 1400 days. Our observations at δt > 1400 days reveal an absence of thermal X-rays, a late-time variability in the nonthermal X-ray emission, and sharp declines in the nonthermal X-ray and radio emission at δt ∼ 2800 days and ∼3000 days, respectively. The UV emission shows no significant evolution at δt > 400 days and remains above the pre-TDE level. We show that a cooling envelope model can explain the thermal emission consistently across all epochs. We also find that a scenario involving episodic ejection of material due to stream–stream collisions can possibly explain the first radio flare. Given the peculiar spectral and temporal evolution of the late-time emission, however, constraining the origins of the second radio flare and the nonthermal X-rays remains challenging. Our study underscores the critical role of long-term, multiwavelength follow-up to fully characterize the extended evolutionary phases of a TDE.

Genome editing holds the potential for curative treatments of human disease, however, clinical realization has proven to be a challenging journey with incremental progress made up until recently. Over the last decade, advances in clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) systems have provided the necessary breakthrough for genome editing in the clinic. The progress of investigational CRISPR therapies from bench to bedside reflects the culmination of multiple advances occurring in parallel, several of which intersect with clinical pharmacology and translation. Directing the CRISPR therapy to the intended site of action has necessitated novel delivery platforms, and this has resulted in special considerations for the complete characterization of distribution, metabolism, and excretion, as well as immunogenicity. Once at the site of action, CRISPR therapies aim to make permanent alterations to the genome and achieve therapeutically relevant effects with a single dose. This fundamental aspect of the mechanism of action for CRISPR therapies results in new considerations for clinical translation and dose selection. Early advances in model-informed development of CRISPR therapies have incorporated key facets of the mechanism of action and have captured hallmark features of clinical pharmacokinetics and pharmacodynamics from phase I investigations. Given the recent emergence of CRISPR therapies in clinical development, the landscape continues to evolve rapidly with ample opportunity for continued innovation. Here, we provide a snapshot of selected topics in clinical pharmacology and translation that has supported the advance of systemically administered in vivo and ex vivo CRISPR-based investigational therapies in the clinic.

Supplementary Figure S1-S6; Supplementary Table S1-S2

Plots of reticulocyte percentages from Cycle 1 Day 1 through Cycle 2 Day 1

Supplementary Data is word format for production

We present the results from a multiyear radio campaign of the superluminous supernova (SLSN) SN 2017ens, which yielded the earliest radio detection of an SLSN to date at the age of ∼3.3 yr after explosion. SN 2017ens was not detected at radio frequencies in the first ∼300 days but reached L ν ≈ 10 28 erg s −1 cm −2 Hz −1 at ν ∼ 6 GHz, ∼1250 days post explosion. Interpreting the radio observations in the context of synchrotron radiation from the supernova shock interaction with the circumstellar medium (CSM), we infer an effective mass-loss rate M ̇ ≈ 10 − 4 M ☉ yr − 1 at r ∼ 10 17 cm from the explosion’s site, for a wind speed of v w = 50–60 km s −1 as measured from optical spectra. These findings are consistent with the spectroscopic metamorphosis of SN 2017ens from hydrogen poor to hydrogen rich ∼190 days after explosion reported by Chen et al. SN 2017ens is thus an addition to the sample of hydrogen-poor massive progenitors that explode shortly after having lost their hydrogen envelope. The inferred circumstellar densities, implying a CSM mass up to ∼0.5 M ☉ , and low velocity of the ejection suggest that binary interactions (in the form of common-envelope evolution and subsequent envelope ejection) play a role in shaping the evolution of the stellar progenitors of SLSNe in the ≲500 yr preceding core collapse.

Background and aims: Waning SARS-CoV-2 specific antibody (Ab) responses and high infection rates has led to the widespread use of 3rd/4th vaccine doses (V3/V4) in vulnerable patients.However, the immune response to V4 in patients with suboptimal prior vaccine responses is unexplored.We recruited liver transplant recipients (LT) and autoimmune hepatitis patients (AIH) to assess the immune responses to V4, including to SARS-CoV-2 omicron (B.1.1.529)variant.Method: Anti-spike (S) and anti-nucleocapsid (N) IgG titres were assessed (Roche assay) after V4 (24 Pfizer BNT162b2, 8 Moderna mRNA-1273) in 32 immunosuppressed patients, including 23 with liver disease (15 LT, 8 AIH) and 9 inflammatory bowel disease (IBD) patients.All patients had absent (13/32 (41%); 11 LT, 2 AIH) or low Ab responses (19/32 (59%); 4 LT, 6 AIH, 9 IBD) after 2 vaccines (V2) defined as anti-S IgG level <400 AU/ml.Anti-S and anti-N IgG titres performed after V2/V3.WT and omicron specific T cell responses were assessed by IFN-γ ELISpot assay in 30/32 patients using peptide pools covering whole-S and minipools of S-specific mutated peptides.Results: There were significant increases in anti-S IgG titres following V3 in all groups, stratified by those with absent and low anti-S Abs post V2 (Fig. 1A).All patients with a low post V2 response had a significant increase in anti-S Ab responses after V3 that was sustained (but not further enhanced) after V4.In liver patients with no anti-S Ab responses after V2, 7/13 (54%) developed anti-S Abs after V3 (0.41 AU/ml vs. 126.72AU/ml; p = 0.016), and importantly these responses were further significantly enhanced following V4 (126.72 AU/ml vs. 3212.90AU/ml; p = 0.002).However, 3/13 (23%) with absent anti-S Abs after V2 remained nonresponsive after V3 and V4.T cell responses to full-S WT and omicron peptides were heterogenous, but generally of high magnitude and detectable in 29/30 patients (Fig. 1B).There was a loss against Omicron (51.8%) when T cell responses were assessed using the variant mini pools (Fig. 1B).LT had significantly reduced response compared to IBD against omicron (mean 796.3 SFC/10 6 vs. 1589 SFC/10 6 ; p = 0.0294) and WT (mean 897.6 SFC/10 6 vs. 1817 SFC/10 6 ; p = 0.0274) (Fig. 1B).Importantly, the 3 seronegative patients after V4, mounted a robust T cell response to WT (mean 882.5 SFC/10 6 ) and omicron (mean 2280 SFC/10 6 ).There was no correlation between humoral and cellular responses (R 2 = 0.01). Conclusion:In liver and IBD patients, low anti-S Ab responses after 2 COVID19 vaccines may be enhanced by V3 and sustained by V4.Patients with absent anti-S Ab responses after 2 doses may have a significant increase in anti-S Ab titres after both V3 and V4.However, a small subset remain non-responsive and should be prioritised for prophylactic strategies.Importantly, immunosuppressed liver patients develop robust T cell responses to WT and omicron independent of anti-S Ab titres.

Background Probody® therapeutics are antibody prodrugs designed to be activated by tumor-associated proteases. This conditional activation restricts antibody binding to the tumor microenvironment, thereby minimizing ‘off-tumor’ toxicity. Here, we report the phase 1 data from the first-in-human study of CX-072 (pacmilimab), a Probody immune checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1), in combination with the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab.Methods Adults (n=27) with advanced solid tumors (naive to PD-L1/programmed cell death protein 1 or CTLA-4 inhibitors) were enrolled in the phase 1 combination therapy dose-escalation portion of this multicenter, open-label, phase 1/2 study (NCT03013491). Dose-escalation pacmilimab/ipilimumab followed a standard 3+3 design and continued until the maximum tolerated dose (MTD) was determined. Pacmilimab+ipilimumab was administered intravenously every 3 weeks for four cycles, followed by pacmilimab administered every 2 weeks as monotherapy. The primary objective was identification of dose-limiting toxicities and determination of the MTD. Other endpoints included the rate of objective response (Response Evaluation Criteria In Solid Tumors v.1.1).Results Twenty-seven patients were enrolled in pacmilimab (mg/kg)+ipilimumab (mg/kg) dose-escalation cohorts: 0.3+3 (n=6); 1+3 (n=3); 3+3 (n=3); 10+3 (n=8); 10+6 (n=6); and 10+10 (n=1). Dose-limiting toxicities occurred in three patients, one at the 0.3+3 dose level (grade 3 dyspnea/pneumonitis) and two at the 10+6 dose level (grade 3 colitis, grade 3 increased aspartate aminotransferase). The MTD and recommended phase 2 dose was pacmilimab 10 mg/kg+ipilimumab 3 mg/kg administered every 3 weeks. Pacmilimab-related grade 3–4 adverse events (AEs) and grade 3–4 immune-related AEs were reported in nine (33%) and six (22%) patients, respectively. Three patients (11%) discontinued treatment because of AEs. The overall response rate was 19% (95% CI 6.3 to 38.1), with one complete (anal squamous cell carcinoma) and four partial responses (cancer of unknown primary, leiomyosarcoma, mesothelioma, testicular cancer). Responses lasted for >12 months in four patients.Conclusions The MTD and recommended phase 2 dose of pacmilimab (10 mg/kg)+ipilimumab (3 mg/kg) every 3 weeks is active and has a favorable tolerability profile.

Abstract Purpose: PROCLAIM-CX-2029 is a phase I first-in-human study of CX-2029, a Probody–drug conjugate targeting CD71 (transferrin receptor 1) in adults with advanced solid tumors. Although the transferrin receptor is highly expressed across multiple tumor types, it has not been considered a target for antibody–drug conjugates (ADCs) due to its broad expression on normal cells. CX-2029 is a masked form of a proprietary anti-CD71 antibody conjugated to monomethyl auristatin E, designed to be unmasked in the tumor microenvironment by tumor-associated proteases, therefore limiting off-tumor toxicity and creating a therapeutic window for this previously undruggable target. Patients and Methods: This was a dose-escalation, multicenter trial to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of CX-2029. The primary endpoint was to determine the maximum tolerated dose (MTD) and cycle 1 dose-limiting toxicity (DLT). CX-2029 was administered i.v. every 3 weeks. Results: Forty-five patients were enrolled in eight dose levels. No DLTs were reported in the dose escalation through 4 mg/kg. At 5 mg/kg, there were two DLTs (febrile neutropenia and pancytopenia). Following expansion of the 4 mg/kg dose to six patients, two additional DLTs were observed (infusion-related reaction and neutropenia/anemia). Both the 4 and 5 mg/kg doses were declared above the maximum tolerated dose. The recommended phase II dose is 3 mg/kg. The most common dose-dependent hematologic toxicities were anemia and neutropenia. Confirmed partial responses were observed in three patients, all with squamous histologies. Conclusions: The Probody therapeutic platform enables targeting CD71, a previously undruggable ADC target, at tolerable doses associated with clinical activity. See related commentary by Oberoi and Garralda, p. 4459

We present a photometric redshift (photo-z) estimation technique for galaxies in the Pan-STARRS1 (PS1) 3π survey. Specifically, we train and test a regression and a classification Random-Forest (RF) models using photometric features (magnitudes, colors and moments of the radiation intensity) from the optical PS1 data release 2 (PS1-DR2) and from the AllWISE/unWISE infrared source catalogs. The classification RF model (RF_clas) has better performance in the local universe (z≲ 0.1), while the second one (RF_reg) is on average better for 0.1 ≲ z≲1. We adopt as labels the spectroscopic redshift of the galaxies from the Sloan Digital Sky Survey (SDSS) data release 16 (SDSS-DR16). We find that the combination of AllWISE/unWISE and PS1-DR2 features leads to an average bias of Δ z_norm=1× 10^-3, a standard deviation σ(Δ z_norm)=0.0225, (where Δ z_norm≡ (z_phot-z_spec)/(1+z_spec)), and an outlier rate of P_0=1.48 % in the test set for the RF_clas model. In the low-redshift Universe (z<0.1) that is of primary interest to many astronomical transient studies, our model produces an error estimate on the inferred magnitude of an object of ≤1 mag in 87% of the test sample.

We present a classification of galaxies in the Pan-STARRS1 (PS1) 3π survey based on their recent star formation history and morphology. Specifically, we train and test two Random Forest (RF) classifiers using photometric features (colors and moments) from the PS1 data release 2. The labels for the morphological classification are taken from Huertas-Company et al., while labels for the star formation fraction (SFF) are from the Blanton et al. catalog. We find that colors provide more predictive accuracy than photometric moments. We morphologically classify galaxies as either early- or late-type, and our RF model achieves a 78% classification accuracy. Our second model classifies galaxies as having either a low-to-moderate or high SFF. This model achieves an 89% classification accuracy. We apply both RF classifiers to the entire PS1 3π dataset, which allows us to assign two scores to each PS1 source: PHSFF, which quantifies the probability of having a high SFF; and Pspiral, which quantifies the probability of having a late-type morphology. Finally, as a proof of concept, we apply our classification framework to supernova (SN) host galaxies from the Zwicky Transient Factory and the Lick Observatory Supernova Search samples. We show that by selecting PHSFF or Pspiral, it is possible to significantly enhance or suppress the fraction of core-collapse SNe (or thermonuclear SNe) in the sample with respect to random guessing. This result demonstrates how contextual information can aid transient classifications at the time of first detection. In the current era of spectroscopically starved time-domain astronomy, prompt automated classification is paramount. Our table is available at 10.5281/zenodo.3990545.

CX‑072 is an anti‑PD‑L1 (programmed death ligand 1) Probody therapeutic (Pb‐Tx) designed to be preferentially activated by proteases in the tumor microenvironment and not in healthy tissue. Here, we report the model‐informed drug development of CX‐072. A quantitative systems pharmacology (QSP) model that captured known mechanisms of Pb‐Tx activation, biodistribution, elimination, and target engagement was used to inform clinical translation. The QSP model predicted that a trough level of masked CX‐072 (intact CX‐072) of 13–99 nM would correspond to a targeted, 95% receptor occupancy in the tumor. The QSP model predictions appeared consistent with preliminary human single‑dose pharmacokinetic (PK) data following CX‐072 0.03–30.0 mg/kg as monotherapy: CX‑072 circulated predominantly as intact CX‐072 with minimal evidence of target‐mediated drug disposition. A preliminary population PK (POPPK) analysis based upon 130 subjects receiving 0.03–30.0 mg/kg as monotherapy included a provision for a putative time‐dependent and dose‐dependent antidrug antibody (ADA) effect on clearance (CL) with a mixture model. Preliminary POPPK estimates for intact CX‐072 time‐invariant CL and volume of distribution were 0.306 L/day and 4.84 L, respectively. Exposure–response analyses did not identify statistically significant relationships with best change from baseline sum of measurements and either adverse events of grade ≥ 3 or of special interest. Simulations suggested that > 95% of patients receiving CX‐072 10 mg/kg every two weeks would exceed the targeted trough level regardless of ADA, and that dose adjustment by body weight was not necessary, supporting a fixed 800 mg dose for evaluation in phase II.

526 Background: CX-2009 is a PROBODY drug conjugate (PDC) directed against CD166 (ALCAM) and conjugated to DM4, a potent microtubule inhibitor (MTI). CD166 is overexpressed in carcinomas but is also ubiquitously expressed in normal epithelium and thus has not been previously considered a viable target for a traditional antibody drug conjugate. PDCs have a peptide mask that blocks normal tissue binding and can be removed by tumor-associated proteases, thereby limiting off-tumor/on-target binding. CX-2009 demonstrated preclinical activity in multiple solid tumor models. Here we report results of the first in human study in patients with advanced cancer. Methods: In this phase I multi-part dose-escalation study, pts with advanced solid tumors received CX-2009 0.25–10 mpk IV every 14 or 21 days (Q2W or Q3W). Tumor types were selected based on expected high CD166 expression and MTI sensitivity. Results: The dose-escalation phase of the trial enrolled 43 pts; 49 additional pts were subsequently enrolled between 4–10 mpk to collect biomarker data and define the recommended phase II dose (RP2D), for a total of 92 pts as of 30 Nov 2019 (39 pts with breast cancer [BC], 22 ovarian [OC], 12 non-small cell lung [NSCLC], 9 head/neck squamous cell [HNSCC], 10 other) with a median of 6 (range 1–19) prior therapies. Median number of CX-2009 doses was 2 (range, 1–15). For Q3W dosing, one dose limiting toxicity (DLT; grade 3 vomiting) was observed at 8 mpk; MTD was not reached up to 10 mpk. The RP2D for Q3W schedule was 7 mpk based on safety, dose-response, and population pharmacokinetic simulations. Q2W dosing continues; DLTs were observed at 6 mpk. Common treatment-related adverse events (TRAEs) at 7 mpk (n=9) were nausea (44%), fatigue, infusion-related reactions (both 33%), vomiting and arthralgias (both 22%). Grade 3 TRAEs occurred in 2 pts (nausea/vomiting; peripheral neuropathy). No pts discontinued at 7 mpk due to TRAEs. Ocular toxicity was dose dependent; mild to moderate reversible keratitis/blurred vision was seen in 3 pts at 7 mpk and mitigated by ocular prophylaxis. Partial responses were seen in 8 pts (2 confirmed, both HR+/HER2- BC) treated between 4–10 mpk, including BC (n=5), OC (n=2), and HNSCC (n=1). SD (≥1 on-study scan) was observed in 21 pts, 5 had SD ≥3 mos. Conclusions: CX-2009 at 7 mpk is the RP2D on Q3W schedule. Phase II expansion has begun in pts with HR+/HER2- BC. The Q2W schedule will continue to enroll pts to define the RP2D. CX-2009 will also be studied in combination with CX-072, a PD-L1 PROBODY therapeutic ( NCT03149549 ) Clinical trial information: NCT03149549 .

3602 Background: PROBODY therapeutics (Pb-Tx) are antibody prodrugs designed to reduce off-tumor, on-target toxicities. The mask inhibits Pb-Tx binding in the periphery yet can be removed by tumor-associated proteases, restricting target engagement to the tumor. This is the first report of preliminary clinical pharmacokinetic (PK) analysis supporting selection of the phase II dose for CX-072, an anti–PD-L1 Pb-Tx, from the ongoing phase I/II PROCLAIM-CX-072 study (NCT03013491). Methods: A quantitative systems pharmacology (QSP) model1 was used to project the CX-072 plasma trough level (Cmin) corresponding to 95% intratumoral receptor occupancy (RO). Human PK and anti-drug antibody (ADA) data were obtained at selected times postdose following IV administration of 0.03–30 mpk CX-072 in PROCLAIM-CX-072. Population PK (POPPK) modeling was performed with NONMEM v7.3.0. Exploratory analysis and simulations were done with R v3.3.1 or later. Covariates were selected for POPPK using forward addition ( P<0.05) followed by backward deletion ( P<0.01). Results: The preliminary POPPK analyses were informed using available PK data as of August, 2019 from 135 subjects receiving CX-072 Q2W as monotherapy in the dose-escalation and expansion cohorts of PROCLAIM-CX-072. A mixture model was used to capture time- and dose-dependent apparent ADA effect on clearance (CL). The preliminary POPPK model estimates for CX-072 CL and volume of distribution (Vd) were 0.306 L/day and 4.84 L, respectively. Statistically significant covariate effects included body weight on the central Vd and CL, and albumin on CL. The QSP model predicted a CX-072 Cmin of 13–99 nM would be required for 95% intratumoral RO. POPPK simulations suggested that >95% of patients receiving CX-072 10 mg/kg Q2W would meet or exceed this targeted Cmin regardless of ADA. Additional observed data indicated that the majority of patients receiving 10 mpk CX-072 Q3W × 4 with 3 mpk ipilimumab (IPI) Q3W × 4 in the CX-072-IPI combination part of PROCLAIM-CX-072 maintained the targeted Cmin. Simulations did not suggest there would be a clinically meaningful change in exposure following a fixed dose of CX-072 800 mg relative to the 10 mpk weight-based dose. Conclusions: Preliminary PK analysis supports selection of 800 mg CX-072 Q2W as the recommended monotherapy dose and 800 mg Q3W when combined with IPI. The combination of 800 mg CX-072 + 3 mpk IPI Q3W × 4 doses, followed by monotherapy administration of 800 mg CX-072 Q2W is being further explored in phase II. Reference: 1) Stroh M et al. CPT. 2019(9):676-84. Clinical trial information: NCT03013491 .

3108 Background: PROBODY therapeutics (Pb-Tx) are masked antibodies designed to be selectively activated in the tumor microenvironment by tumor-associated proteases and to remain largely inactive in normal tissue. CX-072, a Pb-Tx directed against PD-L1, is designed to reduce the potential for immune-associated adverse events in normal tissues while maintaining anti-tumor activity. CX-072 is being investigated in PROCLAIM-CX-072 (NCT03013491), a first-in-human phase 1/2 trial. CX-072 is administered as monotherapy or in combination with ipilimumab to patients with metastatic or recurrent solid tumors or lymphomas for which approved PD-1/-L1–based therapy is not available. We present the updated results of a tissue-based biomarker program designed to assess activation, localization, and mechanism of action of CX-072 in patient tumors. Methods: Tumor biopsies were collected during the screening phase, and also 3–5 days after the first or third dose of 0.3–30 mg/kg CX-072. Tumor-associated protease activity was measured by tissue zymography. Intratumoral CX-072 activation was measured using capillary immunoelectrophoresis, and PD-L1 levels were measured by an ultrasensitive ELISA. Intratumoral CD8 expression was analyzed using immunohistochemistry. Intact and total CX-072 in plasma were measured by LC-MS/MS. Results: Twenty-six of 30 (87%) evaluable predose biopsies had detectable levels of relevant protease activity. Intratumoral activation of CX-072 was quantifiable in 3 of 8 (38%) biopsies from patients treated with CX-072 at 3 mg/kg and in 12 of 12 (100%) biopsies from patients treated with ≥10 mg/kg. In contrast, CX-072 remained predominantly in the intact form in circulation. The molar ratio of activated intratumoral CX-072 to total intratumoral PD-L1 ranged from ~14x to > 100x in patients dosed at 10 mg/kg, and the calculated tumor receptor occupancy for these patients was ≥99%, congruent with quantitative systems pharmacology model predictions. An increase in CD8+ T cells and elevation of cytotoxic T-cell markers was observed in the tumors of 11 of 18 (61%) CX-072 monotherapy patients, consistent with inhibition of the PD-L1 pathway. Conclusions: These results demonstrate that the Pb-Tx CX-072 behaves as designed in patients. Clinical trial information: NCT03013491 .

3599 Background: PROBODY therapeutics are antibody prodrugs with cleavable peptide masks designed to reduce off-tumor, on-target toxicities. The mask blocks binding in the periphery and is removed by tumor-associated proteases resulting in intratumoral binding. CX-2009 is a PROBODY drug conjugate directed against CD166/ALCAM, which is a target overexpressed in carcinomas but not suitable for traditional ADC targeting because it is expressed in normal epithelium. CX-2009 is conjugated to DM4, a potent microtubule inhibitor. Here we report preliminary clinical pharmacokinetic (PK) and exploratory dose-response (DR) analyses for CX-2009 from the ongoing phase 1/2 PROCLAIM-CX-2009 study (NCT03149549). Methods: Human PK and anti-drug antibody (ADA) data were obtained at selected times post-dose following IV 0.25–10 mpk CX-2009 Q3W and of 6 mpk Q2W. Covariates were selected for population PK (POPPK) based on multivariate screening at P< 0.01. Preliminary exploratory DR analyses were conducted for selected endpoints including adverse events of special interest and response data (CR, PR, SD, and PD). Results: Preliminary CX-2009 PK data from 92 subjects were available as of October 2019. Median free DM4 levels circulated at ≤0.3% of Total CX-2009 (masked + activated CX-2009) levels across the 1–10 mpk dose levels. A two-compartment POPPK model with linear elimination was fit to the Intact (masked form) CX-2009 data. The preliminary CX-2009 POPPK model estimates for Intact CX-2009 clearance (CL), volume of distribution, and half-life were 0.47 L/day, 4.51 L, and 7.14 days, respectively, with 91% of CX-2009 circulating as Intact CX-2009. ADA was not a statistically significant covariate on Intact CX-2009 CL. Evidence of clinical activity was observed at doses of 4 mpk Q3W or higher. DR analysis suggested that the frequency of grade ≥3 ocular toxicity events increased significantly at dose equivalents ≥8 mpk Q3W. POPPK simulations suggested that the targeted 90 nM trough concentration (based on nonclinical data) would be contained within the 90% prediction interval of predicted Intact CX-2009 levels following CX-2009 7 mpk. Conclusions: Preliminary CX-2009 PK data following CX-2009 0.25-10 mpk suggest that CX-2009 circulates predominantly as Intact CX-2009, and that Intact CX-2009 PK is not strongly influenced by target-mediated drug disposition or ADA. Preliminary DR and POPPK simulations support further evaluation of 7 mpk CX-2009 Q3W in selected cohort expansions. Clinical trial information: NCT03149549 .