Lumos Pharma (United States)

Abstract Disclosure: A. Roslan: Lumos Pharma, Inc.. R. Nass: None. P. Veldhuis: None. J. McKew: Lumos Pharma, Inc. P. Pitukcheewanont: Lumos Pharma, Inc. E. Brincks: Lumos Pharma, Inc. P.E. Clayton: Lumos Pharma, Inc. M. Thorner: Lumos Pharma, Inc. A. Stevens: Lumos Pharma, Inc.. Background: Ibutamoren (IB, LUM-201), an investigational oral GH secretagogue, increased pulsatile GH secretion and fat-free mass (FFM) in healthy older adults to levels seen in young adults in a double-blind, placebo-controlled trial to assess its potential as treatment for sarcopenia (Nass et al Ann Intern Med. 2008). In children with moderate GH deficiency the growth response to IB is related to both the amount and pattern of GH secretion; the latter was identified using functional principal component analysis (FPCA) to define the timing and extent of the dominant variation in 12hr day-time GH profiles (FC15.2, ESPE 2024). This study uses FPCA to assess the effect of the first 6 months of treatment with IB in adults on the relationship between change in FFM and patterns of GH secretion in 12hr day-time and 24hr GH profiles. Methods: 65 healthy adults (23 men, 25 women on HRT, 17 not on HRT) ranging from 60-81 years old received oral IB 25 mg (n=43) or placebo (n=22) once daily for 6m. FFM (kg) was measured by DXA and samples for GH were drawn every 10mins for 24hr at baseline and 6m in the IB and placebo groups. GH secretory dynamics were assessed using deconvolution; analysis was undertaken on the 12hr day-time data and the full 24hr GH secretion profile (µg/L/min). FPCA defines the GH profile variation as Eigen Functions, with the first EF [EF1] used in this analysis. L2 Norm (the Euclidean distance between the EF1 profile at baseline and 6m) was used to define differences in IB and placebo groups. For the FPCA, the change in FFM over 6m in IB and placebo groups were both stratified into tertiles and the total GH production and EF1 profiles in each tertile were compared within and between groups. Significance was evaluated by Kruskal-Wallis and Wilcoxon tests. Results: In the whole cohort over 6m, total GH production increased in the IB-treated group (median change +23, range -21 to 92 µg/L over 24hr) but not on placebo (+2.3, -56 to +162), p<0.0001. FFM increased in the IB group (median +1, range -2.7 to +4.1kg) but not on placebo (-0.1, -3.7 to +2.9kg), p<0.001. Across the FFM tertiles in IB and placebo groups, total GH production over 24hr was not different (with the placebo group having lower levels, as expected), suggesting that amount of GH alone was not accounting for the range of FFM changes. However across FFM tertiles the differences in the EF1 profiles over 6m derived from the 12hr day-time and 24hr GH profiles for IB and for placebo were significant (both p<0.0001). Additionally within each FFM tertile the EF1 profiles were different between IB and placebo groups (all p<0.0001). Conclusions: This analysis indicates both the amount and the variation in GH secretion in healthy older adults treated with IB influences changes in body composition, in both for the 12hr day-time GH secretion and for the full 24hr profile. These effects of Ibutamoren on physiological GH secretion reinforce the importance of pulse profiles to GH action. Presentation: Sunday, July 13, 2025

BackgroundRecurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy.MethodsWe conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing.ResultsEighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39–77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2–62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7–29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4–61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2–62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype.ConclusionsIndoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors.

A severe winter storm in February 2021 impacted multiple infrastructure systems in Texas, leaving over 13 million people without electricity and/or water, potentially $100 billion in economic damages, and almost 250 lives lost. While the entire state was impacted by temperatures up to 10 °C colder than expected for this time of year, as well as levels of snow and ice accumulation not observed in decades, the responses and outcomes from communities were inconsistent and exacerbated prevailing social and infrastructure inequities that are still impacting those communities. In this contribution, we synthesize a subset of multiple documented inequities stemming from the interdependence of the water, housing, transportation, and communication sectors with the energy sector, and present a summary of actions to address the interdependency of infrastructure system inequities.

Acute respiratory infections (ARIs) account for most outpatient visits. Discriminating bacterial vs viral etiology is a diagnostic challenge with therapeutic implications. To investigate whether FebriDx, a rapid, point-of-care immunoassay, can differentiate bacterial- from viral-associated host immune response in ARI through measurement of myxovirus resistance protein A (MxA) and C-reactive protein (CRP) from finger-stick blood. This diagnostic study enrolled adults and children who were symptomatic for ARI and individuals in a control group who were asymptomatic between October 2019 and April 2021. Included participants were a convenience sample of patients in outpatient settings (ie, emergency department, urgent care, and primary care) who were symptomatic, aged 1 year or older, and had suspected ARI and fever within 72 hours. Individuals with immunocompromised state and recent vaccine, antibiotics, stroke, surgery, major burn, or myocardial infarction were excluded. Of 1685 individuals assessed for eligibility, 259 individuals declined participation, 718 individuals were excluded, and 708 individuals were enrolled (520 patients with ARI, 170 patients without ARI, and 18 individuals who dropped out). Bacterial and viral immunoassay testing was performed using finger-stick blood. Results were read at 10 minutes, and treating clinicians and adjudicators were blinded to results. Bacterial- or viral-associated systemic host response to an ARI as determined by a predefined comparator algorithm with adjudication classified infection etiology. Among 520 participants with ARI (230 male patients [44.2%] and 290 female patients [55.8%]; mean [SD] age, 35.3 [17.7] years), 24 participants with missing laboratory information were classified as unknown (4.6%). Among 496 participants with a final diagnosis, 73 individuals (14.7%) were classified as having a bacterial-associated response, 296 individuals (59.7%) as having a viral-associated response, and 127 individuals (25.6%) as negative by the reference standard. The bacterial and viral test correctly classified 68 of 73 bacterial infections, demonstrating a sensitivity of 93.2% (95% CI, 84.9%-97.0%), specificity of 374 of 423 participants (88.4% [95% CI, 85.0%-91.1%]), positive predictive value (PPV) of 68 of 117 participants (58.1% [95% CI, 49.1%-66.7%), and negative predictive value (NPV) of 374 of 379 participants (98.7% [95% CI, 96.9%-99.4%]).The test correctly classified 208 of 296 viral infections, for a sensitivity of 70.3% (95% CI, 64.8%-75.2%), a specificity of 176 of 200 participants (88.0% [95% CI, 82.8%-91.8%]), a PPV of 208 of 232 participants (89.7% [95% CI, 85.1%-92.9%]), and an NPV of 176 of 264 participants (66.7% [95% CI, 60.8%-72.1%]). In this study, a rapid diagnostic test demonstrated diagnostic performance that may inform clinicians when assessing for bacterial or viral etiology of ARI symptoms.

There is a plethora of chromatographic supports available in different shapes, sizes, functionalities, and chemical compositions, that could be employed for the numerous applications such as purification, scavenging, and target quantification. Therefore, it becomes critical to understand the chemical nature of these materials to select optimum conditions for ligand immobilization. In this chapter, we have explained some commonly employed ligand immobilization techniques to graft the ligand on the resin surfaces. For a quick reference, we have also included some functionalities of the resins that are commercially available.

Monoclonal antibodies (mAbs) are key components of revolutionary disease immunotherapies and are also essential for medical diagnostics and imaging. The impact of cost is illustrated by a price >$200,000 per year per patient for mAb-based cancer therapy. Purification represents a major issue in the final cost of these immunotherapy drugs. Protein A (PrA) resins are widely used to purify antibodies, but resin cost, separation efficiency, reuse, and stability are major issues. This paper explores a synthesis strategy for low-cost, reusable, stable PrA-like nanopockets on core-shell silica-coated magnetic nanoparticles (NPs) for IgG antibody isolation. Mouse IgG2a, a strong PrA binder, was used as a template protein, first attaching it stem-down onto the NP surface. The stem-down orientation of IgG2a on the NP surface before polymerization is critical for designing the films to bind IgGs. Following this, 1-tetraethoxysilane and four organosilane monomers with functional groups capable of mimicking binding interactions of proteins with IgG antibody stems were reacted to form a thin polymer coating on the NPs. After blocking nonspecific binding sites, removal of the mouse IgG2a provided nanopockets on the core-shell NPs that showed binding characteristics for antibodies remarkably similar to PrA. Both smooth and rough core-shell NPs were used, with the latter providing much larger binding capacities for IgGs, with an excellent selectivity slightly better than that of commercial PrA magnetic beads. This paper is the first report of IgG-binding NPs that mimic PrA selectivity. These nanopocket NPs can be used for at least 15 regeneration cycles, and cost/use was 57-fold less than a high-quality commercial PrA resin.

To assess the safety and tolerability of nilotinib (150–300mg QD) in moderate/advanced and early/de novo PD subjects.

Introduction: An obesity paradox exists in non-STEMI in which patients with mild obesity have lower mortality than normal weight patients. It is not known if this paradox exists among older patients with STEMI and among individuals with extreme obesity over the long term. Methods: Patients ≥65 years of age with STEMI from the NCDR ACTION Registry-GWTG who survived to hospital discharge were linked to Medicare claims data. Patients were stratified by body mass index (BMI, kg/m 2 ) into normal weight (18.5-24.9), overweight (25-29.9), class I obese (30-34.9), class II obese (35-39.9), and class III (extreme) obese categories (≥40). Multivariable Cox proportional hazards models were used to evaluate the association between BMI category and all-cause mortality for 3 years after hospital discharge. Models were adjusted for clinical and socioeconomic (SES) characteristics and in-hospital outcomes. Differences in number of days alive and out of hospital (DAOH) were also assessed. Results: Of 19,499 patients included in the analysis, 70% were overweight or obese. Normal weight patients (30%) were more likely to be older and smoke and extremely obese patients (3%) more likely to be younger, female, and black, with lower SES and more comorbidity (P≤0.001). After multivariable adjustment, a U-shaped association was observed between BMI and long term mortality. Patients with mild (class I) obesity were at lowest risk, while normal weight or extremely obese patients had higher all-cause mortality ( Figure ). Normal weight and extremely obese individuals also had lower DAOH at 3 years compared with mildly obese (median 894 vs. 950 days, respectively, P<0.05). Conclusions: The obesity paradox persists in older STEMI patients over long term with regards to death and readmission but is not seen with extreme obesity. Normal weight and extreme obesity are associated with consistently worse outcomes highlighting a need for aggressive treatment paradigms for these populations after STEMI.

Introduction: A recent study in clinic patients found serum activity of the anti-oxidative, anti-inflammatory HDL-associated enzyme paraoxonase 1 (PON1) inversely associated with plasma brain natriuretic peptide (BNP), a marker of heart failure, and predictive of cardiovascular events. We tested whether PON1 protects from hypertensive heart disease in a population sample. Methods: The Dallas Heart Study measured blood biomarkers at baseline in a population sample of 3480 subjects. Left ventricular mass and ejection fraction were measured by cardiac MRI. Serum PON1 activity was measured by the standard arylesterase enzymatic assay. Incident deaths and causes of death were ascertained for 9 years from baseline through the National Death Index where ICD-9 codes I10 –I13.1 indicated hypertensive heart disease. Multivariable models controlled for age, sex, race, cystatin-C, LDL, HDL, high sensitivity C-reactive protein and uncontrolled hypertension. Preliminary mechanistic studies explored effect modification of 34 biomarkers by PON1. Results: In a general linear model PON1 activity was independently associated inversely with log Pro-BNP (standardized r = -0.11, s.e. 0.015, P<0.001) and log BNP (std r = -0.07, s.e. 0.017, P<0.001). It was also inversely associated with left ventricular mass (std r = -0.05, s.e. 0.012, P<0.001) but not with ejection fraction (std r = -0.02, s.e. 0.018, P=0.19). In multivariable logistic regression low PON1 activity predicted the 28 incident deaths from hypertensive heart disease (odds ratio for PON1 activity below the median = 3.58, 95% CI 1.42 – 9.05, P=0.007). Significant interactions indicated that high PON1 activity mitigates the strong association of log Pro-BNP with periostin, a matricellular protein associated with cardiac fibrotic remodeling (P interaction < 0.001, Fig.). Conclusions: The findings suggest that PON1, a component of HDL, may protect from hypertensive heart disease by mitigating cardiac remodeling.