H-1337 / Allysta Pharma, D. Western Therapeutics Institute - LARVOL DELTA

A Phase 2b Randomized, Double-masked, Active-controlled, Dose-response Study of the Safety and Efficacy of H-1337 in Subjects with Primary Open Angle Glaucoma (POAG) or Ocular Hypertension (ARVO 2025) - "Purpose Evaluate the ocular hypotensive efficacy of 3 dose regimens of H-1337 compared to timolol maleate 0.5% in subjects with POAG or OHT dosed up to 28 days bilaterally. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • P2b data • Glaucoma • Ophthalmology

Open-Label Study of Safety of H1337 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: D. Western Therapeutics Institute, Inc. | Recruiting ➔ Completed

Trial completion • Cardiovascular • Glaucoma • Ophthalmology

Open-Label Study of Safety of H1337 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: D. Western Therapeutics Institute, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Glaucoma • Ophthalmology

Study of Safety and Efficacy of H-1337 in Subjects With Primary Open Angle Glaucoma or Ocular Hypertension (clinicaltrials.gov) - P2 | N=201 | Completed | Sponsor: D. Western Therapeutics Institute, Inc. | Trial primary completion date: Dec 2025 ➔ Aug 2024 | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Aug 2024

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Glaucoma • Ophthalmology

Open-Label Study of Safety of H1337 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: D. Western Therapeutics Institute, Inc.

New P1 trial • Cardiovascular • Glaucoma • Ophthalmology

Study of Safety and Efficacy of H-1337 in Subjects With Primary Open Angle Glaucoma or Ocular Hypertension (clinicaltrials.gov) - P2 | N=200 | Active, not recruiting | Sponsor: D. Western Therapeutics Institute, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Glaucoma • Ophthalmology

Short- and Long-term Variabilities of Blood Oxygen Saturation in Extremely Preterm Infants (ATS 2024) - "We previously showed that extremely preterm infants in this cohort with Unfavorable respiratory outcomes have more frequent and longer IH events than those in the Favorable group. Findings of lower short-term and long-term variability of inter-IH-episode durations in the Unfavorable group offer new information about regularity of these events and may indicate that IH events are not clustered but occur more regularly throughout day/night in the Unfavorable group than in the Favorable group. This observation, along with greater SpO2 variability (CoV) in the Unfavorable group, indicates that SpO2 fluctuations are not well regulated despite traditional conservative clinical oxygenation guidelines."

Prematurity • Critical care

Airway colonization alters the tracheo-alveolar inflammatory profile in mechanically ventilated extremely preterm infants (PAS 2024) - "90 infants were enrolled. Of these, 26 mechanically ventilated infants were selected based on availability of TAF samples pre- and post- first colonization. 10 infants were colonized with GP and 10 with GN."

Prematurity • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases • EGF • IL13 • TNFA

Preeclampsia alters the inflammasome component profiles of tracheal aspirate fluid in extremely premature infants (PAS 2024) - "The cohort included 61 preterm infants of whom 16 were born to mothers with PE. Demographics are shown in Table 1. Infants born to mothers with PE had significantly higher caspase-1 and ASC levels in the TAF compared to non-PE infants (Table 2)."

Gynecology • Inflammation

Study of Safety and Efficacy of H-1337 in Subjects With Primary Open Angle Glaucoma or Ocular Hypertension (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: D. Western Therapeutics Institute, Inc. | Phase classification: P2b ➔ P2

Phase classification • Cardiovascular • Glaucoma • Ophthalmology

Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study. (PubMed, Elife) - "This study was supported by R01GM120523 (QF), R01HL163854 (QF), R35GM131770 (CMS), HL133786 (WQW), and Vanderbilt Faculty Research Scholar Fund (QF)...The authors wish to acknowledge the expert technical support of the VANTAGE and VANGARD core facilities, supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA068485) and Vanderbilt Vision Center (P30 EY08126). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication."

Journal • Retrospective data • Infectious Disease • Nephrology • Oncology • Renal Disease • Septic Shock

Study of Safety and Efficacy of H-1337 in Subjects With Primary Open Angle Glaucoma or Ocular Hypertension (clinicaltrials.gov) - P2b | N=200 | Recruiting | Sponsor: D. Western Therapeutics Institute, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Glaucoma • Ophthalmology

Study of Safety and Efficacy of H-1337 in Subjects With Primary Open Angle Glaucoma or Ocular Hypertension (clinicaltrials.gov) - P2b | N=200 | Not yet recruiting | Sponsor: D. Western Therapeutics Institute, Inc.

New P2b trial • Cardiovascular • Glaucoma • Ophthalmology

Cardiorespiratory Physiological Trajectories in Extremely Preterm Infants (ATS 2023) - "Funding: NIH grants U01HL133708, HL133708-05S1, U01HL133643, U01HL133704, U01HL133536, U01HL133689, U01HL133700... This study describes the natural histories of apnea/PB/IH/bradycardia in a large cohort of extremely preterm infants. Transitory manifestations of immature cardioventilatory control may require intervention but do not necessarily imply structural heart or lung disease or need for long-term support. Knowledge of typical longitudinal patterns of physiologic instability can help identify individual patients that may be outliers and serve as the basis for further research into the links between physiologic biomarkers and patient outcomes."

Prematurity • Cardiovascular • Pulmonary Disease • Respiratory Diseases

Cardiorespiratory Coupling in Extremely Preterm Infants (ATS 2023) - "Funding: NIH grants U01 HL133708, U01 HL133704... This pattern of increasing CRC as a function of PMA indicates increased cardiorespiratory maturation as the extremely preterm-born infants advance in age. Establishing a normal trajectory of this pattern would enable better tracking of maturation in individual infants, potentially serving as a biomarker for health and an added factor for clinical decision-making."

Prematurity • Cardiovascular

Preeclampsia alters tracheo-alveolar fluid proteomic angiogenic profile in extremely premature infants (PAS 2023) - "The cohort included 48 infants of whom 10 were born to mothers with PE. Demographics are shown in Table 1. Pro-angiogenic factors hepatocyte growth factor (HGF) and heparin-binding epidermal growth factor (HB-EGF) were decreased in the PE compared to the non-PE group (Table 2)."

Gynecology • EGF • ENG • FGF2 • HBEGF • HGF • LEP

Phase 1 / 2 Double-Masked Randomized Vehicle-Controlled Study H-1337 Ophthalmic Solution in Glaucoma and Ocular Hypertension. (PubMed, Ophthalmol Glaucoma) - "H-1337 Ophthalmic Solution showed clinically and statistically significant ocular hypotensive activity and was well tolerated, with a relatively low incidence of hyperemia."

Journal • Cardiovascular • Dermatology • Glaucoma • Ophthalmology

First-in-Human, Double-Masked Randomized Vehicle-Controlled Study of H-1337 Ophthalmic Solution in Glaucoma and Ocular Hypertension (AAO 2022) - "In the active groups, diurnally-adjusted mean change in IOP from baseline showed a decrease of 4.1 to 5.2 mm Hg at the presumed trough on Day 14 at 8:00 hours, and 4.4 to 5.7 mm Hg at the presumed peak at 10:00 hours, in contrast to a vehicle effect of 2.0 mm Hg (P < 0.0001). Treatment-emergent adverse events occurred in 49% of subjects receiving H-1337 and in 18% of subjects receiving vehicle. The majority of TEAEs were mild in severity.ConclusionH-1337 Ophthalmic Solution showed clinically and statistically significant ocular hypotensive activity and was well tolerated, with a relatively low incidence of hyperemia."

Clinical • P1 data • Glaucoma • Ophthalmology

The Isoquinoline-Sulfonamide Compound H-1337 Attenuates SU5416/Hypoxia-Induced Pulmonary Arterial Hypertension in Rats. (PubMed, Cells) - "Furthermore, H-1337 suppressed aggravation of right ventricle hypertrophy. In conclusion, our data demonstrated that inhibition of ROCK and mTOR pathways with H-1337 suppressed the progression of pulmonary vascular remodeling, pulmonary hypertension, and right ventricular remodeling."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

H-1337 Ophthalmic Solution Phase 1/2 (clinicaltrials.gov) - P1/2; N=87; Completed; Sponsor: Allysta Pharmaceutical; Phase classification: P2 ➔ P1/2

Clinical • Phase classification • Glaucoma • Hypertension • Ophthalmology