Woolsey Pharmaceuticals, Inc.

NEW YORK, Dec. 9, 2024 /PRNewswire/ -- Woolsey Pharmaceuticals, a clinical-stage pharmaceutical company developing BRAVYL (oral fasudil) for the treatment of Amyotrophic Lateral Sclerosis (ALS), announced that a poster by Dr. Daniel Linseman's laboratory at the University of Denver presented at the 35th International Symposium on ALS/MND held in Montreal, Canada on December 6th showed that treatment with BRAVYL significantly reduced TDP-43 aggregation and cytoplasmic redistribution. In ALS, TDP-43 pathology is understood to spread via extracellular vesicles, including neuronal exosomes, which are secreted by sick neurons and can be taken up by healthy ones. TDP-43 pathology is characterized by the translocation of TDP-43 from the nucleus, where it normally resides, to the cytoplasm and the formation of aggregates. To assess whether BRAVYL affects this process, neuron-derived exosomes (NDEs) were isolated from the plasma of two healthy control subjects and from six ALS patients, at baseline and after six months of treatment with BRAVYL (180 mg/day). A mouse motor neuron model was used to assess TDP-43 pathology. NSC-34 cells were transfected with plasmid expressing wild-type human TDP-43 linked to td-tomato fluorescent protein. Transfected cells were then differentiated into motor neuron-like cells using retinoic acid. Differentiated cells were incubated with NDEs and examined by confocal microscopy to observe changes in td-tomato-TDP-43 subcellular localization and aggregation. Key Findings Include: Cells treated with baseline NDEs from ALS patients showed marked aggregation and redistribution of TDP-43 into the cytoplasm, indicating that NDEs from ALS patients can confer TDP-43 pathology in this system. In contrast, when exposed to NDEs from the same patients following treatment for 6 months with BRAVYL, TDP-43 aggregation and cytoplasmic redistribution were significantly reduced by 60% (p=0.0006) and 61% (p<0.0001) respectively. The findings indicate treatment with BRAVYL may be beneficially affecting the neuronal exosome-mediated spread of TDP-43 pathology in ALS. Further work is underway to identify the specific cargo responsible for this effect and the precise mechanism of action. "We have previously shown that 6-month treatment of ALS patients with BRAVYL reduces Neurofilament Light Chain (NfL)," notes Sven Jacobson, CEO of Woolsey. "Now we have evidence that BRAVYL can reduce the spread of toxic TDP-43, a truly novel discovery. These findings highlight BRAVYL's potential to transform ALS treatment." Woolsey recently announced it had completed recruitment of 31 ALS patients into the REAL study's high-dose (300 mg/day) cohort, which was added following promising NfL biomarker and clinical findings along with an excellent safety profile in patients treated at 180 mg/day. Results are expected in June 2025. ABOUT ALS ALS is a fatal neurodegenerative disease characterized by inevitable, and often rapid, decline in patients as the disorder advances (mean survival time is only two to five years). Accordingly, the ability to impede any worsening represents a meaningful advancement in efforts to enhance the prognosis and quality of life of individuals impacted by this devastating condition. ABOUT WOOLSEY PHARMACEUTICALS Woolsey Pharmaceuticals is expanding the boundaries of medical science. Our lead indication is Amyotrophic Lateral Sclerosis (ALS), a progressive and debilitating disease that ultimately is fatal. Our mission is to help usher in a new era of neurodegenerative disease treatment, saving and improving the lives of patients in need. SOURCE Woolsey Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

NEW YORK, Nov. 12, 2024 /PRNewswire/ -- Woolsey Pharmaceuticals today announced the successful completion of patient recruitment (n=31) in the high-dose (300 mg/day) cohort of the REAL study, which is assessing BRAVYL® (oral fasudil) for the treatment of Amyotrophic Lateral Sclerosis (ALS). This follows promising biomarker and clinical findings from the study's standard-dose cohort. At the 180 mg/day dose (n=31), the biomarker Neurofilament Light (NfL), a sensitive indicator of neuronal damage and rate of ALS progression, decreased by 15% from baseline to 6 months (p=0.0006); of note, increased levels of NfL are associated with more rapid decline in function. Additionally, there were directionally positive clinical improvements compared to a matched historical control — a 17% lower decline in ALSFRS-R, a 37% lower decline in slow vital capacity (SVC), and a 56% lower decline in muscle strength. Moreover, greater decreases in NfL were correlated with less deterioration on the ALSFRS-R (p=0.028). Given these encouraging biomarker and clinical findings at the 180 mg/day dose, along with an excellent safety profile, Woolsey Pharmaceuticals made the decision to re-open the REAL study to explore the effects of BRAVYL at an increased dose of 300 mg/day. "Experience with this higher dose in ALS patients will be invaluable as we progress to a larger study," said Sven Jacobson, CEO of Woolsey Pharmaceuticals. "Furthermore, recently published results from a university-led, three-arm, double-blind study of fasudil in ALS patients found a relationship between dose and improved motor neuron function, which is very encouraging for our ongoing research," Jacobson stated, referencing "Safety, tolerability, and efficacy of fasudil in amyotrophic lateral sclerosis [ROCK-ALS]: a phase 2, randomised, double-blind, placebo-controlled trial, Jan C Koch et at, The Lancet Neurology, November 2024)." Study results from the 300 mg/day dosing cohort are expected to be released by mid-2025. About ALS ALS is a fatal neurodegenerative disease characterized by inevitable, and often rapid, decline in patients as the disorder advances. Mean survival time is only two to five years. Accordingly, the ability to impede worsening represents a meaningful advancement in efforts to enhance the prognosis and quality of life of individuals impacted by the devastating condition. About Woolsey Pharmaceuticals Woolsey Pharmaceuticals' mission is to help usher in a new era of neurodegenerative disease treatment, saving and improving the lives of patients in need. SOURCE Woolsey Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

NEW YORK, July 8, 2024 /PRNewswire/ -- Woolsey Pharmaceuticals, a clinical-stage drug development company, announced that the first patient has started treatment at 300 mg/day in the REAL study, which is evaluating the effects of BRAVYL in Amyotrophic Lateral Sclerosis (ALS). As recently announced, participants treated with 180 mg/day BRAVYL in the REAL study experienced a 15.5% decrease (improvement) in NfL from baseline to 6 months (p<0.001). Since NfL in the ALS population tends to increase by a mean of 11% in 6 months, this suggests that 180 mg/day BRAVYL could potentially reduce NfL up to 26% versus a control group. Moreover, greater decreases in NfL were correlated with less deterioration on the ALSFRS-R (Spearman's coefficient = -0.45, p=0.028) implying that early clinical benefits of reducing NfL may be seen contemporaneously with the NfL reductions by BRAVYL. A "propensity matched" analysis was performed wherein 12-month clinical outcomes from REAL were compared with those from a matched cohort selected by identifying 31 patients from the Ceftriaxone ALS Study database that were most similar (based on pre-treatment age, ALSFRS-R, time from onset of ALS, and other important parameters) to each REAL patient. The rate of deterioration in ALSFRS-R was improved in REAL vs. the matched controls by 28% (p=0.12). REAL patients also had a 42% (p=0.05) slower deterioration in SVC (breathing) and a 50% (p=0.06) slower rate of muscle strength decline, driven mostly by lower limb muscles with a 71% (p=0.04) reduction in weakening and a more modest 37% (p=0.22) reduction in weakening of upper limb muscles. An analysis that matched REAL patients recruited in Australia to the Australian MND Registry (a longitudinal registry, not a study) yielded directionally similar ALSFRS-R and SVC findings while muscle strength could not be analyzed as the registry does not contain such data. "The dosing of the first participant at 300 mg is another important program milestone," notes Sven Jacobson, CEO of Woolsey. "This next phase will allow us to evaluate the safety and tolerability of a higher dose, in preparation for our planned phase 2b study. Our goal is to continue to advance development of BRAVYL for people living with ALS, in hopes that we can slow the progression of the disease and improve their quality of life." ABOUT ALS ALS is a fatal neurodegenerative disease characterized by inevitable, and often rapid, decline in patients as the disorder advances (mean survival time is only two to five years). Accordingly, the ability to impede any worsening represents a meaningful advancement in efforts to enhance the prognosis and quality of life of individuals impacted by this devastating condition. ABOUT WOOLSEY PHARMACEUTICALS Woolsey Pharmaceuticals is expanding the boundaries of medical science. Our lead indication is Amyotrophic Lateral Sclerosis (ALS), a progressive and debilitating disease that ultimately is fatal. Our mission is to help usher in a new era of neurodegenerative disease treatment, saving and improving the lives of patients in need. SOURCE Woolsey Pharmaceuticals, Inc.