OUR LEAD INDICATION IS AMYOTROPHIC LATERAL SCLEROSIS (ALS)

OUR LEAD INDICATION IS AMYOTROPHIC LATERAL SCLEROSIS (ALS)

A PROGRESSIVE AND DEBILITATING NEURODEGENERATIVE DISEASE.

A PROGRESSIVE AND DEBILITATING NEURODEGENERATIVE DISEASE.

ALS impacts nerve cells in the brain and spinal cord. This condition leads to the gradual degeneration and death of motor neurons, preventing the brain from initiating and controlling muscle movement.

As voluntary muscle action diminishes, individuals progressively lose the ability to speak, eat, move, and breathe. Breathing failure is the most common cause of death for those with ALS.

ALS, a progressive and debilitating neurodegenerative disease, impacts nerve cells in the brain and spinal cord … Presently, there exists no cure for ALS.

"ALS, a progressive and debilitating neurodegenerative disease, impacts nerve cells in the brain and spinal cord … Presently, there exists no cure for ALS."

In the U.S., around 30,000 people, and globally, an estimated 225,000 people, cope with the burden of ALS. Diagnosed at an average age of 55, half of those affected succumb within 14 to 18 months. The typical life expectancy post-diagnosis is only two to five years.

The impact of an ALS diagnosis extends beyond the individual, thrusting families into a whirlwind of challenges. These include the emotional toll, financial strains, social isolation, caregiver burnout, and complex decision-making surrounding end-of-life care.

Presently, there exists no cure for ALS. Treatment strategies revolve around symptom management, enhancing quality of life, and offering support. Ongoing research strives to unveil the root causes of ALS and develop potential therapies to decelerate or halt its progression.

EXCITING NEWS:

RESULTS FROM OUR PHASE 2A STUDY OF BRAVYL IN ALS...

EXCITING NEWS:

RESULTS FROM OUR PHASE 2A STUDY OF BRAVYL IN ALS

YIELD IMPORTANT AND EXCITING FINDINGS

YIELD IMPORTANT AND EXCITING FINDINGS

There is a large and convincing body of preclinical evidence that Woolsey Pharmaceutical’s drug, BRAVYL (oral fasudil), has a positive effect on ALS in animal models.

In January 2024, we completed the primary phase of our Phase 2a in ALS patients. REAL (Rho kinasE inhibition in Amyotrophic Lateral sclerosis) was an open-label single-armed study designed to assess preliminary safety, tolerability, and effect on clinical outcomes as well as neurodegeneration biomarkers of BRAVYL in patients with ALS. The study enrolled 31 participants, of whom 25 completed 24 weeks of treatment on BRAVYL. Of that number 20 continued on to the extension phase of the study.

Analyses of the primary phase of REAL have yielded important and exciting findings.

On the primary endpoint of safety, BRAVYL was found to be safe and well tolerated, and no participants were withdrawn from the study for drug-related adverse events. We are also happy to report that there have been no unexpected or concerning safety findings in the extension phase, with some of the patients treated for as long as 18 months.

Importantly, BRAVYL was shown to significantly decrease the biomarker Neurofilament Light Chain (NfL) following 24 weeks of treatment.

NfL is a sensitive and specific marker of cytoskeletal damage in the neuronal axon, and elevated levels of NfL in blood have been shown to be a reliable indicator of the rate of ALS disease progression. Reduced NfL levels in response to disease-modifying treatments have been shown to precede discernable clinical benefit such as prolongation of event-free survival, and improvements in clinical trajectories measured using ALSFRS-R (the ALS Functional Rating Scale – Revised), Vital Capacity (VC, a measure of breathing capacity, which includes slow vital capacity), and muscle strength — the three well-accepted measures for evaluating clinical outcomes in ALS studies.

In REAL, we observed a statistically significant 15% decrease (improvement) in NfL from baseline to 6 months (p<0.001). Since NfL in the ALS population tends to increase (mean of 11% and maximum up to 15% in 6 months), this suggests that 180 mg/day BRAVYL could potentially reduce NfL up to 30% versus a placebo group over 6 months.

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.

As there was no placebo group in REAL, to estimate clinical effects of BRAVYL, we performed a “propensity matched” analysis wherein 12-month outcomes from REAL were compared with those from a matched cohort. The matched control was 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.

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.

Any updated results from the REAL Phase 2a study will be posted on our Newsroom page.

NOTE: BRAVYL is not yet approved for commercial use.

In REAL, we observed a statistically significant 15% decrease (improvement) in NfL from baseline to 6 months (p<0.001). Since NfL in the ALS population tends to increase (mean of 11% and maximum up to 15% in 6 months), this suggests that 180 mg/day BRAVYL could potentially reduce NfL up to 30% versus a placebo group over 6 months.

In REAL, we observed a statistically significant 15% decrease (improvement) in NfL from baseline to 6 months (p<0.001). Since NfL in the ALS population tends to increase (mean of 11% and maximum up to 15% in 6 months), this suggests that 180 mg/day BRAVYL could potentially reduce NfL up to 30% versus a placebo group over 6 months.

WE ARE CONSTANTLY LOOKING TO EXPAND OUR PIPELINE

WE ARE CONSTANTLY LOOKING TO EXPAND OUR PIPELINE

TO ADDRESS PATIENTS' UNMET MEDICAL NEEDS

TO ADDRESS PATIENTS' UNMET MEDICAL NEEDS

Our determination to find answers for patients and their families is driven by the significant unmet need for effective therapies for those people whose lives are disrupted by highly debilitating and often fatal neurodegenerative diseases.

OTHER INDICATIONS IN THE PIPELINE

We are continuously developing and expanding our pipeline to address patients’ unmet medical needs.

BRAVYL has applicability in a number of indications in addition to ALS — Alzheimer’s Disease, Frontotemporal Dementia, CADASIL (an inherited type of vascular disease leading to vascular dementia), levodopa-induced dyskinesia in Parkinson’s Disease, 16p11.2 deletion syndrome (an autism spectrum disorder), and schizophrenia, among others.

NOTE: BRAVYL is not yet approved for commercial use.