INNOVATION & PIPELINE
For the treatment of Schizophrenia
We are developing MIN-101, our lead product candidate, as a treatment for schizophrenia, in particular the negative symptoms of the disease that can persist chronically throughout patients’ lifetimes and contribute to poor quality of life and functional outcomes. MIN-101 has been shown to block serotonin receptors and sigma receptors, two receptors in the brain that are involved in the regulation of mood, cognition, sleep and anxiety.
MIN-101 is meant to block a specific subtype of serotonin receptor called 5-HT2A. When 5-HT2A is blocked, certain symptoms of schizophrenia, such as hallucinations, delusions, agitation and thought and movement disorders, as well as the side effects associated with antipsychotic treatments, can be minimized. Additionally, blocking 5-HT2A promotes slow wave sleep, a sleep stage often disrupted in patients with schizophrenia.
Importantly, MIN-101 is also meant to block a specific subtype of sigma receptor called sigma2, which is involved in movement control, psychotic symptom control and learning and memory. Blocking sigma2 also modulates other neurotransmitters in the brain, in particular dopamine, which is important as individuals with schizophrenia often have elevated levels of dopamine in their brains. Blocking sigma2 also increases calcium levels in neurons in the brain, which can improve memory. Recent literature has also indicated that a sub-type of progesterone protein complex might also be a putative binding site for sigma2 receptors and might explain the effects on cognition of MIN-101.
Most currently approved therapies for schizophrenia are primarily directed toward positive symptoms. As a result, patients with predominantly negative symptoms are often underserved. Negative symptoms constitute the main burden of illness and represent an important unmet need as no treatment is currently approved for these symptoms. These symptoms are responsible for the poor psychosocial functioning and vocational and social capabilities of patients. Side effects of current pharmaceutical treatment options include sedation, uncontrollable muscle movements, weight gain, cognitive impairment, and sleep disorders.
In May 2016, we announced top line results from a prospective Phase IIb, 12-week, randomized, double-blind, placebo-controlled parallel clinical trial evaluating the efficacy, safety and tolerability of MIN-101 in patients with negative symptoms of schizophrenia. The study achieved its primary endpoint, demonstrating the statistically significant benefit of MIN-101 over placebo in improving negative symptoms as measured by the pentagonal structure model, or PSM, of the Positive and Negative Syndrome Scale, or PANSS. The effect was shown for both doses tested: 32 mg: < 0.022 with an effect size of 0.45, and 64 mg: p < 0.003 with effect size of 0.58. The study also demonstrated statistically significant benefit of MIN-101 over placebo on the PANSS three factors negative symptoms subscale for both doses tested: 32 mg: p < 0.006, with an effect size of 0.55, and 64 mg: p < 0.001 with an effect size of 0.70. Furthermore, the statistically significant benefit of MIN-101 over placebo was demonstrated on the PANSS total score (not significant for the 32 mg dose; p < 0.003 for the 64 mg dose), with effect sizes of 0.35 and 0.59, respectively.
The consistency and robustness of the effect was also supported by the demonstrated statistically significant benefit of MIN-101 over placebo in at least one dose size in multiple secondary endpoints as measured by the following: the PANSS general psychopathology subscale, Brief Negative Symptoms Scale total score, Clinical Global Impression of Improvement, Personal and Social Performance total score and Brief Assessment of Cognition in Schizophrenia. Positive symptoms were observed to remain stable, and the absence of extra-pyramidal symptoms throughout the three month trial is consistent with the hypothesis that MIN-101 has a direct and specific effect on negative symptoms rather than an indirect effect mediated by improvements of positive symptoms.
MIN-101 was generally reported to be well tolerated, and the incidence and types of side effects did not differ significantly between the MIN-101 group and the placebo group. Based upon previous non-clinical and clinical experience, QTcF, a measurement of cardiac function, was closely monitored. Discontinuation criteria based on QTcF prolongation were incorporated in the protocol. Two patients out of 162 who received MIN-101 were discontinued based upon these criteria; both of these patients received the higher dose (64 mg). No metabolic adverse effects, no weight gain and no extra-pyramidal symptoms were observed.
Learn more about schizophrenia.