Sojournix Announces Positive Top-Line Phase 1 Data Demonstrating Clinical Proof of Mechanism and Once-Daily (QD) Pharmacokinetics for SJX-653

WALTHAM, Mass., Feb. 13, 2019 /PRNewswire/ -- Sojournix, a clinical stage biopharmaceutical company focused on developing and commercializing novel therapies for the treatment of women's health and neuroendocrine disorders, today announced positive top-line data from a first-in-human Phase 1 clinical study of SJX-653.  SJX-653 is a novel, selective, neurokinin-3 (NK3) antagonist in development as a once-daily (QD) non-hormonal therapy for menopausal vasomotor symptoms (VMS) or "hot flashes." In this study SJX-653 demonstrated clinical proof-of-mechanism through statistically significant and dose-dependent activity on pharmacodynamic markers of NK3 receptor target engagement, once-daily pharmacokinetics, and a well-tolerated profile.

This randomized, placebo-controlled, double-blind, single ascending dose (SAD) escalation study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally administered SJX-653.  To demonstrate proof-of-mechanism, the study was performed in healthy adult men (N=42) and measured changes in luteinizing hormone (LH) and total testosterone (T) levels.  LH and T levels in men are known to be especially sensitive to NK3 antagonists.  Consequently, LH and T have become established pharmacodynamic markers of NK3 receptor target engagement and useful for demonstrating NK3 antagonist clinical proof-of-mechanism.

Sojournix is also evaluating SJX-653 in ongoing Phase 1 studies in postmenopausal women, the target population for vasomotor symptoms.

"In this initial Phase 1 study, SJX-653 significantly reduced levels of LH and T in men in a potent, dose-dependent, and reversible manner, indicating proof-of-mechanism and NK3 receptor target engagement," commented Professor Richard Anderson, the Elsie Inglis Professor of Clinical Reproductive Science at the University of Edinburgh.  "The pharmacokinetic and pharmacodynamic relationship data from this study, combined with data from the ongoing Phase 1 studies in postmenopausal women, will help inform the selection of doses for a Phase 2 clinical trial of SJX-653 for the treatment of moderate to severe vasomotor symptoms."

"We are pleased with the results from this first-in-human trial with SJX-653, demonstrating NK3 mediated pharmacodynamic responses and providing initial clinical evidence of a favorable tolerability and pharmacokinetic profile," said Daniel Grau, President and CEO of Sojournix.  "In advancing SJX-653 for the treatment of menopausal vasomotor symptoms, we aim to address the well-recognized unmet medical need among patients for a safe and effective non-hormonal treatment option."

SJX-653 First-In-Human Phase 1 Study Results

SJX-653 was well tolerated in this study. There were no serious adverse events or clinically-meaningful changes in clinical laboratory values, vital sign measurements, or ECG parameters, and the incidence of adverse events was similar between subjects treated with SJX-653 and those treated with placebo.

SJX-653 exhibited a human half-life in the range of 10-13 hours, consistent with once-daily (QD) dosing, as well as dose-linear pharmacokinetics and low inter-subject variability.

SJX-653 administration was associated with statistically significant and dose-dependent reductions in LH and T, pharmacodynamic responses indicative of NK3 receptor target engagement and consistent with previous NK3 antagonists.  The maximum mean LH reduction in subjects treated with SJX-653 was 70% at 6 hours, versus 10% in placebo-treated subjects at the same timepoint (p = 0.0006).  The maximum mean T reduction in subjects treated with SJX-653 was 68% at 8 hours, versus 18% in placebo-treated subjects at the same timepoint (p < 0.0001).

Sojournix plans to present results from this study at a future medical conference.

About SJX-653

SJX-653 is a novel and selective neurokinin-3 (NK3) antagonist in clinical development as a once-daily non-hormonal therapy for moderate to severe vasomotor symptoms (commonly called "hot flashes") due to menopause.

About Neurokinin-3 (NK3)

Vasomotor symptoms are believed to be caused by excessive NK3 signaling in the median preoptic nucleus, an area of the brain responsible for regulating body temperature.  During menopause, the decline in estrogen levels leads to an over-production of neurokinin B (NKB), an endogenous neurotransmitter that binds to and activates NK3 receptors in the median preoptic nucleus.  By reducing the excessive signaling of NKB at the NK3 receptor, NK3 antagonism helps restore the body's normal thermoregulation capacity, and therefore has the potential to alleviate menopausal vasomotor symptoms.  As a mechanism of action for treating vasomotor symptoms, NK3 antagonism is clinically validated and has demonstrated efficacy comparable to hormone therapy.  In addition, a human genome study has revealed a genetic association between vasomotor symptoms and the tachykinin 3 gene that encodes the NK3 receptor.

About Vasomotor Symptoms (VMS)

Vasomotor symptoms are characterized by sudden and recurrent sensations of intense heat, or "hot flashes," often accompanied by elevated heart rate, sweating, skin reddening, and the disruption of both daily activities and sleep.  Over 2 million women enter menopause each year in the United States alone and the majority of them experience vasomotor symptoms.  The median duration of vasomotor symptoms due to menopause is approximately 7 years.

While hormone therapy is an effective treatment for menopausal VMS, many women choose to avoid hormone therapy due to concerns about safety risks highlighted in hormone therapy product labels.  Hormone therapy is contraindicated in women who have a history of certain medical conditions.  Currently available non-hormonal agents, such as selective serotonin reuptake inhibitors (SSRI), used primarily as anti-depressants, are known to have limited efficacy.  As a result, SJX-653 has the potential to address the high unmet medical need for a safe and effective non-hormonal therapy for menopausal VMS.

Highlighting the size of the menopausal VMS market opportunity, products containing conjugated estrogens, a form of hormone therapy indicated for the treatment of menopausal VMS, accounted for the largest number of prescriptions of all drugs sold in the United States in 2000.  Following the 2002 publication of results from the Women's Health Initiative clinical study describing hormone therapy safety risks, approximately 65% of women taking hormones stopped therapy.

Vasomotor symptoms are also a common and sometimes debilitating side effect of certain cancer treatments, including tamoxifen or aromatase inhibitors used for breast cancer in women and androgen deprivation therapy used for prostate cancer in men.  These agents can induce an abrupt onset of vasomotor symptoms, making it challenging for patients to adhere to their cancer treatment.  Addressing drug-induced VMS in this setting represents another potential development opportunity for SJX-653.

About Sojournix

Sojournix is a clinical stage biopharmaceutical company focused on developing and commercializing novel therapies for the treatment of women's health and neuroendocrine disorders.  We are advancing SJX-653, a novel and selective NK3 antagonist in clinical development as a once-daily non-hormonal therapy for moderate to severe vasomotor symptoms (commonly called "hot flashes") due to menopause.  To learn more about Sojournix, please visit our website at www.soujournixpharma.com.

SOURCE Sojournix

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