SJX-653 DEMONSTRATES STATISTICALLY SIGNIFICANT ACTIVITY ON NK3 PHARMACODYNAMIC MARKERS AT DOSES AS LOW AS 15MG, A LONG PLASMA HALF-LIFE SUPPORTING ONCE-DAILY (QD) DOSING, AND A WELL-TOLERATED PROFILE
WALTHAM, Ma. March 23, 2019. Sojournix, a clinical-stage biopharmaceutical company dedicated to developing and commercializing transformative new medicines for the treatment of women’s health and neuroendocrine disorders, today presented positive data from a first-in-human Phase 1 clinical study of SJX-653 at ENDO 2019, the Endocrine Society's 101st Annual Meeting held in New Orleans, LA. In a poster presentation titled “SJX-653, A Novel Selective NK3 Antagonist, Demonstrates Activity on Pharmacodynamic Markers of NK3 Target Engagement,” study results were presented in which SJX-653 demonstrated clinical proof-of-mechanism through statistically significant and dose-dependent activity on pharmacodynamic markers of NK3 receptor target engagement, with doses as low as 15 mg achieving near maximal effect, a long plasma half-life supporting once-daily (QD) dosing, and a well-tolerated profile. SJX-653 is a novel, selective, neurokinin-3 (NK3) antagonist in development as a once-daily (QD) non-hormonal therapy for moderate to severe vasomotor symptoms (VMS), or “hot flashes,” due to menopause.
This randomized, placebo-controlled, double-blind, single ascending dose (SAD) 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). LH and T levels in men are known to be especially sensitive to NK3 antagonists and therefore, LH and T have become established pharmacodynamic markers of NK3 receptor target engagement in the brain.
“We are pleased to present these data at ENDO demonstrating clinical proof-of-mechanism for SJX-653 through reductions in known pharmacodynamic markers of NK3 receptor target engagement,” said Philip Graham, PhD, Senior Vice President, Strategy and Product Development at Sojournix. “In this study, SJX-653 demonstrated statistically significant pharmacodynamic activity at doses of 15 mg and above as well as an attractive pharmacokinetic profile including a 10-13 hour half-life consistent with once-daily (QD) dosing.”
“Our successful proof-of-mechanism study with SJX-653 represents an important development milestone for Sojournix as we advance SJX-653 for the treatment of moderate to severe vasomotor symptoms due to menopause, a condition with a well-recognized and significant unmet medical need for a safe and effective non-hormonal treatment option,” said Daniel Grau, President and CEO of Sojournix.
Highlights of the Sojournix Poster Presentation at ENDO include:
SJX-653 demonstrated statistically significant, dose-dependent and reversible reductions in LH and T (pharmacodynamic markers of NK3 receptor target engagement) in healthy adult men vs placebo at 15 mg and above and with 15 mg already reaching near maximal effect.
SJX-653 15 mg achieved 57% reduction in LH and 55% reduction in T (vs. 4% and 23% with placebo at the corresponding timepoints).
Maximum LH reduction of 70% achieved with 30 mg and maximum T reduction of 68% achieved with 60 mg (vs. 10% and 18% with placebo at the corresponding timepoints).
Reduction in T delayed by 2-3 hours compared to reductions in LH, consistent with the longer plasma half-life of T and underlying biology.
SJX-653 has a pharmacokinetic profile supporting once-daily (QD) dosing.
Long plasma half-life of 10-13 hours and a low ratio of Cmax to C24 which would predict a peak trough ratio of about 3:1 upon repeat dosing.
Dose-proportional pharmacokinetics across the doses tested (0.5 to 90 mg) with 175-fold and 143-fold increases mean Cmax and AUC0-24, respectively.
SJX-653 exhibited a well-tolerated safety profile.
No serious adverse events or clinically-meaningful changes in clinical laboratory values, vital sign measurements, or ECG parameters, and a similar incidence of adverse events between subjects treated with SJX-653 and those treated with placebo.
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 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 link between vasomotor symptoms and the tachykinin 3 gene that encodes the NK3 receptor.
About Vasomotor Symptoms (VMS)
Vasomotor symptoms (VMS) are sudden sensations of intense heat, or “hot flashes,” sweating and skin reddening which can occur frequently, disrupting both sleep and daily activities, and are associated with increased rates of insomnia, depression and cognitive impairment. Over 2 million women in the United States enter menopause each year and the majority experience VMS, with symptoms typically persisting for many years during and after menopause. Current treatment options are limited to hormone therapy, which patients and physicians often avoid due to safety concerns, or non-hormonal agents, known to have limited efficacy. As a result, there is a well-recognized and significant unmet medical need for a safe and effective non-hormonal therapy for menopausal VMS.
VMS is also a common and sometimes debilitating side effect of commonly-used treatments for breast and prostate cancer, 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.
Sojournix is a clinical-stage biopharmaceutical company dedicated to developing and commercializing transformative new medicines for the treatment of women’s health and neuroendocrine disorders. We are developing SJX-653, a novel and selective neurokinin 3 (NK3) antagonist, as an oral, once-daily, non-hormonal therapy for moderate to severe vasomotor symptoms due to menopause (commonly called “hot flashes”). Vasomotor symptoms (VMS) are sudden sensations of intense heat, sweating, and skin reddening which can occur frequently, disrupting both sleep and daily activities, and are associated with increased rates of insomnia, depression, and anxiety. Highly prevalent among menopausal women, VMS typically persist for many years during and after menopause. Current treatment options are limited to hormone therapy, which is often avoided due to safety concerns, or non-hormonal agents known to have limited efficacy. NK3 antagonism is a clinically and genetically validated new approach that targets the underlying cause of VMS by reducing excessive NK3 signaling in the area of the brain that regulates heat dissipation. To learn more about Sojournix, please visit www.sojournixpharma.com.
President and CEO