- SAGE-547 in Super-Refractory Status Epilepticus (SRSE): Enrollment is on track for the STATUS Trial, a global, Phase 3, randomized, double-blind, placebo-controlled clinical trial of SAGE-547 for the treatment of patients with SRSE. In August, SAGE reached agreement with the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the STATUS Trial.
- Postpartum Depression (PPD): SAGE has initiated its placebo-controlled proof-of-concept clinical trial of SAGE-547 in patients with PPD. The multi-center, placebo-controlled study is planned to enroll up to 32 patients diagnosed with severe PPD. The Company expects to report top-line results in the first half of 2016. The placebo-controlled study is intended to validate the activity signal observed in an initial open-label study of SAGE-547 as a treatment for PPD.
- SAGE-217: SAGE is currently dosing subjects in a Phase 1 single ascending dose trial evaluating SAGE-217 in healthy volunteers. Initial top-line results from the study are expected in the first half of 2016. SAGE-217 is a next generation positive allosteric modulator that has been optimized for selectivity of synaptic and extrasynaptic GABA A receptors and for a pharmacokinetic profile allowing once-daily oral dosing. SAGE is developing SAGE-217 for high frequency seizures associated with select neurological disorders, including orphan epilepsies, and other GABA A dysfunction-related disorders, such as essential tremor. In September 2015, SAGE announced positive top-line proof-of-concept data from an exploratory, placebo-controlled study of SAGE-547 in patients with essential tremor.
- SAGE-689: SAGE is delaying the commencement of Phase 1 clinical development of SAGE-689 to respond to requests from the U.S. Food and Drug Administration for additional non-clinical study data unrelated to toxicology. SAGE-689, a next generation positive allosteric modulator of GABA A receptors, is being developed as an acute parenteral therapy for the treatment of indications where a high degree of anti-seizure activity and sedation are desirable prior to the introduction of general anesthesia, such as status epilepticus.
- SAGE-105 and SAGE-324: SAGE has selected SAGE-105 and SAGE-324 as its next GABA development candidates. Both molecules are differentiated, next generation positive allosteric modulators of GABA A receptors, and are intended to be studied for undisclosed GABA A dysfunction-related disorders.
- Publication on SAGE Extrasynaptic-Selective GABA A Modulator: In August, SAGE scientists and collaborators published an article in The Journal of Neuroscience Research describing preclinical data from animal studies of a next generation extrasynaptic-selective GABA A positive allosteric modulator, SGE-872, suggesting a potential novel therapeutic approach to treat disorders associated with GABA A-related dysfunction.
- SAGE-718: SAGE announced today the selection of SAGE-718 as its first NMDA development candidate planned to enter IND-enabling studies. SAGE-718 is being developed as a first-in-class, oxysterol-based positive allosteric modulator of NMDA receptors, a critical excitatory receptor system implicated in a broad range of CNS disorders. In 2013, SAGE scientists and collaborators published an article in The Journal of Neuroscience describing data from animal studies demonstrating that 24(S)-Hydroxycholesterol (cerebrosterol), a naturally occurring oxysterol, is a potent and selective positive allosteric modulator of NMDA receptors acting at a novel oxysterol modulatory site. SAGE-718 has been designed to be a highly potent and selective modulator with an optimized pharmacokinetic profile intended to support oral dosing. SAGE-718 has demonstrated robust activity in preclinical models of NMDA receptor hypofunction. The initial indications selected by SAGE for development are two NMDA-related orphan disorders - Smith-Lemli-Opitz Syndrome and Anti-NMDA Receptor Encephalitis, for which there are currently no approved treatments. The focus of SAGE-718 development efforts will be the potential treatment of the neurological symptoms of these disorders through enhancing NMDA receptor function.
- Smith-Lemli-Opitz Syndrome (SLOS): SLOS is a rare metabolic disorder caused by a mutation in the DHCR7 (7-dehydrocholesterol reductase) gene which codes for an enzyme that is involved in the production of cholesterol in the brain. SLOS is associated with significantly decreased plasma levels of cerebrosterol, suggesting that normal oxysterol-based modulation of NMDA receptors is disrupted in these patients. People affected by SLOS are unable to make enough of the necessary cholesterol in the brain to support normal growth and development, and are affected by a broad range of neuropsychiatric and neurodevelopmental symptoms. Decreased cerebrosterol levels may also represent a biomarker to identify for future study a range of indications with broader patient populations characterized by certain phenotypes of cognitive dysfunction and neuropsychiatric symptoms resulting from NMDA receptor hypofunction.
- Anti-NMDA Receptor Encephalitis (ANRE): ANRE is a rare autoimmune disorder in which antibodies attack NMDA receptors. Symptoms of ANRE include a highly characteristic set of neuropsychiatric deficits, including cognitive and behavioral disturbances, movement disorders and loss of consciousness. Beyond ANRE, measuring levels of anti-NMDA antibodies may represent a biomarker to identify, for future study, other indications within dementia and psychosis where neuropsychiatric deficits are associated with NMDA hypofunction.
- Cash Position: Cash and cash equivalents as of September 30, 2015 were $204.9 million, compared with $127.8 million at December 31, 2014. The increase was primarily due to net proceeds of $129.1 million from the company's follow-on public offering completed in April 2015.
- R&D Expenses: Research and development expenses were $17.5 million, including $1.5 million of non-cash stock-based compensation expense, in the third quarter of 2015, compared to $6.6 million, including $0.3 million of non-cash stock-based compensation expense, in the third quarter of 2014. The increase in R&D expenses was primarily due to increased spending on activities related to the SAGE-547 development program and its advancement into Phase 3 clinical development, increased personnel-related R&D expenses to support the advancement of SAGE's pipeline of programs, and other expenses associated with clinical, non-clinical and discovery efforts.
- G&A Expenses: General and administrative expenses were $6.6 million, including $2.9 million of non-cash stock-based compensation expense, in the third quarter of 2015, compared to $2.9 million, including $0.4 million of non-cash stock-based compensation expense, in the third quarter of 2014. The increase in G&A expenses was primarily due to personnel-related costs, and professional fees associated with operating as a public company and related to general operations.
- Net Loss: Net loss was $24.0 million for the third quarter of 2015 compared to net loss of $9.9 million for the third quarter of 2014.
- Financial Guidance: SAGE reiterates its expectation that its cash and cash equivalents on hand as of the date hereof will be sufficient to fund its operations through mid-2017.
|Sage Therapeutics, Inc. and Subsidiaries|
|Consolidated Balance Sheets|
|(in thousands, except share and per share data)|
|September 30, 2015||December 31, 2014|
|Cash and cash equivalents||$||204,877||$||127,766|
|Prepaid expenses and other current assets||2,604||1,056|
|Total current assets||207,481||128,822|
|Property and equipment, net||249||163|
|Deferred tax assets||641||641|
|Liabilities and Stockholders' Equity|
|Deferred tax liabilities||641||641|
|Total current liabilities||10,291||7,757|
|Commitments and contingencies|
|Preferred stock, $0.0001 par value; 5,000,000 shares authorized at September 30, 2015 and December 31, 2014, respectively; no shares issued or outstanding at September 30, 2015 and December 31, 2014, respectively||-||-|
|Common stock, $0.0001 par value; 120,000,000 shares authorized at September 30, 2015 and December 31, 2014, respectively; 28,788,885 and 25,621,791 shares issued and outstanding at September 30, 2015 and December 31, 2014, respectively||3||3|
|Additional paid-in capital||330,879||188,727|
|Total stockholders' equity||198,104||121,885|
|Total liabilities and stockholders' equity||$||208,410||$||129,665|
|Sage Therapeutics, Inc. and Subsidiaries|
|Consolidated Statements of Operations and Comprehensive Loss|
|(in thousands, except share and per share data)|
|Three Months Ended September 30,||Nine Months Ended September 30,|
|Research and development||17,478||6,601||48,981||15,155|
|General and administrative||6,604||2,869||17,057||6,294|
|Total operating expenses||24,082||9,470||66,038||21,449|
|Loss from operations||(24,082||)||(9,470||)||(66,038||)||(21,449||)|
|Interest income, net||53||3||115||4|
|Other expense, net||(6||)||(1||)||(10||)||(5||)|
|Net loss and comprehensive loss||(24,035||)||(9,468||)||(65,933||)||(21,450||)|
|Accretion of redeemable convertible preferred stock to redemption value||-||(391||)||-||(2,294||)|
|Net loss attributable to common stockholders||$||(24,035||)||$||(9,859||)||$||(65,933||)||$||(23,744||)|
|Net loss attributable to common stockholders per common share - basic and diluted||$||(0.84||)||$||(0.50||)||$||(2.40||)||$||(3.08||)|
|Weighted-average shares outstanding - basic and diluted||28,737,743||19,581,624||27,430,275||7,711,038|