ZURZUVAE Approval and Commercialization - ZURZUVAE was approved by the FDA in August 2023 and became commercially available in the U.S. in December 2023 as the first oral treatment specifically indicated for postpartum depression (PPD)[261] - The company expects revenues from ZURZUVAE for PPD treatment to be significantly lower than if it had received regulatory approval for major depressive disorder (MDD)[262] - The company's future business prospects depend heavily on the successful commercialization of ZURZUVAE for PPD treatment in the U.S.[260] - The company may not be able to generate revenues from ZURZUVAE at expected levels or timing due to potential market acceptance issues and payer reimbursement restrictions[261] - The commercial success of ZURZUVAE depends on market acceptance, reimbursement levels, and awareness among healthcare professionals, patients, and payors[307] - Reimbursement and coverage by third-party payors are critical for patient access to ZURZUVAE, with potential restrictions and limitations varying significantly among payors[308] - Inadequate reimbursement rates for ZURZUVAE could materially affect the company's operating results, commercialization efforts, and financial condition[309] - Obtaining reimbursement approval for ZURZUVAE is a costly and time-consuming process, with downward pricing pressures from industry competition[310] - Market acceptance of ZURZUVAE depends on factors such as efficacy, safety, pricing, and the availability of alternative treatments[311] - The FDA has imposed post-marketing commitments for ZURZUVAE, including pharmacokinetic and safety studies, which could lead to delays or unexpected results[313] - ZURZUVAE and ZULRESSO are regulated as Schedule IV controlled substances, which could limit their commercialization due to additional regulatory requirements[315] - The FDA may require a REMS for ZURZUVAE, potentially increasing costs and imposing restrictions on sales, which could reduce revenue[317] - ZURZUVAE faces competition from existing therapies like SSRIs and SNRIs, as well as emerging treatments such as LPCN 1154 and BRII-296[322] - The company achieved U.S. regulatory approval for ZURZUVAE for the treatment of adults with PPD in collaboration with Biogen[330] ZULRESSO Challenges and Market Limitations - ZULRESSO, approved for PPD treatment in June 2019, faces significant barriers to revenue growth due to complex administration requirements and REMS program compliance[273] - The company's commercial operations for ZULRESSO are limited to geographies with existing active treatment sites, and the availability of ZURZUVAE may further limit ZULRESSO's revenue opportunity[274] - ZULRESSO faces significant challenges in reimbursement and coverage, with state Medicaid systems varying widely in terms of availability, terms, and timing of coverage, leading to revenue generation issues[275] - ZULRESSO's commercialization is hindered by healthcare providers' unwillingness to adopt the treatment due to product profile and reimbursement challenges, as well as competition from lower-cost antidepressants[277] - ZURZUVAE's oral treatment option for PPD may reduce healthcare settings' willingness to become infusion-ready for ZULRESSO, further limiting its market potential[277] - ZULRESSO's use is primarily focused on women with severe PPD symptoms due to its administration requirements and REMS limitations, restricting its broader market adoption[277] Regulatory and Clinical Trial Challenges - The FDA issued a complete response letter (CRL) for zuranolone's new drug application (NDA) for MDD, indicating that additional clinical trials are required for approval[265] - The FDA issued a CRL for zuranolone's NDA for MDD treatment, citing insufficient evidence of effectiveness and requiring additional clinical trials, delaying potential approval[280] - The FDA imposed post-approval obligations for ZURZUVAE, including pharmacokinetic and safety studies, which may delay or complicate its market launch[282] - The FDA rescinded Breakthrough Therapy Designation for zuranolone for MDD treatment in November 2023, impacting its development pathway and regulatory review process[284] - Positive results from non-clinical studies and clinical trials may not predict future outcomes, and interim results may not reflect final trial results[287][288] - Ongoing clinical trials for dalzanemdor (SAGE-718) and SAGE-324 may fail to meet primary endpoints, and safety issues could arise in later-stage trials[288][289] - Non-clinical animal model results may not replicate in human clinical trials, especially for central nervous system disorder treatments[290] - Delays in clinical trial commencement, enrollment, or completion could increase costs and delay regulatory approval[292][293] - Clinical trials may be suspended or terminated due to regulatory, safety, or operational challenges, including FDA holds or adverse events[294][295] - New regulatory requirements, such as the FDA's diversity action plan for Phase 3 trials, could impact trial timelines and enrollment[296] - Marketing approval outside the U.S. may require additional studies, and pricing and reimbursement approvals could face delays or restrictions[297][298] Supply Chain and Manufacturing Risks - The company relies entirely on third-party manufacturers for clinical and commercial drug supplies, exposing it to supply chain risks[300][301] - Contract manufacturers must comply with cGMPs, and FDA inspections could lead to delays or supply shortages if deficiencies are found[302][303] - Long-term supply agreements are in place for ZURZUVAE and ZULRESSO, but no redundant supply arrangements exist for SAGE-324 or dalzanemdor (SAGE-718)[305] - ZURZUVAE and ZULRESSO rely on third-party contract manufacturers for commercial production, and any delays in regulatory approvals or manufacturing issues could significantly impact product availability[306] Intellectual Property and Patent Risks - The company faces risks related to intellectual property rights, including potential challenges to patent validity and enforceability, which could impact its competitive position[365][369] - The company may be unable to prevent unauthorized disclosure or use of its technical knowledge or trade secrets, particularly in foreign countries with weaker intellectual property protections[370] - The company may face intellectual property infringement claims from third parties, which could delay product development or increase commercialization costs[374][376] - The company's patent applications may not mature into issued patents, and even if they do, the patents may not provide sufficient protection or competitive advantage[367][368] - The company may be subject to claims challenging the inventorship or ownership of its patents, potentially leading to loss of valuable intellectual property rights[378][380] - The company relies on unpatented trade secrets and technological innovation to maintain its competitive position, but these could be independently developed or disclosed by competitors[373] - The company may incur substantial costs and divert management attention in defending against intellectual property litigation, even if successful[375][376] - The company's ability to enforce its patent rights depends on its ability to detect infringement, which can be difficult and costly[370] - Patent protection could be reduced or eliminated due to noncompliance with procedural, documentary, and fee payment requirements imposed by governmental patent agencies[381] - Competitors may infringe patents, leading to expensive and time-consuming litigation, with potential risks of patents being invalidated or interpreted narrowly[382] - Interference or derivation proceedings could result in the company ceasing use of related technology or needing to license rights from the prevailing party[383] - Intellectual property litigation may lead to the disclosure of confidential information, potentially affecting the company's stock price[384] - Issued patents could be found invalid or unenforceable if challenged in court, particularly in the U.S. where counterclaims alleging invalidity are common[385] - The company may not seek patent protection in all jurisdictions due to high costs, and intellectual property rights in some countries may be less extensive than in the U.S.[386] - Competitors may use the company's technologies in jurisdictions where patent protection is not pursued, potentially leading to competition with the company's products[388] - The company is dependent on licensed intellectual property for ZULRESSO and certain product candidates, and losing these rights could impact development and commercialization[391] - Failure to comply with license agreements could result in termination, affecting the company's ability to market products covered by the licenses[392] - Intellectual property generated through U.S. government funding may be subject to federal regulations, including "march-in rights" and manufacturing preference requirements[399] - The company has obtained NCE exclusivity for brexanolone and zuranolone, and plans to seek NCE exclusivity for current and future product candidates, with a five-year period of non-patent marketing exclusivity in the U.S. for new chemical entities[401] - The Hatch-Waxman Act permits a patent restoration term of up to five years, but the company may not be granted an extension if it fails to satisfy applicable requirements, potentially leading to earlier competition[402] - The America Invents Act and recent U.S. Supreme Court rulings have increased uncertainties and costs surrounding patent prosecution and enforcement, potentially weakening the company's ability to protect its products[403][404][405] - The CREATES Act exposes the company to possible litigation and damages by competitors, which could lead to increased generic competition and lower revenues for products like ZURZUVAE and ZULRESSO[407] - Proposed U.S. legislation could limit patent exclusivity on drug products, potentially facilitating earlier entry of generic versions and adversely affecting the company's products[408][409] Financial and Operational Risks - The company has incurred significant operating losses, with a net loss of $541.5 million for the year ended December 31, 2023, and an accumulated deficit of $2.6 billion as of December 31, 2023[432] - The company received $75.0 million in milestone payments for the first commercial sale of ZURZUVAE in the U.S. in Q4 2023[432] - The company expects operating expenses to decrease in 2024 compared to 2023 due to a strategic corporate reorganization and pipeline reprioritization[433] - The company's cash, cash equivalents, and marketable securities totaled $753.2 million as of December 31, 2023[432] - The company anticipates continued significant operating losses as it commercializes ZURZUVAE and advances other product candidates[434] - The company's ability to generate revenue depends on successful commercialization of ZURZUVAE and other products, as well as market acceptance and reimbursement[435] - The company may need to raise additional capital in the future to fund operations, which could dilute existing stockholders' ownership[437] - Cash, cash equivalents, and marketable securities totaled $753.2 million as of December 31, 2023[439][594] - The company anticipates existing cash and funding will support operations into 2026, but no milestone payments from collaborations are expected for the remainder of 2024[439] - The company may need to seek additional funds sooner than planned through equity or debt financings, collaborations, or other strategic arrangements[439] - Failure to obtain capital could force the company to delay, limit, or terminate product development efforts or other operations[443] - The company's stock price is volatile and may fluctuate due to factors such as commercialization efforts, clinical trial results, regulatory activities, and macroeconomic conditions[445] - The company has broad discretion in the use of its cash and proceeds from potential future offerings, which may not yield significant returns for stockholders[446] - Anti-takeover provisions in the company's charter documents and Delaware law could make acquisitions or management changes more difficult[447] - Future sales of common stock, including shares no longer subject to lockup periods, could significantly reduce the market price of the company's stock[448] - The company has exposure to fluctuations in foreign exchange rates due to contracts with vendors in foreign countries and subsidiaries in Europe, Canada, and Bermuda[595] - Inflation increased the company's cost of labor and clinical trial costs, but did not have a material effect on results of operations for the year ended December 31, 2023[597] Regulatory and Legal Compliance Risks - The company may face challenges in complying with the Medicaid Drug Rebate Program and other governmental pricing programs, which could impact financial results[342] - Compliance with Medicaid Drug Rebate Program and other federal/state drug pricing programs could increase costs, with potential civil monetary penalties of up to $100,000 per false item submitted[344] - Potential termination of Medicaid drug rebate agreement or 340B program participation could result in no federal payments for covered outpatient drugs under Medicaid or Medicare Part B[344] - Federal False Claims Act imposes penalties including mandatory treble damages and significant per-claim penalties for false or fraudulent claims[347] - GDPR compliance for EU clinical trials imposes strict data transfer rules and fines up to €20 million or 4% of global annual turnover for violations[353] - California Consumer Privacy Act (CCPA) and California Privacy Rights Act (CPRA) impose significant penalties, including civil fines up to $7,500 per violation and private right of action for data breaches[354] - EU-U.S. Data Privacy Framework adopted in July 2023, but challenges from privacy advocacy groups may impact data transfer mechanisms[358] - Off-label promotion of products like ZURZUVAE or ZULRESSO could result in significant liability, including civil and criminal fines under the False Claims Act[359] - Expansion into foreign markets may face regulatory burdens, price controls, and reimbursement challenges, impacting profitability[360] - Pricing of prescription drugs in foreign markets is subject to governmental control, potentially leading to delays in pricing negotiations and reduced profitability if reimbursement is limited or pricing is unsatisfactory[361][362] - Brexit may continue to adversely affect regulatory conditions in the EU and the UK, potentially impairing the company's ability to transact business in these regions[363] Competition and Market Risks - The company faces competition from Marinus Pharmaceuticals, Inc., which received FDA approval for ganaxolone to treat seizures associated with CDKL5 deficiency disorder[325] - SAGE-324, a novel GABAA receptor positive allosteric modulator, is in Phase 2 development for essential tremor[326] - Dalzanemdor (SAGE-718) is being explored for cognition-related disorders associated with NMDA receptor dysfunction, including Huntington's, Parkinson's, and Alzheimer's diseases[327] - The company may face delays or disputes in collaborations with Biogen and Shionogi, potentially impacting development and commercialization efforts[328] - The company's future success depends on its ability to attract, retain, and motivate qualified personnel[338] - The company maintains product liability insurance coverage with a $20.0 million annual aggregate coverage limit[341] - The company relies on third parties, including CROs, to conduct clinical trials for its product candidates[336] - The company's drug development programs and commercialization efforts require substantial additional cash to fund expenses[329] Healthcare Policy and Pricing Risks - The ACA and IRA have introduced measures such as Medicare price negotiations, inflation rebates, and coverage gap discounts, which could negatively impact the company's revenue and pricing strategies[412][417][418] - Medicare sequester reductions, currently at 2%, will increase to 4% by fiscal year 2031, potentially affecting the company's product pricing and reimbursement[413] - The IRA requires Medicare price negotiations for high-cost drugs starting in 2026, with biologics eligible for negotiation 11 years post-approval, which could impact the company's future revenue and development decisions[418][419] - The IRA imposes civil monetary penalties and excise taxes on drug manufacturers for non-compliance with price regulations, including a cap on Medicare out-of-pocket drug costs at $2,000 annually starting in 2025[420] - The IRA may result in reduced reimbursement for products, potentially impacting the company's business, operations, and financial condition[422] - State-level legislation and regulations are increasingly targeting pharmaceutical pricing, including price transparency measures and restrictions on product access[423]

SAGE Therapeutics, Inc. (NASDAQ:SAGE) Q3 2023 Earnings Conference Call November 7, 2022 8:00 AM ET Company Participants Ashley Kaplowitz - Director, IR Barry Greene - President, CEO & Director Christopher Benecchi - Chief Business Officer Kimi Iguchi - CFO & Treasurer Laura Gault - Chief Medical Officer Conference Call Participants Ritu Baral - TD Cowen Anupam Rama - JPMorgan Chase & Co. Tazeen Ahmad - Bank of America Merrill Lynch Salveen Richter - Goldman Sachs Group Jay Olson - Oppenheimer Ami Fadia - Ne ...

2023 Financial Results • Forward-looking statements in this presentation include statements regarding: plans and goals for commercialization of ZURZUVAE as a treatment for women with PPD and expected timelines; our belief in the potential benefit and profile of ZURZUVAE in the treatment of PPD; our plans, goals, and expectations regarding access to ZURZUVAE for women with PPD and reimbursement; the potential for success of our other product candidates in various indications, including the potential profile ...

l UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Form 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to . Commission file number: 001-36544 Sage Therapeutics, Inc. (Exact name of registrant as specified in its Charter) (State or other jurisdiction of in ...

Sage Therapeutics, Inc. (NASDAQ:SAGE) Business Update Call August 8, 2023 8:00 PM ET Company Participants Ashley Kaplowitz - Investor Relations Barry Greene - Chief Executive Officer Laura Gault - Chief Medical Officer Chris Benecchi - Chief Business Officer Kimi Iguchi - Chief Financial Officer Conference Call Participants Salveen Richter - Goldman Sachs Ritu Baral - TD Cowen Paul Matteis - Stifel Yasmeen Rahimi - Piper Sandler Anupam Rama - JPMorgan Tazeen Ahmad - Bank of America Brian Abrahams - RBC Capi ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Form 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to . Commission file number: 001-36544 Sage Therapeutics, Inc. (Exact name of registrant as specified in its Charter) Delaware 27-4486580 (State or other juris ...

Sage Therapeutics, Inc. (NASDAQ:SAGE) Q1 2023 Earnings Conference Call May 2, 2023 8:00 AM ET Company Participants Helen Rubinstein - Director of Investor Relations Barry Greene - Chief Executive Officer Jim Doherty - Chief Development Officer Chris Benecchi - Chief Business Officer Kimi Iguchi - Chief Financial Officer Laura Gault - Chief Medical Officer Conference Call Participants Anupam Rama - JPMorgan Ritu Baral - PD Cowen Yasmeen Rahimi - Piper Sandler Jay Olson - Oppenheimer Paul Matteis - Stifel Sum ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Form 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to . Commission file number: 001-36544 Sage Therapeutics, Inc. (Exact name of registrant as specified in its Charter) Delaware 27-4486580 (State or other juri ...

Sage Therapeutics, Inc. (NASDAQ:SAGE) Q4 2022 Earnings Conference Call February 16, 2023 8:00 AM ET Company Participants Helen Rubinstein - Director of Investor Relations Barry Greene - Chief Executive Officer Jim Doherty - Chief Development Officer Chris Benecchi - Chief Business Officer Kimi Iguchi - Chief Financial Officer Laura Gault - Chief Medical Officer Conference Call Participants Tazeen Ahmad - Bank of America Salveen Richter - Goldman Sachs Anupam Rama - JPMorgan Ritu Baral - Cowen Eason Lee - Ne ...

Planned activities and anticipated timelines | --- | --- | --- | --- | |-------------------------------------------------------------------------------------|--------------------------|--------------------------|-------| | NDA development and related processes | FDA Advisory Committee* | DEA Scheduling Period^ | | | Medical affairs, health economics, value and access, and commercialization planning | | | | FDA = U.S. Food and Drug Administration; DEA = Drug Enforcement Administration; MDD = major depressive ...