Gangliosidosis, GM1

-- Completed Enrollment of 190 Patients for Primary Endpoint Analysis in SELECT-MDS-1 Phase 3 Trial; Pivotal CR Data Expected by Mid-4Q 2024 -- -- Additional Data from SELECT-AML-1 Phase 2 Trial Also Expected in 2024 -- -- Completed a $45.0 Million Equity Offering, Extending Cash Runway into 2Q 2025 -- -- Management to Host Conference Call at 8:30 AM ET Today -- CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, today reported financial results for the quarter and full year ended December 31, 2023 and provided a corporate update. “We are entering 2024 poised for a major transformation,” said Conley Chee, Chief Executive Officer of Syros. “We recently completed enrollment of the 190 patients necessary for our primary endpoint analysis in the SELECT-MDS-1 Phase 3 trial, and we remain on track to report pivotal CR data by the middle of the fourth quarter of this year. We are optimistic about this data, which we believe will further reinforce tamibarotene’s potential as a differentiated, biologically targeted approach for the approximately 50% of HR-MDS patients who are positive for RARA overexpression.” Mr. Chee continued, “In addition, we expect to report additional data from SELECT-AML-1 this year. In December, we shared initial results from a prespecified analysis of randomized patients, and we were highly encouraged by the 100% CR/CRi rate observed following treatment with the triplet combination of tamibarotene, venetoclax and azacitidine. We believe the triplet combination could alter the treatment paradigm in AML, with the potential to offer a more effective and well-tolerated option. Following our equity offering in the fourth quarter of 2023, we are well-positioned to execute on our upcoming clinical milestones, while beginning to prepare for our first new drug application filing and planned HR-MDS launch in the United States. We look forward to delivering tamibarotene as a new standard-of-care for the frontline treatment of MDS and AML patients with RARA overexpression in need of better treatments.” UPCOMING MILESTONES Report pivotal complete response (CR) data from the SELECT-MDS-1 Phase 3 trial in newly diagnosed HR-MDS patients with RARA gene overexpression by mid-Q4 2024. Report additional data from SELECT-AML-1 Phase 2 trial in unfit AML patients with RARA gene overexpression in 2024. RECENT PIPELINE HIGHLIGHTS On March 25, 2024, Syros announced the completion of enrollment for the 190 patients in the SELECT-MDS-1 Phase 3 clinical trial necessary to support the CR primary endpoint analysis and subsequent NDA filing in the United States. The trial will continue to enroll up to 550 patients to evaluate overall survival (OS) as a key secondary endpoint. In December 2023, Syros announced encouraging initial data from the randomized SELECT-AML-1 Phase 2 clinical trial evaluating tamibarotene in combination with venetoclax and azacitidine. Data demonstrated a 100% CR/CRi (complete response/complete response with incomplete hematologic recovery) rate in response-evaluable patients (nine of nine) treated with the triplet regimen of tamibarotene, venetoclax and azacitidine, as compared to 70% among patients (seven of ten) treated with venetoclax and azacitidine alone. The median time to CR/CRi response was rapid; all patients treated with the triplet regimen achieved a CR/CRi by the end of cycle one. Consistent with prior clinical experience, tamibarotene in combination with approved doses of venetoclax and azacitidine was generally well tolerated, and the overall safety pro no additive toxicities or new safety signals, and no evidence of increased myelosuppression compared to treatment with the doublet combination of venetoclax and azacitidine. Read more here. CORPORATE In December 2023, Syros priced an equity offering of 4,939,591 shares of common stock at an offering price of $4.42 per share, and, in lieu of common stock to investors who so chose, pre-funded warrants to purchase 5,242,588 shares of its common stock at an offering price of $4.419 per pre-funded warrant. Gross proceeds to Syros were approximately $45.0 million, before underwriting discounts and commissions and offering expenses payable by Syros. Fourth Quarter and Full Year 2023 Financial Results Revenues were $0.4 million for the fourth quarter of 2023 and $9.9 million for the year ended December 31, 2023, as compared to negative $0.8 million in the fourth quarter of 2022 and $14.9 million for the year ended December 31, 2022. The decrease for the year ended December 31, 2023 compared to the year ended December 31, 2022 reflects the early termination of our collaboration agreement with Pfizer. Research and development expenses were $21.5 million for the fourth quarter of 2023 and $108.2 million for the year ended December 31, 2023, as compared to $27.9 million for the fourth quarter of 2022 and $111.9 million for the year ended December 31, 2022. The decrease for the fourth quarter of 2023 compared to the same period in 2022 and the decrease for the year ended December 31, 2023 compared to the year ended December 31, 2022 were primarily due to the restructuring of our operations to prioritize key development and pre-launch activities to advance tamibarotene. General and administrative (G&A) expenses were $5.9 million for the fourth quarter of 2023 and $28.3 million for the year ended December 31, 2023, as compared to $7.3 million for the fourth quarter of 2022 and $29.3 million for the year ended December 31, 2022. The decrease for the fourth quarter of 2023 compared to the same period in 2022 and the decrease for the year ended December 31, 2023 compared to the year ended December 31, 2022 were primarily due to decrease in facilities costs, consulting and other professional fees. For the fourth quarter of 2023, Syros reported a net loss of $64.4 million, or $2.18 per share, compared to a net loss of $4.8 million, or $0.17 per share, for the same period in 2022. For the full year ended December 31, 2023, Syros reported a net loss of $164.6 million, or $5.81 per share, compared to a net loss of $94.7 million, or $7.49 per share, for the same period in 2022. Cash and Financial Guidance Cash, cash equivalents and marketable securities as of December 31, 2023, were $139.5 million, as compared with $202.3 million on December 31, 2022. Based on its current plans, Syros believes that its existing cash, cash equivalents and marketable securities will be sufficient to fund its anticipated operating expenses and capital expenditure requirements into the second quarter of 2025, beyond pivotal Phase 3 data from the SELECT-MDS-1 trial and additional data from the randomized portion of the SELECT-AML-1 trial. Conference Call and Webcast Syros will host a conference call today at 8:30 a.m. ET to discuss the fourth quarter and full-year 2023 financial results and provide a corporate update. To access the live conference call, please dial (888) 259 6580 (domestic) or (416) 764 8624 (international) and refer to conference ID 21905455. A webcast of the call will also be available on the Investors & Media section of the Syros website at . An archived replay of the webcast will be available for approximately 30 days following the presentation. About Syros Pharmaceuticals Syros is committed to developing new standards of care for the frontline treatment of patients with hematologic malignancies. Driven by the motivation to help patients with blood disorders that have largely eluded other targeted approaches, Syros is developing tamibarotene, an oral selective RARα agonist in frontline patients with higher-risk myelodysplastic syndrome and acute myeloid leukemia with RARA gene overexpression. For more information, visit and follow us on Twitter (@SyrosPharma) and LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including without limitation statements regarding Syros’ clinical development plans, the progression of its clinical trials, the timing to report clinical data, the ability to commercialize tamibarotene and deliver benefit to patients, and the sufficiency of Syros’ capital resources to fund its operating expenses and capital expenditure requirements into the second quarter of 2025. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hope,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including Syros’ ability to: advance the development of its programs under the timelines it projects in current and future clinical trials; demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; sustain the response rates and durability of response seen to date with its drug candidates; successfully develop a companion diagnostic test to identify patients with the RARA biomarker; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; obtain and maintain necessary regulatory approvals; identify, enter into and maintain collaboration agreements with third parties; manage competition; manage expenses; raise the substantial additional capital needed to achieve its business objectives; attract and retain qualified personnel; and successfully execute on its business strategies; risks described under the caption “Risk Factors” in Syros’ Annual Report on Form 10-K for the year ended December 31, 2023, which is on the Securities and Exchange Commission; and risks described in other filings that Syros makes with the Securities and Exchange Commission in the future. Financial Tables Syros Pharmaceuticals, Inc. Selected Condensed Consolidated Balance Sheet Data (in thousands) (unaudited) September 30, 2023 December 31, 2022 Cash, cash equivalents and marketable securities (current and noncurrent) $ 139,526 $ 202,304 Working capital1 108,229 180,614 Total assets 168,174 244,486 Total stockholders’ equity 16,662 127,736 (1) The Company defines working capital as current assets less current liabilities. See the Company’s condensed consolidated financial statements for further details regarding its current assets and current liabilities. Syros Pharmaceuticals, Inc. Condensed Consolidated Statement of Operations (in thousands, except share and per share data) (unaudited) Three Months Ended Years Ended December 31, December 31, 2023 2022 2023 2022 Revenue $ 387 $ (754 ) $ $9,936 $ 14,880 Operating expenses: Research and development 21,503 27,914 108,153 111,944 General and administrative 5,893 7,329 28,282 29,299 Transaction related expenses — — — 9,510 Restructuring cost 132 — 2,489 — Total operating expenses 27,528 35,243 138,924 150,753 Loss from operations (27,141 ) (35,977 ) (128,288 ) (135,873 ) Interest income 1,283 1,594 6,816 2,132 Interest expense (1,328 ) (1,126 ) (5,127 ) (4,134 ) Change in fair value of warrant liabilities (37,198 ) 30,756 (37,275 ) 43,221 Net loss applicable to common stockholders $ (64,384 ) $ (4,773 ) $ (164,574 ) $ (94,654 ) Net loss per share applicable to common stockholders - basic and diluted $ (2.18 ) $ (0.17 ) $ (5.81 ) $ (7.49 ) Weighted-average number of common shares used in net loss per share applicable to common stockholders - basic and diluted 29,541,899 27,753,257 28,325,779 12,631,968

BETHESDA, Md., March 26, 2024 (GLOBE NEWSWIRE) -- Gain Therapeutics, Inc. (Nasdaq: GANX) (“Gain”, or the “Company”), a clinical-stage biotechnology company leading the discovery and development of the next generation of allosteric small molecule therapies, today reports financial results for the year ended December 31, 2023 and provides a corporate update. Corporate Highlights from Q4 2023 to Date Presented data at AD/PD 2024 demonstrating mechanism of action of GT-02287, the Company’s lead compound being investigated for the treatment of GBA1 Parkinson’s diseaseAnnounced the initiation of the Multiple Ascending Dose (MAD) part of the Phase 1 clinical trial of GT-02287, a novel GCase-targeting small molecule therapy for GBA1 Parkinson’s diseasePresented late-breaking data at the WORLDSymposium showing GT-02287 displays neuroprotection and completely restores motor function in preclinical models of Parkinson’s disease following delayed administrationPublished data in PLOS ONE demonstrating therapeutic potential for galactosidase beta 1 (GLB1)-related lysosomal storage disorders (LSDs), including GM1 gangliosidosisRaised $10.1 million in gross proceeds from public offering and concurrent private placement of common stock and warrants “With the tremendous progress we have made over the course of 2023 and entering 2024, we believe Gain is well positioned to achieve multiple clinical data driven value inflection points with our lead program GT-02287 for GBA1 Parkinson’s disease during the course of this year and into 2025. We believe our cash position and operational plans are strong and allow us to meet our near-term milestones,” said Matthias Alder, Gain Therapeutics’ CEO. “We are encouraged by the safety and tolerability profile of GT-02287 in healthy subjects that we have observed so far in the ongoing Phase 1 clinical trial and remain on track to complete that study by mid-year,” concluded Mr. Alder. 2023 Year End Financial Results Research and development (R&D) expenses increased by $3.1 million to $11.5 million for the year ended December 31, 2023, from $8.4 million for the year ended December 31, 2022. The increase in research and development expenses was primarily attributable to increases in external R&D services and external expenses related to the commencement and conduct of our Phase 1 clinical trial with our lead drug candidate GT-02287 for the treatment of GBA1 Parkinson’s disease. General and administrative (G&A) expenses increased by $1.3 million to $10.8 million for the year ended December 31, 2023, from $9.5 million for the year ended December 31, 2022. The increase in general and administrative expenses was primarily attributable to increases in professional fees for corporate compliance consulting and non-cash costs related to share-based compensation. Net loss for the year ended December 31, 2023 was $22.3 million, compared to a net loss of $17.6 million for the year ended December 31, 2022. Net loss as of December 31, 2023 included non-cash compensation expenses of $3.3 million as compared to 2022 non-cash compensation expenses of $1.5 million. The increase in net loss for 2023 compared to 2022 was primarily attributable to increases in R&D expenses of $3.1 million and G&A expenses of $1.3 million. GAAP basic and diluted net loss per share for the year ended December 31, 2023 was $1.71, as compared to basic and diluted net loss per share of $1.48 as of December 31, 2022. Cash, cash equivalent and marketable securities were $16.8 million as of December 31, 2023. We anticipate that our existing cash, cash equivalent and marketable securities will be sufficient to support operations into Q1 2025. About Gain Therapeutics, Inc. Gain Therapeutics, Inc. is a clinical-stage biotechnology company leading the discovery and development of next generation allosteric therapies. Gain’s lead drug candidate GT-02287 for the treatment of GBA1 Parkinson’s disease, is currently being evaluated in a Phase 1 clinical trial. Leveraging AI-supported structural biology, proprietary algorithms and supercomputer-powered physics-based models, the company’s Magellan™ drug discovery platform can identify novel allosteric binding sites on disease-implicated proteins, pinpointing pockets that cannot be found or drugged with current technologies. Magellan™ is the next generation of Gain’s original SEE-Tx® (Site-Directed Enzyme Enhancement Therapy) platform, which was enhanced and expanded with new AI and machine-learning tools and virtual screening capabilities to access the emerging on-demand compound libraries covering vast chemical spaces of over 50 billion compounds. Gain’s unique approach enables the discovery of novel, allosteric small molecule modulators that can restore or disrupt protein function. Deploying its highly advanced platform, Gain is accelerating drug discovery and unlocking novel disease-modifying treatments for untreatable or difficult-to-treat disorders including neurodegenerative diseases, rare genetic disorders and oncology. For more information, please visit GainTherapeutics.com and follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements in this press release other than statements of historical facts are “forward-looking statements”. In some cases, you can identify these statements by forward-looking words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “goal,” “intend,” “seek,” “potential” or “continue,” the negative of these terms and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the development of the Company’s current or future product candidates including GT-02287; expectations regarding the timing of results from a Phase 1 clinical study for GT-02287; the potential therapeutic and clinical benefits of the Company’s product candidates; and the amount of time the Company’s current cash, cash equivalents and marketable securities will support operations. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause the Company’s preclinical and future clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. These statements are not historical facts but instead represent the Company's belief regarding future results, many of which, by their nature, are inherently uncertain and outside the Company's control. Many factors may cause differences between current expectations and actual results, including the impacts of the post-COVID-19 environment and other global and macroeconomic conditions on the Company’s business; clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials, clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled “Risk Factors,” in the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 23, 2023 and its other documents subsequently filed with or furnished to the Securities and Exchange Commission from time to time. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Investor Contact:CORE IR(516) 222-2560 ir@gaintherapeutics.com Media Contacts:Russo PartnersNic Johnson and Elio Ambrosionic.johnson@russopartnersllc.comelio.ambrosio@russopartnersllc.com(212) 845-4242 Gain Therapeutics, Inc.Consolidated Statement of Operations Year Ended December 31, 2023 2022 Revenues: Collaboration revenues$55,180 $132,640 Other income — 7,468 Total revenues 55,180 140,108 Operating expenses: Research and development (11,520,613) (8,377,290) General and administrative (10,787,700) (9,539,863) Total operating expenses (22,308,313) (17,917,153) Loss from operations (22,253,133) (17,777,045) Other income (expense): Interest income, net 494,234 375,357 Foreign exchange loss, net (429,346) (96,074) Loss before income tax$(22,188,245) $(17,497,762) Income tax (79,275) (92,976) Net loss$(22,267,520) $(17,590,738) Net loss per shares: Net loss per share attributable to common stockholders - basic and diluted$(1.71) $(1.48) Weighted average common stock - basic and diluted 13,011,361 11,883,368 Gain Therapeutics, Inc.Consolidated Balance Sheets December 31,2023 December 31,2022 Assets Current assets: Cash and cash equivalents$11,794,949 $7,311,611 Marketable securities - current 4,999,704 12,826,954 Tax credits 242,577 103,877 Prepaid expenses and other current assets 741,638 848,854 Total current assets$17,778,868 $21,091,296 Non-current assets: Marketable securities - non-current$— $1,941,488 Property and equipment, net 125,962 144,379 Internal-use software 193,375 213,967 Operating lease - right of use assets 459,215 659,933 Restricted cash 34,021 30,818 Long-term deposits and other non-current assets 17,890 17,506 Total non-current assets 830,463 3,008,091 Total assets$18,609,331 $24,099,387 Liabilities and stockholder's equity Current liabilities: Accounts payable$1,318,965 $1,626,100 Operating lease liability - current 229,693 229,080 Other current liabilities 2,160,366 2,106,756 Deferred income - current 1,122,138 55,180 Loans - current 118,797 108,135 Total current liabilities$4,949,959 $4,125,251 Non-current liabilities: Defined benefit pension plan$307,454 $157,580 Operating lease liability - non-current 229,855 441,784 Deferred income - non-current 94,786 — Loans - non-current 449,053 495,258 Total non-current liabilities 1,081,148 1,094,622 Total liabilities$6,031,107 $5,219,873 Stockholders’ equity Preferred stock, $0.0001 par value; 10,000,000 shares authorized; nil shares issued and outstanding as of December 31, 2023 and 2022$— $— Common stock, $0.0001 par value: 50,000,000 shares authorized; 16,206,680 shares issued and outstanding as of December 31, 2023 and 11,883,368 shares issued and outstanding as of December 31, 2022 1,621 1,189 Additional paid-in capital 73,113,079 57,358,895 Accumulated other comprehensive income 247,241 35,627 Accumulated deficit (38,516,197) (20,925,459) Loss of the period (22,267,520) (17,590,738) Total stockholders’ equity 12,578,224 18,879,514 Total liabilities and stockholders’ equity$18,609,331 $24,099,387

-- On track to report pivotal complete response data by mid-4Q 2024 -- CAMBRIDGE, Mass.--(BUSINESS WIRE)--Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, today announced that the enrollment of 190 patients has been completed in the SELECT-MDS-1 Phase 3 clinical trial evaluating tamibarotene in newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA gene overexpression. This initial cohort of 190 patients is necessary to support the complete response (CR) primary endpoint analysis. Syros expects to report these pivotal data by the middle of the fourth quarter of 2024. “We are pleased to announce the completion of enrollment of the 190 patients necessary to support the primary CR endpoint in SELECT-MDS-1. This marks an important step in advancing tamibarotene through late-stage clinical development and brings us closer to delivering our RARα agonist as a frontline treatment option for the approximately 50 percent of HR-MDS patients with RARA overexpression,” said David A. Roth, M.D., Chief Medical Officer of Syros. “We look forward to reporting pivotal data later this year which, if successful, will allow us to first New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) and, ultimately, execute on our vision of fundamentally changing the standard of care in hematologic malignancies.” The Phase 3 SELECT-MDS-1 clinical trial is a double-blind, placebo-controlled study evaluating tamibarotene in newly diagnosed HR-MDS patients with RARA overexpression randomized 2:1 to receive tamibarotene in combination with azacitidine or azacitidine alone. The primary endpoint is CR rate in the first 190 patients enrolled in the trial which, together with supporting durability data, can serve as the basis for accelerated approval or full approval; the key secondary endpoint in SELECT-MDS-1 is overall survival (OS) in a total of 550 patients. This study design reflects an efficient “one-trial” approach and could allow SELECT-MDS-1 to serve as a confirmatory study, if needed, to convert from accelerated to full approval. Enrollment is ongoing to reach the 550-patient target. Syros is also evaluating tamibarotene in combination with venetoclax and azacitidine in the SELECT-AML-1 Phase 2 clinical trial in newly diagnosed unfit acute myeloid leukemia patients with RARA gene overexpression. Syros previously reported initial data from the study, observing a 100% CR/CRi (complete response/complete response with incomplete hematologic recovery) rate in response-evaluable patients treated with the triplet regimen of tamibarotene, venetoclax and azacitidine without increased toxicity, as compared to 70% among patients treated with venetoclax and azacitidine alone. Syros expects to report additional data from SELECT-AML-1 in 2024. Read more here. About Syros Pharmaceuticals Syros is committed to developing new standards of care for the frontline treatment of patients with hematologic malignancies. Driven by the motivation to help patients with blood disorders that have largely eluded other targeted approaches, Syros is developing tamibarotene, an oral selective RARα agonist in frontline patients with higher-risk myelodysplastic syndrome and acute myeloid leukemia with RARA gene overexpression. For more information, visit and follow us on Twitter (@SyrosPharma) and LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, including without limitation statements regarding Syros’ clinical development plans, the progression of its clinical trials, the timing to report clinical data, and the ability to commercialize tamibarotene and deliver benefit to patients. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hope,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “target,” “should,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including Syros’ ability to: advance the development of its programs under the timelines it projects in current and future clinical trials; demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; sustain the response rates and durability of response seen to date with its drug candidates; successfully develop a companion diagnostic test to identify patients with the RARA biomarker; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; obtain and maintain necessary regulatory approvals; identify, enter into and maintain collaboration agreements with third parties; manage competition; manage expenses; raise the substantial additional capital needed to achieve its business objectives; attract and retain qualified personnel; and successfully execute on its business strategies; risks described under the caption “Risk Factors” in Syros’ Annual Report on Form 10-K for the year ended December 31, 2022 and Quarterly Reports on Form 10-Q for the quarters ended March 31, 2023, June 30, 2023 and September 30, 2023, each of which is on the Securities and Exchange Commission; and risks described in other filings that Syros makes with the Securities and Exchange Commission in the future.