Nerve Degeneration

NEW YORK, March 19, 2024 /PRNewswire/ -- Seelos Therapeutics, Inc. (Nasdaq: SEEL) ("Seelos"), a clinical-stage biopharmaceutical company focused on the development of therapies for central nervous system disorders and rare diseases, today provided an update on top-line data of the Phase 2/3 HEALEY ALS Platform trial. This study was performed in collaboration with The Sean M. Healey and AMG Center, which is viewed as an influential force in ALS research and in caring for the ALS community. Their unique and innovative approach continues to be a benefit to the ALS community and its contributions have helped bring the last two FDA approved therapies for ALS to market. We plan to request a meeting with the FDA to discuss potential next steps for the program The study was designed to evaluate SLS-005 (IV trehalose), a low molecular weight disaccharide that stabilizes misfolded proteins and activates autophagy, in decreasing the slope of the ALS Functional Rating Scale (ALSFRS-R) and separation from placebo in Function and Mortality in an all-comers population of Persons with ALS (PALS). While the study did not meet statistical significance in the primary and secondary endpoint in the Full Analysis Set (FAS)2, by showing a 13% improvement in Function and Mortality with an 88% success probability (versus the pre-specified 98%), it showed a potential signal of efficacy in a pre-specified subgroup (ERF)1. In the pre-specified subgroup of PALS treated with SLS-005, without RELYVRIO®, the top-line data favored SLS-005 versus placebo in efficacy measures in the Efficacy RELYVRIO® Free (ERF)1 data set (n=130), including: a 22% improvement in slope of change in ALSFRS-R assessment adjusted for mortality, with an 89% success probability, at 24 weeks the rate of decline in ALSFRS-R slope (points per month) also favored the SLS-005 treatment group versus placebo over 6 months (-0.80 and -1.07 points per month, respectively) a 25% slowing of Slow Vital Capacity (SVC) decline versus placebo (-11.5% for SLS-005 and -15.4% for placebo) at 24 weeks Additional analysis and information from these data accessible here. "The HEALEY platform is designed to detect signals of efficacy and we believe the observed signal and success probability is competitive to other recently FDA-approved therapies for ALS which also failed to achieve statistical significance when measured for function and mortality on similar primary and efficacy endpoints," said Raj Mehra Ph.D., Chairman and Chief Executive Officer of Seelos. "We plan to request a meeting with the FDA to discuss potential next steps for the program and will continue our potential partner discussions." Seelos has not yet received the full dataset and upon receiving it in the near future, Seelos plans to run additional analyses, including biomarkers of neurodegeneration, neurofilament light chain (NfL), exploratory efficacy results, subgroups and post-hoc analyses. SLS-005 was generally well-tolerated and comparable to placebo in safety. There was an imbalance of deaths/death equivalents observed in the study, with more events seen in the SLS-005 group compared to placebo, all were considered unrelated to the study drug. Populations – ERF1, FAS2 and ERO3: Seelos received top-line results for Regimen E (RGE). This included a Full Analysis Set (FAS), an Efficacy Regimen Only (ERO) population and an Efficacy RELYVRIO® Free (ERF) population. FAS includes shared placebo from all regimens, including RGE (n=204) and the RGE SLS-005 participants (n=120). The Efficacy Regimen Only (ERO) population includes 120 RGE SLS-005 and 41 RGE placebo participants. 31 participants in the ERO population received RELYVRIO® during the SLS-005 RGE study, thus confounding results from this population. The ERF analyses exclude participants who initiated RELYVRIO® during the study. ERF represents the participants who followed the protocol as envisioned (n=130, i.e., the ERF population comprises 81% of ERO/RGE participants). About SLS-005 (trehalose injection, 90.5 mg/mL for intravenous infusion) SLS-005 is a low molecular weight disaccharide (0.342 kDa) that crosses the blood brain barrier and is thought to stabilize proteins and activate autophagy through the activation of Transcription Factor EB (TFEB), a key factor in lysosomal and autophagy gene expression. The activation of TFEB is an emerging therapeutic target for a number of diseases with pathologic accumulation of storage material. In animal models of several diseases associated with abnormal cellular protein aggregation or storage of pathologic material, SLS-005 has been shown to reduce aggregation of misfolded proteins and reduce accumulation of pathologic material. SLS-005 has previously received Orphan Drug Designation for the treatment of ALS from the U.S. Food and Drug Administration and from the European Medicines Agency in the EU. SLS-005 is an investigational treatment and is not currently approved by any health authority for medicinal use. About Amyotrophic Lateral Sclerosis (ALS) According to the National Institute of Neurological Disorders and Stroke, amyotrophic lateral sclerosis (ALS) is a group of rare neurological diseases that mainly involve the nerve cells (neurons) responsible for controlling voluntary muscle movement. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die and stop sending messages to the muscles. Unable to function, the muscles gradually weaken, start to twitch (called fasciculations), and waste away (called atrophy). Eventually, the brain loses its ability to initiate and control voluntary movements. The disease is progressive, meaning the symptoms get worse over time. The majority of ALS cases (90 percent or more) are considered sporadic. This means the disease seems to occur at random with no clearly associated risk factors and no family history of the disease. Although family members of people with sporadic ALS are at an increased risk for the disease, the overall risk is very low, and most will not develop ALS. Most people with ALS eventually die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. However, about 10 percent of people with ALS survive for 10 or more years. Currently, there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease. A 1-point change in the ALSFRS-R score can indicate a meaningful difference in a person's ability to function independently with activities of daily living (ADL's), including eating, bathing, dressing or walking.4 4. FDA Center for Drug Evaluation and Research, Application Number 209176Orig1s000, Office Director Memo, Ellis F. Unger, MD, May 4, 2017. Paganoni S, et al. New Eng J Med. 2020. About Seelos Therapeutics Seelos Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development and advancement of novel therapeutics to address unmet medical needs for the benefit of patients with central nervous system (CNS) disorders and other rare diseases. The Company's robust portfolio includes several late-stage clinical assets targeting indications including Acute Suicidal Ideation and Behavior (ASIB) in Major Depressive Disorder (MDD), amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia (SCA), as well as early-stage programs in Huntington's disease, Alzheimer's disease, and Parkinson's disease. For more information, please visit our website: , the content of which is not incorporated herein by reference. Forward Looking Statements Statements made in this press release, which are not historical in nature, constitute forward-looking statements for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. These statements include, among others, those regarding the Phase 2/3 study of SLS-005, statements regarding the competitiveness of the results to recently approved FDA therapies for ALS, statements regarding any planned meetings and discussions with the FDA, statements regarding The Sean M. Healey and AMG Center's contributions to the ALS community, statements regarding the timing of Seelos's receipt of the full dataset for the trial, statements regarding additional analyses to be run by Seelos and statements regarding SLS-005's prospects and any future analyses that may be conducted. These statements are based on Seelos' current expectations and beliefs and are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Risks associated with Seelos' business and plans described herein include, but are not limited to, the risk of not successfully executing its preclinical and clinical studies, not being able to move forward with the development of SLS-005, and not gaining marketing approvals for SLS-005 and/or its other product candidates; the risk that prior clinical results may not be replicated in future studies and trials (including the risk that the results from the prior studies of SLS-005 may not be replicated or may be materially different from the results of the top-line data from the SLS-005 study); the risks that clinical study results may not meet any or all endpoints of a clinical study and that any data generated from such studies may not support a regulatory submission or approval; the risks associated with the implementation of Seelos' business strategy; the risks related to raising capital to fund its development plans and ongoing operations; the risks related to Seelos' current stock price; as well as other factors expressed in Seelos' periodic filings with the U.S. Securities and Exchange Commission, including its most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. Although we believe that the expectations reflected in our forward-looking statements are reasonable, we do not know whether our expectations will prove correct. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, even if subsequently made available by us on our website or otherwise. We do not undertake any obligation to update, amend or clarify these forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. Contact Information: Anthony Marciano Chief Communications Officer Seelos Therapeutics, Inc. (Nasdaq: SEEL) 300 Park Avenue, 2nd Floor New York, NY 10022 (646) 293-2136 anthony.marciano@seelostx.com Mike Moyer Managing Director LifeSci Advisors, LLC 250 West 55th St., Suite 3401 New York, NY 10019 (617) 308-4306 mmoyer@lifesciadvisors.com Company Codes: NASDAQ-NMS:SEEL

ST. LOUIS--( BUSINESS WIRE )--New research finds that C₂N Diagnostics, LLC’s proprietary algorithm used in its PrecivityAD2 blood test, which is used by healthcare providers to determine Alzheimer’s disease (AD) pathology in individuals with early cognitive impairment, can identify brain amyloid status with “sensitivity, specificity, positive and negative predictive values that approximate those of amyloid positron emission tomography (PET) imaging.” C₂N Diagnostics believes the findings in “ Alzheimer's & Dementia: The Journal of the Alzheimer's Association ” are significant as the healthcare sector needs a PET scan alternative that’s widely accessible, accurate and cost-effective that can aid in the differential diagnosis of AD and AD-related dementias. The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2 (APS2), was 0.94, yielding 88% agreement with brain amyloid status based on a single cut-off value. Diagnostic performance of the APS2 was similar by ethnicity, sex, age and apoE4 status. The APS2 result was the most robust method among the individual plasma amyloid and tau analytes measured to identify disease. The research findings also showed that the AUC-ROC for the %p-tau217 (0.94), one of the core components of the APS2 algorithm, was superior to that for the p-tau217 concentration (0.91) for identifying brain amyloidosis. The researchers define %p-tau217 as the percentage of p-tau217 relative to np-tau217. These data showing the superiority of %p-tau217 over p-tau217 alone reaffirm the findings of another ground-breaking study recently published involving C 2 N’s technology to identify amyloid pathology in pre-clinical AD with high accuracy comparable to amyloid PET. Data Give Healthcare Providers Assurance as Patients Want Answers In the published study, the PrecivityAD2 blood test was clinically validated in 583 individuals with cognitive impairment across two independent cohorts. The robustness of the findings was enhanced by the fact that one of the study cohorts, PARIS, included a prospective, difficult-to-diagnose, real-world population of U.S. Medicare beneficiaries presenting with memory concerns to clinics as part of a substudy of IDEAS 1 . The PrecivityAD2 blood test determines a patient’s likelihood (positive or negative) for the presence of amyloid plaques in the brain, one of the brain pathology findings of Alzheimer’s disease. In addition to helping healthcare providers determine Alzheimer’s disease pathology, the PrecivityAD2 test aids in medical management and treatment decisions. Dr. Joel Braunstein, C₂N’s CEO says, “This latest research adds to the growing body of data that affirms the PrecivityAD2 test’s outstanding diagnostic performance and builds further confidence in the healthcare sector. The PrecivityAD2 blood test provides a less costly, more accessible and vitally needed option for healthcare providers who must conduct diagnostic testing for their patients facing memory and dementia care issues. We’re excited that additional studies are underway throughout the world that are seeking to further demonstrate the robust clinical performance and generalizability of the APS2 model.” Dr. Braunstein and others note the PrecivityAD2 test’s appeal because of PET’s limitations for screening large number of patients as new disease-modifying drugs that can specifically treat the underlying causes of AD become available. These limitations include: PET’s cost for research use (currently estimated at around $6,500); that it exposes patients to radiation; and that it’s not easily accessible outside of large cities. The PrecivityAD2 blood test is intended for use in patients aged 55 and older with signs or symptoms of mild cognitive impairment or dementia who are undergoing evaluation of Alzheimer’s disease or dementia. Only a healthcare provider can order the PrecivityAD2 test. The test is available in 49 states, the District of Columbia and Puerto Rico; the exception is New York, which requires an individual state process for CLIA labs. C₂N is working toward obtaining the requisite certification that will permit the PrecivityAD2 test to be available in New York in the near future. Healthcare providers interested in ordering the PrecivityAD2 test can call 1.877.C2N.DIAG (226.3424) or visit https://precivityad.com . About C 2 N Diagnostics, LLC C ₂ N is a specialty diagnostics company with a vision to bring Clarity Through Innovation®. C ₂ N strives to provide exceptional clinical laboratory services and advanced diagnostic solutions in the field of brain health. C ₂ N’s high-resolution mass spectrometry-based biomarker services and products are used for: clinical decision-making to improve patient care, including diagnosis and treatment monitoring; maximizing the quality and efficiency of clinical trials that test novel treatments for neurodegeneration; and providing innovative tools to help healthcare researchers better understand novel mechanisms of disease, identify new treatment targets, and conduct important epidemiologic studies to improve global public health. C ₂ N assays have been used in over 150 Alzheimer’s disease and other research studies throughout the U.S. and the world. This includes landmark treatment and prevention trials involving disease-modifying therapies (DMTs) that are changing the trajectory of Alzheimer’s disease. C ₂ N has ongoing collaborations with multi-national pharmaceutical and biotech companies, leading academic institutions, National Institute on Aging, Alzheimer’s Association, and other non-profits and consortiums. Over 15,000 Precivity™-related biomarker measures have been reported through peer-reviewed publications, with many more manuscripts currently under review. The company acknowledges generous support from National Institute on Aging, GHR Foundation, Alzheimer’s Drug Discovery Foundation, BrightFocus Foundation and Alzheimer’s Association. For more information visit www.C2N.com . 1 www.ideas-study.org/Original-Study ; ClinicalTrials.gov Identifier: NCT02420756.

Gain Therapeutics’ Former CEO and current Board Member Eric Richman to participate in fireside chat hosted by Public Ventures President Lou Basenese and Aberdeen Investment Management President Jeb Terry, Sr.BETHESDA, Md., March 15, 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 announced participation in the upcoming Public Ventures Discovery Day on March 19, 2024 at Old Parkland in Dallas, TX. Public Ventures Discovery DayDate: Tuesday, March 19, 2024Presentation: 2:30 PM CSTLocation: Pecan Room, Old Parkland, 3819 Maple Avenue, Dallas TX 75219 A video replay of the fireside chat will be available shortly after the conclusion of the event on the Investors and Media section of the company’s website at www.gaintherapeutics.com. Public Ventures, LLC, a wholly owned subsidiary of MDB Capital Holdings, LLC, (NASDAQ: MDBH), is the first invite-only investor community and self-clearing broker-dealer platform dedicated to backing visionary public companies with the potential to become market leaders in their technology category. Discovery Day is a unique event for investors to learn about a curated group of venture-stage, deep-tech companies; share feedback and questions with company leaders; and connect with like-minded investors. To register for Discovery Day, please email community@publicventures.com. Please note that spots are limited, and attendance preference will be given to existing MDBH shareholders. About GT-02287 Gain Therapeutics’ lead drug candidate, GT-02287, is in clinical development for the treatment of GBA1 Parkinson’s disease (GBA1-PD). The orally administered, brain-penetrant small molecule is an allosteric protein modulator that restores the function of the lysosomal protein enzyme glucocerebrosidase (GCase) which becomes misfolded and impaired due to a GBA1 gene mutation, the most common genetic abnormality associated with PD. In preclinical models of PD, GT-02287 restored GCase enzymatic function, reduced aggregated α-synuclein, neuroinflammation and neuronal death, increased dopamine levels and improved motor function. Additionally, GT-02287 significantly reduced plasma neurofilament light chain (NfL) levels, an emerging biomarker for neurodegeneration. Gain’s lead program in Parkinson’s disease has been awarded funding support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The Silverstein Foundation for Parkinson’s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse – Swiss Innovation Agency. About GBA1 Parkinson’s Disease GBA1 Parkinson’s disease is caused by mutations in the GBA1 gene, found in up to 15% of patients with Parkinson’s disease and making it the primary genetic risk factor. The mutation causes dysfunctional misfolding of the lysosomal enzyme glucocerebrosidase (GCase), reducing its activity in the brain and leading to the subsequent accumulation of α-synuclein and degeneration of dopamine-containing nerve cells. Patients with GBA1-PD tend to have earlier onset and faster symptom progression than those with sporadic PD, a progressive neurodegenerative disease characterized by a motor syndrome consisting of bradykinesia (slowness of movement), rigidity, resting tremors, and postural instability. With current therapies treating only the symptoms of Parkinson’s disease without affecting the underlying progression of the disease, there is an unmet need to develop novel disease-modifying therapies such as GT-02287 that have the potential to slow or stop disease progression and help improve outcomes in this patient population. 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; and the potential therapeutic and clinical benefits of the Company’s product candidates. 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