Cochin Institute

$121.1 Million In Cash and Cash Equivalents at December 31, 2023, With an Additional $21.8 Million Raised In 2024 From Exercise of Warrants.A Total of Over 555 Study Participants Have Completed Our Phase 3 Studies.Topline Data Readout for Our 52-Week Phase 3 Trial Expected Year-End 2024.Internal Investigation by Outside Counsel Has Found No Evidence to Substantiate Allegations of Research Misconduct by the Company. AUSTIN, Texas, Feb. 28, 2024 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (Nasdaq: SAVA), a biotechnology company focused on Alzheimer’s disease, today reported financial and operating results for the full year ended December 31, 2023 and presented corporate updates. “I see Alzheimer’s disease as one of the last great frontiers in medicine,” said Remi Barbier, President & CEO. “It’s clear to me these patients need new and more simplified treatment options. In 2024 and beyond, we’ll continue to try to make a meaningful difference in the lives of people who suffer from Alzheimer’s disease. I believe our Phase 3 program of simufilam in Alzheimer’s will reach important milestones in 2024, particularly in patients with mild disease.” Simufilam is Cassava Sciences’ investigational drug candidate for the proposed treatment of Alzheimer's disease dementia. Net loss for full year 2023 was $97.2 million, or $2.32 per share, compared to a net loss of $76.2 million, or $1.90 per share, in 2022. Net cash used in operations full-year 2023 was $82.0 million, consistent with previous guidance. Cash use for operations for the first half of 2024 is expected to be $35 to $45 million, driven primarily by expenses for our clinical program in Alzheimer’s disease. In 2024, the Company raised gross proceeds of approximately $21.8 million from the exercise of common stock warrants though February 26, 2024. “We expect our research and development expenses to decrease modestly in 2024 as a result of decreased spending for our Phase 3 program, as patient screening and enrollment are now complete for the Phase 3 clinical studies,” said Eric Schoen, Chief Financial Officer. “We also expect the decrease in Phase 3 program costs to be partially offset by increased enrollment in the open-label study as well as higher expenses in other parts of our operations.” Financial Results for Full-year 2023 At December 31, 2023, cash and cash equivalents were $121.1 million, compared to $201 million at December 31, 2022, with no debt.In 2024 through February 26, 2024, we received gross proceeds of $21.8 million from the exercise of warrants, resulting in the issuance of 989,000 shares of common stock. (This amount is not included in the above cash and cash equivalents at December 31, 2023.)Net loss was $97.2 million, or $2.32 per share. This compares to a net loss of $76.2 million, or $1.90 per share, in 2022. Net loss increased due primarily to increases in patient enrollment and associated costs to conduct the Phase 3 clinical program, as well as other studies with simufilam.Net cash used in operations full-year 2023 was $82 million.Net cash use in operations for first half 2024 is expected to be $35 to $45 million, driven primarily by expenses for our program in Alzheimer’s disease.Research and development (R&D) expenses were $89.4 million. This compared to $68 million for 2022. R&D expenses increased due primarily to increasing patient enrollment and costs to conduct the Phase 3 clinical program, as well as other studies with simufilam.General and administrative (G&A) expenses were $16.5 million. This compared to $12.0 million for 2022. G&A expenses increased due to increases in stock-based compensation as well as activities and expenses related to legal services. Recent corporate highlights include the following: In January 2024, we completed a dividend distribution of common stock warrants to shareholders. The warrants allow the holder to purchase additional shares of our common stock. The warrants trade on Nasdaq (SAVAW), separate from our common stock (SAVA). Unless earlier redeemed, the warrants will expire and cease to be exercisable on November 15, 2024. The warrants are redeemable at our sole option at any time with a redemption date on or after April 15, 2024. Cassava Sciences will provide at least 20 calendar days’ notice by press release of the date selected, if any, for a redemption.In February 2024, we reported that patients with mild Alzheimer’s disease who received simufilam treatment continuously for two years (n=47) had no decline in ADAS-Cog scores (± 1.51 SE) as a group. Patients with mild Alzheimer’s who received simufilam treatment non-continuously for two years (n=40) declined 1 point on ADAS-Cog (± 1.65 SE) as a group. Continuous treatment consisted of one year on open-label drug, six months randomized to drug and six months back on open-label drug. Non-continuous treatment consisted of the same, except randomized to placebo in that six-month period.In December 2023, we reported the appointment of three new members to the Board of Directors. Clause Nicaise, MD, Pierre Gravier, MS and Robert Anderson, Jr. are all highly respected, astute leaders in their fields. Their collective expertise in drug development, M&A, cybersecurity and dealing with large, complex governmental agencies will add a balance of experience and perspectives to the Board.In October 2023, we reported a potentially significant safety finding based on interim magnetic resonance imaging (MRI) brain data from Alzheimer’s patients who are enrolled in our 76-week Phase 3 trial (REFOCUS-ALZ). These MRI data suggest simufilam is not associated with treatment-emergent amyloid-related imaging abnormalities, or ARIA. ARIA is a medical term used to describe a spectrum of brain MRI imaging abnormalities, such as edema and brain bleeds, and is a known risk factor for patients taking monoclonal antibody infusion drugs directed against beta amyloid.In September 2023, we reported a positive interim safety review of simufilam in on-going Phase 3 clinical trials in patients with Alzheimer’s disease. A routine, scheduled meeting of a Data and Safety Monitoring Board (DSMB) recommended that both of Cassava Sciences’ Phase 3 studies of simufilam continue as planned, without modification.In September 2023, we also reported new research that confirms the biological activity of simufilam. Researchers at the Cochin Institute (Paris, France) used a highly precise cell-based assay to show that simufilam interrupts amyloid binding to the α7 nicotinic acetylcholine receptor (α7nAChR). Their data show that simufilam potently disrupts a known pathological action of amyloid β using a robust and highly sensitive assay based on a technique called TR-FRET. Four academic institutions have now generated data in support of the biological activity of simufilam.In June 2023, we reported new research that examined the effects of simufilam on the mechanistic Target of Rapamycin (mTOR). Scientific literature shows overactive mTOR plays a key role in aging, Alzheimer’s disease and other conditions. When functioning normally, mTOR monitors cellular needs and is activated by insulin. The new published research shows mTOR is overactive in lymphocytes isolated from blood collected from Alzheimer's patients versus healthy controls. After oral administration of simufilam 100 mg twice daily to Alzheimer's patients for 28 days, lymphocytes showed normalized mTOR activity and restored sensitivity to insulin. These data suggest a meaningful impact of simufilam on mTOR signaling. The suppression of overactive mTOR signaling and its improved responsiveness to insulin represents a mechanistic benefit of simufilam beyond the disruption of pathogenic signaling pathways of soluble amyloid. These improvements in mTOR signaling may also result from reversing an altered conformation of FLNA, allowing FLNA to dissociate from the insulin receptor when insulin binds and initiates signaling. Because mTOR contributes to age-related cellular changes, simufilam’s suppression of mTOR overactivation, concurrent with improved insulin sensitivity, may slow certain aging processes and attenuate this pathological feature of Alzheimer’s disease, potentially benefiting brain function and memory.In August 2021, certain individuals, later revealed to be short sellers of the Company’s securities, publicly alleged that we had engaged in research misconduct. Today we report that an internal investigation conducted by outside counsel engaged by our Board of Directors has found no evidence to substantiate allegations that the Company or its employees engaged in or were aware of research misconduct. Status of Phase 3 Clinical ProgramBackground - Our Phase 3 program consists of two global, double-blind, randomized, placebo-controlled studies of simufilam in patients with mild-to-moderate Alzheimer’s disease dementia. Phase 3 Trials – In Fall 2021, we announced the initiation of two pivotal Phase 3 studies of simufilam in Alzheimer’s disease. Our first Phase 3 study, called RETHINK-ALZ, is designed to evaluate the safety and efficacy of simufilam 100 mg tablets twice-daily versus matching placebo over 52 weeks (NCT04994483). Our second Phase 3 study, called REFOCUS-ALZ, is designed to evaluate the safety and efficacy of oral simufilam 100 mg and 50 mg tablets twice-daily versus matching placebo over 76 weeks (NCT05026177). Clinical sites are in the United States, Canada, Puerto Rico, Australia, and South Korea. Premier Research International is the clinical research organization (CRO) supporting the conduct of our Phase 3 clinical program. Entry Criteria – Criteria that potential patients must meet to be included in a Phase 3 study include an MMSE score of 16 to 27; a Clinical Dementia Rating (CDR)-Global Scale score of 0.5, 1 or 2; elevated plasma p-tau181 or prior evidence of Alzheimer’s neuropathology by PET or cerebrospinal fluid; and other inclusion/exclusion eligibility criteria. Patient Enrollment – In November 2023, we announced the completion of patient enrollment in both Phase 3 studies. Approximately 1,900 patients are randomized in these studies, with approximately 800 patients randomized in the 52-week study (RETHINK-ALZ) and approximately 1,100 patients randomized in the 76-week study (REFOCUS-ALZ). Preliminary Baseline Characteristics (all numbers are approximate) – Mean patient age for both studies is 74. Seventy percent (70%) of patients entered the studies with mild Alzheimer’s disease (MMSE 20-27), with remaining patients entering the study with moderate disease (MMSE 16-19). Both studies have a mean MMSE score of 22. Both studies have a mean ADAS-Cog score of 25. Both studies have a mean ADCS-ADL score of 65. Patient Completion – Over 340 patients have completed the 52-week RETHINK-ALZ study. Over 215 patients have completed the 76-week REFOCUS-ALZ study, for a total of over 555 completers. Efficacy Outcomes – Efficacy endpoints are ADAS-Cog12, a cognitive scale, and ADCS-ADL, a functional scale and iADRS, which is a combination of scores from ADAS-Cog and ADCS-ADL. Because the distribution of study participants is numerically skewed towards mild patients, we expect to rely predominantly on mild patients to evaluate drug safety and efficacy. Phase 3 Efficacy Results – All efficacy data from our Phase 3 program remain blinded. No interim analyses on efficacy outcomes are planned. We anticipate top-line data readout for our 52-week study (RETHINK-ALZ) approximately year-end 2024. We anticipate top-line data readout for our 76-week study (REFOCUS-ALZ) approximately mid-year 2025. Statistical Analysis Plan – We have initiated a discussion with the U.S. Food and Drug Administration (FDA) to finalize a statistical analysis plan (SAP), which is a formal document defining the detailed analysis that our independent biostatisticians will undertake as to efficacy data collected in our Phase 3 trials. The SAP includes in-depth technical details and descriptions on the intended clinical trial analysis, the statistical methods and models that will be used, the population being analyzed, the data variables that will be analyzed, how missing data will be accounted for, descriptions of covariates to be included in the statistical model, and other statistical factors, all of which will be prospectively defined, documented and finalized prior to unblinding of any efficacy outcomes. Open-label Extension Study – In October 2022, we announced the initiation of an open-label extension study for our Phase 3 program. This study is designed to provide no-cost access to oral simufilam for up to one year to Alzheimer’s patients who have successfully completed a Phase 3 study of simufilam and who meet other entry criteria. Patient enrollment for this study began in November 2022. To date, over 500 patients entered the open-label extension study. Update on SavaDxSavaDx is an early-stage program focused on detecting the presence of Alzheimer’s disease from a small sample of blood. Development activity related to SavaDx accounts for less than 1% of our research budget. Working with third parties, we continue to evaluate the use of mass spectrometry to detect FLNA or other proteins of interest. The data and information generated from these evaluations continues to be under review for potential intellectual property rights. Findings of Internal InvestigationBeginning in August 2021, certain individuals, later revealed to be short sellers of the Company’s securities, publicly alleged that the Company and certain of its employees and third-party collaborators had engaged in research misconduct in connection with the development of simufilam. These allegations related in part to research that was conducted at the City University of New York (CUNY) pursuant to research contracts with the Company. The Company takes allegations of research misconduct seriously. Accordingly, the Company’s Board of Directors engaged the law firm Orrick Herrington & Sutcliffe LLP to investigate these allegations. The investigation had access to Company personnel, communications, documents, data, and information, and counsel was assisted by technical experts with relevant experience and knowledge. The investigation has found no evidence to substantiate allegations that the Company or its employees engaged in or were aware of research misconduct. About SimufilamSimufilam is Cassava Sciences’ proprietary oral drug candidate. This investigational drug binds to altered filamin A protein in the brain and restores its normal shape and function. By targeting altered filamin A, simufilam may help patients with Alzheimer’s achieve better health outcomes. Cassava Sciences owns exclusive, worldwide rights to its investigational product candidates and related technologies, without royalty obligations to any third party. About Cassava Sciences, Inc.Cassava Sciences is a clinical-stage biotechnology company based in Austin, Texas. Our mission is to detect and treat neurodegenerative diseases, such as Alzheimer’s disease. Our novel science is based on stabilizing—but not removing—a critical protein in the brain. For more information, please visit: https://www.CassavaSciences.com For More Information Contact:Eric Schoen, Chief Financial Officer(512) 501-2450 or ESchoen@CassavaSciences.com Cautionary Note Regarding Forward-Looking Statements: This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that may include but are not limited to statements regarding: the design, scope, conduct, continuation, completion, intended purpose, or future results of our on-going Phase 3 program of simufilam in patients with Alzheimer's disease; the timing of anticipated milestones; the suitability of clinical data from our Phase 3 program to support the filing of an NDA; interim MRI safety data for the Phase 3 program, including ARIA; the finalization of our SAP; the treatment of people with Alzheimer’s disease dementia; the safety or efficacy of simufilam in people with Alzheimer’s disease dementia; expected cash use in future periods; comments made by our employees regarding simufilam, drug effect, and the treatment of Alzheimer’s disease; and potential benefits, if any, of our product candidates. These statements may be identified by words such as “anticipate,” “believe,” “could,” “expect,” “forecast,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” and other words and terms of similar meaning. Such statements are based largely on our current expectations and projections about future events. Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks relating to the ability to conduct or complete clinical studies on expected timelines, the ability to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates, the apparent ability of simufilam to favor patients with mild Alzheimer’s disease; the apparent safety or tolerance of simufilam in our open-label clinical trials; our current expectations regarding timing of clinical data for our Phase 3 studies; any expected clinical results of Phase 3 studies; the treatment of people with Alzheimer’s disease dementia; the safety or efficacy of simufilam in people with Alzheimer’s disease dementia, comments made by our employees regarding simufilam, drug effect, and the treatment of Alzheimer’s disease; potential benefits, if any, of our product candidates and including those described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2022, and future reports to be filed with the SEC. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from expectations in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this news release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, we disclaim any intention or responsibility for updating or revising any forward-looking statements contained in this news release. For further information regarding these and other risks related to our business, investors should consult our filings with the SEC, which are available on the SEC's website at www.sec.gov. All our pharmaceutical assets under development are investigational product candidates. These have not been approved for use in any medical indication by any regulatory authority in any jurisdiction and their safety, efficacy or other desirable attributes, if any, have not been established in any patient population. Consequently, none of our product candidates are approved or available for sale anywhere in the world. Our clinical results from earlier-stage clinical trials may not be indicative of future results from later-stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements or any scientific data we present or publish. We are in the business of new drug discovery, development and commercialization. Our research and development activities are long, complex, costly and involve a high degree of risk. Holders of our common stock should carefully read our Annual Report on Form 10-K in its entirety, including the risk factors therein. Because risk is fundamental to the process of drug discovery, development and commercialization, you are cautioned to not invest in our publicly traded securities unless you are prepared to sustain a total loss of the money you have invested. – Financial Tables Follow – CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(unaudited, in thousands, except per share amounts) Three months ended December 31, Year Ended December 31, 2023 2022 2023 2022Operating expenses Research and development, net of grant reimbursement$18,731 $17,652 $89,423 $68,032 General and administrative 4,058 3,285 16,534 11,988 Total operating expenses 22,789 20,937 105,957 80,020 Operating loss (22,789) (20,937) (105,957) (80,020)Interest income 1,579 1,554 7,833 2,777 Other income, net 291 249 907 997 Net loss$(20,919) $(19,134) $(97,217) $(76,246) Net loss per share, basic and diluted$(0.50) $(0.47) $(2.32) $(1.90) Weighted-average shares used in computing net loss per share, basic and diluted 42,188 40,775 41,932 40,202 CONDENSED CONSOLIDATED BALANCE SHEETS(unaudited, in thousands) Year Ended December 31, 2023 2022Assets Current assets Cash and cash equivalents $121,136 $201,015 Prepaid expenses and other current assets 8,497 10,211 Total current assets 129,633 211,226 Property and equipment, net 21,854 22,864 Operating lease right-of-use assets — 122 Intangible assets, net 176 622 Total assets $151,663 $234,834 Liabilities and stockholders' equity Current liabilities Accounts payable and other accrued expenses $10,573 $4,017 Accrued development expense 3,037 2,280 Accrued compensation and benefits 200 170 Operating lease liabilities, current — 104 Other accrued liabilities 385 492 Total current liabilities 14,195 7,063 Operating lease liabilities, non-current — 35 Other non- current liabilities — 197 Total liabilities 14,195 7,295 Stockholders' equity Common Stock and additional paid-in-capital 518,237 511,091 Accumulated deficit (380,769) (283,552)Total stockholders' equity 137,468 227,539 Total liabilities and stockholders' equity $151,663 $234,834

INSIDE INFORMATIONS BioSenic publishes new evidence of beneficial effects of arsenic trioxide treatment supporting clinical trial for systemic sclerosis Arsenic trioxide (ATO) therapeutic potential to treat systemic sclerosis (SSc) is now confirmed in a new preclinical model - Fra2- characterized by severe pulmonary lesions Mont-Saint-Guibert, Belgium, September 19, 2023, 7.00 am CEST – BIOSENIC (Euronext Brussels and Paris: BIOS), the clinical-stage company specializing in serious autoimmune and inflammatory diseases and cell therapy, today announces the publication of data providing additional key indications of its lead API (Active Pharmaceutical Ingredient) arsenic trioxide (ATO) to treat systemic sclerosis (SSc) in a peer-reviewed international journal. The data are published in an article entitled ‘Arsenic trioxide demonstrates efficacy in a mouse model of preclinical systemic sclerosis’ in the international journal “Arthritis Research & Therapy”. This work studies the effects of ATO on a preclinical auto-immune disease model, that develops severe abnormal vascular remodeling of pulmonary arterioles and nonspecific interstitial pneumonia-like lung disease, closely resembling human systemic sclerosis (SSc)-associated pulmonary hypertension. Marked beneficial effects of ATO on skin and lung fibrosis, vascular damage and scleroderma-like lesions have been previously described by Kavian et al. (J Immunol 2012 May; Arthritis Rheum 2012 Oct) in vitro and in SSc preclinical models, at the Cochin Institute’s facilities in Paris, France. The new data, in a third valuable preclinical model, show a significant reduction in inflammatory infiltration and a strong improvement in vascular remodeling, mediated by an immune status improvement, particularly involving T-cells. These findings represent a substantial advancement in understanding of the complex interplay between inflammation-driven fibrosis and the pathophysiology of SSc. These results give ground to the proposed clinical relevance of ATO treatment in SSc, and more generally in autoimmune pathologies, where lung is often impacted by fibrosis and vascular remodeling. In oncology, ATO is now recognized as a first-line treatment for acute promyelocytic leukaemia, with demonstrated safety and long-term remission. BioSenic had recently further demonstrated the safety and efficacy of ATO treatment in successful clinical programs targeting chronic Graft-versus-Host Disease, in a phase 2 and Systemic Lupus Erythematosus (SLE), in a phase 2a trial. BioSenic believes that the clinical data it has helped to generate over the past decade, together with its ongoing efforts to understand the cellular pathways that are controlled by ATO administration at the right dose and time, now allow for further expansion of clinical trials targets. This applies to new indications in autoimmunity and inflammatory diseases. This is a reason why BioSenic specifically selected SSc for a systematic clinical approach to testing ATO as a novel first-in-class therapy. François Rieger, PhD, Chairman and CEO, BioSenic said: "BioSenic is now focusing on the final preparations for its phase 3 trial with ATO targeting chronic Graft-versus-Host Disease, one of the most common complications affecting survival of allogeneic hematopoietic stem cell transplantation patients. It is also essential that BioSenic continues to pave the way for clinical progression of its ATO programs to treat systemic lupus erythematosus and systemic sclerosis. These new pre-clinical data add to the raft of in vitro and in vivo experimental data generated by BioSenic, by the scientific community and across the industry, supporting the potential of arsenic salt medication in correcting the pathophysiological parameters of the immune system gone awry in a number of autoimmune diseases. These results demonstrate the potential of ATO on the cellular characteristics of damaged organs, with chronic and aggravating functional abnormalities. This will provide invaluable knowledge for BioSenic’s ATO application and formulation for the ongoing clinical development, and further contribute towards the future success of ATO’s late-stage clinical development. Compounded observations, both widely published and collected in various international studies, fully justify the initiation of trials on SSc patients, in need of new and decisive medications, other than existing palliative ones. The hope for success is high and BioSenic is working hard in translating the present fundamental results into real therapeutic advances with the necessary help of available international funding.” About BioSenic BioSenic is a leading biotech company specializing in the development of clinical assets issued from: (i) the arsenic trioxide (ATO) platform (with key target indications including Graft-versus-Host Disease (GvHD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) and (ii), the development of innovative products to meet unmet needs in orthopedics.Following a reverse merger in October 2022, BioSenic combined a strategic positionings and strengths to use, separately and combined, an entirely new arsenal of various anti-inflammatory and anti-autoimmune formulations using the immunomodulatory properties of ATO/oral ATO (OATO) with its innovative cell therapy platform and strong IP for tissue repair protection.BioSenic is based in the Louvain-la-Neuve Science Park in Mont-Saint-Guibert, Belgium. Further information is available at http://www.biosenic.com. About BioSenic technology platforms BioSenic’s technology is based on two main platforms: The ATO platform, which has been successfully developed, has immunomodulatory properties with fundamental effects on the activated cells of the immune system. The first effect is the increase of the cell oxidative stress in activated B, T and other cells of the innate/adaptative immune system to the point they will enter a cell death program (apoptosis) and be eliminated. The second effect is potent immunomodulatory properties on several cytokines involved in inflammatory or autoimmune cell pathways, with return to homeostasis. One direct application is its use in onco-immunology to treat GvHD (Graft-versus-Host Disease) in its chronic, established stage. cGvHD is one of the most common and clinically significant complications affecting long-term survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT). cGvHD is primarily mediated by the transplanted immune cells that can lead to severe multiorgan damage. BioSenic has been successful in a Phase 2 trial with its intravenous formulation, which has orphan drug designation status by FDA and EMA. The Company is heading towards an international Phase 3 confirmatory study, with its new, IP-protected, OATO formulation. Another selected target is moderate-to-severe forms of systemic lupus erythematosus (SLE), using the same oral formulation. ATO has shown good safety and significant clinical efficacy on several affected organs (skin, mucosae and the gastrointestinal tract) in an early Phase 2a study. Systemic sclerosis is also part of the clinical pipeline of BioSenic. This serious chronic disease badly affects skin, lungs or vascularization, and has no actual current effective treatment. Preclinical studies on pertinent animal models are positive, giving good grounds to launch a Phase 2 clinical protocol. The allogeneic cell and gene therapy platform developed by BioSenic, with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs), which can be stored at the point of use in hospitals. ALLOB represents a unique and proprietary approach to organ repair and specifically to bone regeneration, by turning undifferentiated stromal cells from healthy donors into bone-forming cells on the site of injury. ALLOB has recently been evaluated in a randomized, double-blind, placebo-controlled Phase 2b study in patients with high-risk tibial fractures, using its optimized production process, after a successful first safety and efficacy study (Phase 1/2a) on fractured long bones, with late-delayed union. However, in June 2023, BioSenic decided to suspend its interventional trial on fracture healing using ALLOB, following negative results obtained for the primary endpoint in this exploratory Phase 2b clinical trial, interpreted as a failure of a too early cell injection, just after fracture. BioSenic is now focusing on determining the best time to optimise the efficacy of ALLOB (choice between early or late treatment). Note: Biosenic has reevaluated a previous important and years-long clinical development program. In March 2023, after the clinical identification of distinct OA subtypes, BioSenic delivered a new post-hoc analysis of its Phase 3 JTA-004 trial on knee OA, demonstrating positive action on the most severely affected patient subpopulation. This new post-hoc analysis drastically changes the therapeutic profile of the combined components and allows for better patient targeting in future clinical developments. This leads to a next generation of JTA, off-the-shelf enhanced viscosupplement to treat knee osteoarthritis (OA), made of a unique combination of mammalian plasma proteins, derivatives of hyaluronic acid (a natural component of synovial fluid in the knee) and a third active component. JTA or some derivatives are intended to provide effective lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic (OA) pain and inflammation. The company, will nevertheless focus its present R&D and clinical activities on a selective, accelerated development of its autoimmune (ATO/OATO) platform. For further information, please contact: BioSenic SAFrançois Rieger, PhD, Chief Executive OfficerTel: +33 (0)671 73 31 59investorrelations@biosenic.com International Media Enquiries:IB CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency For French Investor Enquiries:Seitosei ActifinGhislaine GasparettoTel: +33 (0)1 56 88 11 22ggasparetto@actifin.fr Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors’ current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such person’s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release. BioSenic publishes new evidence of beneficial effects of arsenic trioxide treatment supporting clinical trial for systemic sclerosis Arsenic trioxide (ATO) therapeutic potential to treat systemic sclerosis (SSc) is now confirmed in a new preclinical model - Fra2- characterized by severe pulmonary lesions Mont-Saint-Guibert, Belgium, September 19, 2023, 7.00 am CEST – BIOSENIC (Euronext Brussels and Paris: BIOS), the clinical-stage company specializing in serious autoimmune and inflammatory diseases and cell therapy, today announces the publication of data providing additional key indications of its lead API (Active Pharmaceutical Ingredient) arsenic trioxide (ATO) to treat systemic sclerosis (SSc) in a peer-reviewed international journal. The data are published in an article entitled ‘Arsenic trioxide demonstrates efficacy in a mouse model of preclinical systemic sclerosis’ in the international journal “Arthritis Research & Therapy”. This work studies the effects of ATO on a preclinical auto-immune disease model, that develops severe abnormal vascular remodeling of pulmonary arterioles and nonspecific interstitial pneumonia-like lung disease, closely resembling human systemic sclerosis (SSc)-associated pulmonary hypertension. Marked beneficial effects of ATO on skin and lung fibrosis, vascular damage and scleroderma-like lesions have been previously described by Kavian et al. (J Immunol 2012 May; Arthritis Rheum 2012 Oct) in vitro and in SSc preclinical models, at the Cochin Institute’s facilities in Paris, France. The new data, in a third valuable preclinical model, show a significant reduction in inflammatory infiltration and a strong improvement in vascular remodeling, mediated by an immune status improvement, particularly involving T-cells. These findings represent a substantial advancement in understanding of the complex interplay between inflammation-driven fibrosis and the pathophysiology of SSc. These results give ground to the proposed clinical relevance of ATO treatment in SSc, and more generally in autoimmune pathologies, where lung is often impacted by fibrosis and vascular remodeling. In oncology, ATO is now recognized as a first-line treatment for acute promyelocytic leukaemia, with demonstrated safety and long-term remission. BioSenic had recently further demonstrated the safety and efficacy of ATO treatment in successful clinical programs targeting chronic Graft-versus-Host Disease, in a phase 2 and Systemic Lupus Erythematosus (SLE), in a phase 2a trial. BioSenic believes that the clinical data it has helped to generate over the past decade, together with its ongoing efforts to understand the cellular pathways that are controlled by ATO administration at the right dose and time, now allow for further expansion of clinical trials targets. This applies to new indications in autoimmunity and inflammatory diseases. This is a reason why BioSenic specifically selected SSc for a systematic clinical approach to testing ATO as a novel first-in-class therapy. François Rieger, PhD, Chairman and CEO, BioSenic said: "BioSenic is now focusing on the final preparations for its phase 3 trial with ATO targeting chronic Graft-versus-Host Disease, one of the most common complications affecting survival of allogeneic hematopoietic stem cell transplantation patients. It is also essential that BioSenic continues to pave the way for clinical progression of its ATO programs to treat systemic lupus erythematosus and systemic sclerosis. These new pre-clinical data add to the raft of in vitro and in vivo experimental data generated by BioSenic, by the scientific community and across the industry, supporting the potential of arsenic salt medication in correcting the pathophysiological parameters of the immune system gone awry in a number of autoimmune diseases. These results demonstrate the potential of ATO on the cellular characteristics of damaged organs, with chronic and aggravating functional abnormalities. This will provide invaluable knowledge for BioSenic’s ATO application and formulation for the ongoing clinical development, and further contribute towards the future success of ATO’s late-stage clinical development. Compounded observations, both widely published and collected in various international studies, fully justify the initiation of trials on SSc patients, in need of new and decisive medications, other than existing palliative ones. The hope for success is high and BioSenic is working hard in translating the present fundamental results into real therapeutic advances with the necessary help of available international funding.” About BioSenic BioSenic is a leading biotech company specializing in the development of clinical assets issued from: (i) the arsenic trioxide (ATO) platform (with key target indications including Graft-versus-Host Disease (GvHD), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) and (ii), the development of innovative products to meet unmet needs in orthopedics.Following a reverse merger in October 2022, BioSenic combined a strategic positionings and strengths to use, separately and combined, an entirely new arsenal of various anti-inflammatory and anti-autoimmune formulations using the immunomodulatory properties of ATO/oral ATO (OATO) with its innovative cell therapy platform and strong IP for tissue repair protection.BioSenic is based in the Louvain-la-Neuve Science Park in Mont-Saint-Guibert, Belgium. Further information is available at http://www.biosenic.com. About BioSenic technology platforms BioSenic’s technology is based on two main platforms:1) The ATO platform, which has been successfully developed, has immunomodulatory properties with fundamental effects on the activated cells of the immune system. The first effect is the increase of the cell oxidative stress in activated B, T and other cells of the innate/adaptative immune system to the point they will enter a cell death program (apoptosis) and be eliminated. The second effect is potent immunomodulatory properties on several cytokines involved in inflammatory or autoimmune cell pathways, with return to homeostasis. One direct application is its use in onco-immunology to treat GvHD (Graft-versus-Host Disease) in its chronic, established stage. cGvHD is one of the most common and clinically significant complications affecting long-term survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT). cGvHD is primarily mediated by the transplanted immune cells that can lead to severe multiorgan damage. BioSenic has been successful in a Phase 2 trial with its intravenous formulation, which has orphan drug designation status by FDA and EMA. The Company is heading towards an international Phase 3 confirmatory study, with its new, IP-protected, OATO formulation. Another selected target is moderate-to-severe forms of systemic lupus erythematosus (SLE), using the same oral formulation. ATO has shown good safety and significant clinical efficacy on several affected organs (skin, mucosae and the gastrointestinal tract) in an early Phase 2a study. Systemic sclerosis is also part of the clinical pipeline of BioSenic. This serious chronic disease badly affects skin, lungs or vascularization, and has no actual current effective treatment. Preclinical studies on pertinent animal models are positive, giving good grounds to launch a Phase 2 clinical protocol. 2) The allogeneic cell and gene therapy platform developed by BioSenic, with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs), which can be stored at the point of use in hospitals. ALLOB represents a unique and proprietary approach to organ repair and specifically to bone regeneration, by turning undifferentiated stromal cells from healthy donors into bone-forming cells on the site of injury. ALLOB has recently been evaluated in a randomized, double-blind, placebo-controlled Phase 2b study in patients with high-risk tibial fractures, using its optimized production process, after a successful first safety and efficacy study (Phase 1/2a) on fractured long bones, with late-delayed union. However, in June 2023, BioSenic decided to suspend its interventional trial on fracture healing using ALLOB, following negative results obtained for the primary endpoint in this exploratory Phase 2b clinical trial, interpreted as a failure of a too early cell injection, just after fracture. BioSenic is now focusing on determining the best time to optimise the efficacy of ALLOB (choice between early or late treatment).Note: Biosenic has reevaluated a previous important and years-long clinical development program. In March 2023, after the clinical identification of distinct OA subtypes, BioSenic delivered a new post-hoc analysis of its Phase 3 JTA-004 trial on knee OA, demonstrating positive action on the most severely affected patient subpopulation. This new post-hoc analysis drastically changes the therapeutic profile of the combined components and allows for better patient targeting in future clinical developments. This leads to a next generation of JTA, off-the-shelf enhanced viscosupplement to treat knee osteoarthritis (OA), made of a unique combination of mammalian plasma proteins, derivatives of hyaluronic acid (a natural component of synovial fluid in the knee) and a third active component. JTA or some derivatives are intended to provide effective lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic (OA) pain and inflammation. The company, will nevertheless focus its present R&D and clinical activities on a selective, accelerated development of its autoimmune (ATO/OATO) platform. For further information, please contact: BioSenic SAFrançois Rieger, PhD, Chief Executive OfficerTel: +33 (0)671 73 31 59investorrelations@biosenic.com International Media Enquiries:IB CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency For French Investor Enquiries:Seitosei ActifinGhislaine GasparettoTel: +33 (0)1 56 88 11 22ggasparetto@actifin.fr Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors’ current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such person’s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

New cell biology data from Europe shows simufilam interrupts a pathogenic signaling pathway in Alzheimer’s disease. Results corroborate prior research from other academic researchers. These data once again confirm the biological activity of simufilam. AUSTIN, Texas, Sept. 11, 2023 (GLOBE NEWSWIRE) --Cassava Sciences Inc. (Nasdaq: SAVA), a biotechnology company focused on Alzheimer’s disease, today announced the publication of new research that confirms the biological activity of simufilam. Simufilam is Cassava Sciences’ novel drug candidate for people with Alzheimer’s disease dementia and is currently under evaluation in a pair of global Phase 3 clinical trials. Researchers at the Cochin Institute (Paris, France) used a highly precise cell-based assay to show that simufilam interrupts amyloid binding to the α7 nicotinic acetylcholine receptor (α7nAChR). Cassava Sciences believes this protein interaction underlies simufilam’s mechanism of action in Alzheimer’s disease. The research appears in a special issue of International Journal of Molecular Sciences, a peer-reviewed scientific publication. “Four academic institutions have now generated data in support of the biological activity of simufilam,” said Remi Barbier, President & CEO. “They can’t all be wrong.” “Today’s data are an elegant confirmation of simufilam’s mechanism of action,” said Lindsay Burns, PhD, VP of Neuroscience at Cassava Sciences and co-author on the publication. “They show that simufilam potently disrupts a known pathological action of amyloid β using a robust and highly sensitive assay based on a technique called TR-FRET.” Journal: International Journal of Molecular Sciences, special issue: Neurodegenerative Disease: From Molecular Basis to Therapy Title: Simufilam Reverses Aberrant Receptor Interactions of Filamin A in Alzheimer’s Disease Access: Available on-line, and expected to be posted shortly in the publication section of Summary of New Research A team of researchers led by Dr. Ralf Jockers at the Cochin Institute (Paris, France) used an amyloid binding assay to measure the ability of simufilam to prevent amyloid β from binding to the α7 nicotinic acetylcholine receptor (α7nAChR). Their study showed that simufilam potently reduced amyloid β binding to α7nAChR. This new data is consistent with prior research showing that simufilam prevents amyloid β from binding to α7nAChR. The Cochin Institute is a biomedical research center affiliated with public research organizations (Inserm and CNRS) and the University of Paris, France. Dr. Jockers and his team developed their amyloid binding assay as a means of determining whether ‘a novel generation of [Alzheimer’s disease] drug candidates could effectively interrupt the high-affinity binding of amyloid β to α7nAChR.’1 The cell-based assay uses time-resolved fluorescence resonance energy transfer (TR-FRET) to accurately measure the degree to which a drug candidate such as simufilam can inhibit amyloid β binding to α7nAChR. Testing several concentrations of a drug in this assay allows calculation of its potency. TR-FRET is different from any prior technique used by other academic collaborators to show the biological activity of simufilam. The Cochin Institute is the fourth academic institution to produce data supporting the biological activity of simufilam on FLNA. Simufilam was developed by Cassava Sciences in collaboration with researchers at CUNY School of Medicine who first showed the effects of simufilam on FLNA and on the signaling pathways of amyloid β in Alzheimer’s disease. In 2020, Dr. Angelique Bordey of Yale University published data showing that simufilam reduced seizure frequency and alleviated neuronal abnormalities in mice with a form of epilepsy associated with FLNA overexpression. In 2023, Dr. Erika Peverelli of the University of Milan showed that simufilam reduced FLNA phosphorylation and enhanced the effects of a pituitary cancer treatment in experiments using both patient tumor biopsies and rat cell lines. On-going Phase 3 Studies with Simufilam Cassava Sciences is evaluating simufilam oral tablets for Alzheimer’s disease dementia in two global Phase 3 clinical studies. These are randomized, double-blind, placebo-controlled trials. The Phase 3 program aims to enroll a total of approximately 1,750 patients with mild-to-moderate Alzheimer’s disease who also meet other study eligibility criteria. Patient enrollment is expected to be completed for both Phase 3 studies by yearend 2023. Both Phase 3 studies have received a Special Protocol Assessment (SPA) from the U.S. Food and Drug Administration. About Simufilam Simufilam is Cassava Sciences’ proprietary, small molecule (oral) drug candidate for the treatment of Alzheimer’s disease dementia. Unlike monoclonal antibody treatments for Alzheimer’s disease, simufilam does not purport to directly remove amyloid β from the brain. Instead, simufilam binds to altered filamin A (FLNA), a receptor-associated protein that amyloid β requires to bind to α7nAChR. By preventing amyloid β from signaling via α7nAChR and other receptors, simufilam reduces the neurodegeneration and neuroinflammation characteristic of Alzheimer’s disease. Cassava Sciences owns worldwide development and commercial rights to its research programs in Alzheimer’s disease, and related technologies, without royalty obligations to any third party. About Cassava Sciences, Inc. Cassava Sciences is a clinical-stage biotechnology company based in Austin, Texas. Our mission is to detect and treat neurodegenerative diseases, such as Alzheimer’s disease. For more information, please visit: Disclosures Cassava Sciences’ product candidates have not been approved by any regulatory authority or health agency, and their safety or efficacy have not been established in humans. The TR-FRET research was conducted by the Cochin Institute and funded by Cassava Sciences. The Cochin Institute has no financial benefit tied to the outcome of the research. The contents of this press release are solely the responsibility of Cassava Sciences and do not represent the views of the National Institutes of Health, the Cochin Institute or any other research or governmental agency. For More Information Contact: Eric Schoen, Chief Financial Officer (512) 501-2450 or ESchoen@CassavaSciences.com Cautionary Note Regarding Forward-Looking Statements: This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to: our current expectations regarding the target patient enrollment numbers for our Phase 3 studies; comments made by our employees regarding the evaluation of simufilam in Phase 3 trials of Alzheimer’s disease; the mechanism of action of simufilam, or any lab methods used to demonstrate such effects; and potential benefits, if any, of our product candidates. These statements may be identified by words such as “may,” “anticipate,” “believe,” “could,” “expect,” “would”, “forecast,” “intend,” “plan,” “possible,” “potential,” and other words and terms of similar meaning. Drug development involves a high degree of risk, and only a small number of research and development programs result in regulatory approval and commercialization of a product. Our interim data and analyses should not be relied upon as predictive of full study results for any of our studies. Our clinical results from earlier-stage clinical trials may not be indicative of full study results, or results from later-stage, or larger scale clinical trials, and do not ensure regulatory approval. You should not place undue reliance on these statements or any scientific data we present or publish. Such statements are based largely on our current expectations and projections about future events. Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks relating to the ability to conduct or complete clinical studies on expected timelines, to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates, the severity and duration of health care precautions given the COVID-19 pandemic, any unanticipated impacts of the pandemic on our business operations, and including those described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2021, and future reports to be filed with the SEC. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from expectations in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this news release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, we disclaim any intention or responsibility for updating or revising any forward-looking statements contained in this news release. For further information regarding these and other risks related to our business, investors should consult our filings with the SEC, which are available on the SEC's website at . ______________________ 1 Cecon E, Dam J, Luka M, Gautier C, Chollet AM, Delagrange P, Danober L, Jockers R. Quantitative assessment of oligomeric amyloid β peptide binding to α7 nicotinic receptor. Br J Pharmacol. 2019 Sep;176(18):3475-3488.