Creutzfeldt-Jakob Syndrome

- PHOENIX Study Did Not Meet Prespecified Primary or Secondary Endpoints - Data From 664-Participant Study Reinforce That AMX0035 is Generally Safe and Well-Tolerated - Within the Next Eight Weeks, Amylyx Will Continue to Engage With Regulatory Authorities and the ALS Community to Share Topline Data; Amylyx Will Share Plans for RELYVRIO/ALBRIOZA in ALS Which May Include Voluntarily Withdrawing RELYVRIO/ALBRIOZA From the Market - At This Time, RELYVRIO/ALBRIOZA Will Continue to be Available for People Living With ALS; Amylyx Has Voluntarily Decided to Pause Promotion; Related Patient Support Services Will Remain in Place - Studies With AMX0035 in Wolfram Syndrome (WS) and Progressive Supranuclear Palsy (PSP) to Continue Based on Data Supporting its Potential in These Diseases - Amylyx to Host Investor Conference Call Today, March 8, at 8:00 a.m. ET CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced topline results from PHOENIX, a global, 48-week, randomized, placebo-controlled Phase 3 clinical trial of AMX0035 (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]; RELYVRIO® in the U.S., ALBRIOZA™ in Canada) in people living with amyotrophic lateral sclerosis (ALS). PHOENIX did not meet its primary endpoint of reaching statistical significance (p=0.667) as measured by change from baseline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at Week 48, nor was there statistical significance seen in secondary endpoints. Amylyx plans to present the data from PHOENIX at an upcoming medical meeting and will publish the results in a medical journal later this year. Amylyx will continue to engage with regulatory authorities and the broader ALS community, including ALS specialists and other multidisciplinary experts, people living with ALS, and advocates, to discuss the results from PHOENIX within the next eight weeks and make informed decisions. Amylyx intends to share plans for RELYVRIO/ALBRIOZA in ALS, which may include voluntarily withdrawing RELYVRIO/ALBRIOZA from the market. At this time, RELYVRIO/ALBRIOZA and its related patient support program will continue to be available for people living with ALS. Amylyx has voluntarily decided to pause promotion of the medication during this time. “We are surprised and deeply disappointed by the PHOENIX results following the positive data from the CENTAUR trial. Our main priority at the moment is sharing the information with people living with ALS and their treating physicians; this is part of our continued commitment to them and our mission. Over the next eight weeks, our team will continue to engage with regulatory authorities and the ALS community to discuss the results from PHOENIX. We will be led in our decisions by two key principles: doing what is right for people living with ALS, informed by regulatory authorities and the ALS community, and by what the science tells us. On behalf of the entire Amylyx team, we are grateful to the ALS community and for the dedication of trial participants, investigators, and study site teams. With data collected from 664 participants in PHOENIX, we are certain there will be important learnings that will help inform future ALS research. We are steadfast in our commitment to the ALS community and our mission, including with AMX0035 where it has shown potential in neurodegenerative diseases such as Wolfram syndrome and progressive supranuclear palsy, and with AMX0114, our investigational antisense oligonucleotide targeting calpain-2, in ALS,” said Justin Klee and Joshua Cohen, Co-CEOs of Amylyx. PHOENIX Study Results: The Phase 3 PHOENIX study enrolled 664 adults living with ALS. Participants were randomized three-to-two to receive either AMX0035 or placebo, with both treatment groups receiving standard-of-care. Continuation of a stable dosing regimen of riluzole and/or edaravone was permitted. PHOENIX did not meet the primary endpoint: There was no significant difference observed between participants treated with AMX0035 and placebo in ALSFRS-R total score change from baseline at Week 48 (p=0.667). No significant difference was observed in the subset of participants who met the CENTAUR trial criteria. There were also no significant differences observed across secondary endpoints. Consistent safety and tolerability profile: AMX0035 was well-tolerated in PHOENIX. There were no new safety signals, reinforcing the favorable and manageable safety pro with AMX0035 to date. European participants who completed the 48-week randomized phase had the option to enroll in an open label extension of the trial of up to two years in duration, which remains ongoing. Science of AMX0035: AMX0035, a specially formulated oral fixed-dose combination of PB and TURSO, has been shown in numerous preclinical studies to have a robust, synergistic effect in targeting two different destructive neurodegenerative disease pathways by mitigating endoplasmic reticulum stress and the associated unfolded protein response and mitochondrial dysfunction thereby reducing neuronal cell death. Additionally, AMX0035 has been shown to also reduce markers associated with neurodegenerative diseases in clinical trials, including a reduction of tau, a key protein aggregate shared across several neurodegenerative diseases, and YKL-40, a marker of neuroinflammation. Update on Ongoing AMX0035 Studies: The global, randomized, double-blind, placebo-controlled Phase 3 ORION clinical study of AMX0035 in PSP remains ongoing. The first participant was dosed in December 2023, and the Company is planning for an interim analysis. Topline results continue to be anticipated in 2025 or 2026. Data from the ongoing 12-participant, single site, open-label Phase 2 HELIOS clinical study are demonstrating evidence of clinical activity of AMX0035 in Wolfram syndrome. This study is fully recruited, and the Company plans to present preliminary data in the second quarter of 2024. Investor Conference Call Information Amylyx’ management team will host a live conference call and webcast today, March 8, 2024, at 8:00 a.m. ET to discuss the results of the PHOENIX trial. To participate in the conference call, please dial +1 (877) 870-4263 (U.S.), +1 (855) 669-9657 (Canada), or +1 (412) 317-0790 (International) at least 10 minutes prior to the start time and ask to be joined into the Amylyx Pharmaceuticals call. All interested parties are invited to access a live broadcast of the call via a webcast, which will be available on the “Events and Presentations” page in the “Investors” section of the Company’s website at investors.amylyx.com/news-events/events. An archived webcast will be available on the Company's website approximately two hours after the conference call and will be available for replay for 90 days following the call. About the PHOENIX Trial PHOENIX was a 48-week, randomized, placebo-controlled, global Phase 3 clinical trial further evaluating the safety and efficacy of AMX0035 (sodium phenylbutyrate and taurursodiol) for the treatment of ALS. The primary efficacy outcome of the trial was change from baseline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score at 48 weeks. Secondary endpoints include quality of life patient-reported outcome assessments, overall survival, and respiratory function as measured by slow vital capacity (SVC). Safety and tolerability were also assessed. European participants who completed the 48-week trial had the option to enroll in an open-label extension (OLE) phase. During this phase, all participants receive AMX0035, and continued safety and efficacy measures will be assessed. About the CENTAUR Trial CENTAUR was a multicenter Phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized, placebo-controlled phase and an open-label long-term follow-up phase. The trial met its primary efficacy endpoint of reducing functional decline as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). Overall, reported rates of adverse events and discontinuations were similar between AMX0035 and placebo groups during the 24-week randomized phase; however, gastrointestinal events occurred with greater frequency (≥2%) in the AMX0035 group. Detailed data from CENTAUR is published in the New England Journal of Medicine (NEJM) and Muscle & Nerve. The CENTAUR trial was funded, in part, by the ALS ACT grant and the ALS Ice Bucket Challenge, and was supported by The ALS Association, ALS Finding a Cure (a program of The Leandro P. Rizzuto Foundation), the Northeast ALS Consortium, and the Sean M. Healey & AMG Center for ALS at Mass General. About AMX0114 AMX0114 is an antisense oligonucleotide designed to target the gene encoding calpain-2, a key contributor to the axonal (Wallerian) degeneration pathway. Axonal degeneration has been recognized as an important early contributor to the clinical presentation and pathogenesis of ALS and other neurodegenerative diseases. Calpain-2 has been implicated in the pathogenesis of ALS based on findings of elevated levels of calpain-2 and its cleavage products in postmortem ALS tissue, therapeutic benefit of calpain-2 modulation in animal models of ALS, and the role of calpain-2 in cleaving neurofilament, a broadly researched biomarker in ALS. Preclinical studies completed to date have shown that AMX0114 achieves potent, dose-dependent, and durable knockdown of CAPN2 mRNA expression and calpain-2 protein levels in human motor neurons. Moreover, in preclinical efficacy studies, treatment with AMX0114 reduced extracellular neurofilament light chain levels following neurotoxic insult in iPSC-derived human motor neurons, and improved survival of iPSC-derived human motor neurons harboring ALS-linked, pathogenic TDP-43 mutations. About ALS Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. More than 90% of people with ALS have sporadic disease, showing no clear family history. ALS affects around 30,000 people in the U.S., and more than 30,000 people are estimated to be living with ALS in Europe (European Union and United Kingdom). People living with ALS have a median survival of approximately two years from diagnosis. About HELIOS The HELIOS trial (NCT05676034) is a 12-participant, open-label proof of biology, Phase 2 trial designed to study the effect of AMX0035 on safety and tolerability, and various measures of endocrinological, neurological, and ophthalmologic function in adult participants living with Wolfram syndrome (WS). About Wolfram Syndrome Wolfram syndrome (WS) is an autosomal recessive neurodegenerative disease characterized by childhood-onset diabetes, optic nerve atrophy, and neurodegeneration. Common manifestations of WS include diabetes mellitus, optic nerve atrophy, central diabetes insipidus, sensorineural deafness, neurogenic bladder, and progressive neurologic difficulties. Genetic and experimental evidence suggest that endoplasmic reticulum (ER) dysfunction is a critical pathogenic component of WS. The prognosis of WS is poor, and many people with the disease die prematurely with severe neurological disabilities. About the ORION Trial The Phase 3 ORION trial (NCT06122662) is a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial designed to assess the efficacy, safety, and tolerability of AMX0035 compared to placebo in people living with progressive supranuclear palsy (PSP). The ORION Phase 3 trial was designed and planned in collaboration with key global academic leaders, people living with PSP and their caregivers, and industry advocacy organizations. About PSP Progressive supranuclear palsy (PSP) is a sporadic, rare and adult-onset neurodegenerative disorder that affects walking and balance, eye movement, swallowing, and speech. People living with PSP have a life expectancy of six to eight years after initial diagnosis, and its epidemiology is similar to that of amyotrophic lateral sclerosis (ALS). PSP typically begins in late-middle age and rapidly progresses over time. The disease affects approximately seven in 100,000 people worldwide, and there are currently no disease-modifying therapies approved for the treatment of PSP. PSP is characterized by abnormal tau inclusions and is consequently also known as a tauopathy. Similar to other neurodegenerative diseases, pathophysiologic changes underlying PSP are multifactorial with several genetic and environmental factors likely contributing to tau dysfunction and aggregation. Multiple pathways, including genetic mutations, endoplasmic reticulum (ER) stress and the activation of unfolded protein response, mitochondrial dysfunction, and neuroinflammation have been implicated as contributors to tau dysfunction and aggregation. About AMX0035 / RELYVRIO® / ALBRIOZA™ AMX0035 is an oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the U.S.). It is approved as RELYVRIO® to treat amyotrophic lateral sclerosis (ALS) in adults in the U.S. and approved with conditions as ALBRIOZA™ for the treatment of ALS in Canada. AMX0035 is being studied for the potential treatment of other neurodegenerative diseases, and Amylyx is exploring its treatment in other populations and regions. The formulation of RELYVRIO, ALBRIOZA, and AMX0035 is identical. RELYVRIO® (sodium phenylbutyrate and taurursodiol) Safety Information for United States WARNINGS AND PRECAUTIONS Risk in Patients with Enterohepatic Circulation Disorders, Pancreatic Disorders, or Intestinal Disorders RELYVRIO contains taurursodiol, which is a bile acid. In patients with disorders that interfere with bile acid circulation, there may be an increased risk for worsening diarrhea, and patients should be monitored appropriately for this adverse reaction. Pancreatic insufficiency, intestinal malabsorption, or intestinal diseases that may alter the concentration of bile acids may also lead to decreased absorption of either of the components of RELYVRIO. Because different enterohepatic circulation, pancreatic, and intestinal disorders have varying degrees of severity, consider consulting with a specialist. Patients with disorders of enterohepatic circulation (e.g., biliary infection, active cholecystitis), severe pancreatic disorders (e.g., pancreatitis), and intestinal disorders that may alter concentrations of bile acids (e.g., ileal resection, regional ileitis) were excluded from the study; therefore, there is no clinical experience in these conditions. Use in Patients Sensitive to High Sodium Intake RELYVRIO has a high salt content. Each initial daily dosage of 1 packet contains 464 mg of sodium; each maintenance dosage of 2 packets daily contains 928 mg of sodium. In patients sensitive to salt intake (e.g., those with heart failure, hypertension, or renal impairment), consider the amount of daily sodium intake in each dose of RELYVRIO and monitor appropriately. ADVERSE REACTIONS The most common adverse reactions (at least 15% and at least 5% greater than placebo) with RELYVRIO were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first 3 weeks of treatment. Please click here for RELYVRIO Full U.S. Prescribing Information. About Amylyx Pharmaceuticals Amylyx Pharmaceuticals, Inc. is committed to supporting and creating more moments for the neurodegenerative disease community through the discovery and development of innovative new treatments. Amylyx is headquartered in Cambridge, Massachusetts and has operations in Canada, EMEA, and Japan. For more information, visit amylyx.com and follow us on LinkedIn and X, (formerly Twitter). For investors, please visit investors.amylyx.com. Forward-Looking Statements Statements contained in this press release and related comments in our earnings conference call regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, Amylyx’ expectations regarding: interactions with regulatory authorities; the continued availability of RELYVRIO/ALBRIOZA for people living with ALS while such interactions are ongoing; the pausing of promotion of RELYVRIO/ALBRIOZA; pathways for continued access for patients if RELYVRIO/ALBRIOZA are withdrawn from the market; the possibility for Amylyx to voluntarily withdraw RELYVRIO/ALBRIOZA from the market; the continued evaluation of AMX0035 in other neurodegenerative diseases, including the timing for expected data readouts in the ORION and HELIOS studies; and the evidence of biological activity of AMX0035 in Wolfram syndrome. Any forward-looking statements in this press release and related comments in the Company's conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2023, and subsequent filings with the SEC. All forward-looking statements contained in this press release and related comments in our conference call speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

4Q 2023 Total Revenue of $73.9 Million; FY 2023 Total Revenue of $258.2 Million 4Q 2023 Adjusted EBITDA(1) of $18.6 Million; FY 2023 Adjusted EBITDA of $40.3 Million 4Q 2023 Adjusted Net Income(2) of $8.5 Million; FY 2023 Adjusted Net Income of $0.7 Million FY 2024 and 2025 Total Revenue Guidance Increased to More Than $330 Million and $380 Million, Respectively FY 2024 Net Income Guidance Increased to More Than $65 Million and Adjusted EBITDA Guidance Increased to More Than $90 Million FY 2025 Net Income Guidance Increased to More than $115 Million and Adjusted EBITDA Guidance Increased to More Than $140 Million Innovative Growth Opportunities Targeting Manufacturing and New Pipeline Hyperimmune Globulin to Advance During 2024 Conference Call Scheduled for Today at 4:30 p.m. ET RAMSEY, N.J. and BOCA RATON, Fla., Feb. 28, 2024 (GLOBE NEWSWIRE) -- ADMA Biologics, Inc. (Nasdaq: ADMA) (“ADMA” or the “Company”), an end-to-end commercial biopharmaceutical company dedicated to manufacturing, marketing and developing specialty biologics, today announced its fourth quarter and full year 2023 financial results and provided a business update. “We are pleased with our 2023 performance, which marked first-time positive adjusted net income on a full year basis. This is a testament to the exponential revenue growth of our commercial specialty biologics product portfolio and effective fiscal and operational management. As ADMA’s forward-looking business trends gain momentum, we're revising financial guidance upwards for both 2024 and 2025, increasing top and bottom-line projections,” said Adam Grossman, President and Chief Executive Officer of ADMA. “We believe our growing commercial success will be sustained by the recent and continuous expansion of ASCENIV utilization. We believe our unwavering focus on the immune deficient patient segment has allowed ADMA to establish itself as a premier provider of specialty biologics. We are confident that there is significant growth for ASCENIV within its addressable market, further penetrating the treatment setting comprised of immune deficient patients grappling with complex comorbidities.” Mr. Grossman continued, “In conjunction with the ongoing expansion of our commercial product portfolio, we look forward to advancing new growth initiatives, including innovations to ADMA’s manufacturing processes and potential yield enhancement, as well as progress with our preclinical S.pneumonia pipeline program. Based upon current market factors, we anticipate 2024 being defined by top-tier revenue and earnings growth, cash generation, and the further de-risking of growth initiatives which, if successful, we believe have the potential to significantly impact ADMA's peak revenue and earnings targets. We believe our proven internal R&D capabilities, broad intellectual property estate and successful establishment of our innovative commercial model position the Company for enduring success in the future.” (1) Adjusted EBITDA is a non-GAAP financial measure. For a reconciliation of Adjusted EBITDA to the most comparable GAAP measure, please see the reconciliation included in the financial tables. (2) Adjusted net income is a non-GAAP financial measure. For reconciliation of Adjusted net income to the most comparable GAAP measure, please see the reconciliation included in the financial tables. 2024-2025 Financial Guidance: FY 2024 and 2025 total revenue now expected to be more than $330 million and $380 million, respectively, increased from prior guidance of $320 million and $370 million, respectively FY 2024 and 2025 net income now expected to exceed $65 million and $115 million, respectively, increased from prior guidance of $60 million and $110 million, respectively FY 2024 Adjusted EBITDA now anticipated to exceed $90 million, increased from $85 million previously; FY 2025 Adjusted EBITDA expected to exceed $140 million Innovative Growth Opportunities: Below are the Company’s ongoing initiatives which, if successful, represent potential upside to newly provided guidance ranges: Biologic Production Yield Enhancement: The Company continues to progress with development scale and laboratory analyses, advancing the Company’s initiative to capture additional immune globulin (IG) production yields with the same quantities of starting raw material. These initiatives are subject to further evaluation, validation of commercial-scale production and requisite regulatory review. If proven successful, we believe these yield enhancements will potentially provide significant upside to the Company’s peak financial targets in the future. New Pipeline Introduction - S. pneumonia Hyperimmune Globulin: S. pneumonia is the primary cause of community-acquired pneumonia (CAP) in the United States, ranking ninth in overall mortality. The increasing prevalence of anti-infective resistance underscores the urgent need for both prophylactic and therapeutic interventions. Annually, about one million U.S. adults contract pneumococcal pneumonia, leading to 400,000 hospitalizations and a 5-7% mortality rate, with approximately 7,000 deaths attributed to anti-infective resistance. Despite available vaccines, vaccine-naive and immune-compromised patients remain at risk, highlighting the potential benefits of immediately available neutralizing antibodies provided by a hyperimmune globulin in both in-patient and out-patient settings. We estimate that, if approved, an S. pneumonia hyperimmune globulin could generate peak annual revenue of $300-500 million. ADMA holds various U.S. and foreign patents, including U.S. Patent Nos. 10,259,865 and 11,084,870, and EP Patent No. 3375789, each with patent terms extending to 2037, along with numerous pending applications. These patents cover ADMA’s proprietary pneumococcal hyperimmune technology, encompassing hyperimmune anti-pneumococcal immune globulin, methods of preparation, and utilization for treating S. pneumonia infections or providing immunotherapy to patients. During 2024, ADMA intends to advance pre-clinical work for the S. pneumonia program. ASCENIV Label Expansion: The ongoing post-marketing pediatric clinical study for ASCENIV may provide label expansion opportunities, further strengthening ADMA’s product portfolio compared to peers, if successful. Fourth Quarter 2023 Financial Results: Total revenues were $73.9 million for the quarter ended December 31, 2023, as compared to $50.0 million for the quarter ended December 31, 2022, an increase of $23.9 million, or approximately 48%. The increase is primarily related to increased sales of our immunoglobulin products, partially offset by a planned decrease in sales of plasma to third parties due to the increasing retention of plasma for internal intravenous immune globulin (IVIG) production. Adjusted EBITDA was $18.6 million for the quarter ended December 31, 2023, as compared to an Adjusted EBITDA loss of $3.5 million for the quarter ended December 31, 2022. Adjusted EBITDA for the quarter includes all non-GAAP reconciliation items, including stock-based compensation, depreciation, amortization and interest expense totaling $10.1 million and loss on debt extinguishment of $26.2 million. Net loss was $17.6 million for the quarter ended December 31, 2023, compared to a net loss of $12.2 million for the quarter ended December 31, 2022. Adjusted net income was $8.5 million for the quarter ended December 31, 2023, accounting for the non-GAAP reconciliation of a $26.2 million loss on extinguishment of debt incurred during the period, compared to an Adjusted net loss of $12.2 million for the quarter ended December 31, 2022. Full Year 2023 Financial Results: Total revenues were $258.2 million for the year ended December 31, 2023, as compared to $154.1 million for the year ended December 31, 2022, an increase of $104.1 million, or approximately 68%. The increase is primarily related to increased sales of our immunoglobulin products, partially offset by a planned decrease in sales of plasma to third parties due to the increasing retention of plasma for internal IVIG production. Adjusted EBITDA was $40.3 million for the year ended December 31, 2023, as compared to an Adjusted EBITDA loss of $27.6 million for the year ended December 31, 2022. Adjusted EBITDA for the full year includes all non-GAAP reconciliation items, including depreciation and amortization, interest expense, stock-based compensation, loss on debt extinguishment and costs related to the IT disruption. Net loss was $28.2 million for the year ended December 31, 2023, as compared to a net loss of $65.9 million for the year ended December 31, 2022. Adjusted net income was $0.7 million for the year ended December 31, 2023, accounting for the non-recurring costs related to the IT systems disruption totaling $2.8 million and the loss on extinguishment of debt totaling $26.2 million, as compared to Adjusted net loss of $59.2 million for the year ended December 31, 2022. As of December 31, 2023, ADMA had working capital of approximately $207.2 million, primarily consisting of $172.9 million of inventory, $51.4 million of cash and cash equivalents and $27.4 million of net accounts receivable, partially offset by current liabilities of $49.8 million, as compared to working capital at December 31, 2022 of $231.1 million, primarily consisting of $163.3 million of inventory, $86.5 million of cash and cash equivalents and $15.5 million of net accounts receivable, partially offset by current liabilities of $39.3 million. Conference Call Information To access the conference call seamlessly on February 28, 2024 at 4:30 PM ET, participants may register for the call here to receive the dial-in numbers and unique PIN. It is recommended that you join 10 minutes prior to the event starting (although you may register and dial in at any time during the call). A live audio webcast of the call will be available under “Events & Webcasts” in the investor section of the Company’s website, . An archived webcast will be available on the Company’s website approximately two hours after the event. About ASCENIV™ ASCENIV (immune globulin intravenous, human – slra 10% liquid) is a plasma-derived, polyclonal, intravenous immune globulin (IVIG). ASCENIV was approved by the United States Food and Drug Administration (FDA) in April 2019 and is indicated for the treatment of primary humoral immunodeficiency (PI), also known as primary immune deficiency disease (PIDD), in adults and adolescents (12 to 17 years of age). ASCENIV is manufactured using ADMA’s unique, patented plasma donor screening methodology and tailored plasma pooling design, which blends normal source plasma and respiratory syncytial virus (RSV) plasma obtained from donors tested using the Company’s proprietary microneutralization assay. ASCENIV contains naturally occurring polyclonal antibodies, which are proteins that are used by the body’s immune system to neutralize microbes, such as bacteria and viruses and prevent against infection and disease. ASCENIV is protected by U.S. Patents: 9,107,906, 9,714,283 and 9,815,886. Certain data and other information about ASCENIV can be found by visiting Information about ADMA and its products can be found on the Company’s website at Additional Important Safety Information About ASCENIV™ WARNING: THROMBOSIS, RENAL DYSFUNCTION AND ACUTE RENAL FAILURE Thrombosis may occur with immune globulin intravenous (IGIV) products, including ASCENIV. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors. Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with the administration of IGIV products in predisposed patients. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. ASCENIV does not contain sucrose. For patients at risk of thrombosis, renal dysfunction or renal failure, administer ASCENIV at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. ASCENIV™ Contraindications: History of anaphylactic or severe systemic reactions to human immunoglobulin. IgA deficient patients with antibodies to IgA and a history of hypersensitivity. ASCENIV™ Warnings and Precautions: IgA-deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions. Have medications such as epinephrine available to treat any acute severe hypersensitivity reactions. [4, 5.1] Thrombotic events have occurred in patients receiving IGIV treatments. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for patients at risk of hyperviscosity. [5.2, 5.4] In patients at risk of developing acute renal failure. monitor renal function, including blood urea nitrogen (BUN), serum creatinine, and urine output. [5.3, 5.9] Hyperproteinemia, increased serum viscosity, and hyponatremia or pseudohyponatremia can occur in patients receiving IGIV treatment. Aseptic meningitis syndrome (AMS) has been reported with IGIV treatments, especially with high doses or rapid infusion. [5.5] Hemolytic anemia can develop subsequent to IGIV treatment. Monitor patients for hemolysis and hemolytic anemia. [5.6] Monitor patients for pulmonary adverse reactions (Transfusion-related acute lung injury [TRALI]). If transfusion related acute lung injury is suspected, test the product and patient for antineutrophil antibodies. [5.7] Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. ASCENIV™ Adverse Reactions: The most common adverse reactions to ASCENIV (≥5% of study subjects) were headache, sinusitis, diarrhea, gastroenteritis viral, nasopharyngitis, upper respiratory tract infection, bronchitis, and nausea To report SUSPECTED ADVERSE REACTIONS, contact ADMA Biologics at (800) 458-4244 or FDA at 1-800-FDA-1088 or . About ADMA Biologics, Inc. (ADMA) ADMA Biologics is an end-to-end commercial biopharmaceutical company dedicated to manufacturing, marketing and developing specialty biologics for the treatment of immunodeficient patients at risk for infection and others at risk for certain infectious diseases. ADMA currently manufactures and markets three United States Food and Drug Administration (FDA)-approved plasma-derived biologics for the treatment of immune deficiencies and the prevention of certain infectious diseases: BIVIGAM® (immune globulin intravenous, human) for the treatment of primary humoral immunodeficiency (PI); ASCENIV™ (immune globulin intravenous, human – slra 10% liquid) for the treatment of PI; and NABI-HB® (hepatitis B immune globulin, human) to provide enhanced immunity against the hepatitis B virus. ADMA manufactures its immune globulin products at its FDA-licensed plasma fractionation and purification facility located in Boca Raton, Florida. Through its ADMA BioCenters subsidiary, ADMA also operates as an FDA-approved source plasma collector in the U.S., which provides its blood plasma for the manufacture of its products. ADMA’s mission is to manufacture, market and develop specialty biologics, human immune globulins targeted to niche patient populations for the treatment and prevention of certain infectious diseases and management of immune compromised patient populations who suffer from an underlying immune deficiency, or who may be immune compromised for other medical reasons. ADMA holds numerous U.S. and foreign patents related to and encompassing various aspects of its products and product candidates. For more information, please visit . Use of Non-GAAP Financial Measures This press release includes certain non-GAAP financial measures that are not prepared in accordance with accounting principles generally accepted in the United States (“GAAP”). The Company believes Adjusted EBITDA/(loss) and Adjusted net income/(loss) are useful to investors in evaluating the Company’s financial performance. The Company uses Adjusted EBITDA/(loss) and Adjusted net income/(loss) as key performance measures because we believe that they facilitate operating performance comparisons from period to period that exclude potential differences driven by the impact of variations of non-cash items such as depreciation and amortization, as well as, in the case of Adjusted EBITDA, stock-based compensation or certain non-recurring items, and in the case of Adjusted net income, certain non-recurring items. The Company believes that investors should have access to the same set of tools used by our management and board of directors to assess our operating performance. Adjusted EBITDA/(loss) and Adjusted net income/(loss) should not be considered as measures of financial performance under GAAP, and the items excluded from Adjusted EBITDA/(loss) and Adjusted net income/(loss) are significant components in understanding and assessing the Company’s financial performance. Accordingly, these key business metrics have limitations as an analytical tool. They should not be considered as an alternative to net income/loss or any other performance measures derived in accordance with GAAP and may be different from similarly titled non-GAAP measures used by other companies. Please refer to the tables below for the reconciliation of GAAP measures to these non-GAAP measures for applicable periods. Cautionary Note Regarding Forward-Looking Statements This press release contains “forward-looking statements” pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about ADMA Biologics, Inc. (“we,” “our” or the “Company”). Forward-looking statements include, without limitation, any statement that may predict, forecast, indicate, or imply future results, performance or achievements, and may contain such words as “confident,” “estimate,” “project,” “intend,” “forecast,” “target,” “anticipate,” “plan,” “planning,” “expect,” “believe,” “will,” “is likely,” “will likely,” “should,” “could,” “would,” “may,” or, in each case, their negative, or words or expressions of similar meaning. These forward-looking statements include, but are not limited to, statements about the Company’s future results of operations, including, but not limited to, revenue, net income and Adjusted EBITDA guidance in future periods, and certain assumptions in connection therewith; the market for ASCENIV and BIVIGAM; and additional growth opportunities, including but not limited to, the Company’s yield enhancement initiative, the newly announced hIG pipeline program targeting S. pneumonia (including the revenue potential) and ASCENIV label expansion. Actual events or results may differ materially from those described in this press release due to a number of important factors. Current and prospective security holders are cautioned that there also can be no assurance that the forward-looking statements included in this press release will prove to be accurate. Except to the extent required by applicable laws or rules, ADMA does not undertake any obligation to update any forward-looking statements or to announce revisions to any of the forward-looking statements. Forward-looking statements are subject to many risks, uncertainties and other factors that could cause our actual results, and the timing of certain events, to differ materially from any future results expressed or implied by the forward-looking statements, including, but not limited to, the risks and uncertainties described in our filings with the U.S. Securities and Exchange Commission, including our most recent reports on Form 10-K, 10-Q and 8-K, and any amendments thereto. COMPANY CONTACT: Skyler Bloom Senior Director, Corporate Strategy and Business Development | 201-478-5552 | sbloom@admabio.com INVESTOR RELATIONS CONTACT: Michelle Pappanastos Senior Managing Director, Argot Partners | 212-600-1902 | michelle@argotpartners.com ADMA BIOLOGICS, INC. AND SUBSIDIARIES CONSOLIDATED STATEMENTS OF OPERATIONS Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (Unaudited) (Unaudited) (in thousands, except share and per share amounts) REVENUES $ 73,904 $ 49,981 $ 258,215 $ 154,080 Cost of product revenue 42,817 35,804 169,273 118,815 Gross profit 31,087 14,177 88,942 35,265 OPERATING EXPENSES: Research and development 445 1,074 3,300 3,614 Plasma center operating expenses 685 5,088 4,266 17,843 Amortization of intangible assets 187 179 724 715 Selling, general and administrative 15,535 13,895 59,020 52,458 Total operating expenses 16,852 20,236 67,310 74,630 INCOME (LOSS) FROM OPERATIONS 14,235 (6,059 ) 21,632 (39,365 ) OTHER INCOME (EXPENSE): Interest income 612 2 1,617 45 Interest expense (6,215 ) (5,737 ) (25,027 ) (19,279 ) Loss on extinguishment of debt (26,174 ) - (26,174 ) (6,670 ) Other expense (101 ) (438 ) (287 ) (635 ) Other expense, net (31,878 ) (6,173 ) (49,871 ) (26,539 ) NET LOSS $ (17,643 ) $ (12,232 ) $ (28,239 ) $ (65,904 ) BASIC AND DILUTED LOSS PER COMMON SHARE $ (0.08 ) $ (0.06 ) $ (0.13 ) $ (0.33 ) WEIGHTED AVERAGE COMMON SHARES OUTSTANDING: Basic and Diluted 225,968,387 202,830,446 223,977,315 197,874,895 ADMA BIOLOGICS, INC. AND SUBSIDIARIES CONSOLIDATED BALANCE SHEETS December 31, December 31, 2023 2022 (Unaudited) (In thousands, except share data) ASSETS Current assets: Cash and cash equivalents $ 51,352 $ 86,522 Accounts receivable, net 27,421 15,505 Inventories 172,906 163,280 Prepaid expenses and other current assets 5,334 5,095 Total current assets 257,013 270,402 Property and equipment, net 53,835 58,261 Intangible assets, net 499 1,013 Goodwill 3,530 3,530 Right-to-use assets 9,635 10,485 Deposits and other assets 4,670 4,770 TOTAL ASSETS $ 329,182 $ 348,461 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $ 15,660 $ 13,229 Accrued expenses and other current liabilities 32,919 24,990 Current portion of deferred revenue 182 143 Current portion of lease obligations 1,045 905 Total current liabilities 49,806 39,267 Senior notes payable, net of discount 130,594 142,833 Deferred revenue, net of current portion 1,690 1,833 End of term fee 1,688 1,500 Lease obligations, net of current portion 9,779 10,704 Other non-current liabilities 419 350 TOTAL LIABILITIES 193,976 196,487 COMMITMENTS AND CONTINGENCIES STOCKHOLDERS' EQUITY Preferred Stock, $0.0001 par value, 10,000,000 shares authorized, no shares issued and outstanding - - Common Stock - voting, $0.0001 par value, 300,000,000 shares authorized, 226,063,032 and 221,816,930 shares issued and outstanding 23 22 Additional paid-in capital 641,439 629,969 Accumulated deficit (506,256 ) (478,017 ) TOTAL STOCKHOLDERS' EQUITY 135,206 151,974 TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY $ 329,182 $ 348,461 NON-GAAP RECONCILIATION RECONCILIATION OF GAAP NET (LOSS) TO ADJUSTED NET INCOME (LOSS) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (Unaudited) (Unaudited) Net loss $ (17,643 ) $ (12,232 ) $ (28,239 ) $ (65,904 ) Loss on extinguishment of debt 26,174 - 26,174 6,670 IT systems disruption - - 2,770 - Adjusted net income (loss) $ 8,531 $ (12,232 ) $ 705 $ (59,234 ) NON-GAAP RECONCILIATION RECONCILIATION OF GAAP NET LOSS TO ADJUSTED EBITDA Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (Unaudited) (Unaudited) Net loss $ (17,643 ) $ (12,232 ) $ (28,239 ) $ (65,904 ) Depreciation 1,921 1,758 7,608 6,398 Amortization 188 178 724 715 Interest expense 6,215 5,737 25,027 19,279 EBITDA (9,319 ) (4,559 ) 5,120 (39,512 ) Stock-based compensation 1,745 1,069 6,187 5,215 IT systems disruption - - 2,770 - Loss on extinguishment of debt 26,174 - 26,174 6,670 Adjusted EBITDA $ 18,600 $ (3,490 ) $ 40,251 $ (27,627 )

While all of the patients in the case series had signs of Alzheimer's in their brains, they differed in their degree of blood vessel disease. The headlines are, at a minimum, a bit sensational: “Alzheimer’s can be transmitted between people.” “What you need to know about Alzheimer’s spreading between humans.” “First evidence of human-to-human transmission of Alzheimer’s disease.”  The nuance, thankfully, is far less frightening, at least from a public health standpoint. A case series published Jan. 29 in Nature Medicine by scientists at University College London reported that five patients who were given growth hormones derived from human cadavers as part of a now-obsolete childhood medical treatment later developed early-onset Alzheimer’s disease.  “This is not a public health crisis by any means. It’s not like we’ve discovered any kind of transmission outside of this rare treatment,” Keith Vossel, M.D., director of the Alzheimer’s Research Center at the University of California, Los Angeles, assured Fierce Biotech Research. But it is the first documented instance of Alzheimer’s disease being contracted iatrogenically, or via a medical procedure, he said. The tragic cases also strengthen some researchers’ hypothesis that the amyloid beta plaques thought to drive the condition behave like prions, self-perpetuating misfolded proteins that cause severe brain disease. “I wouldn’t go so far as to say that it validates a theory, but I think it just adds one more strong piece of evidence for the prion-like hypothesis of Alzheimer’s seeding and trans-synpatic spreading,” said Vossel, who was not involved with the new research. So how did the patients in the case series wind up with Alzheimer’s? Call it a major medical mishap: They were part of a cohort of more than 1,800 people who, between the years of 1959 and 1985, were treated for various diseases with injections of human cadaveric pituitary-derived growth hormone, or c-hGH. Unbeknownst to the clinicians performing the treatment, the c-hGH contained amyloid beta plaques, presumably from the brains of the deceased donors. The treatment also contained other prions that led to at least 200 other patients developing Creutzfeldt-Jakob disease, a rapidly progressive neurodegenerative prion disease, as the researchers reported in an earlier paper. In the three to four decades following, five of the eight patients described in the case series developed Alzheimer’s, most of them during their late 30s and 40s. Two of the others had some degree of cognitive impairment while the last one was asymptomatic. Analyses conducted after they died revealed that all eight patients had some signs of Alzheimer’s pathology, such as the presence of amyloid beta plaques or brain volume changes, including the patient who didn’t show symptoms before death. Notably, they had varying degrees of the cerebral vessel disease that’s typically associated with Alzheimer’s, suggesting their form of the condition might be unique.  To rule out genetic causes, the University College London team ran genomic analysis to look for gene mutations linked to neurodegenerative disease on five of the patients. (Samples weren’t available for the other three.) Aside from a single risk allele in a gene associated with Alzheimer’s in one case—which is far from a guarantee of developing the disease—the researchers didn’t find any variants that could explain what happened.  After examining all the other factors over the course of the patients’ lives that could have led them to develop Alzheimer’s so young, the researchers asserted that the contaminated c-hGH was to blame. Their conclusion was bolstered by findings from a mouse study they published back in 2019 in which mice that were injected with some of the same c-hGH from the period developed amyloid beta plaques in their brains.  If iatrogenic transmission did indeed occur in these patients via prions, this could have implications for the scientific understanding of Alzheimer’s and for designing drugs to treat it, the University College London scientists wrote in their paper. Prions come in different strains that can differ in how quickly they replicate within tissues, move between tissue types and are cleared by the body, as this review in Nature explains. If amyloid beta plaques are prions, and a therapy targets only the most common strain, treatment could ultimately backfire.  “Structurally diverse [prion forms], present as minor components, may be selected for propagation by a drug that binds to the dominant species, potentially leading to the development of resistance,” the researchers wrote. Other scientists have found evidence of amyloid beta strains in microscopy studies, they noted. On top of that, the patients in the case series presented differently than those who develop Alzheimer’s due to genetics, with earlier disease onset and more rapid progression but without a clear pattern of blood vessel disease.  “We hypothesize that iatrogenic [amyloid-beta disease] caused by c-hGH can result in a clinical phenotype (possibly mediated by amyloid-beta strain type), in which clinical [blood vessel disease] is less prominent,” the researchers wrote. “Additionally, it is entirely possible that some iatrogenic cases of Alzheimer’s disease may differ markedly from sporadic and inherited forms … the full spectrum of dementias caused by amyloid-beta transmission remains to be elucidated.”  Yet despite the evidence so far, Vossel believes the findings are still vulnerable to what he described as a “referral bias.” While the patients were young and lacked genes that would predispose them to Alzheimer’s, it’s still possible that they would have ultimately developed the disease anyway, Vossel said. “I think a lot of people assume that if someone has early Alzheimer's disease that it should be genetic in cause, but the truth is that most Alzheimer’s disease is sporadic in nature,” he said. “I think it’s a little premature to put too much weight on this one article. We can gather more information.”