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 )

作者 | 赵宝龙编辑 | 芝麻核桃自FDA于2017年8月批准第一款CAR-T产品至今不过7年时间，国内已有4款CAR-T产品上市。随着我国细胞治疗产业的快速发展，越来越多的细胞治疗产品开始进入市场，完成从研发到商业化的华丽转身。诸多技术实力强劲的国内企业不仅积极推进国内注册临床，同时也瞄准了国际市场，期望在全球范围内展示中国创新药物的力量。与传统药物不同，CGT产品来源更多样、生物学特性更复杂，因此，细胞治疗产品作为一类新兴的治疗技术，也大大增加了新的潜在风险。作为细胞治疗产品最关键起始物料的供者材料因其具有人源性、起始物料稀缺性、具有潜在病毒风险等特性，所以在整个生产流程中发挥着牵一发而动全身的作用，其质量优劣直接影响着批生产是否成功、回输后是否安全有效；与之相对应的质量标准或监管要求却分散于各个指南或标准没有形成统一。因此对于企业来讲，从源头进行严格的风险管控也变的至关重要。本文将基于中美两国现有的相关规定从以下几方面进行分析：01检测机构相同点双方都要求检测机构具备相应的资质和认证，以确保其检测结果的准确性和可靠性；都要求检测机构遵守相关的法律法规和标准，包括质量管理体系、实验室安全等方面的要求；都要求检测机构进行定期的内部质量控制和外部质量评估，以确保其检测结果的一致性和可比性。不同点美国：监管方面主要由CMS（医疗保险和医疗补助服务中心）进行认证和监管；资质认证方面更加注重市场认可，实验室需要根据《临床实验室改进修正案》（Clinical Laboratory Improvement Amendments,CLIA）的规定设立；更加注重符合国际标准和行业最佳实践；质量控制方面更加注重外部评估和认证。中国：监管方面主要由政府部门管理和监督（国家卫生健康委员会（简称“卫健委”）和县级以上地方人民政府卫生行政部门）；资质认证方面更加注重政府的认可和授权；质量管理体系方面更加注重符合国家和行业标准；质量控制方面更加注重内部控制和监督。分析中美对检测机构的要求等同，只不过美国比较在意协会的力量（在美国，流程确认可以通过AABB和FACT，积累数据通过CIBMTR，流程标准化通过ICCBBA等。这一套内容也不是为了CART建立的，而是当年为了骨髓移植就建立好了），中国目前主要是依靠血液制品相关的法规。02供者材料相同点两国都比较重视细胞治疗产品供者材料的安全性切都有相应的法规监管体系对供者筛查和供者材料进行了要求。不同点美国：所有供者一般筛查项目主要包含HIV、HBV、HCV、TSE(阮病毒，包含克雅氏病(CJD)、梅毒；如果是自体使用，可以豁免所有供者筛查（当然企业也可以选择不豁免）。如果豁免，则需要标签标明"FOR AUTOLOGOUS USE ONLY"，以及"NOT EVALUATED FOR INFECTIOUS SUBSTANCES"；淋巴细胞供者额外筛查：HTLV-1/HTLV-2, CMV；异体来源的，增捡与异种移植相关的其他传染病；富含白细胞的细胞或组织的，需检测（HTLV-Ⅰ、HTLV-Ⅱ,人类嗜T细胞病毒）；生殖细胞或组织的筛查，必须检查项目包含沙眼衣原体、淋病奈瑟菌；对于1个月以内的新生儿，可以不检测本人的样本，但是必须检测生母的标本。中国：采集前应对供者进行筛查，包括健康状况的全面检查（如一般信息、既往病史和家族性遗传病等）、病原微生物的感染筛查和在危险疫区停留情况的调查等。企业应当建立供者筛查和检测标准及供者材料的质量标准，并综合考虑微生物的生物安全等级、传染病类别和细胞产品的预定用途等因素进行风险评估，定期回顾其适用性。对用于异体干细胞临床研究的供者，必须检测人源特定病毒（包括HIV、HBV、HCV、HTLV、EBV、CMV等）、梅毒螺旋体。必要时收集供者的ABO血型、HLA-I类和II类分型资料。分析中国对自体/异体供者的监管范围更广、要求更严；美国对细胞治疗产品监管更为成熟和细化。03检测试剂盒相同点中美两国都要求使用各自批准上市的品种进行供者筛查，这意味着两国都重视确保使用的检测试剂盒的安全性和有效性。不同点美国：使用适当的FDA许可、批准或批准的供体筛查测试进行测试。中国：用于特定传染病病原体（HIV、HBV、HCV及梅毒螺旋体等）标志物检测的体外诊断试剂，应当优先选择获得药品监督管理部门批准的产品，且应当首选获得药品监督管理部门批准的用于血源筛查的产品。分析中国对检测试剂盒的要求更明确，但是国内大部分的血站和医院可能由于血源筛查试剂盒价格较高或者由于认识水平、监管要求或采购政策等因素并没有使用血源筛查试剂盒。04窗口期要求不同点美国：采集时检测或恢复前后最多7天，但不包含（外周血干细胞/祖细胞、骨髓（如果没有§1271.3(d)(4)规定的例外情况）样本，该类样本可以在康复前30天内收集样本进行检测）；重复采集的供者（6个月内），如果间隔期无新发疾病或原有疾病无进展的情况下可以适当简化筛查项目。中国：企业需要考虑窗口期对筛查的影响。分析美国有明确的窗口期时间限定。我国有这方面的要求，但是没有明确的法规条文规定。企业一般是结合内部质量体系的规定、自身产品工艺特点、检测指标特性和方法性能等，经过综合的风险评估制定合理的检测窗口期。05执行层面相同点无论是中国还是美国，对于细胞治疗产品的供者筛查都实行严格的监管措施，以确保细胞治疗产品的安全性和有效性。两国都会根据细胞治疗产品的风险大小进行评估，并制定相应的规范来调整监管策略。不同点美国：因为有更为成熟和细化的法规体系和较为明确的筛查检测项目要求，企业在实际执行层面有章可循。中国：现阶段相关的规定未能做到归口的统一，在实际执行中会存在一些难点，如：供者筛查一般由医院完成，企业的质量体系无法覆盖到；大部分医院就是按照输血要求进行传染病4项检测；大部分企业就是拿到医院的检测结果之后审核放行，不会开展复测或者扩展其他检测项目；传染病检测如果委托第三方检验机构，企业往往不能提供医疗机构证明等。分析国内需要加强企业、医疗机构、监管机构的沟通与合作，探索适合本国国情、科学可行的监管框架与质量管理规范。小结根据以上资料，中美两国在细胞治疗产品供者筛查方面的要求在总体上呈现出一致性，但在具体实施过程中还是展现出一些差异，如筛查标准、材料质量标准等方面的差异。因此，在产品开发过程中，我们需要特别注意这些差异，并作出相应的调整。企业需要根据国家相关规定来制定自己的质量标准，企业的质量标准不能低于国家的相关规定标准，企业应当适当提高供体来源的细胞或组织的功能评价标准，以免供体细胞或组织影响到细胞产品的整个生产制备过程。作者简介赵宝龙上海医药集团生物治疗技术有限公司（注册部 高级经理）在细胞治疗领域工作十余年，曾担任多家大型制药公司注册事务管理人员。在药厂厂房建设、实验室建设、质量控制、体系搭建、确认与验证、技术转移、注册与申报、实验室日常运营等方面具有丰富的实践经验，参与过多家公司多个细胞治疗产品的技术开发，临床申报和注册申报，均获得了临床批件和/或生产批件，对国内外法规有丰富的实战经验，数次参加与CDE等药政监管部门沟通交流会，现为国内一家大型医药集团生物治疗注册事务负责人。声明：本文仅代表作者个人观点，不代表任何组织及本公众号立场，如有不当之处，敬请指正。如需转载，请注明作者及来源：蒲公英Biopharma。