作者: Bachelder, Eric M ; Simpson, Sean R ; Islam, Md Jahirul ; Batty, Cole J ; Hendy, Dylan A ; Ainslie, Kristy M ; Lukesh, Nicole Rose ; Roque, John A ; Dixon, Timothy A ; Pena, Erik S ; Lifshits, Liubov M ; Ontiveros-Padilla, Luis

Vaccines represent a pivotal health advancement for preventing infection. However, because carrier systems with repeated administration can invoke carrier-targeted immune responses that diminish subsequent immune responses (e.g., PEG antibodies), there is a continual need to develop novel vaccine platforms. Zinc carnosine microparticles (ZnCar MPs), which are composed of a one-dimensional coordination polymer formed between carnosine and the metal ion zinc, have exhibited efficacy in inducing an immune response against influenza. However, ZnCar MPs' limited suspendability hinders clinical application. In this study, we address this issue by mixing mannan, a polysaccharide derived from yeast, with ZnCar MPs. We show that the addition of mannan increases the suspendability of this promising vaccine formulation. Additionally, since mannan is an adjuvant, we illustrate that the addition of mannan increases the antibody response and T cell response when mixed with ZnCar MPs. Mice vaccinated with mannan + OVA/ZnCar MPs had elevated serum IgG and IgG1 levels in comparison to vaccination without mannan. Moreover, in the mannan + OVA/ZnCar MPs vaccinated group, mucosal washes demonstrated increased IgG, IgG1, and IgG2c titers, and antigen recall assays showed enhanced IFN-γ production in response to MHC-I and MHC-II immunodominant peptide restimulation, compared to the vaccination without mannan. These findings suggest that the use of mannan mixed with ZnCar MPs holds potential for subunit vaccination and its improved suspendability further promotes clinical translation.

2024-01-01·Journal of Medical Virology

Th2 and Th17‐associated immunopathology following SARS‐CoV‐2 breakthrough infection in Spike‐vaccinated ACE2‐humanized mice

Article

作者: Carossino, Mariano ; August, Avery ; McGee, Michael C. ; Magazine, Nicholas ; Kousoulas, Konstantin G. ; Huang, Weishan ; Zhang, Tianyi ; Veggiani, Gianluca

AbstractVaccines have demonstrated remarkable effectiveness in protecting against COVID‐19; however, concerns regarding vaccine‐associated enhanced respiratory diseases (VAERD) following breakthrough infections have emerged. Spike protein subunit vaccines for SARS‐CoV‐2 induce VAERD in hamsters, where aluminum adjuvants promote a Th2‐biased immune response, leading to increased type 2 pulmonary inflammation in animals with breakthrough infections. To gain a deeper understanding of the potential risks and the underlying mechanisms of VAERD, we immunized ACE2‐humanized mice with SARS‐CoV‐2 Spike protein adjuvanted with aluminum and CpG‐ODN. Subsequently, we exposed them to increasing doses of SARS‐CoV‐2 to establish a breakthrough infection. The vaccine elicited robust neutralizing antibody responses, reduced viral titers, and enhanced host survival. However, following a breakthrough infection, vaccinated animals exhibited severe pulmonary immunopathology, characterized by a significant perivascular infiltration of eosinophils and CD4+ T cells, along with increased expression of Th2/Th17 cytokines. Intracellular flow cytometric analysis revealed a systemic Th17 inflammatory response, particularly pronounced in the lungs. Our data demonstrate that aluminum/CpG adjuvants induce strong antibody and Th1‐associated immunity against COVID‐19 but also prime a robust Th2/Th17 inflammatory response, which may contribute to the rapid onset of T cell‐mediated pulmonary immunopathology following a breakthrough infection. These findings underscore the necessity for further research to unravel the complexities of VAERD in COVID‐19 and to enhance vaccine formulations for broad protection and maximum safety.

2024-01-01·International Immunopharmacology

A multi-epitope subunit vaccine based on CU/ZN-SOD, OMP31 and BP26 against Brucella melitensis infection in BALB/C mice

Article

作者: Wang, Yueli ; Miao, Yuhe ; Sheng, Jinliang ; Cui, Lijin ; Wu, Aodi ; Xu, Zhenyu ; Wang, Yong ; Yi, Jihai ; Zhang, Huan ; Li, Honghuan ; Chen, Chuangfu ; Zhumanov, Kaiat ; Liu, Yajing ; Fu, Shuangshuang ; Xu, Yimei

Brucellosis, a zoonosis caused by Brucella, is highly detrimental to both humans and animals. Most existing vaccines are live attenuated vaccines with safety flaws for people and animals. Therefore, it is advantageous to design a multi-epitope subunit vaccine (MEV) to prevent Brucella infection. To this end, we applied a reverse vaccinology approach. Six cytotoxic T cell (CTL) epitopes, seven T helper cell (HTL) epitopes, and four linear B cell epitopes from CU/ZN-SOD, Omp31, and BP26 were obtained. We linked the CTL, HTL, B-cell epitopes, the appropriate CTB molecular adjuvant, and the universal T helper lymphocyte epitope, PADRE, with linkers AAY, GPPGG, and KK, respectively. This yielded a 412-amino acid MEV construct, which we named MEVcob. The immunogenicity, stability, safety, and feasibility of the construct were evaluated by bioinformatics tools (including the AlphaFold2 prediction tool, the AlphaFold2 tool, NetMHC-I pan 4.0 server, IEDB MHC-I server, ABCpred service, and C-ImmSim server); the physicochemical properties, secondary and tertiary structures, and binding ability of MEVocb to toll-like receptor 4 (TLR4) was analyzed. Then, codon adaptation and computer cloning studies were performed. MEVocb is highly immunogenic in immunostimulation experiments, The proteins translated by these sequences were relatively stable, exhibiting a high antigenic index. Furthermore, mouse experiments confirmed that the MEVocb construct could raise IFN-γ, IgG, IgG2a, IgG1, IL-2, TNF-α levels in mice, indicating that induced a specific humoral and cellular immune response in BALB/c mice. This vaccine induced a statistically significant level of protection in BALB/c mice when challenged with Brucella melitensis 043 in Xinjiang. Briefly, we utilized immunoinformatic tools to design a novel multi-epitope subunit candidate vaccine against Brucella. This vaccine aims to induce host immune responses and confer specific protective effects. The study results offer a theoretical foundation for the development of a novel Brucella subunit vaccine.

项与 DerG-PG275Cit 相关的新闻（医药）

2023-08-11

·BioSpace

CEL-SCI Corporation Reports Third Quarter Fiscal 2023 Financial Results

VIENNA, Va.--(BUSINESS WIRE)-- CEL-SCI Corporation (NYSE American: CVM) today reported financial results for the quarter ended June 30, 2023, as well as key clinical and corporate developments. Clinical and Corporate Developments this quarter include: CEL-SCI had a productive pre-submission meeting with Canada’s regulator, Health Canada, to determine the best regulatory path toward market approval. Health Canada advised CEL-SCI to request advance consideration for approval under a Notice of Compliance with Conditions (NOCC) policy which facilitates earlier access for physicians and patients to promising new drugs for patients suffering from serious, life-threatening, or severely debilitating diseases. CEL-SCI is preparing an application for the NOCC approval as suggested and plans to by early next year. If Health Canada grants the NOCC, then it is possible that CEL-SCI could begin commercialization in 2024. Europe is a priority market for CEL-SCI, as Europe has more than twice the number of head and neck cancer cases diagnosed each year as compared to the United States (US). CEL-SCI is seeking conditional marketing authorization for Multikine in Europe. Based on the published guidelines, the Company believes it meets the requirements for conditional approval of Multikine and has plans for meetings with regulators in the fall. CEL-SCI had a collaborative and positive meeting with the U.S. Food and Drug Administration (FDA). The FDA acknowledged the great need for improved treatments for head and neck cancer, particularly the locally advanced oral cavity that CEL-SCI is targeting and is open to close collaboration with CEL-SCI to help demonstrate that Multikine could fill this need. Preliminary feedback from the FDA included that the selection criteria developed by CEL-SCI from its Phase 3 data could be used to determine which locally advanced oral cavity cancer patients might benefit from Multikine treatment. CEL-SCI is preparing additional information about its Multikine development plan for a follow-up meeting with the FDA based on this feedback. A confirmatory clinical trial will be conducted based on the agreed upon selection criteria for patients that will be treated with Multikine as assessed by methods including PET-CT/MRI screening. CEL-SCI will collaborate closely with the FDA on the design of a clinical protocol that will allow the Company to generate, as expeditiously as possible, the confirmatory data they will require for approval of Multikine in the US. Importantly, this study is also expected to have intermediate endpoints during study enrollment for potential accelerated approval based on interim results. Potentially quite impactful PD-L1 biomarker data from CEL-SCI’s Phase 3 study was presented at the American Head and Neck Cancer Society’s 11th Annual International Conference on Head and Neck Cancer titled “Tumor cell PD-L1 biomarker confirms Leukocyte Interleukin Injection (LI) treatment (Tx) survival outcome advantage in naïve locally advanced primary head & neck squamous cell carcinoma (SCCHN), the IT-MATTERS Study”. The data demonstrated that the tumors of patients who responded best to Multikine in the Phase 3 study had low levels of the PD-L1 biomarker. Currently approved checkpoint inhibitors (Keytruda and Opdivo) which are indicated for treatment of unresectable or recurrent or metastatic head and neck cancer are known to work best in patients whose tumors express high PD-L1 levels and are less likely to work in patients whose tumors express low PD-L1. These contrasting PD-L1 data observed in patients responsive to Multikine vs those observed in patients treated with checkpoint inhibitors are very significant. The data are expected to be helpful in key ways: Supporting marketing approval by using PD-L1 as a marker to select patients who are most likely to benefit from Multikine Positioning Multikine as a combination therapy with checkpoint inhibitors Combination studies may be conducted in partnership with a larger pharma company that has an approved PD-L1 checkpoint inhibitor Should combination studies with checkpoint inhibitors be successful not only would patients benefit substantially, but the financial benefits to CEL-SCI could be very large The global PD-L1/PD-1 therapeutics market was valued at $34.8 billion in 2022 Data presented at the European Society for Radiotherapy and Oncology (ESTRO) 2023 Congress in May confirmed that Multikine significantly prolonged overall survival in head and neck cancer. The presentation titled “Histopathology population (HPP) confirms Multikine* [Leukocyte Interleukin Injection (LI)] treatment (Tx) outcome in naïve locally advanced primary head & neck squamous cell carcinoma SCCHN)” provided findings from a histopathology and tumor biomarker analysis of its Phase 3 study that confirmed Multikine-treated subjects had improved 5-year survival, showed improved progression free survival and improved local regional control, and a significantly lowered death rate compared to control subjects who received standard of care alone. “The growing body of data on the efficacy of Multikine presented at peer-reviewed conferences is highly encouraging as we move forward with regulatory meetings and submissions with the world’s most respected regulators in the world in addition to FDA. The data has also allowed us to define very well the population of patients who have the greatest benefit from Multikine treatment. This is a crucial part of our approval strategy in this unmet medical need as we are aiming for conditional/accelerated approval pathways with multiple regulators,” stated CEL-SCI CEO, Geert Kersten. “We are also excited about the new prospect of developing Multikine in conjunction with a pharma partner as a combination therapy with a checkpoint inhibitor to boost patient outcomes. Financial Results CEL-SCI reported a loss per share for the quarter ending June 30, 2023 of $0.19 versus a loss of $0.23 for the quarter of June 30, 2022. About CEL-SCI Corporation CEL-SCI believes that boosting a patient’s immune system while it is still intact should provide the greatest possible impact on survival. Therefore, in the Phase 3 study, CEL-SCI studied patients who were newly diagnosed with locally advanced primary squamous cell carcinoma of the head and neck (oral cavity and soft-palate) with the investigational product Multikine first, BEFORE they received surgery and radiotherapy or surgery plus concurrent radiotherapy and chemotherapy (the current standard of care for these patients). We believe this approach is unique. Most other cancer immunotherapies are administered only after conventional therapies have been tried and/or failed. Multikine is designed to help the immune system “target” the tumor at a time when the immune system is still relatively intact and thereby thought to be better able to mount an attack on the tumor. The Phase 3 study enrolled 928 patients. Multikine (Leukocyte Interleukin, Injection) received Orphan Drug designation from the FDA for neoadjuvant therapy in patients with squamous cell carcinoma (cancer) of the head and neck. The Company has operations in Vienna, Virginia, and near/in Baltimore, Maryland. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Such statements include, but are not limited to, statements about the terms, expected proceeds, use of proceeds and closing of the offering. Factors that could cause or contribute to such differences include an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI's filings with the Securities and Exchange Commission, including but not limited to its report on Form 10-K for the year ended September 30, 2022. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. * Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy. This proprietary name is subject to FDA review in connection with the Company's future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use. CEL-SCI CORPORATION CONDENSED STATEMENTS OF OPERATIONS NINE MONTHS ENDED JUNE 30, 2023 AND 2022 (UNAUDITED) 2023 2022 Operating expenses: Research and development $ 17,203,823 $ 18,893,857 General and administrative 6,804,729 8,220,768 Total operating expenses 24,008,552 27,114,625 Operating loss (24,008,552 ) (27,114,625 ) Gain on derivative instruments - 366,791 Other non-operating losses - (30,793 ) Interest expense, net (493,522 ) (1,460,055 ) Other expense (61,525 ) - Net loss (24,563,599 ) (27,603,969 ) Modification of warrants (171,552 ) (294,409 ) Net loss available to common shareholders $ (24,735,151 ) $ (28,533,091 ) Net loss per common share – basic and diluted $ (0.57 ) $ (0.66 ) Weighted average common shares outstanding – basic and diluted 43,761,395 43,124,972 CEL-SCI CORPORATION CONDENSED STATEMENTS OF OPERATIONS THREE MONTHS ENDED JUNE 30, 2023 AND 2022 (UNAUDITED) 2023 2022 Operating expenses: Research and development $ 5,727,789 $ 6,286,873 General and administrative 2,453,968 2,432,518 Total operating expenses 8,181,757 8,719,391 Operating loss (8,181,757 ) (8,719,391 ) Interest expense, net (181,670 ) (913,193 ) Other expense (3,854 ) - Net loss (8,367,281 ) (8,997,871 ) Modification of Warrants - (294,409 ) Net loss available to common shareholders $ (8,367,281 ) $ (9,926,993 ) Net loss per common share – basic and diluted $ (0.19 ) $ (0.23 ) Weighted average common shares outstanding – basic and diluted 44,254,363 43,174,775

临床3期临床结果免疫疗法财报

2023-05-15

·Business Wire

Histopathology and Tumor Biomarker Analysis Confirm CEL-SCI’s Multikine Significantly Prolonged Overall Survival in Head & Neck Cancer—Phase 3 Data Presented at ESTRO 2023

VIENNA, Va.--( BUSINESS WIRE )-- CEL-SCI Corporation (NYSE American: CVM) today announced that the latest results from its pivotal Phase 3 study of Multikine, a presurgical cancer immunotherapy, were presented at the European Society for Radiotherapy and Oncology (ESTRO) 2023 Congress in Vienna, Austria in a poster presentation titled “Histopathology population (HPP) confirms Multikine* [Leukocyte Interleukin Injection (LI)] treatment (Tx) outcome in naïve locally advanced primary head & neck squamous cell carcinoma SCCHN)” during the Head & Neck Cancer Session on Saturday, May 13, 2023. CEL-SCI’s IT-MATTERS pivotal Phase 3 study, the largest study ever conducted in newly diagnosed locally advanced squamous cell carcinoma of the head and neck, reported a statistically significant 14.1% absolute 5-year overall survival benefit in the intent to treat (ITT) subjects who were categorized as lower risk to recurrence (LR) per National Comprehensive Cancer Network (NCCN) guidelines and received Multikine followed by surgery and radiotherapy, as compared to control LR subjects who received only standard of care (SOC) (surgery plus radiotherapy). The ESTRO presentation focused on pathology analysis of Phase 3 patients’ tumors at surgery. In summary, it confirmed that Multikine pre-surgery treatment led to significant changes in the tumors of the patients treated with Multikine and that these changes were not seen in control patients who did not get Multikine. The tumor tissue and biomarker analyses demonstrated that these changes were statistically significant and important in bringing about the beneficial responses seen. The tumor and tumor microenvironment changes induced by Multikine explain the increased survival, improved progression free survival, and improved local regional control, as well as the significantly lowered death rate compared to control subjects in the study. These findings from the Phase 3 study also confirm Multikine’s mechanism of action which was previously determined from samples collected during Phase 2 studies from Multikine treated subjects. The results from the Phase 2 studies were previously reported in the Journal of Clinical Oncology (Timar et al). The ESTRO presentation reported that patient responses to Multikine were determined following 3 weeks of Multikine treatment by comparing baseline tumor/lymph node measurements at screening (per RECIST) with tumor/lymph node measurements made just prior to and confirmed by pathology following surgery. Histopathology (HP) samples (n=453), were representative of the study ITT population (n=923) in all manner of subjects’ characteristics, and showed that: Multikine treated subjects had a different tumor and tumor microenvironment cellular profile at surgery than that exhibited by SOC (control) treated subjects. This was determined by pathologists who were blinded to the study using predefined low/high thresholds for 20 biomarkers (5 tumor, 15 tumor microenvironment). The histopathology analysis showed association with improved overall survival, progression free survival and local regional control that significantly favored Multikine-treated [(61/279 or 21.9% >> 2.5% by chance alone) vs SOC-treated (5/279 (or 1.9% < 2.5% by chance alone)] (conditional binomial; p<0.0001). HP LR Multikine-treated vs HP LR SOC 5-year efficacy measures of success were: Overall Survival of 63.9% vs 44.4% (hazard ratio: 0.64 [95% CI 0.41, 1.01]) Progression Free Survival of 56.9% vs 41.1% (hazard ratio 0.67 [95% CI 0.44, 1.02]) Local Regional Control of 73.1% vs 63.6% (hazard ratio 0.62 [95% CI 0.35,1.09]) HP LR Multikine-treated subjects had a significantly lower (39.1% [45/115]) death rate versus a 53.7% (51/95) death rate for HP LR SOC alone (two-sided Fisher Exact Test p=0.038) These statistical results for the HP LR analyzed subjects are supportive of the efficacy advantages demonstrated for LR Multikine-treated vs LR SOC alone treated patients in the Phase 3 study. “We are building a growing body of peer-reviewed data that points to the efficacy of Multikine in advanced primary head and neck cancer in the hopes that a population of patients, for whom no new treatment options have been forthcoming in more than five decades, may soon benefit from a longer and better life. Based on the totality of the data, we are preparing to file for regulatory approval, including through accelerated and early access pathways, in the U.S., Canada, and Europe,” stated CEL-SCI CEO, Geert Kersten. “ESTRO 2023 marks our fourth presentation of the Phase 3 study data at a major global peer-reviewed cancer conference in the past twelve months.” About CEL-SCI Corporation CEL-SCI believes that boosting a patient’s immune system while it is still intact should provide the greatest possible impact on survival. Therefore, in the Phase 3 study, CEL-SCI studied patients who were newly diagnosed with locally advanced primary squamous cell carcinoma of the head and neck with the investigational product Multikine first, BEFORE they received surgery and radiotherapy or surgery plus concurrent radiotherapy and chemotherapy (the current standard of care for these patients). This approach is unique. Most other cancer immunotherapies are administered only after conventional therapies have been tried and/or failed. Multikine (Leukocyte Interleukin, Injection) received Orphan Drug designation from the FDA for neoadjuvant therapy in patients with squamous cell carcinoma (cancer) of the head and neck. CEL-SCI believes that this Phase 3 study is the largest Phase 3 study in the world for the treatment of locally advanced primary head and neck cancer. Multikine is designed to help the immune system “target” the tumor at a time when the immune system is still relatively intact and thereby thought to be better able to mount an attack on the tumor. The Phase 3 study was started in early 2011 and was fully enrolled with 928 patients in September 2016. To test for an overall survival benefit, the study required CEL-SCI to wait until at least 298 (deaths) events had occurred among the two main comparator groups. The Company has operations in Vienna, Virginia, and near/in Baltimore, Maryland. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Such statements include, but are not limited to, statements about the terms, expected proceeds, use of proceeds and closing of the offering. Factors that could cause or contribute to such differences include an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI's filings with the Securities and Exchange Commission, including but not limited to its report on Form 10-K for the year ended September 30, 2022. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. * Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy. This proprietary name is subject to FDA review in connection with the Company's future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use.

临床结果临床3期免疫疗法孤儿药ASCO会议

2023-05-12

·Business Wire

CEL-SCI Corporation Reports Second Quarter Fiscal 2023 Financial Results

VIENNA, Va.--( BUSINESS WIRE )--CEL-SCI Corporation (NYSE American: CVM) today reported financial results for the quarter ended March 31, 2023, as well as key clinical and corporate developments. Clinical and Corporate Developments include: In addition to pursuing approval by the US Food and Drug Administration (FDA), CEL-SCI is also pursuing marketing approval for Multikine in the treatment of head and neck cancer in Canada and the European Union. In April 2023, CEL-SCI had a productive pre-submission meeting with Canada’s regulator, Health Canada, to determine the best regulatory path toward market approval. Based on the existing data that was summarized and presented, Health Canada advised CEL-SCI to request advance consideration for approval under a Notice of Compliance with Conditions (NOC/c) policy which facilitates earlier access for physicians and patients to promising new drugs for patients suffering from serious, life-threatening or severely debilitating diseases. CEL-SCI has engaged a highly regarded regulatory consultancy with expertise in Europe to prepare the documents for a meeting with the European Medicines Agency (EMA) to determine the most efficient pathway to obtain marketing approval for Multikine in Europe. The regulations for conditional approval, similar to Canada’s NOC/c, are detailed on the EMA’s site at this link: Conditional Marketing Authorisation . Europe has almost twice the number of head and neck cancer patients than the US. In March 2023, Eyal Talor, Ph.D., CEL-SCI’s Chief Scientific Officer, presented a poster titled “ Leukocyte Interleukin Injection (LI) immunotherapy followed by radiotherapy extends overall survival (OS) in treatment naïve locally advanced primary squamous cell carcinoma of the head & neck: the IT-MATTERS Study ” at the 10th European Congress on Head & Neck Oncology (ECHNO). Key study findings for the intended Multikine patient population who received radiotherapy, as recommended by National Comprehensive Cancer Network (NCCN) guidelines, following surgery include: The overall survival advantage accelerated and increased over time, with the benefit of adding Multikine+CIZ to the treatment regimen as compared to Standard of Care (SOC) alone increasing from 2.8% at 3 years (36 months), to 8.3% at 4 years (48 months), to 15.6% at 5 years (60 months), with a 49.7% survival for control vs. 65.3% for the Multikine treated group at 5 years. The hazard ratio was 0.70 (95% CI: [0.49 - 1.00]) which represents a 43% survival extension. Progression free survival was 8.4% higher at 5 years for patients treated with Multikine+ CIZ+SOC as compared to patients treated with SOC control alone. 16.5% of these patients were early tumor responders, including complete tumor responders (confirmed by pathology at surgery), following the 3-week treatment with Multikine as compared to 0% responders of patients who were treated with SOC alone. Multikine patients who had an early tumor response had significantly improved survival. Their death rate was only 15.6% vs. 48.7% death rate for the control patients at 5 years. Even the patients who did not have an early tumor response had a better survival than did the control group patients, with a 43.8% death rate vs. 48.7% death rate for control at 5 years. CEL-SCI is close to reaching validation of the dedicated Multikine manufacturing facility. This process had been delayed by the US Defense Production Act which gave preference to supplies for companies working on COVID products as described on FEMA’s site: Applying the Defense Production Act . Fortunately, the COVID emergency has now officially ended and validation, an important step in the FDA approval process, is moving toward completion. “We are pleased with the results of our discussions with Health Canada regarding approval pathways for Multikine. Our Phase 3 study spanned over 20 countries, and we hope to make Multikine available to head and neck cancer patients in need across all those countries and more,” stated CEL-SCI CEO, Geert Kersten. “A stellar team of regulatory advisors and top-tier physician consultants are working with us as we are laser-focused on regulatory approval. At the same time, by presenting our growing body of data at leading medical conferences, we are building awareness of Multikine amongst the oncologists who we hope will be integrating our immunotherapy into their practice upon its approval.” Financial Results CEL-SCI reported a loss per share for the quarter ending March 31, 2023 of $0.19 versus a loss of $0.23 for the quarter of March 31, 2022. CEL-SCI had $10 million in cash and cash equivalents on March 31, 2023. On May 2, 2023, CEL-SCI received $1.4 million in net proceeds from a small financing. Cash used during the six months ended March 31, 2023 included a one-time $2.3 million deposit for the Company’s manufacturing facility and various other expenses that are expected to decline as key projects are being completed. About CEL-SCI Corporation CEL-SCI believes that boosting a patient’s immune system while it is still intact should provide the greatest possible impact on survival. Therefore, in the Phase 3 study, CEL-SCI studied patients who were newly diagnosed with locally advanced primary squamous cell carcinoma of the head and neck with the investigational product Multikine first, BEFORE they received surgery and radiotherapy or surgery plus concurrent radiotherapy and chemotherapy (the current standard of care for these patients). This approach is unique. Most other cancer immunotherapies are administered only after conventional therapies have been tried and/or failed. Multikine (Leukocyte Interleukin, Injection) received Orphan Drug designation from the FDA for neoadjuvant therapy in patients with squamous cell carcinoma (cancer) of the head and neck. CEL-SCI believes that this Phase 3 study is the largest Phase 3 study in the world for the treatment of locally advanced primary head and neck cancer. Multikine is designed to help the immune system “target” the tumor at a time when the immune system is still relatively intact and thereby thought to be better able to mount an attack on the tumor. The Phase 3 study was started in early 2011 and was fully enrolled with 928 patients in September 2016. To test for an overall survival benefit, the study required CEL-SCI to wait until at least 298 (deaths) events had occurred among the two main comparator groups. The Company has operations in Vienna, Virginia, and near/in Baltimore, Maryland. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Such statements include, but are not limited to, statements about the terms, expected proceeds, use of proceeds and closing of the offering. Factors that could cause or contribute to such differences include an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI's filings with the Securities and Exchange Commission, including but not limited to its report on Form 10-K for the year ended September 30, 2022. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. * Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy. This proprietary name is subject to FDA review in connection with the Company's future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use. CEL-SCI CORPORATION CONDENSED STATEMENTS OF OPERATIONS SIX MONTHS ENDED MARCH 31, 2023 AND 2022 (UNAUDITED) 2023 2022 Operating expenses: Research and development $ 11,476,034 $ 12,606,984 General and administrative 4,350,761 5,788,250 Total operating expenses 15,826,795 18,395,234 Operating loss (15,826,795 ) (18,395,234 ) Gain on derivative instruments - 366,791 Other non-operating losses - (30,793 ) Interest expense, net (311,852 ) (546,862 ) Other expense (57,671 ) - Net loss (16,196,318 ) (18,606,098 ) Modification of warrants (171,552 ) - Net loss available to common shareholders $ (16,367,870 ) $ (18,606,098 ) Net loss per common share – basic and diluted $ (0.38 ) $ (0.43 ) Weighted average common shares outstanding – basic and diluted 43,513,571 43,100,070 CEL-SCI CORPORATION CONDENSED STATEMENTS OF OPERATIONS THREE MONTHS ENDED MARCH 31, 2023 AND 2022 (UNAUDITED) 2023 2022 Operating expenses: Research and development $ 6,083,488 $ 6,523,817 General and administrative 2,092,758 3,028,042 Total operating expenses 8,176,246 9,551,859 Operating loss (8,176,246 ) (9,551,859 ) Gain on derivative instruments - 2,195 Interest expense, net (159,063 ) (273,828 ) Other expense (7,500 ) - Net loss (8,342,809 ) (9,823,492 ) Net loss available to common shareholders $ (8,342,809 ) $ (9,823,492 ) Net loss per common share – basic and diluted $ (0.19 ) $ (0.23 ) Weighted average common shares outstanding – basic and diluted 43,588,381 43,122,671

临床结果免疫疗法临床3期孤儿药财报

100 项与 DerG-PG275Cit 相关的药物交易

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