GP2 peptide vaccine(Cancer Insight LLC)

STAFFORD, Texas, Feb. 14, 2024 (GLOBE NEWSWIRE) -- Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GLSI-100, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, today provided the following update on the Phase III clinical trial, Flamingo-01. Data Safety Monitoring Board (DSMB) The Flamingo-01 DSMB met twice in 2023 and recommended to continue the study as is without modification. No serious adverse events related to GLSI-100 have been reported to date. US Clinical Sites Participating in Flamingo-01 Approximately 30 clinical sites with 87 locations at multiple hospitals and the largest oncology network in the US are currently recruiting patients and are listed below. While the first site was activated in August 2022, the first patient was screened and treated in December 2022. Other sites enrolled their first patients in 2023 with additional sites being activated throughout the year. The Company anticipates adding up to an additional 10 sites in 2024, bringing the total sites in the US to approximately 35-40 sites. European Clinical Sites and Networks Participating in Flamingo-01 Pending European regulatory approval, which is expected in 2024, contracts are in place to add up to an additional 105-120 sites in Europe including Spain (38), France (21), Germany (32), Italy (9), Poland (6), and potentially additional countries in Europe, bringing the total number of potential sites in Flamingo-01 to approximately 140-160 sites between the US and Europe. With a peak enrollment estimate of approximately 2 - 4 patients per site per year, 150 active sites in Flamingo-01 could see peak enrollment of up to 300-600 patients per year. The logistics to supply GP2 and Leukine labeled in each language, to collect patient samples, and to supply all other clinical supplies have been contracted in Europe and are in the final stages of being implemented. European academic networks in each country are planning to participate in Flamingo-01 and are listed below. These networks represent the largest oncology focused hospitals and centers in Europe, where breast cancer leaders work in a collaborative manner to help advance promising therapies and they hold annual scientific meetings where Flamingo-01 has been introduced and where the company may present in the future. GEICAM is the leading group in breast cancer research in Spain and currently consists of more than 900 experts, who work in more than 200 centers throughout Spain. Since its establishment in 1995, GEICAM has carried out more than one hundred studies in which more than 66,000 women and men have participated. UCGB or Unicancer is the federation of French comprehensive cancer centers, a major player in cancer research and a network of 20 private, non-profit healthcare centers specialized in oncology, brought together in a health cooperation group. GBG Forschungs GmbH is one of the world's leading breast cancer research institutes that works together with the academic study group German Breast Group (GBG). With more than 67,000 study participants and 3,500 new patients per year, GBG is the largest breast cancer study group in Germany, consisting of more than 1,000 doctors in over 800 centers. GIM (Gruppo Italiano Mammella) is a cooperative Italian network for breast cancer research and therapy. GIM brings together over 150 participating centers and around 500 investigators. SABCS Update & Flamingo-01 Steering Committee At the 2023 San Antonio Breast Cancer Symposium (SABCS) and 2023 ASCO Annual Meeting, the Company met with the Flamingo-01 Steering Committee and clinicians from the US and various countries in Europe who are participating or planning to participate in Flamingo-01. The Steering Committee is comprised of the following members: Dr. Mothaffar F. Rimawi – Professor of Medicine at the Baylor College of Medicine and Executive Medical Director and Co-Leader, Breast Cancer Program of the Dan L Duncan Comprehensive Cancer Center Dr. Francois-Clement Bidard – Professor of Medical Oncology, UVSQ/Paris Saclay University, Head of Breast Cancer Group, Institut Curie, Vice-Chair of the French Breast Cancer research group UCBG (Unicancer) Dr. William J. Gradishar – Professor of Medicine at the Feinberg School of Medicine at Northwestern University, Chief of Hematology and Oncology in the Department of Medicine, and Betsy Bramsen Professor of Breast Oncology Dr. Sara A. Hurvitz – Professor of Medicine, Head of Division of Hematology/Oncology at University of Washington, Senior Vice President of the Clinical Research Division at the Fred Hutchinson Cancer Center Dr. Sibylle Loibl – Professor (apl) Goethe University Frankfurt/M, Clinical Consultant Centre for Haematology and Oncology/Bethanien Frankfurt/M, CEO of GBG Forschungs GmbH & Chair of the German Breast Group (GBG) Dr. Miguel Martin – Professor of Medicine, Head, Medical Oncology Service, Gregorio Marañón General University Hospital, Complutense University, Madrid, Chairman of GEICAM Dr. Joyce A. O'Shaughnessy – Celebrating Women Chair in Breast Cancer, Baylor University Medical Center and Chair, Breast Cancer Program, Texas Oncology, US Oncology, Dallas, Texas Dr. Hope S. Rugo – Professor of Medicine and Winterhof Family Professor of Breast Oncology and Director, Breast Oncology and Clinical Trials Education, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center Dr. Laura M. Spring – Assistant Professor, Medicine, Harvard Medical School, Attending Physician, Medical Oncology, Massachusetts General Hospital The Steering Committee discussed unpublished data, including new research the Company conducted in 2023, that suggests that GP2 may bind to various HLA types and not just HLA-A*02, in addition to discussing the prior data that supports the third arm of the Phase III trial, where 100 non-HLA-A*02 patients are currently planned to be enrolled. The Steering Committee agreed to expand this third arm to 250 patients. Given the encouraging data and the Steering Committee's guidance, the Company will amend the Flamingo-01 protocol to allow up to 250 patients to enroll in the open-label arm of the study. Dr. Rimawi, Chair of the Steering Committee, commented, "Among my peers, the level of interest in the Flamingo-01 trial is very high. The new sites in Europe will make significant contributions to the trial in terms of patient enrollment as well as overall conduct of the trial. The expansion of the unblinded non-HLA-A*02 arm is also significant as it reflects the interest among patients and investigators in exploring the activity of GLSI-100 in these patients, which may expand the patient population who could benefit from this exciting vaccine." Dr. Jaye Thompson, VP Clinical and Regulatory Affairs, commented, "We welcome the new US and European members to the Steering Committee and are honored to be receiving their continued guidance in the development of GP2 and oversight of Flamingo-01. The Company spent considerable time in Europe in 2023 planning and organizing in each country. We have trained the country specific research networks in each country with the assistance of the key opinion leaders of these countries and worked closely as a group as we applied through a central European regulatory process to allow Flamingo-01 to expand into Europe. We expect to be able to expand the third arm to 250 patients in a cost-effective manner as 85-100% of the global sites plan to enroll into the third arm. We have also seen an increase in interest from third parties in India and China, countries with the largest prevalence of breast cancer, who are interested in further developing GP2 for their patient populations." Planned Interim Analysis In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in the third arm. For the HLA-A*02 randomized arms, the trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater. CEO Snehal Patel commented, "With the addition of the European sites and approximately 150 total sites, peak enrollment rates could be reached by the end of 2024 allowing for a refinement in the interim analysis. Currently, enrollment will likely end before the interim analysis is triggered by 14 events. However, the interim analysis could be modified such that an additional sizing interim analysis is conducted before enrollment ends to reaffirm the size of the 2 randomized arms. While the hazard ratio of 0.3 assumes that the recurrence rate of the treated arm will be 30% of the recurrence rate in the placebo arm and thus a 70% reduction in recurrence rate, and while the Phase II trial showed even greater reduction in recurrence rate, we are likely to see recurrences in the treated arm of the Phase III trial and have designed the trial accordingly. Using the early Phase III trial data to reaffirm the size of the arms of the Phase III trial may be the best information we could use to reduce risk and improve the chances of success of Flamingo-01." Mr. Patel further added, "While we may have high expectations for the interim analysis midway through the trial, Roche's successful Herceptin and Kadcyla products reduced recurrences by only 50%, while still requiring that all HER2 positive patients be treated. Thus, we believe a similar clinical outcome for Flamingo-01 could occur and could generate similar returns to stakeholders as did Roche's franchise drugs, which at their peak significantly exceeded $5 billion in revenue per year." Preparation for Filing of BLA in the US In addition to the submission of the Phase III clinical data, submitting commercial manufacturing data and study reports on the prior clinical trials will be critical to the filing of a BLA for GLSI-100 and for regulatory filings in other countries. Commercial Manufacturing: The first 3 commercial lots of GP2 active ingredient were completed and released in 2023, representing an important step towards commercialization. The 3 lots in total could be used to prepare approximately 200,000 doses of GP2. In 2024, the first of 3 commercial lots filling GP2 into vials for commercial sale or for clinical use is planned. Data on these commercial lots will be submitted to the FDA in the US and other regulatory agencies in Europe or elsewhere when a marketing application is filed seeking approval to sell GP2 in these respective markets. Phase II Clinical Trial Study Report: The Company is preparing a comprehensive study report of the Phase II trial for the FDA prior to the filing of a BLA. This report will include the patients with breast cancer recurrences, the last known date of patients who did not recur (censoring data), the adverse events, immune responses, and other final study report analyses. This report will serve to complement the Phase III data and to provide a drug product dossier that can also be submitted to regulatory agencies in other countries for marketing approval. The use of GM-CSF as an adjuvant in GLSI-100 may also be included in the dossier as GM-CSF is only commercially available in the US at this time. Mr. Patel commented, "We have experienced significant interest from investors, strategics, analysts, and regulators in the 5 year follow-up data we published and the 3 and 4 year follow-up data independently published by the clinical investigators. The differences between these publications can be best explained by the increased maturity of the data as each year progressed. In all 3 publications, no recurrences or a 100% reduction in recurrence rate, were reported in the sub-population that the Flamingo-01 design has been based on and any differences between the number of patients in the treated or placebo groups has been shown to be immaterial." The Company did not have responsibility for the conduct of the trial or for the data from the Phase II trial. After the trial had already started, the Company received the rights to the Phase II trial data pursuant to a license agreement with the Henry Jackson Foundation (HJF) that entitled the Company to all of the GP2 data from the Phase II trial and all prior trials, but did not provide the Company with the ability to participate in the Phase II trial as a regulatory clinical sponsor. The lead clinicians and HJF were responsible for project and site management, medical monitoring, data monitoring of case report forms (CRFs), correspondence with the FDA, and creation, data entry and management of the database. The Company was provided study updates but was not provided an opportunity to participate in any of the above activities or to review the publications of the 3 and 4 year follow-up data by the lead clinicians. Thus, the comprehensive study report will rely on cooperation from HJF and the clinical sites who are responsible for providing the final data accurately to the Company. The Company is currently comparing the final CRFs and database provided by HJF and has noted the following inconsistencies as the comprehensive study report is being prepared. The lead clinicians reported in an annual report to the FDA and in their publication of 4 year follow-up data a 6th recurrence in the HER2 positive control arm of the study. The Company conservatively chose not to report this 6th recurrence since it was not reported in the data provided by HJF, even though adding this recurrence to the control arm would significantly lower the p-value and improve the evidence of efficacy of GLSI-100. As a result of detailed due diligence, the Company became aware in Q4 of 2023 of a potential recurrence in the HER2 positive treated arm. This patient was not reported as a recurrence in the database, on a CRF that should be used for a recurrence, in reports from the lead clinicians to the FDA, or in the 3 or 4 year follow-up data published by the lead clinicians. Some CRFs report a recurrence, but the critical CRF that confirms a recurrence was not completed or entered into the database provided by HJF. The Company has since initiated an effort to confirm with HJF and the clinicians who treated this patient the status of this patient, and if the final CRFs and database should be modified. It appears that this patient, who had completed treatment with GLSI-100, experienced a local recurrence that responded well to additional treatment and survived without additional evidence of disease or distant metastasis for the duration of study follow-up. Any discrepancies noted to date in the review of the censoring date recorded in the database do not materially change the study results and the median duration of follow-up remains 5 years. Mr. Patel added, "While a recurrence in the control arm would decrease the p-value and still result in a 100% reduction in the recurrence rate, a recurrence in the treated arm would increase the p-value and would result in an 80% reduction in the recurrence rate. In either case, we believe that the reduction in recurrence rate is clinically meaningful and substantial compared to the approximately 20-50% reduction in recurrences of all other approved breast cancer drugs for this patient population. These findings have not materially affected the power of the Phase III study as the assumptions for that design were selected conservatively." Additional Clinical Trials Under Consideration The following trials are under consideration, pending additional funding and resources: Phase IIb trial to add an additional 5 years of follow-up to the prior Phase IIb trial: If possible, extending the follow-up period of the prior Phase IIb trial to up to 10 years may increase the understanding of the length of protection offered by GP2 and the need for additional boosters after the current booster regimen ends. This data may also shed some insight on how to optimize vaccination, how to vaccinate the 3 million survivors in the U.S. who are many years removed from adjuvant treatment, and how to vaccinate long term metastatic breast cancer survivors. Such a trial extension would require a new follow-up protocol and the cooperation of clinicians and patients who participated in the prior Phase II trial. Phase II/III trial of all low risk HER2 positive patients not eligible for Flamingo-01: If possible, the Company could leverage the current trial infrastructure in the US and Europe to potentially treat all HER2 positive patients and not just those who are high-risk, which is the current design of Flamingo-01. Some patients in the prior Phase II trial were low-risk, which suggests that GP2 may also work in the low-risk population. This trial would be large and lengthy due to fewer recurrence events, but starting it now would be cost effective given the 150 sites which would have access to these patients. Mr. Patel further commented, "If successful, vaccinating HER2 positive patients who are long term survivors or are at low risk for recurrence could more than double the patient population being pursued in Flamingo-01. Low HER2 breast cancer patients and HER2 positive patients in other cancers also remain possible patient populations to pursue in the future, especially in combination with checkpoint inhibitors and Herceptin antibody drug conjugates." New Intellectual Property In the first quarter of 2023, a new patent application was filed with regards to the use of GLSI-100 to reverse a suppressed immune state and to activate an immune response against HER2 positive cancer cells if they reappear. Plans are in place to potentially patent applications with regards to GP2 manufacturing, pharmacy, or injection processes. The Company is developing an assay that may be applicable to the manufacturing of GP2 and is exploring alternative formulations to minimize the reconstitution process in the pharmacy, both of which may provide additional patent opportunities. 2023 Corporate Events The Company's events in 2023 are listed below and on the events calendar (view here), and for the first time included 3 invitations to present at scientific and clinical conferences, a recognition of the promising GP2 clinical data and the potential of Flamingo-01: Think Tank (a collaborative conference with research and clinical experts in breast cancer), Hawaii Breast (featuring the majority of US KOLs), and the 16th International Symposium on Translational Research in Oncology (featuring European scientific and clinical academia). Dec 15, 2023 – 2023 Annual Meeting of Stockholders Dec 5 - 9, 2023 – 2023 San Antonio Breast Cancer Symposium (SABCS) Nov 6 - 8, 2023 – BIO-Europe Fall 2023 Oct 20 - 22, 2023 – European Society for Medical Oncology (ESMO) Congress 2023 Oct 7, 2023 – 2023 Komen Houston Race for the Cure Sep 27 - 29, 2023 – 16th International Symposium on Translational Research in Oncology Sep 11 - 13, 2023 – H.C. Wainwright 24th Annual Global Investment Conference Aug 16 - 19, 2023 – Hawaii Breast 2023 Jun 5 - 8, 2023 – BIO 2023 International Convention Jun 2 - 6, 2023 – 2023 American Society of Clinical Oncology (ASCO) Annual Meeting May 11 - 13, 2023 – European Society for Medical Oncology (ESMO) Breast Cancer 2023 Apr 15 - 19, 2023 – American Association for Cancer Research (AACR) Annual Meeting 2023 Feb 6 - 9, 2023 – 2023 BIO CEO & Investor Conference Jan 9 - 13, 2023 – Breast Cancer Think Tank Conference List of US Clinical Sites Participating in Flamingo-01 Phase III Clinical Trial Patients who are interested in participating in the Flamingo-01 Phase III clinical trial can learn more about the study at . Each clinical trial site location is listed on the website under "Contacts and Locations" with a new feature showing each site on a map. Patients should contact a participating clinical trial site near them or Flamingo-01@GreenwichLifeSciences.com for screening. The current listing of US sites from the clinicaltrials.gov website with email contact information for some sites is shown below and will be continually updated during the trial. Additional sites are planned to be opened at large hospitals in Boston, Philadelphia, and Baltimore/Washington DC. Arizona Arizona Oncology Associates, PC - HOPE Tucson, Arizona, United States, 85745 Contact: Stacey Kimbell, R.N. Stacey.Kimbell@usoncology.com Principal Investigator: Aisha Ahmed, MD California Comprehensive Blood and Cancer Center Bakersfield, California, United States, 93309 Principal Investigator: Ravindranath Patel, MD Providence Medical Foundation Fullerton, California, United States, 92835 Contact: Rebeca Sanchez 714-446-5177 rebeca.sanchez2@providence.org Contact: Linda Gozar linda.gozar@stjoe.org Principal Investigator: Monica Lee, MD University of Southern California Los Angeles, California, United States, 90033 Contact: Kimberly Arieli Kimberly.Arieli@med.usc.edu Principal Investigator: Danielle Sterrenberg, MD University of California, Los Angeles Los Angeles, California, United States, 90404 Contact: Monica Rocha MPRocha@mednet.UCLA.edu Principal Investigator: Aashini Master Stanford Women's Cancer Center Palo Alto, California, United States, 74304 Contact: Sasha Madan madan2@stanford.edu Principal Investigator: Fauzia Riaz, MD University of California, San Francisco Helen Diller Family Cancer Center San Francisco, California, United States, 94158 Principal Investigator: Hope Rugo, MD Torrance Memorial Physicians Network Torrance, California, United States, 90505 Contact: Jessica Yoshinaga jyoshinaga@mednet.ucla.edu Principal Investigator: David Chan, MD PIH Hospital - Whittier Whittier, California, United States, 90602 Contact: Kristine Bradbury Kristine.Bradbury@pihhealth.org Principal Investigator: Lisa Wang, MD Colorado Rocky Mountain Cancer Centers Denver, Colorado, United States, 80220 Contact: Jennifer Hege Jennifer.Hege@USOncology.com Principal Investigator: Mabel Mardones, MD Connecticut Yale University New Haven, Connecticut, United States, 06511 Principal Investigator: Michael DiGiovanna, MD Florida University of Miami Coral Gables, Florida, United States, 33146 Contact: Maria Ferrer-Guerra mtf89@med.miami.edu Principal Investigator: Mauricio Escobar, MD Orlando Health Cancer Institute Orlando, Florida, United States, 32806 Contact: Melinda Porter Janice.Porter@orlandohealth.com Principal Investigator: Nikita Shah, MD Moffitt Cancer Center Tampa, Florida, United States, 33612 Contact: Julian Guerrero Julian.Guerrero@Moffitt.org Principal Investigator: Aixa Soyano, MD Illinois Northwestern University Chicago, Illinois, United States, 60611 Contact: clinicaltrials@northwestern.edu Principal Investigator: William Gradishar, MD Maryland Maryland Oncology Hematology (USOR) Annapolis, Maryland, United States, 21401 Contact: Gloria Seho-Ahiable Gloria.Seho-Ahiable@USOncology.com Principal Investigator: Jeanine Werner, MD Missouri Washington University Siteman Cancer Center Saint Louis, Missouri, United States, 63110 Principal Investigator: Faisal Fa'ak, MD Nebraska Nebraska Cancer Specialists (USOR) Omaha, Nebraska, United States, 68114 Contact: Heather Cordes hcordes@nebraskacancer.com Principal Investigator: Mary Wells, MD University of Nebraska Medical Center Omaha, Nebraska, United States, 68198 Principal Investigator: Jairam Krishnamurthy, MD Nevada Comprehensive Cancer Centers of Nevada Henderson, Nevada, United States, 89052 Contact: Lindsay Kondo lindsay.kondo@usoncology.com Principal Investigator: Stephani Christensen, MD New York New York Oncology Clifton Park, New York, United States, 12065 Contact: Josephine Faruol josephine.faruol@usoncology.com Principal Investigator: Karen Tedesco, MD Columbia University New York, New York, United States, 10032 Contact: cancerclinicaltrials@CUMC.Columbia.edu Principal Investigator: Julia McGuinness, MD Stony Brook University Stony Brook, New York, United States, 11794 Contact: Pushpa Talanki Pushpa.talanki@stonybrookmedicine.edu Contact: Jules Cohen jules.cohen@stonybrookmedicine.edu Principal Investigator: Jules Cohen, MD Ohio Oncology Hematology Care Clinical Trials Cincinnati, Ohio, United States, 45211 Contact: Douglas Hart Douglas.Hart@usoncology.com Principal Investigator: Patrick Ward, MD Oregon Compass Oncology (USOR) Tigard, Oregon, United States, 97223 Contact: Jennifer Thompson Jennifer.Thompson@usoncology.com Principal Investigator: Jay Andersen, MD Pennsylvania Redeemer Health Meadowbrook, Pennsylvania, United States, 19046 Contact: Nadine Varney 215-544-5832 nvarney@holyredeemer.com Principal Investigator: Pallav Mehta, MD Texas Texas Oncology - Austin Austin, Texas, United States, 78745 Contact: Sara Manning Sara.Manning@usoncology.com Principal Investigator: Debra A Patt, MD Texas Oncology - Dallas (USOR) Dallas, Texas, United States, 75246 Contact: Christine Terraciano Christine.Terraciano@usoncology.com Principal Investigator: Cynthia Osborne, MD Texas Oncology - Dallas Presbyterian Hospital Dallas, Texas, United States, 75231 Contact: Nancy Jones nancy.jones@usoncology.com Principal Investigator: Kristi McIntyre, MD The University of Texas Southwestern Medical Center Dallas, Texas, United States, 75390 Principal Investigator: Nisha Unni, MD Baylor College of Medicine Houston, Texas, United States, 77057 Contact: Rebecca Hildebrandt Rebecca.Hildebrandt@BCM.edu Principal Investigator: Mothaffar Rimawi, MD Texas Oncology San Antonio (USOR) San Antonio, Texas, United States, 78240 Contact: Shannon Syring Shannon.Syring@usoncology.com Principal Investigator: Emmalind Aponte, MD Texas Oncology - Gulf Coast Sugar Land, Texas, United States, 77479 Contact: Melissa Howell Melissa.Howell@usoncology.com Principal Investigator: Jorge Darcourt, MD Texas Oncology - Tyler (USOR) Tyler, Texas, United States, 75702 Contact: Shelly Maxfield Shelly.Maxfield@USOncology.com Principal Investigator: Nanna Sulai, MD Utah University of Utah Huntsman Cancer Institute Salt Lake City, Utah, United States, 84112 Principal Investigator: Mei Wei, MD Virginia Virginia Cancer Specialists Fairfax, Virginia, United States, 22031 Contact: Carrie Friedman Carrie.Friedman@USOncology.com Principal Investigator: Shruti Tiwari, MD About Flamingo-01 and GLSI-100 Flamingo-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2/neu positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US clinical sites from university-based hospitals and cooperative networks with plans to expand into Europe and to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater. For more information on Flamingo-01, please visit the Company's website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: flamingo-01@greenwichlifesciences.com About Breast Cancer and HER2/neu Positivity One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels. About Greenwich LifeSciences, Inc. Greenwich LifeSciences is a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery. GP2 is a 9 amino acid transmembrane peptide of the HER2/neu protein, a cell surface receptor protein that is expressed in a variety of common cancers, including expression in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels. Greenwich LifeSciences has commenced a Phase III clinical trial, Flamingo-01. For more information on Greenwich LifeSciences, please visit the Company's website at and follow the Company's Twitter at . Forward-Looking Statement Disclaimer Statements in this press release contain "forward-looking statements" that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "believe," "contemplate," "could," "estimate," "expect," "intend," "seek," "may," "might," "plan," "potential," "predict," "project," "target," "aim," "should," "will," "would," or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Greenwich LifeSciences Inc.'s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including statements regarding the intended use of net proceeds from the public offering; consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section entitled "Risk Factors" in Greenwich LifeSciences' Annual Report on Form 10-K for the year ended December 31, 2022 and other periodic reports filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Greenwich LifeSciences, Inc. undertakes no duty to update such information except as required under applicable law. Company Contact Snehal Patel Investor Relations Office: (832) 819-3232 Email: info@greenwichlifesciences.com Investor & Public Relations Contact for Greenwich LifeSciences Dave Gentry RedChip Companies Inc. Office: 1-800-RED CHIP (733 2447) Email: dave@redchip.com

关键词肿瘤疫苗；研究进展；mRNA疫苗尽管癌症治疗已经取得了很大进展，人们依然谈癌色变。据2021年世界卫生组织国际癌症研究机构（IARC）发布的数据，2020年全球新发癌症病例预计为1929万例，全球癌症死亡病例预计为996万例。随着人口老龄化，以及吸烟、饮酒、不健康饮食、缺乏运动和空气污染等多种危险因素，全球癌症发病率、死亡率都在增加。癌症的治疗给家庭、国家带来巨大的经济负担。据德国海德堡大学/中国医学科学院北京协和医学院陈思邈教授等在JAMA Oncology期刊发表的题为《Estimates and Projections of the Global Economic Cost of 29 Cancers in 204 Countries and Territories From 2020 to 2050》的研究论文，2020年至2050年这30年，全世界将为癌症花费25.2万亿美元。随着对疾病研究的深入，以及生物技术的发展，目前癌症治疗取得了巨大的进步，新型靶向疗法、免疫疗法、细胞疗法不断涌现。疫苗在癌症预防、治疗中占有重要地位，然而进展相对较缓，不过肿瘤疫苗的研发从未终止。肿瘤疫苗肿瘤疫苗是利用肿瘤抗原，通过主动免疫方式诱导机体产生特异性抗肿瘤效应,激发机体自身的免疫保护机制,达到肿瘤治疗或预防复发的作用，属于主动免疫治疗范畴。肿瘤抗原通常被分为肿瘤特异性抗原（TSA）和肿瘤相关抗原（TAA），其中TSA包括病毒抗原和由非同义体细胞突变产生的新表位，TAA则包括组织特异性抗原和发育特异性抗原。根据用途的不同，肿瘤疫苗可分为预防性肿瘤疫苗（如HPV疫苗）和治疗性肿瘤疫苗（主要以肿瘤抗原为基础，用于放化疗或手术切除后的辅助治疗）。而根据肿瘤抗原组分和性质的不同，肿瘤疫苗可分为以细胞为载体的肿瘤疫苗、病毒疫苗、蛋白/多肽疫苗、核酸疫苗（DNA疫苗）、抗独特型疫苗和异种疫苗等。据不完全统计，目前全球已经批准了能预防肝癌的乙肝病毒（HBV）疫苗（中国70%左右肝癌和乙肝病毒相关）、预防宫颈癌的人乳头瘤病毒（HPV）疫苗（99%的宫颈癌和人乳头瘤病毒相关），以及治疗前列腺癌的疫苗Sipuleucel-T、治疗肺癌的疫苗CIMAvax-EGF和Vaxira、治疗头颈鳞癌的疫苗CIMAher、治疗皮肤癌的疫苗Heberferon和治疗实体瘤的疫苗（如德国LANEX-DC和日本WT1肽抗原树突细胞疫苗）。Sipuleucel-TSipuleucel-T是一种自体细胞来源的免疫治疗药，由自体树突状细胞（DCs）与融合蛋白PA2024在体外共孵化获得（PA2024是一种由前列腺酸性磷酸酶（PAP）和粒细胞巨噬细胞集落刺激因子(GM-CSF)构建的融合蛋白 (PAP-GM-CSF)，PAP-GM-CSF再与自身抗原呈递细胞（PAC）共同培养，融合蛋白可分解成小肽呈现在PAC表面，提高对肿瘤细胞的免疫应答能力）。2020年，Sipuleucel-T被FDA批准用于治疗无症状或症状轻微转移性去势抵抗性前列腺癌。CIMAvax-EGFCIMAvax-EGF主要由表皮生长因子（EGF）和一种叫P64K蛋白质组成。CIMAvax-EGF可以激活人体免疫系统产生EGF抗体，抗体与身体内的EGF结合迫使癌细胞接收不到EGF的信号，由于接受不到EGF信号，癌细胞就会感到饥饿，从而阻止癌细胞的增殖和转移。2011年，CIMAvax-EGF被批准进入古巴肺癌治疗的临床使用。VaxiraVaxira是二代疫苗，2012年在古巴上市。Vaxira主要成分包括Racotumomab和氢氧化铝辅剂。Racotumomab是针对AcM P3的IGI同种型的单克隆抗体，它专门识别AcM P3单克隆抗体并抑制其与神经节苷脂NeuGcGM3的结合（神经节苷脂NeuGcGM3是一种特异性的肿瘤抗原，在不同类型的肿瘤细胞如非小细胞肺癌，乳腺癌和黑色素瘤中高表达）。此外，目前全球还有多款在研肿瘤疫苗（详见下表），其中多款已进入III期临床。在研肿瘤疫苗大多被开发用于实体瘤的治疗。疫苗类型上，在研肿瘤疫苗包括肽疫苗、DC疫苗、DNA疫苗和mRNA疫苗等。企业上看，国内外药企均在积极布局。尤其是mRNA肿瘤疫苗领域，除了mRNA三大巨头BioNTech、Moderna、CureVac等国外药企，我国药企，如斯微生物、新合生物、嘉晨西海等也在积极布局布局mRNA肿瘤疫苗领域。值得一提的是，全球首款mRNA肿瘤新抗原疫苗即将出线，Moderna在其肿瘤新抗原mRNA疫苗mRNA-4157/V940于今年2月被FDA授予突破性疗法认证之后寻求其加速批准。全球部分在研肿瘤疫苗资料来源：公开资料NeuVaxNeuVax是一种基于肽的癌症免疫疗法，是来源于HER2蛋白的一种免疫原性肽。NeuVax被用作一种疫苗，与免疫佐剂粒细胞-巨噬细胞集落刺激因子（GM-CSF）联合应用时，被证实能够引起强大的抗HER2免疫应答。已公布的2期临床试验结果显示：NeuVax可改善HER-2阳性乳腺癌患者的总生存率，且耐受性良好。NeuVax曾被FDA授予快速通道资格（FTD），用于治疗接受标准护理治疗的HER2表达为低至中等水平（HER2 1+或2+）早期乳腺癌。目前，NeuVax正在进行III期研究，评估NeuVax疫苗（NPS+粒细胞-巨噬细胞集落刺激因子[GM-CSF]）联合曲妥珠单抗、GM-CSF单药疗法作为维持疗法，用于TNBC患者在接受标准护理治疗后进行辅助治疗。Adagloxad simoleninAdagloxad simolenin是一种以肿瘤相关糖类抗原Globo H为作用靶点的主动免疫抗癌疗法，由Globo H与载体蛋白KLH（钥孔戚血蓝蛋白）共价相连而成（Globo H是一种在乳腺癌、前列腺癌、胃癌、肺癌、结肠癌、胰腺癌与卵巢癌等肿瘤表面大量表达的一种抗原）。Adagloxad simolenin与皂苷佐剂OBI-821联合使用，可以诱导机体产生免疫反应，进而达到抗肿瘤的效果。2021年7月，Adagloxad Simolenin治疗高危早期-Globo H-阳性的三阴性乳腺癌患者的随机、开放、国际多中心3期研究GLORIA启动。GP2GP2是一种多肽肿瘤疫苗，是HER2/neu衍生的短肽疫苗。HER2/neu是一种细胞表面受体蛋白，通常表达于HER2阳性乳腺癌及其他各种常见的恶性肿瘤中。2020年圣安东尼奥乳腺癌大会上公布的最新临床试验结果显示：在5年的随访后，46例接受GP2+GM-CSF治疗的HER2+患者的5年DFS发生率为100%，而接受GM-CSF治疗的50例安慰剂患者的5年DFS（无病生存期）发生率为89.4%，GP2将5年生存率提高了近11%。DCVax-LDCVax-L是一种完全个性化的免疫疗法，由患者自身肿瘤样本中的树突细胞和抗原（生物标记物）制成。2022年11月，Northwest Biotherapeutics宣布其自体肿瘤裂解液树突状细胞疫苗DCVax-L在新诊断和复发性胶质母细胞瘤脑癌患者中，中位生存期和生存率均延长，达到具有统计学意义的主要和次要终点。VGX-3100VGX-3100是东方略与Inovio Pharmaceuticals合作研发的一款DNA免疫治疗产品，用于治疗由人类HPV导致的癌前病变。2021年3月，Inovio Pharmaceuticals宣布VGX-3100与器械CELLECTRATM 5PSP联合治疗HPV-16/18相关宫颈高度鳞状上皮内病变（HSIL）的III期临床试验（REVEAL 1）取得积极结果，在全部可评估受试者中，达到临床疗效的主要终点和所有次要终点。mRNA-4157/V940mRNA-4157/V940是一种基于mRNA的新型研究性个性化癌症疫苗，所包含的编码由多达34种新抗原的单一合成mRNA分子组成。该疫苗是根据每位患者肿瘤独特的DNA序列突变特征设计制成，当疫苗被注入患者体内后，会促使患者体内产生特定的T细胞抗肿瘤反应。已公布mRNA-4157/V940联合Keytruda治疗III/IV期黑色素瘤的2b期临床试验KEYNOTE-942/mRNA-4157-P201结果显示：与Keytruda单药治疗相比，mRNA-4157/V940联合Keytruda治疗组使患者的复发或死亡风险降低44%，符合试验的无复发生存期（RFS）的主要终点。2023年2月，FDA基于该试验数据授予mRNA-4157/V940突破性疗法认证，联合Keytruda辅助治疗高危黑色素瘤。BNT111BNT111是基于BioNTech完全拥有的FixVac平台的开发的肿瘤疫苗，该平台利用mRNA编码的肿瘤相关抗原的固定组合，旨在触发针对癌症的强大而精确的免疫反应。已发表的BNT111治疗晚期黑色素瘤的I期临床试验结果显示：BNT111可诱导新颖的抗原特异性抗肿瘤免疫应答，并增强针对所编码的黑色素瘤相关抗原（NY-ESO-1、MAGE-A3、酪氨酸酶、TPTE）预先存在的免疫应答，这4种抗原在90%以上的皮肤黑色素瘤中表达，显示出了良好的安全性和初步抗肿瘤效果。2021年11月，BNT111被FDA授予快速通道资格。目前，BNT111已进入II期临床，联和Libtayo（cemiplimab）治疗抗PD-1疗法难治性/复发性不可切除III期或IV期黑色素瘤。BNT113BNT-113是一款使用脂质体包裹的mRNA疫苗，编码HPV-16衍生的E6和E7修饰序列，针对HPV16+癌症。已公布的BNT113联合Keytruda一线治疗不可切除复发/转移性头颈部鳞状细胞癌的初步安全数据显示：截至2022年7月5日，在接受治疗的15例患者中，12例已完成安全磨合。安全磨合中的所有患者均有≥1次AE，最常见的是发热（8例）和寒战（6例）。BNT122BNT122是利用BioNTech的iNeST技术平台研发的个体化新抗原mRNA疫苗，利用该平台设计的疫苗含有未经修饰的、优化后的mRNA，能够编码多达20种不同的特异性新抗原。2022 ASCO大会上公布的I期临床试验数据显示：BNT122联合PD-L1抑制剂atezolizumab和化疗在接受手术切除的胰腺癌患者中展现出良好的疗效和安全性。BNT116BNT116是基于BioNTech的FixVac技术平台开发的癌症疫苗。它表达一组在NSCLC中经常表达的共享肿瘤相关抗原。这些通过mRNA表达的抗原可以激发强力和精准的先天和适应性免疫反应。CV-8102CV-8102是一款基于RNA的单链非编码TLR-7/8和RIG-1激动剂，早在2017年就已开展了I期临床研究，用于晚期黑色素瘤、皮肤鳞状细胞癌、头颈部鳞状细胞癌或腺样囊性癌患者的治疗。JCXH-211JCXH-211是一款具有差异化优势的自复制型mRNA产品，可在体内长效表达IL-12，潜在适用于多种实体瘤的治疗。结合嘉晨西海自主开发的脂质纳米颗粒递送载体及特有的自复制mRNA技术平台，JCXH-211在临床前研究的多个小鼠和PDX疾病模型中都表现出了优异的肿瘤清除效力，优于采用传统非复制mRNA的类似研究药物。数据显示，JCXH-211在小鼠模型中能有效杀伤肿瘤细胞，消除远端瘤，并预防肿瘤复发。这一优异的肿瘤清除效果来源于RNA复制子引发的强烈的抗病毒免疫反应以及IL-12激活的强效抗肿瘤免疫反应。安全性方面，依托嘉晨西海优化设计的自复制RNA构建以及成熟的CMC工艺平台，JCXH-211在综合GLP毒理学研究中显示出了近乎完美的安全性。而JCXH-212是一款肿瘤新抗原mRNA疫苗。EB病毒mRNA疫苗威斯津生物的EB病毒mRNA疫苗由其联合创始人宋相容教授牵头研发，历时长达5年。动物试验研究显示，该mRNA疫苗可显著抑制针EBV阳性肿瘤细胞的生长，安全性较好。2023年2月，威斯津生物在全球首次启动治疗EBV病毒相关恶性肿瘤的mRNA疫苗药物的注册临床试验。靶向Survivin DC细胞注射液启辰生生物靶向Survivin DC细胞注射液是将抗原mRNA负载的树突状细胞（DC），分别通过皮内注射和静脉回输的方式给予患者，诱导抗原特异的CD4+和CD8+T淋巴细胞，为原发性脑胶质母细胞瘤患者术后清除肿瘤残余细胞，防止复发，延长生存期，实现长期抗肿瘤效果提供全新的治疗手段。前期非临床研究和研究者发起的探索性临床试验数据已经表明，该mRNA-DC疫苗可诱导出抗Survivin特异性肿瘤免疫反应，安全性良好，有效性显著，试验患者的总生存期显著延长。2023年1月，启辰生生物靶向Survivin DC细胞注射液获批临床，成为全球首个获批开展临床试验的靶向Survivin的mRNA-DC肿瘤治疗性疫苗产品。CUD002CUD002是中国首款基于肿瘤新生抗原的mRNA编辑DC肿瘤治疗性疫苗，根据患者独特的突变信息定制设计并制造，能激发患者自身免疫系统识别卵巢癌抗原，产生抗肿瘤免疫反应并杀伤肿瘤细胞。2022年8月，CUD002注射液的IND正式获CDE受理。XH101XH101是新合生物研发的靶向胃癌公共新抗原的治疗性mRNA肿瘤疫苗，该靶点为全球首创靶点。该公共新抗原是新合生物通过独家研发的肿瘤新抗原预测算法平台、免疫原性Elispot验证平台及细胞杀伤平台，从大量胃癌患者中筛选、预测、验证出的一段免疫原性强、覆盖度广的肿瘤公共新抗原序列。与传统药物相比，该疫苗具有更强的免疫原性，可诱发人体天然的免疫反应，不仅可以缩短疫苗制备周期，降低患者的治疗成本，还可以在患者体内产生持久有效的免疫记忆，为肿瘤防复发、防转移提供可能。同时，XH101对晚期肿瘤和转移性肿瘤，还可起到有效抑制作用。临床前研究数据显示XH101能够有效激发患者的T细胞免疫应答及肿瘤细胞杀伤效应，具有显著的临床治疗潜力。近年来全球药企围绕肿瘤疫苗达成多项合作 012014年9月，勃林格殷格翰与CureVac公司宣布达成一项排他性全球授权和研发合作协议，获得后者在研肿瘤治疗性疫苗CV9202的全球独家研发和商业化的权利。 022016年9月，BioNTech公司已与罗氏旗下Genentech签订全球合作协议，共同开发、生产和商业化基于信使RNA的个性化肿瘤疫苗。据协议，基因泰克将支付BioNtech 3.1亿美元的预付款和近期里程金。 032017年10月，CureVac与礼来联手共同开发多达5款癌症疫苗产品，合作总额逾18亿美元。 042019年11月，复星医药产业与MimiVax公司达成授权合作，在中国大陆、香港及澳门地区独家临床开发和商业化SurVaxM，授权的适应症为胶质母细胞瘤以及其他肿瘤和非肿瘤疾病。 052021年9月，臻和生物与依莫纳达成战略合作，共同开发基于mRNA技术平台的个体化新抗原肿瘤疫苗。 062022年3月，BioNTech宣布扩展与再生元的战略研发合作，将联合推动BNT116与PD-1抑制剂Libtayo（cemiplimab）联用的临床试验，用于治疗晚期非小细胞肺癌（NSCLC）患者。 072022年5月，CureVac与myNEO达成合作，通过确定特定的癌症抗原开发用于癌症疫苗的新型mRNA免疫疗法。 082022年10月，新合生物与信达生物达成合作协议，就个性化新抗原疫苗与信迪利单抗联合治疗肿瘤开展了临床研究。 092022年10月，默沙东和Moderna根据现有合作和许可协议的条款，默沙东行使选择权，与Moderna共同开发和商业化mRNA-4157/V940。 102023年1月，德国公司BioNTech宣布与英国政府合作，一同测试用于治疗癌症和其他疾病的mRNA疫苗技术。 112023年1月，GreenLight生物科学公司和EpiVax Therapeutics签署独家合作协议，共同开发和商业化个性化mRNA癌症的候选疫苗。 122023年1月，启辰生生物与华润生物签订战略合作协议，合作开发治疗脑胶质母细胞瘤的mRNA疫苗。 132023年3月，康宁杰瑞与斯微生物建立战略合作伙伴关系，重点开展肿瘤领域双特异性抗体药物及mRNA疫苗药物的临床研发合作。总结疫苗被誉为20世纪最伟大的科学进步之一，然而目前大多疫苗被应用于传染性疾病的预防。随着肿瘤发病率的增加，疫苗也逐渐被开发用于肿瘤的预防和治疗。从目前研发状况来看，肿瘤疫苗有望成为一种新型的肿瘤免疫疗法。而且，随着高通量基因测序和生物信息学分析技术的快速发展，新抗原不断被筛选和鉴定，个性化癌症疫苗也将成为肿瘤疫苗研发的新方向。从疫苗类型上看，随着mRNA新冠疫苗的成功，mRNA肿瘤疫苗研发进展迅速。据Nature Review的综述预测，2035年全球mRNA预防性疫苗市场规模将达到120-150亿美元，个性化肿瘤疫苗市场规模约为70-100亿美元，蛋白替代疗法等市场规模约40-50亿美元，对应mRNA在治疗和预防领域总市场空间约230-300亿美元。END👇关注药渡数据媒体矩阵