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MELBOURNE, Australia and PRINCETON, N.J., March 19, 2024 (GLOBE NEWSWIRE) -- Opthea Limited (ASX:OPT; NASDAQ:OPT; “Opthea”), a clinical-stage biopharmaceutical company developing novel therapies to treat highly prevalent and progressive retinal diseases, today announced it will host a virtual key opinion leader (KOL) event on Wednesday, April 3, 2024, from 10:00 to 11:30 am ET, featuring presentations from global retina experts: Arshad M. Khanani, MD, MA, FASRS, Sierra Eye Associates and University of Nevada, Reno School of Medicine Charles C. Wykoff, MD, PhD, Retina Consultants of Texas and Blanton Eye Institute, Houston Methodist Hospital Veeral S. Sheth, MD, MBA, FASRS, FACS, University Retina and Macula Associates, University of Illinois at Chicago This event will focus on the potential of sozinibercept to transform patient outcomes by delivering superior vision gains in wet age-related macular degeneration (wet AMD), with KOL perspectives on (1) the wet AMD treatment landscape and unmet medical need addressed by sozinibercept’s novel mechanism of action, (2) the Phase 2b data demonstrating superiority in combination with standard-of-care therapy, and (3) the company's two ongoing global Phase 3 registrational trials (COAST and ShORe) evaluating sozinibercept in combination with standard-of-care VEGF-A inhibitors. Additionally, Opthea will provide a strategic outlook. A live question and answer session will follow the formal presentations. To register for this live webcast, click here. A replay of the webcast will be made available on the Company’s website. About Arshad M. Khanani, MD, MA, FASRS Arshad M. Khanani, MD, MA, FASRS is dedicated to advancing innovative treatment options for patients suffering from retinal diseases. Over a decade ago, he established the clinical research department at Sierra Eye Associates, which has since evolved into one of the foremost clinical research sites nationwide. With a wealth of experience, he has assumed the role of principal investigator for more than 120 clinical trials, consistently ranking as a top enroller in the nation across multiple Phase 1-3 trials. Notably, Dr. Khanani recently chaired the Phase 3 GATHER2 steering committee for IZERVAY™, playing a pivotal role in IZERVAY's approval for geographic atrophy. His contributions extend to over 100 authored or contributed scientific publications in prominent ophthalmology journals. Dr. Khanani actively participates as a member of national and international clinical trial steering committees, in addition to serving on scientific advisory boards. Dr. Khanani also serves as the lead principal investigator for multiple national and global clinical trials. He is often sought after as a guest speaker and lecturer at prestigious national and international gatherings. In pursuit of advancements in vitreoretinal care, Dr. Khanani initiated the Clinical Trials at the Summit (CTS) meeting, aiming to foster dialogue on clinical trial execution, design, and data analysis. Dr. Khanani holds elected membership in esteemed organizations such as the Macula Society and Retina Society, in addition to being the recipient of numerous distinguished awards. In 2019, he was honored with the Nevada Business Magazine Healthcare Heroes Physician of the Year award in recognition of his unwavering commitment to the field of ophthalmology. Dr. Khanani has been bestowed with the Senior Honor Award from the American Society of Retina Specialists (ASRS) and was also awarded the prestigious ASRS Presidents’ Young Investigator Award in 2021. Furthermore, in 2023, he was invited to deliver the esteemed Ernst Bodenheimer Memorial Lecture at the Wilmer Eye Institute at Johns Hopkins University. In February 2024, Dr. Khanani joined Opthea as its Chief Medical Advisor, while retaining his practice, sponsorship, and research activities. Prior to his new role at Opthea, Dr. Khanani served as a principal investigator for Opthea’s ShORe Phase 3 pivotal trial. About Charles C. Wykoff, MD, PhD Charles C. Wykoff, MD, PhD is a board-certified Medical and Surgical Retina Specialist and ophthalmologist with Retina Consultants of Texas (RCTX). Leading a top international research facility for vitreoretinal diseases, Dr. Wykoff serves as Director of Research at RCTX and the Greater Houston Retina Research Foundation (GHRRF), and Chairman of the Research and Clinical Trials Subcommittee, Retina Consultants of America. In addition, he serves as the elected Deputy Chair of Ophthalmology for the Blanton Eye Institute, Houston Methodist Hospital. Dr. Wykoff has been awarded the American Academy of Ophthalmology Secretariat and Achievement Awards as well as the American Society of Retina Specialists Senior Honor and Young Investigator Awards. Dr. Wykoff serves as the Chief Investigator for Opthea’s COAST Phase 3 pivotal trial and is on Opthea’s Clinical Advisory Board. About Veeral S. Sheth, MD, MBA, FASRS, FACS Veeral Sheth, MD, MBA, FACS, is a native Chicagoan that specializes in diseases of the retina and vitreous. He also is a Clinical Assistant Professor at the University of Illinois at Chicago. Dr. Sheth completed his ophthalmology residency at the Illinois Eye and Ear Infirmary where he served as Chief Resident. After residency, Dr. Sheth completed his fellowship at the University of Chicago in Retinal Surgery. He completed his MBA at Northwestern University’s Kellogg School of Management. Dr. Sheth is a Partner at University Retina and Macula Associates. He is Director of Clinical Trials at one of the busiest clinical trial sites in the country. He has been principal investigator for over 60 clinical trials and has research interests in macular degeneration, diabetic retinopathy, vein occlusion, as well as surgical pathology. He is involved in clinical trials developing new drugs, delivery devices, and gene therapy. Dr. Sheth is an active member of the American Society of Retina Specialists, Retina Society, American Academy of Ophthalmology, The Association for Research in Vision and Ophthalmology, and the European Society of Retina Specialists. He is the Chairman Emeritus of the Board of Directors for Meals on Wheels Chicago. Dr. Sheth is fluent in English, Spanish, and Gujarati. Dr. Sheth is a principal investigator for Opthea’s ShORe Phase 3 pivotal trial. About Sozinibercept Sozinibercept (OPT-302) is a soluble form of vascular endothelial growth factor receptor 3 (VEGFR-3) expressed as an immunoglobulin G1 (IgG1) Fc-fusion protein. It binds and neutralizes the activity of VEGF-C and VEGF-D on their endogenous receptors, VEGFR-2 and VEGFR-3. Research indicates that targeted inhibition of VEGF-C and VEGF-D can prevent blood vessel growth and vascular leakage, which contribute to the pathophysiology of retinal diseases including wet AMD. Sozinibercept has received Fast Track Designation from the U.S. FDA for the treatment of wet AMD. Positive results from the Phase 2b study of sozinibercept, administered in combination with standard of care, LUCENTIS® (ranibizumab), for the treatment of wet AMD, published in Ophthalmology, met the pre-specified primary efficacy endpoint of a statistically superior gain in visual acuity at 24 weeks, compared to ranibizumab alone. In addition, secondary outcomes were positive for the combination therapy with sozinibercept, including more participants with gains in vision of 10 or more letters and improved anatomy, with a reduction in swelling and vascular leakage, with a favorable safety profile. About Opthea Opthea (ASX:OPT; NASDAQ:OPT) is a biopharmaceutical company developing novel therapies to address the unmet need in the treatment of highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME). Opthea’s lead product candidate, sozinibercept, is being evaluated in two pivotal Phase 3 clinical trials (COAST, NCT04757636, and ShORe, NCT04757610,) for use in combination with standard-of-care anti-VEGF-A monotherapies to improve overall efficacy and deliver superior vision gains compared to the standard-of-care anti-VEGF-A agents. To learn more, visit our website and follow us on X and LinkedIn. IZERVAY™ is a registered trademark of Astellas Pharma Inc. LUCENTIS® is a registered trademark of Genentech USA, Inc. A member of the Roche Group. Authorized for release to ASX by Fred Guerard, CEO Investor Enquiries PJ Kelleher LifeSci Advisors Email: pkelleher@lifesciadvisors.com Phone: 617-430-7579 Media Silvana Guerci-Lena NorthStream Global Partners Email: silvana@nsgpllc.com Join our email database to receive program updates: Tel: +61 (0) 3 9826 0399 Email: info@opthea.com Source: Opthea Limited

ISELIN, N.J., March 18, 2024 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to achieve the first approval for an ophthalmic formulation of bevacizumab for the treatment of retinal diseases in the US and the EU, today announced that it has closed its previously announced private placement, for upfront gross proceeds of approximately $60 million from the issuance and sale of shares of the Company’s common stock and accompanying warrants, before deducting placement agent fees and offering expenses. Outlook Therapeutics has the potential to receive additional gross proceeds of up to $99 million upon the full cash exercise of the warrants issued in the private placement, before deducting placement agent fees and offering expenses. The private placement was led by Great Point Partners, LLC, with participation from existing investor GMS Ventures as well as new investors Altium Capital, Armistice Capital, Caligan Partners LP, Schonfeld Strategic Advisors, Sphera Healthcare, Velan Capital, Woodline Partners LP, and an undisclosed life sciences dedicated investor. BofA Securities and BTIG acted as co-placement agents in connection with the financing. About the Private Placement Pursuant to the securities purchase agreement entered into on January 22, 2024, Outlook Therapeutics issued to purchasers in the private placement an aggregate of 8,571,423 shares of common stock and accompanying warrants to purchase an aggregate of 12,857,133 shares of common stock, at a price of $7.00 per share and accompanying warrant to purchase one and one-half shares of common stock. The warrants have an exercise price of $7.70 per share and are exercisable only for cash until their expiration on the fifth anniversary of the issuance date. The warrants include a feature that allows Outlook Therapeutics to require holders to cash exercise the warrants if certain stock price and milestone conditions are met. All of the securities in the private placement were offered by the Company. Outlook Therapeutics intends to use the net proceeds from the private placement to fund its ONS-5010 clinical development programs, including the ongoing NORSE EIGHT clinical trial, and for working capital and other general corporate purposes. As previously disclosed, Outlook Therapeutics also entered into a securities purchase agreement with Syntone Ventures, another existing stockholder, to purchase $5 million in shares of common stock and warrants on the same terms as the private placement. The closing of the Syntone investment remains subject to receipt of regulatory approvals and other customary closing conditions. The offer and sale of the foregoing securities were made by Outlook Therapeutics in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the “Act”), and/or Regulation D promulgated thereunder, and such securities have not been registered under the Act or applicable state securities laws. Accordingly, such securities may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws. Outlook Therapeutics has agreed to file a resale registration statement with the U.S. Securities and Exchange Commission for purposes of registering the resale of the common stock issued or issuable in connection with the private placement. This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities described herein nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. About ONS-5010 / LYTENAVA™ (bevacizumab-vikg, bevacizumab gamma) ONS-5010/LYTENAVA™ is an investigational ophthalmic formulation of bevacizumab under development as an intravitreal injection for the treatment of wet AMD and other retinal diseases. Because no FDA or European Commission approved ophthalmic formulations of bevacizumab are available currently, clinicians wishing to treat retinal patients with bevacizumab have had to use repackaged IV bevacizumab provided by compounding pharmacies—products that have known risks of contamination and inconsistent potency and availability. If approved, ONS-5010/LYTENAVA™ would provide an approved option for physicians to treat wet AMD. Bevacizumab-vikg/bevacizumab gamma is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab-vikg to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina. About Outlook Therapeutics, Inc. Outlook Therapeutics is a biopharmaceutical company working to achieve FDA and European Commission approval for the launch of ONS-5010/ LYTENAVA™ (bevacizumab-vikg or bevacizumab gamma) as the first approved ophthalmic formulation of bevacizumab for use in retinal indications, including wet AMD, DME and BRVO. If ONS-5010 ophthalmic bevacizumab is approved, Outlook Therapeutics expects to commercialize it as the first and only FDA and/or EC approved ophthalmic formulation of bevacizumab for use in treating retinal diseases in the United States, EU, United Kingdom, Europe, Japan, and other markets. As part of the Outlook Therapeutics' multi-year commercial planning process, Outlook Therapeutics and Cencora entered into a strategic commercialization agreement to expand the Outlook Therapeutics’ reach for connecting to retina specialists and their patients. Cencora will provide third-party logistics (3PL) services and distribution, as well as pharmacovigilance services and other services in the United States. Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “continue,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “target,” “will,” or “would” the negative of terms like these or other comparable terminology, and other words or terms of similar meaning. These include, among others, the private placement, including expected proceeds from the exercise of the warrants and uses of proceeds, expectations concerning the relationship with Cencora and the benefits and potential expansion thereof, and other statements that are not historical fact. Although Outlook Therapeutics believes that it has a reasonable basis for the forward-looking statements contained herein, they are based on current expectations about future events affecting Outlook Therapeutics and are subject to risks, uncertainties and factors relating to its operations and business environment, all of which are difficult to predict and many of which are beyond its control. These risk factors include those risks associated with developing pharmaceutical product candidates, risks of conducting clinical trials and risks in obtaining necessary regulatory approvals, the content and timing of decisions by the FDA, as well as those risks detailed in Outlook Therapeutics’ filings with the Securities and Exchange Commission (the SEC), including the Annual Report on Form 10-K for the fiscal year ended September 30, 2023, filed with the SEC on December 22, 2023, and future quarterly reports Outlook Therapeutics files with the SEC, which include uncertainty of market conditions and future impacts related to macroeconomic factors, including as a result of the ongoing overseas conflict, high interest rates, inflation and potential future bank failures on the global business environment. These risks may cause actual results to differ materially from those expressed or implied by forward-looking statements in this press release. All forward-looking statements included in this press release are expressly qualified in their entirety by the foregoing cautionary statements. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Outlook Therapeutics does not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of new information, future events or otherwise, except as may be required under applicable securities law. Investor Inquiries: Jenene Thomas Chief Executive Officer JTC Team, LLC T: 833.475.8247 OTLK@jtcir.com

Two Poster Presentations Will Feature Updated Ivonescimab Data from the AK112-201 and AK112-202 Phase II Studies in Advanced or Metastatic NSCLC Patient Populations Posters to be Presented by Dr. Li Zhang and Dr. Jack West on Friday, March 22 in Prague MIAMI--(BUSINESS WIRE)--Summit Therapeutics Inc. (NASDAQ: SMMT) (“Summit,” “we,” or the “Company”) today announced that data for its novel, potential first-in-class investigational bispecific antibody, ivonescimab, will be presented at the 2024 European Lung Cancer Congress (ELCC 2024) in Prague, Czech Republic. Two posters featuring updated ivonescimab data will be displayed on Friday, March 22 from 12:00 to 12:45pm Central European Time. The first poster, “Intracranial Activity of Ivonescimab Alone or in Combination with Platinum Doublet Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) and Brain Metastases” includes data from patients with asymptomatic brain metastases at baseline. These patients were enrolled in either AK112-202 (NCT04900363), in which ivonescimab is delivered as monotherapy, or AK112-201 (NCT04736823), in which ivonescimab is delivered in combination with platinum doublet chemotherapy, both of which are Phase II clinical trials for patients with advanced or metastatic NSCLC. The second poster titled, “Phase 2 Results of Ivonescimab a Novel PD-1/VEGF Bispecific in Combination with Chemotherapy for First Line Treatment of Patients with Advanced / Metastatic Squamous Non-Small Cell Lung Cancer” includes updated data from the Phase II trial AK112-201 centered around the cohort of patients in which ivonescimab is combined with chemotherapy for first line treatment of advanced or metastatic NSCLC in patients without actionable genomic alterations (e.g., positive for endothelial growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK)). The posters will be presented by, amongst others, Dr. Li Zhang, Sun Yat-Sen University Cancer Center, and Dr. H. Jack West, Vice President of Clinical Development at Summit with data generated and analyzed by our collaboration and licensing partner, Akeso Inc. (HKEX Code: 9926.HK), with contribution by Summit staff. Summit continues its clinical development of ivonescimab in order to establish its efficacy and safety in two NSCLC indications: HARMONi Phase III trial: ivonescimab combined with chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) HARMONi-3 Phase III trial: ivonescimab combined with chemotherapy in first-line metastatic squamous NSCLC patients About the ELCC 2024 Posters Poster Title: Phase 2 Results of Ivonescimab a Novel PD-1/VEGF Bispecific in Combination with Chemotherapy for First Line Treatment of Patients with Advanced / Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC) ELCC Presentation No.: 68P Session Date & Time: Friday, March 22, 12:00 to 12:45pm CET Poster Title: Intracranial Activity of Ivonescimab Alone or in Combination with Platinum Doublet Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer and Brain Metastases ELCC Presentation No.: 174P Session Date & Time: Friday, March 22, 12:00 to 12:45pm CET About Ivonescimab Ivonescimab, known as SMT112 in Summit’s license territories, the United States, Canada, Europe, and Japan, and as AK112 in China and Australia, is an investigational, novel, potential first-in-class bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays cooperative binding with each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF. This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro (Zhong, et al, SITC, 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets. Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two Phase III clinical trials. Ivonescimab is an investigational therapy that is not approved by any regulatory authority. About Summit Therapeutics Summit was founded in 2003 and our shares are listed on the Nasdaq Global Market (symbol ‘SMMT’). We are headquartered in Miami, Florida, and we have additional offices in Menlo Park, California, and Oxford, UK. Summit’s mission, in part, is to develop patient, physician, caregiver, and societal-friendly medicinal therapies intended to improve quality of life, increase potential duration of life, and resolve serious unmet medical needs. For more information, please visit and follow us on X (formerly Twitter) @summitplc. Summit Forward-looking Statements Any statements in this press release about the Company’s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Company’s product candidates, entry into and actions related to the Company’s partnership with Akeso Inc., the Company's anticipated spending and cash runway, the therapeutic potential of the Company’s product candidates, the potential commercialization of the Company’s product candidates, the timing of initiation, completion and availability of data from clinical trials, the potential submission of applications for marketing approvals, potential acquisitions, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including the results of our evaluation of the underlying data in connection with the development and commercialization activities for ivonescimab, the outcome of discussions with regulatory authorities, including the Food and Drug Administration, the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials, the results of such trials, and their success, and global public health crises, that may affect timing and status of our clinical trials and operations, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, whether business development opportunities to expand the Company’s pipeline of drug candidates, including without limitation, through potential acquisitions of, and/or collaborations with, other entities occur, expectations for regulatory approvals, laws and regulations affecting government contracts and funding awards, availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" section of filings that the Company makes with the Securities and Exchange Commission. Any change to our ongoing trials could cause delays, affect our future expenses, and add uncertainty to our commercialization efforts, as well as to affect the likelihood of the successful completion of clinical development of ivonescimab. Accordingly, readers should not place undue reliance on forward-looking statements or information. In addition, any forward-looking statements included in this press release represent the Company’s views only as of the date of this release and should not be relied upon as representing the Company’s views as of any subsequent date. The Company specifically disclaims any obligation to update any forward-looking statements included in this press release. Appendix: Glossary of Critical Terms Contained Herein Affinity – Affinity is the strength of binding of a molecule, such as a protein or antibody, to another molecule, such as a ligand. Avidity – Avidity is the accumulated strength of multiple binding interactions. Angiogenesis – Angiogenesis is the development, formation, and maintenance of blood vessel structures. Without sufficient blood flow, tissue may experience hypoxia (insufficient oxygen) or lack of nutrition, which may cause cell death.i Cooperative binding – Cooperative binding occurs when the number of binding sites on the molecule that can be occupied by a specific ligand (e.g., protein) is impacted by the ligand’s concentration. For example, this can be due to an affinity for the ligand that depends on the amount of ligand bound or the binding strength of the molecule to one ligand based on the concentration of another ligand, increasing the chance of another ligand binding to the compound.ii Immunotherapy – Immunotherapy is a type of treatment, including cancer treatments, that help a person’s immune system fight cancer. Examples include anti-PD-1 therapies.iii Intracranial – Within the cranium or skull. PD-1 – Programmed cell Death protein 1 is a protein on the surface of T cells and other cells. PD-1 plays a key role in reducing the regulation of ineffective or harmful immune responses and maintaining immune tolerance. However, with respect to cancer tumor cells, PD-1 can act as a stopping mechanism (a brake or checkpoint) by binding to PD-L1 ligands that exist on tumor cells and preventing the T cells from targeting cancerous tumor cells.iv PD-L1 – Programmed cell Death Ligand 1 is expressed by cancerous tumor cells as an adaptive immune mechanism to escape anti-tumor responses, thus believed to suppress the immune system’s response to the presence of cancer cells. v PD-L1 TPS – PD-L1 Tumor Proportion Score represents the percentage of tumor cells that express PD-L1 proteins. PFS – Progression-Free Survival. SQ-NSCLC – Non-small cell lung cancer tumors of squamous histology. T Cells – T cells are a type of white blood cell that is a component of the immune system that, in general, fights against infection and harmful cells like tumor cells.vi Tetravalent – A tetravalent molecule has four binding sites or regions. Tumor Microenvironment – The tumor microenvironment is the ecosystem that surrounds a tumor inside the body. It includes immune cells, the extracellular matrix, blood vessels and other cells, like fibroblasts. A tumor and its microenvironment constantly interact and influence each other, either positively or negatively.vii VEGF – Vascular Endothelial Growth Factor is a signaling protein that promotes angiogenesis.viii ___________________________________ i Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105. ii Stefan MI, Le Novère N. Cooperative binding. PLoS Comput Biol. 2013;9(6) iii US National Cancer Institute, a part of the National Institute of Health (NIH). . Accessed October 2023. iv Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. v Han Y, et al. PD-1/PD-L1 Pathway: Current Researches in Cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. vi Cleveland Clinic. . Accessed October 2023. vii MD Anderson Cancer Center. . Accessed October 2023. viii Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105.