On April 7, 2021 Gilead Sciences, Inc. (Nasdaq: GILD) reported that the U.S. Food and Drug Administration (FDA) has granted full approval to Trodelvy (sacituzumab govitecan-hziy) for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease (Press release, Gilead Sciences, APR 7, 2021, View Source [SID1234577702]). The approval is supported by data from the Phase 3 ASCENT study, in which Trodelvy demonstrated a statistically significant and clinically meaningful 57% reduction in the risk of disease worsening or death (progression-free survival (PFS)), extending median PFS to 4.8 months from 1.7 months with chemotherapy (HR: 0.43; 95% CI: 0.35-0.54; p<0.0001). Trodelvy also extended median overall survival (OS) to 11.8 months vs. 6.9 months (HR: 0.51; 95% CI: 0.41-0.62; p<0.0001), representing a 49% reduction in the risk of death.

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Trodelvy is directed to the Trop-2 receptor, a protein frequently expressed in multiple types of epithelial tumors, including TNBC, where high expression is associated with poor survival and relapse. Prior to the FDA approval of Trodelvy, patients with previously treated metastatic TNBC had few treatment options in this high unmet-need setting. The FDA granted accelerated approval to Trodelvy in April 2020 based on objective response rate and duration of response results in a Phase 1/2 study. Today’s approval expands the previous Trodelvy indication to include treatment in adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.

"Women with triple-negative breast cancer have historically had very few effective treatment options and faced a poor prognosis," said Aditya Bardia, MD, MPH, Director of Breast Cancer Research Program, Mass General Cancer Center and Assistant Professor of Medicine at Harvard Medical School, and global principal investigator of the ASCENT study. "Today’s FDA approval reflects the statistically significant survival benefit seen in the landmark ASCENT study and positions sacituzumab govitecan-hziy as a potential standard of care for pre-treated TNBC."

"A metastatic TNBC diagnosis is frightening. As an aggressive and difficult-to-treat disease, it’s a significant advance to have an FDA-approved treatment option with a proven survival benefit for patients with metastatic disease that continues to progress," said Ricki Fairley, Founder and CEO of Touch, the Black Breast Cancer Alliance. "For far too long, people with metastatic TNBC had very few treatment options. Today’s news continues the progress of bringing more options to treat this devastating disease."

Among all patients evaluable for safety in the ASCENT study (n=482), Trodelvy had a safety profile consistent with the previously approved FDA label. The most frequent Grade ≥3 adverse reactions for Trodelvy compared to single-agent chemotherapy were neutropenia (52% vs. 34%), diarrhea (11% vs. 1%), leukopenia (11% vs. 6%) and anemia (9% vs. 6%). Adverse reactions leading to treatment discontinuation occurred in 5% of patients receiving Trodelvy.

"Today’s approval is the culmination of a multi-year development program and validates the clinical benefit of this important treatment in metastatic TNBC," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "Building upon this milestone, we are committed to advancing Trodelvy with worldwide regulatory authorities so that, pending their decision, Trodelvy may become available to many more people around the world who are facing this difficult-to-treat cancer."

Regulatory submissions for Trodelvy in metastatic TNBC have been filed in the United Kingdom, Canada, Switzerland and Australia as part of Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE) that provides a framework for concurrent submission and review of oncology products among international partners, as well as in Singapore through our partner Everest Medicines. The European Medicines Agency has also validated a Marketing Authorization Application for Trodelvy in the European Union. All filings are based on data from the Phase 3 ASCENT study.

Trodelvy Boxed Warning

The Trodelvy U.S. Prescribing Information has a BOXED WARNING for severe or life-threatening neutropenia and severe diarrhea; see below for Important Safety Information.

About Trodelvy

Trodelvy (sacituzumab govitecan-hziy) is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein frequently expressed in multiple types of epithelial tumors, including metastatic triple-negative breast cancer (TNBC), where high expression is associated with poor survival and relapse.

Trodelvy is also being developed as an investigational treatment for metastatic urothelial cancer, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER 2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.

About Triple-Negative Breast Cancer (TNBC)

TNBC is an aggressive type of breast cancer, accounting for approximately 15% of all breast cancers. The disease is diagnosed more frequently in younger and premenopausal women and is more prevalent in African American and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER 2. Medicines targeting these receptors therefore are not typically effective in treating TNBC.

About the ASCENT Study

The Phase 3 ASCENT study, an open-label, active-controlled, randomized confirmatory trial, enrolled more than 500 patients with relapsed/refractory metastatic triple-negative breast cancer (TNBC) who had received two or more prior systemic therapies (including a taxane), at least one of them for metastatic disease. Patients were randomized to receive either Trodelvy or a chemotherapy chosen by the patients’ treating physicians. The primary efficacy outcome was progression-free survival (PFS) in patients without brain metastases at baseline, as measured by a blinded, independent, centralized review using RECIST v1.1 criteria. Additional efficacy measures included PFS for the full population (all patients with and without brain metastases) and overall survival (OS). More information about ASCENT is available at View Source

Important Safety Information for Trodelvy

BOXED WARNING: NEUTROPENIA AND DIARRHEA

Severe, life-threatening, or fatal neutropenia may occur. Withhold TRODELVY for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patient with febrile neutropenia without delay.
Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity. At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold TRODELVY until resolved to ≤ Grade 1 and reduce subsequent doses.
CONTRAINDICATIONS

Severe hypersensitivity to TRODELVY
WARNINGS AND PRECAUTIONS

Neutropenia: Dose modifications may be required due to neutropenia. Neutropenia occurred in 62% of patients treated with TRODELVY, leading to permanent discontinuation in 0.5% of patients. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 6%.

Diarrhea: Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3 diarrhea occurred in 12% of patients. Neutropenic colitis occurred in 0.5% of patients. Withhold TRODELVY for Grade 3-4 diarrhea and resume when resolved to ≤ Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments.

Hypersensitivity and Infusion-Related Reactions: TRODELVY can cause severe and life-threatening hypersensitivity and infusion-related reactions, including anaphylactic reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients. Grade 3-4 hypersensitivity occurred in 1% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.4%. Pre-infusion medication is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Medication to treat such reactions, as well as emergency equipment, should be available for immediate use.

Nausea and Vomiting: Nausea occurred in 67% of all patients treated with TRODELVY. Grade 3-4 nausea occurred in 5% of patients. Vomiting occurred in 40% of patients and Grade 3-4 vomiting occurred in 3% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold TRODELVY doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤ 1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting.

Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with TRODELVY. The incidence of Grade 3-4 neutropenia in genotyped patients was 69% in patients homozygous for the UGT1A1*28, 48% in patients heterozygous for the UGT1A1*28 allele and 46% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia in genotyped patients was 24% in patients homozygous for the UGT1A1*28 allele, 8% in patients heterozygous for the UGT1A1*28 allele, and 10% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function.

Embryo-Fetal Toxicity: Based on its mechanism of action, TRODELVY can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. TRODELVY contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRODELVY and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRODELVY and for 3 months after the last dose.

ADVERSE REACTIONS

In the ASCENT study (IMMU-132-05), the most common adverse reactions (incidence ≥25%) were nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite, and abdominal pain. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced hemoglobin, lymphocytes, leukocytes, and neutrophils.

DRUG INTERACTIONS

UGT1A1 Inhibitors: Concomitant administration of TRODELVY with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with TRODELVY.

UGT1A1 Inducers: Exposure to SN-38 may be substantially reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with TRODELVY

On April 7, 2021 Tempus, a leader in artificial intelligence and precision medicine, reported abstracts accepted for poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, which will convene virtually on April 10-15 and May 17-21 (Press release, Tempus, APR 7, 2021, View Source [SID1234577701]). The research leverages Tempus’ unparalleled library of multi-modal data to facilitate discovery, development, and delivery of optimized therapeutic options for patients.

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"We’re proud to present our recent research that demonstrates the power and depth of our database," said Dr. Kim Blackwell, Chief Medical Officer at Tempus. "As evidenced by the collection of abstracts, we are utilizing data-driven tools that empower physicians to optimize patient care."

Tempus will present eight posters; including two in collaboration with outside investigators from Baylor College of Medicine, Harris Health Ben Taub Hospital, and the Dan L Duncan Comprehensive Cancer Center. Four of the abstracts accepted for poster presentation at AACR (Free AACR Whitepaper) 2021 are highlighted below and the complete list can be found at www.tempus.com/publications.

Incidence of Molecular Alterations in KRAS and Other Known Cancer Genes in Patients With Pancreatic Cancer Assessed With a Commercial Genomic Profiling Panel Compared to TCGA Results
Overview: Tempus’ xT LDT assay detected common alterations in genes such as KRAS, TP53, and SMAD4 in a Baylor College of Medicine pancreatic cancer cohort at a similar incidence to The Cancer Genome Atlas Program. Approximately 13% of pancreatic cancer patients had an alteration in the homologous recombination repair pathway. Lens, Tempus’ next-generation data exploration and analysis platform, allowed researchers to identify the incidence of targetable molecular alterations landscape in patients with pancreatic cancer.
Genomic Characterization and Monitoring Molecular Response to Treatment in African Americans (AA) Advanced Prostate Cancer (PC) Patients (Pts) via Next-Generation Sequencing (NGS); Real-world Experience in a Safety Net Hospital Oncology Clinic
Overview: Tempus’ xF liquid biopsy LDT assay allows for longitudinal monitoring of treatment response and resistance in patients with advanced prostate cancer. This study reported the incidence of key prostate cancer driver gene alterations, including TP53, SPOP, AR and BRCA2, in both the Ben Taub Hospital cohort and Tempus database, and revealed the value of longitudinal xF monitoring in 4 case studies: (1) Response to first line hormonal therapy, (2) Nonresponse to third line darolutamide, and (3) Two cases of response to pembrolizumab in MSI-H metastatic prostate cancer.
Comprehensive Validation of RNA Sequencing for Clinical NGS Fusion Genes and RNA Expression Reporting
Overview: Tempus sequenced both DNA and the whole-transcriptome RNA to improve coverage and provide the most comprehensive patient molecular profile. This study reported results from the clinical and analytical validation of fusion calling for improved gene rearrangement detection, and the analytical validation of RNA expression for research purposes. The orthogonal testing concordance for targeted fusions was 100%, with 99.9% sensitivity and 99.9% specificity, and for untargeted fusions, the overall concordance was 97%, with 97% sensitivity. The enhanced RNA-sequencing assay offers unbiased detection of common and novel fusions, as well as validated gene expression data for comprehensive research analyses.
Leveraging Clinical RNA Sequencing for Scalable Tumor Immune Repertoire Profiling
Overview: Characterizing tumor-infiltrating lymphocytes (TILs) by repertoire sequencing (rep-seq) at scale can help maximize patient benefit from data-driven treatment options. This study presents a scalable method for TIL rep-seq from whole-transcriptome RNA data in approximately 500 tumors from 38 cancer types. Results of this study were consistent with an orthogonal DNA-seq method and confirmed expected trends in receptor profiles across the cohort, including monoclonality of lymphocyte receptors in T-cell/B-cell-driven malignancies, high repertoire richness in TIL-high cancers (e.g., NSCLC) and low in TIL-low cancers (e.g., multiforme glioblastoma). This method can be seamlessly integrated for improved TIL characterization from routine RNA-sequencing.

On April 7, 2021 Nucleix, a liquid biopsy company revolutionizing cancer treatment by detecting the disease earlier, reported that it has secured $55 million from a syndicate of leading life science investors in an oversubscribed financing round (Press release, Nucleix, APR 7, 2021, View Source [SID1234577700]).

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The round was led by RA Capital Management, with participation from new investors including funds and accounts managed by BlackRock, Lilly Asia Ventures, LYFE Capital and MILFAM. Existing investors participating in the round include OrbiMed, Aurum Ventures, DSC Investment, OCI Bio Investments and Zohar Zisapel. Nucleix will utilize the proceeds of the financing to continue the rapid advancement of its unique methylation technology, known as EpiCheck, and to develop Lung EpiCheck, its lead product for the early detection of lung cancer.

"Early detection of cancer from a blood sample is like listening for a whisper in a crowded room – you need to separate a faint signal from considerable background noise. EpiCheck minimizes sample loss and background noise while detecting minute cancer epigenetic signals with greater sensitivity than other technologies," said Chris Hibberd, chief executive officer of Nucleix. "This new funding enables us to further demonstrate the power of the technology through a focused program in lung cancer, advancing tests designed to be highly sensitive, easily deployed and cost effective."

EpiCheck is an ultra-sensitive technology for the detection of methylation changes and is compatible with both next-generation sequencing (NGS) and polymerase chain reaction (PCR) platforms. Nucleix is applying the NGS application of EpiCheck for deep discovery, to reveal new biomarkers that may be used in the early detection and monitoring of cancer. In turn, these discoveries can be advanced as highly sensitive tests using the PCR application of EpiCheck, with the potential to run cost-effectively in both centralized and local laboratories.

Lung EpiCheck is a highly sensitive, methylation-based blood assay for the early detection of lung cancer. The test analyzes subtle, disease-specific changes in DNA methylation markers meeting the needs of its target population – current and past smokers – to catch cancer earlier when treatment can be most effective. In October 2020, clinical data on the first generation of Lung EpiCheck was published in the European Respiratory Journal. Nucleix is now developing an improved version of the assay and will initiate a prospective study to validate the test, with the goal of making it available in 2022.

"The U.S. Preventive Services Task Force (USPSTF) recently updated the screening guidelines for high-risk lung cancer patients to double the number of people who qualify for annual screening1, but a challenge remains as less than 10% of those eligible in the United States follow the guidelines today," said Aharona Shuali, M.D., VP Medical. "Lung EpiCheck has the potential to provide an effective screening option that increases compliance and drives more patients to follow guidelines in the United States – increasing chances of patients having a long-term benefit."

About Lung EpiCheck

Lung EpiCheck is designed to provide a simple blood test that detects lung cancer at its earliest stages. The test utilizes NGS and PCR-based technology for highly sensitive analysis of subtle, disease-specific changes in DNA methylation markers. Lung EpiCheck is being developed for potential use in individuals with a history of smoking who are at high-risk of developing lung cancer, and do not comply with the guidelines for annual screening with low-dose computed tomography (LDCT) scans. The test is not yet commercially available.

On April 7, 2021 Daiichi Sankyo Company, Limited (hereafter Daiichi Sankyo) reported the first patient has been dosed in the first-in-human phase 1/2 study of DS-1594, a selective small-molecule menin inhibitor, in adults with relapsed/refractory acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) (Press release, Daiichi Sankyo, APR 7, 2021, https://www.businesswire.com/news/home/20210407005234/en/Phase-12-Trial-Initiated-for-Daiichi-Sankyo%E2%80%99s-Menin-Inhibitor-DS-1594-in-Patients-with-Acute-Myeloid-Leukemia-and-Acute-Lymphoblastic-Leukemia [SID1234577699]). The trial is being conducted by The University of Texas MD Anderson Cancer Center under an existing strategic research collaboration.

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Inhibition of the menin protein is being studied as a novel treatment approach for acute leukemias with MLL rearrangement (MLLr) or NPM1 mutation (NPM1m), two gene alterations that drive cancer development and growth.1 MLLr occurs in approximately 5 to 10% of acute leukemia patients and is associated with aggressive disease, reduced treatment response and poor prognosis.2 NPM1m occurs in about 30% of patients with AML.3 There are currently no medicines specifically approved for MLLr or NPM1m leukemias and no approved menin inhibitors.

"Research has shown that the menin protein, which binds to MLL, plays a critical role in the development and growth of leukemias with MLL rearrangement," said Arnaud Lesegretain, Vice President, Oncology R&D and Head, Alpha Portfolio, Daiichi Sankyo. "Our scientists designed DS-1594 to inhibit the menin-MLL interaction and disrupt the intracellular activity implicated in leukemogenesis. Together with MD Anderson, we will evaluate DS-1594 as a potential therapeutic option for patients with AML or ALL who have exhausted standard treatments."

The collaboration with MD Anderson is focused on accelerating development of Daiichi Sankyo pipeline therapies for AML, including phase 1 and 2 clinical trials to evaluate single and combination regimens, translational research to explore novel biomarkers, and pre-clinical studies aimed at identifying resistance mechanisms.

About the Study

MD Anderson will sponsor and lead an open-label, non-randomized, multi-arm phase 1/2 study to evaluate DS-1594 in single and combination regimens for patients with relapsed/refractory AML and ALL.

The primary objective of the phase 1 part of the study is to determine the maximum tolerated dose and recommended phase 2 dose of DS-1594 in up to 54 patients with AML or ALL regardless of mutation status. Primary endpoints include dose-limiting toxicities, recommended phase 2 dose and safety profile. Secondary endpoints include complete remission rate (CR) and CR with partial hematologic recovery rate (CRh).

In the phase 2 part of the study, DS-1594 will be further evaluated at the established dose in four expansion cohorts of patients with specific genetic markers. Patients with relapsed/refractory AML with MLLr or NPM1m will receive DS-1594 as monotherapy (Cohorts A and B) or in combination with azacitidine and venetoclax (Cohort C), and patients with ALL with MLLr will receive DS-1594 in combination with a mini-HCVD regimen (Cohort D). The primary endpoints are safety, CR/CRh rates for the AML cohorts, and CR/CR with incomplete hematologic recovery rates (CRi) for patients in the ALL cohort.

A number of secondary efficacy and pharmacokinetic endpoints along with exploratory pharmacodynamic and biomarker endpoints will also be evaluated. Up to 170 patients will be enrolled in the study, which will initially be conducted only at MD Anderson with global expansion planned for phase 2. For more information, visit Clinicaltrials.gov.

About Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia

More than 474,500 new cases of leukemia were reported globally in 2020 with more than 311,500 deaths.4 In the U.S., there were approximately 60,530 new cases of leukemia and 23,100 deaths in 2020.5

AML is the most common form of acute leukemia in adults, accounting for about 33% of all new cases.6 An aggressive and heterogenous cancer originating in bone marrow, AML is characterized by a five-year survival rate of 28.7%, the lowest by far among the major leukemia subtypes.7 Standard chemotherapy remains the main treatment option for most patients with AML with or without targeted therapy. Newer treatments for genetically defined AML subtypes have increased options and improved response rates and outcomes for some patients, but primary and secondary resistance remain a challenge and new types of therapies continue to be researched.8

ALL is a less common form of leukemia with 6,150 new cases estimated in the U.S. in 2020.9 The overall five-year survival rate for ALL is 68.8% among patients of all ages but significantly lower for adults.10 ALL is typically treated with standard chemotherapy-based regimens with or without targeted therapy.9

About MLL, NPM1 and Menin

The MLL (mixed-lineage leukemia) gene, also known as KMT2A, is important in sustaining hematopoietic stem cells and is known to undergo chromosomal translocations or epigenetic changes resulting in the expression of MLL fusion proteins that ultimately drive formation and growth of leukemia.11 Approximately 5 to 10% of acute leukemias harbor the MLL rearrangement, with a five-year overall survival rate of about 35%.11

The NPM1 (nucleophosmin 1) mutation causes aberrant expression of the NPM1 protein, which is involved in functions, including cell proliferation. NPM1m is observed in approximately 30% of AML patients with a five-year overall survival rate of about 50%.3

Menin is a scaffold protein that interacts with a multitude of other proteins to regulate gene expression and cell signaling.11 The interaction between menin and MLL proteins is critical to the leukemogenic activity in MLLr leukemia and is also reported to play a key role in development of NPM1m leukemia.1 Scientific evidence supports inhibition of the menin-MLL interaction as a therapeutic approach for acute leukemias.11 There are currently no medicines specifically approved for MLLr or NPM1m leukemias and no approved menin inhibitors.

About DS-1594

DS-1594 is a potent and selective small molecule menin inhibitor in clinical development in the Alpha portfolio of Daiichi Sankyo. DS-1594 was designed to target and disrupt the protein-protein interaction of menin and MLL to inhibit leukemic cell growth and proliferation. In preclinical studies, DS-1594 displayed selective growth inhibition against AML and ALL cells with MLLr and demonstrated robust and durable anti-tumor activity in AML models with an acceptable safety profile.12 DS-1594 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

On April 7, 2021 Sesen Bio (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of patients with cancer, reported that leading independent proxy advisory firms Institutional Shareholder Services, Inc. ("ISS") and Glass, Lewis & Co., LLC ("Glass Lewis") have both recommended Sesen Bio’s (the "Company") stockholders vote "FOR" the proposal to increase the number of authorized shares of common stock by 200 million ("Proposal 2") which is on the ballot for the Company’s Annual Meeting of Stockholders on May 3, 2021 (the "Annual Meeting") (Press release, Sesen Bio, APR 7, 2021, View Source [SID1234577698]).

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ISS and Glass Lewis are widely recognized as leading independent voting advisory firms. Their impartial analyses and reports are developed with the objective of delivering transparency to help investors make informed investment decisions.

Notably, ISS stated in its report that support for Proposal 2 is warranted given that the proposed increase in the number of authorized shares is reasonable and that there is a specific and severe risk to stockholders if Proposal 2 is not approved.

Glass Lewis also concluded in its report that the proposed increase in the number of authorized shares is reasonable, citing the relatively limited amount of shares currently available to the Company (only 7% of its issued share capital as of March 18, 2021, which is the record date for the Annual Meeting). As part of its methodology, Glass Lewis undertakes an analysis to ensure that the additional shares are truly needed.

"The ISS and Glass Lewis recommendations are consistent with our view that an increase in the number of authorized shares is both needed and in the best interest of our stockholders," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "We have not requested an increase since going public in 2014, and we believe the requested increase will allow us to execute on our strategy as we transition into a commercial, revenue generating company. We are committed to issue shares to support our strategic initiatives which we believe drive value for stockholders, such as the planned commercialization of Vicineum and advancing our promising pipeline."

Since the proposed increase to the number of authorized shares of common stock will not affect the number of shares outstanding, it will not by itself have a dilutive effect on the Company’s current stockholders. Sesen Bio believes this increase will be enough to achieve corporate profitability, and therefore the Company is hopeful this may be the last time it needs to request additional shares.

Sesen Bio’s stockholders are encouraged to vote as ISS and Glass Lewis recommend by voting "FOR" the proposed increase in authorized shares. Voting will be open through the conclusion of the Annual Meeting on May 3, 2021 at 8:00 a.m. EDT. Stockholders with questions about how to vote may contact the Company’s proxy solicitor, Okapi Partners, at (888) 785-6709 or [email protected].

Stockholders who have already voted and want to change their vote can update their vote at any time – Sesen Bio will count your vote in accordance with the last instruction received prior to the closing of the polls.

ISS and Glass Lewis are independent proxy advisory firms and do not have any business relationship with Sesen Bio. Sesen Bio did not engage or compensate either firm for their analysis or recommendations.

Where to Find Additional Information

On March 25, 2021, the Company filed a definitive proxy statement with the SEC in connection with the Annual Meeting (such proxy statement and any supplements or amendments thereto, "the Annual Meeting Proxy Materials"). The Annual Meeting Proxy Materials contain important information about the Annual Meeting. Stockholders are urged to read the Annual Meeting Proxy Materials carefully. Stockholders are able to obtain free copies of the Annual Meeting Proxy Materials and other documents filed with the SEC by the Company through the web site maintained by the SEC at www.sec.gov and at View Source The Company, its directors and executive officers may be deemed participants in the solicitation of proxies from stockholders in respect of the Annual Meeting. Detailed information regarding the identity of participants, and their respective interests in the Company by security holdings or otherwise, are set forth in the definitive proxy statement for the Annual Meeting.

1This amount is preliminary and is subject to change upon completion of the Company’s financial statements for the quarterly period ended March 31, 2021.

About Vicineum

Vicineum, a locally administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Vicineum is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicineum is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently in the follow-up stage of a Phase 3 registration trial in the US for the treatment of BCG-unresponsive NMIBC. In February 2021, the FDA accepted for filing the Company’s BLA for Vicineum for the treatment of BCG-unresponsive NMIBC and granted the application Priority Review with a PDUFA date of August 18, 2021. Additionally, Sesen Bio believes that cancer cell-killing properties of Vicineum promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. For this reason, the activity of Vicineum in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.