On December 7, 2020 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported the presentation of a clinical data set on AFM13 at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Affimed, DEC 7, 2020, View Source [SID1234572356]). Dr. Ahmed Sawas, Assistant Professor of Medicine at Columbia University College of Physicians and Surgeons and the New York-Presbyterian Hospital, and principal investigator presented the updated results of a phase 1b/2a study in patients with CD30-expressing lymphoma with cutaneous involvement.

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AFM13 is a bispecific tetravalent Innate Cell Engager (ICE) targeting CD30 on tumor cells and CD16A on NK cells and macrophages.

2971: Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma with Cutaneous Presentation: A Biomarker Phase Ib/IIa Study (NCT03192202)

This updated analysis of the AFM13 monotherapy study in patients with relapsed or refractory CD30-positive lymphoma with cutaneous presentation showed an Objective Response Rate (ORR) of 42 percent (6/14) and demonstrated clinical activity after brentuximab vedotin failure in two of four patients. Flow cytometry of peripheral blood revealed decreased circulating NK cell numbers during therapy and tumor biopsies of responders exhibited an increased pre-therapy CD56+ NK cell infiltration versus non-responders. Granzyme B expression was detected in responders, indicating NK cell cytotoxicity. Together, these data suggest that AFM13 may initiate NK cell tumor infiltration and recruit and engage NK cells. In addition, AFM13 was well tolerated. "The therapeutic need for this heavily pretreated patient group is extremely high. We are therefore happy to see that AFM13 monotherapy was well tolerated and demonstrated a promising ORR," commented Dr. Ahmed Sawas. "Our biological evaluation is the first to demonstrate that innate cell engagers modulate NK cell populations in patient peripheral blood and tumors, which seems to be associated with patient benefit."

On December 7, 2020 Provectus (OTCQB: PVCT) reported that updated preliminary patient response, safety, and immune correlative data, as well as new preliminary PV-10-treated lesion response data, from the Company’s ongoing Phase 1b/2 study of autolytic cancer immunotherapy PV-10, an injectable formulation of Provectus’ proprietary small molecule rose bengal disodium (RBD), in combination with KEYTRUDA (pembrolizumab) for the treatment of advanced cutaneous melanoma in patients refractory to immune checkpoint blockade (CB) was presented at Melanoma Bridge 2020, held online from December 3-5, 2020 (Press release, Provectus Biopharmaceuticals, DEC 7, 2020, View Source [SID1234572355]).

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The oral presentation, entitled "Response for combination of PV-10 autolytic immunotherapy and immune checkpoint blockade in checkpoint-refractory patients," was presented by Dr. Jonathan Zager, Chief Academic Officer at Moffitt Cancer Center (Moffitt), and a surgical oncologist and Senior Member in Moffitt’s Departments of Cutaneous Oncology and Sarcoma. Dr. Zager is also the Director of Regional Therapies at Moffitt’s Donald A. Adam Comprehensive Melanoma Research Center and a Professor of Surgery at the Morsani School of Medicine of the University of South Florida.

Presentation materials are available on Provectus’ website by clicking on the links immediately below:

A video of Dr. Zager’s oral presentation,
A copy of the presentation slides, and
A copy of the slides together with Dr. Zager’s print commentary.
Key highlights of the Melanoma Bridge 2020 presentation:

Safety data on 18 patients
Consistent with the established patterns for single-agent use of each drug
Principally grades 1 and 2 injection-site reactions to PV-10
Principally grades 1 to 3 immune-mediated reactions to KEYTRUDA
14 patients evaluable for overall efficacy
Investigator-assessed RECIST v1.1
All patients (14): 7% complete response (CR) (1/14), 36% overall response rate (ORR) (3/14), and 64% disease control rate (DCR) (8/14)
Refractory to anti-PD-1 (4): 75% ORR (3/4)
Refractory to anti-CTLA-4 and anti-PD-1 combination therapy (9): 11% CR (1/9) and 56% DRR (5/9)
16 lesions treated with PV-10
38% CR (6/16), 50% ORR (8/16), and 69% DCR (11/16)
5 patient-completed immune correlative assessments
DAMPs and T cells present in peripheral blood are indicative of innate and adaptive immune signaling, respectively
Upregulation of innate and adaptive immune responses appears to be maintained in CB-refractory subjects
PV-10-hallmark DAMP and functional T cell responses in CB-refractory patients are consistent with responses in CB-naïve patients who received either single-agent PV-10 or PV-10 and KEYTRUDA combination therapy in other Provectus melanoma clinical trials
Dominic Rodrigues, Vice Chair of the Company’s Board of Directors said, "Immune checkpoint blockade-refractory metastatic melanoma is a high unmet medical need that only continues to grow, with low response, poor survival rates, and limited patient treatment options. This need is particularly acute for deeply refractory melanoma patients who fail ipilimumab and nivolumab combination therapy. This study’s safety, efficacy, and immune correlative data suggest PV-10 may play a critical role in overcoming acquired resistance to checkpoint blockade."

About the Phase 1b/2 Combination Therapy Trial (NCT02557321)

A first expansion cohort of the Phase 1b portion of the study began enrolling patients with metastatic cutaneous melanoma who were CB-refractory in December 2018. This CB-refractory cohort extended an exploratory group of refractory patients enrolled into the study’s main cohort that primarily enrolled CB-naïve patients. CB-refractory patients with at least one injectable lesion and who were candidates for KEYTRUDA were eligible. Eligible subjects received the combination treatment of PV-10 and KEYTRUDA every three weeks for up to five cycles (i.e., over a period of up to 12 weeks), followed by only KEYTRUDA every three weeks for up to 24 months. The protocol allows for additional cycles of PV-10 beyond the fifth cycle for patients with additional injectable disease. The primary endpoint for the Phase 1b trial was safety and tolerability. ORR and progression-free survival were key secondary endpoints (both assessed via RECIST 1.1 after five treatment cycles, and then every 12 weeks thereafter).

About PV-10

Intralesional (IL) (aka intratumoral) administration of PV-10 for the treatment of solid tumor cancers can yield immunogenic cell death within hours of tumor injection, and induce tumor-specific reactivity in circulating T cells within days.1,2,3 This IL PV-10-induced functional T cell response may be enhanced and boosted in combination with CB.4 In CB-refractory advanced cutaneous melanoma, IL PV-10 may restore disease-specific T cell function, which may also be prognostic of clinical response. IL PV-10 has been administered to over 450 patients with cancers of the skin and of the liver. It is administered under visual, tactile or ultrasound guidance to superficial malignancies, and under CT or ultrasound guidance to tumors of the liver. In this Phase 1b/2 study, IL PV-10 was administered to melanoma tumors located at cutaneous, subcutaneous, soft tissue and nodal sites (it was not administered to visceral sites).

About Rose Bengal Disodium

RBD is 4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein disodium, a halogenated xanthene and Provectus’ proprietary lead molecule. Provectus’ current Good Manufacturing Practices (cGMP) RBD is a proprietary pharmaceutical-grade drug substance produced by the Company’s quality-by-design (QbD) manufacturing process to exacting regulatory standards that avoids the formation of uncontrolled impurities currently present in commercial-grade rose bengal. Provectus’ RBD and cGMP RBD manufacturing process are protected by composition of matter and manufacturing patents as well as trade secrets.

An IL formulation (i.e., by direct injection) of cGMP RBD drug substance, cGMP PV-10, is being developed as an autolytic immunotherapy drug product for solid tumor cancers. By targeting tumor cell lysosomes, RBD treatment may yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells, including a T cell mediated immune response against treatment refractory and immunologically cold tumors.1,2,3 Adaptive immunity can be enhanced by combining CB with RBD.4 IL PV-10 is undergoing clinical study for relapsed and refractory adult solid tumor cancers, such skin and liver cancers.

IL PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers, such as neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.5,6

A topical formulation of cGMP RBD drug substance, PH-10, is being developed as a clinical-stage immuno-dermatology drug product for inflammatory dermatoses, such as atopic dermatitis and psoriasis. RBD can modulate multiple interleukin and interferon pathways and key cytokine disease drivers.7

Oral formulations of cGMP RBD are undergoing preclinical study for relapsed and refractory pediatric blood cancers, such as acute lymphocytic leukemia and acute myelomonocytic leukemia.8,9

Oral formulations of cGMP RBD are also undergoing preclinical study as prophylactic and therapeutic treatments for high-risk adult solid tumor cancers, such as head and neck, breast, pancreatic, liver, and colorectal cancers.

Different formulations of cGMP RBD are also undergoing preclinical study as potential treatments for multi-drug resistant (MDR) bacteria, such as Gram-negative bacteria.

Topical formulations of cGMP RBD are also undergoing preclinical study as potential treatments for diseases of the eye, such as infectious keratitis

Tumor Cell Lysosomes as the Seminal Cancer Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.10 Cancer progression and metastasis are associated with lysosomal compartment changes11,12, which are closely correlated (among other things) with invasive growth, angiogenesis, and drug resistance13.

RBD selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus1,14, external collaborators5, and other researchers15,16,17 have independently shown that RBD triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via RBD: RBD-induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine hepatocellular carcinoma (HCC) cells can be viewed in this Provectus video of the process (ethidium homodimer 1 [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames, with a duration of approximately one hour). Exposure to RBD triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video of the process, with a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators in neuroblastoma cells to show that lysosomes are disrupted upon exposure to RBD.5

Tumor Autolytic Death via RBD: RBD causes acute autolytic destruction of injected tumors (via autolytic cell death), mediating the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens; release of these signaling factors may initiate an immunologic cascade where local response by the innate immune system may facilitate systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Mediated immune signaling pathways may include an effect on STING, which plays an important role in innate immunity.9

Orphan Drug Designations (ODDs)

ODD status has been granted to RBD by the U.S. Food and Drug Administration for metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Intellectual Property (IP)

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which cGMP RBD and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial-grade rose bengal in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of RBD and CB (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035; US patent application numbers include 20200138942.

On December 7, 2020 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported the initiation of Cohort 3 of CONTESSA TRIO, which will evaluate tesetaxel monotherapy in approximately 60 non-elderly patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) (Press release, Odonate Therapeutics, DEC 7, 2020, View Source [SID1234572354]). Cohort 3 of CONTESSA TRIO will complement Cohort 2 of CONTESSA TRIO, which is evaluating tesetaxel monotherapy in approximately 60 elderly patients with HER2-negative MBC.

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Cohorts 2 and 3 of CONTESSA TRIO will expand on results from TOB203, a Phase 2 study that evaluated tesetaxel monotherapy in 38 patients with hormone receptor-positive, HER2-negative MBC. In this study, the confirmed response rate was 45%. Neutropenia was the most common Grade ≥3 adverse event and occurred in 32% of patients, and febrile neutropenia occurred in 5% of patients. The results of TOB203 were presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

"Taken together, TOB203 and CONTESSA TRIO will evaluate tesetaxel monotherapy in more than 150 patients with metastatic breast cancer," said Lee Schwartzberg, M.D., FACP, Chief Medical Director, West Cancer Center & Research Institute. "The promising clinical results to date, combined with tesetaxel’s unique, once-every-three-weeks oral dosing regimen, make this investigational agent an exciting potential new treatment option for patients."

About Tesetaxel

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Tesetaxel has several pharmacologic properties that make it unique among taxanes, including: oral administration with a low pill burden; a long (~8-day) terminal plasma half-life in humans, enabling the maintenance of adequate drug levels with relatively infrequent dosing; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors. In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two multicenter, Phase 2 studies. Tesetaxel currently is the subject of three studies in breast cancer, including a multinational, multicenter, randomized, Phase 3 study in patients with metastatic breast cancer, known as CONTESSA. Odonate recently announced positive top-line results from CONTESSA, and full results are scheduled to be presented at the San Antonio Breast Cancer Symposium in December 2020.

About CONTESSA TRIO

CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with metastatic breast cancer (MBC).

In Cohort 1, approximately 200 patients with triple-negative MBC who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus either: (1) nivolumab at 360 mg by intravenous (IV) infusion on the first day of each 21-day cycle; (2) pembrolizumab at 200 mg by IV infusion on the first day of each 21-day cycle; or (3) atezolizumab at 1,200 mg by IV infusion on the first day of each 21-day cycle. Nivolumab and pembrolizumab (programmed cell death protein 1 [PD-1] inhibitors) and atezolizumab (a programmed death-ligand 1 [PD-L1] inhibitor) are immuno-oncology (IO) agents approved for the treatment of multiple types of cancer. Two of these agents, atezolizumab and pembrolizumab, have been approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with triple-negative MBC. The primary endpoints for Cohort 1 are objective response rate (ORR) and progression-free survival (PFS) in patients with PD-L1 positive status. The secondary endpoints are ORR and PFS in all patients, duration of response (DoR) and overall survival (OS). Efficacy results for each of the three PD‑(L)1 inhibitor combinations will be assessed for correlation with the results of each of the three approved PD-L1 diagnostic assays.
In Cohort 2, approximately 60 elderly patients with human epidermal growth factor receptor 2 (HER2)‑negative MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy dosed orally at 27 mg/m2 on the first day of each 21-day cycle. The primary endpoints for Cohort 2 are ORR and PFS in patients with hormone receptor‑positive, HER2‑negative disease. The secondary endpoints are ORR and PFS in patients with triple‑negative disease, DoR and OS.
In Cohort 3, approximately 60 non-elderly adult patients with HER2-negative MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy dosed orally at 27 mg/m2 on the first day of each 21-day cycle. The primary endpoints for Cohort 3 are ORR and PFS in patients with hormone receptor-positive, HER2-negative disease. The secondary endpoints are ORR and PFS in patients with triple-negative disease, DoR and OS.

On December 7, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that safety data from its ongoing pivotal Phase 3 SIERRA trial of Iomab-B in patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML) were presented at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (Press release, Actinium Pharmaceuticals, DEC 7, 2020, View Source [SID1234572353]). The oral presentation highlighted Iomab-B’s targeting ability and corresponding safety data from 110 patients from the SIERRA trial for which detailed safety data was available. Iomab-B targets CD45, an antigen expressed on leukemia and lymphoma cancer cells and immune cells including bone marrow stem cells but not cells outside of the blood forming or hematopoietic system. This allows high amounts of radiation to be delivered to the bone marrow via Iomab-B while sparing healthy organs. As a result, statistically significant lower rates of sepsis were reported as well as lower rates of febrile neutropenia, mucositis and non-relapse transplant related mortality in patients receiving Iomab-B and bone marrow transplant (BMT) compared to patients that received salvage therapy and a BMT. In addition, patients that crossed over to receive Iomab-B and went to BMT after receiving salvage therapy but not achieving a complete response also had lower rates of sepsis, febrile neutropenia, mucositis and non-relapse transplant related mortality.

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Dr. Mark Berger, Actinium’s Chief Medical Officer, commented, "We are pleased that the engraftment and safety profile of Iomab-B remains positive and consistent with prior interim safety results at 75% of patient enrollment in SIERRA and also consistent with the large body of historical data from Iomab-B. Collectively, this data gives excitement as we approach the upcoming ad hoc interim analysis for SIERRA that will be completed by year-end and the ultimate potential of Iomab-B for patients with R/R AML and other blood cancers as a targeted conditioning regimen."

Safety data presented in ASH (Free ASH Whitepaper) oral presentation are highlighted in the table below:

ASH Oral Presentation: High Doses of Targeted Radiation with Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] Do Not Correlate with Incidence of Mucositis, Febrile Neutropenia or Sepsis in the Prospective, Randomized Phase 3 Sierra Trial for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Adverse Event

1 Adverse Event data available for 46 of 47 evaluable patients

2 Adverse Event data available for 27 of 30 evaluable patients

3 Iomab-B arm: 4 patients unevaluable. Conventional Care Arm: 4 patients unevaluable

Patient Group

No. of
Patients

Radiation dose delivered to
the Marrow. Median (range)

Radiation dose to GI tract.
Median (range)

Iomab-B

Vijay Reddy, Vice President, Clinical Development and Head of BMT, "The targeted nature of Iomab-B makes it highly differentiated from current BMT conditioning regimens that are largely comprised of non-targeted cytotoxic chemotherapies. These data from SIERRA showing higher rates of sepsis, neutropenia and mucositis in patients receiving chemotherapy are consistent with the literature and unfortunately what we expected but hope to address with Iomab-B. Particularly, chemotherapy’s effect on the GI tract and resulting mucositis, which we believe is leading to the higher rates of sepsis seen in the control arm. We are highly encouraged by the lower rates of adverse events and the universal engraftment reported from SIERRA and excited for the potential of targeted conditioning could have an BMT access, patient outcomes and quality of life."

About Iomab-B

Iomab-B (I-131 apamistamab) via the monoclonal antibody apamistamab, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, B cells and stem cells. Apamistamab is linked to the radioisotope iodine-131 (I-131) and once attached to its target cells emits energy that travels about 100 cell lengths, destroying a patient’s cancer cells and ablating their bone marrow. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer and marrow cells.

Iomab-B is currently being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are age 55 and above. The SIERRA trial is being conducted at preeminent transplant centers in the U.S. with the primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival at one year. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than the non-targeted intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Additional information on the Company’s Phase 3 clinical trial in R/R can be found at www.sierratrial.com.

On December 7, 2020 Sesen Bio (Nasdaq: SESN), a late-stage clinical company developing targeted fusion protein therapeutics for the treatment of patients with cancer, reported that on Friday, December 4, 2020 the Company entered into a commercial manufacturing and supply framework agreement (the "CMO Agreement") with the Company’s partner in China, Qilu Pharmaceutical Co., Ltd. ("Qilu") (Press release, Sesen Bio, DEC 7, 2020, View Source [SID1234572352]).

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Under the CMO Agreement, Qilu will be part of the contract manufacturing network for global commercial supply of Vicineum. The Company’s lead program, Vicineum, is currently in the follow-up stage of a Phase 3 registration trial in the United States ("US") for the treatment of high-risk, BCG-unresponsive non-muscle invasive bladder cancer ("NMIBC"). The Company is on track to complete the BLA for Vicineum and submit to the FDA later this month.

In July 2020, the Company and Qilu entered into an agreement which grants Qilu an exclusive license to develop, manufacture and commercialize Vicineum in China.

"NMIBC is a disease area that has chronically suffered from manufacturing and CMC issues with significant impacts on patient care," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "Given this, we have taken a thoughtful approach to our supply chain and partnerships in order to meet the significant anticipated global demand for Vicineum. Qilu has a large and experienced manufacturing team and currently supplies products for commercial sale around the world. The CMO Agreement represents an exciting expansion of our strong partnership with Qilu and will help Sesen Bio to reliably meet the projected global demand, while also creating an opportunity to reduce the cost of goods."

The Company believes that the technology transfer to Qilu for manufacturing of Vicineum is on track to be completed in mid-2021. Upon completion of the technology transfer, Sesen Bio is entitled to receive a $2M milestone payment.

In addition to Fujifilm and Baxter, the CMO partnership with Qilu expands the Company’s network of world-class partners committed to providing reliable supply of Vicineum around the world.

About Vicineum

Vicineum, a locally administered fusion protein, is Sesen Bio’s lead product candidate being developed for the treatment of high-risk 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 conducting the Phase 3 VISTA trial, designed to support the registration of Vicineum for the treatment of high-risk NMIBC in patients who have previously received a minimum of two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. 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. 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.