On October 13, 2020 Tyme Technologies, Inc. (NASDAQ: TYME), an emerging biotechnology company developing cancer metabolism-based therapies (CMBTs), reported that its leadership will present at the Jefferies Virtual Global Healthcare Conference on November 17-19 (Press release, TYME, OCT 13, 2020, View Source [SID1234568421]). In one-on-one sessions, the Company will present its corporate overview for fiscal year 2021 with a special focus on multiple growth opportunities driven by advances in the science of cancer cell metabolism, SM-88 (racemetyrosine) late-stage trials in pancreatic cancer, SM-88 HopES trial in ultra-rare metastatic sarcoma, proof-of-concept RESPOnD trial evaluating TYME-19 in COVID-19, and expanding clinical plans for its cancer-metabolism pipeline candidate SM-88 in prostate, breast and hematological cancers.

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Event: Jefferies Virtual Global Healthcare Conference
Place: Waldorf Hilton, London
Presentation Date: November 17-19, 2020
Format: One-on-one sessions

The presentation will be accessible on the events page under the investor relations section of Tyme Technologies’ website at www.tymeinc.com.

About SM-88

SM-88 is an oral investigational modified proprietary tyrosine derivative that is believed to interrupt the metabolic processes of cancer cells by breaking down the cells’ key defenses and leading to cell death through oxidative stress and exposure to the body’s natural immune system. Clinical trial data have shown that SM-88 has demonstrated encouraging tumor responses across 15 different cancers, including pancreatic, lung, breast, prostate and sarcoma cancers with minimal serious grade 3 or higher adverse events. Learn more.

About TYME-18

TYME-18 is composed of a proprietary surfactant delivery agent with a specific sulfonic acid component. It is designed for intra-tumoral administration of difficult to treat tumors and leverages the acidic tumor microenvironment and signaling pathways to kill cancer cells. TYME-18 is distinct in composition, but like SM-88, aims to leverage susceptibilities of a cancer that are related to its altered metabolism. Initial preclinical data for TYME-18 in animal tumor models demonstrate rapid and complete tumor regression, with no reported local or systemic toxicities. TYME-18 continues to be studied as a potential therapy for difficult to treat tumors that may not be eligible for surgical or other interventions. Learn more.

About TYME-19

TYME-19 is a potent, well characterized synthetic antiviral bile acid that is being evaluated as a potential oral therapy for COVID-19. In preclinical testing, TYME-19 repeatedly prevented COVID-19 viral replication without attributable cytotoxicity in treated cells. COVID-19 hijacks a cell’s ability to make proteins and lipids and divert these processes to make viral proteins and lipids in order to reproduce. COVID-19 accomplishes this by inducing stress in the endoplasmic reticulum (ER), where cells process proteins, which enables the virus to remodel protein and lipid synthesis. In preclinical testing, TYME-19 has been shown to counteract these effects, preventing viral replication, by reducing ER stress. TYME-19 is believed to physically degrade viruses by solubilizing the protective lipid layer and other structural components, which prevent a virus from binding to and infecting a cell.

About TYME-88-Panc Pivotal Trial

The TYME-88-Panc pivotal trial applies the latest advances in the field of cancer metabolism by evaluating the efficacy and safety of an oral investigational compound that targets the metabolic mechanisms of the disease at its source. A prospective, open label pivotal trial in metastatic pancreatic cancer for patients who have failed two lines of any prior systemic therapy. The trial is designed to evaluate the safety and efficacy of SM-88 used with MPS (methoxsalen, phenytoin and sirolimus) in advanced pancreatic cancer and will measure multiple endpoints, including overall survival, progression free survival, relevant biomarkers, quality of life, safety, and overall response rate. Learn more.

On October 13, 2020 CytRx Corporation (OTCQB:CYTR) ("CytRx" or the "Company"), a specialized biopharmaceutical company focused on research and development for the oncology and neurodegenerative disease categories, highlighted that ImmunityBio, Inc. and NantKwest, Inc. (collectively, the "Companies") reported the addition of a third cohort to their ongoing Phase 2 study of a novel combination immunotherapy – which includes CytRx’s licensed drug aldoxorubicin – for locally advanced or metastatic pancreatic cancer (QUILT-88) (Press release, CytRx, OCT 13, 2020, View Source [SID1234568419]). According to the Companies, the third cohort will enable pancreatic cancer patients who have failed all approved standards of care to participate in the study.

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As previously noted in CytRx’s October 7, 2020 press release regarding the reportedly promising treatment delivered to former Senator Harry Reid for his stage IV pancreatic cancer, this randomized, open-label study is evaluating the safety and efficacy of a combination immunotherapy that includes aldoxorubicin, ImmunityBio’s IL-15 superagonist Anktiva (N-803), NantKwest’s PD-L1 t-haNK, and standard of care. The study results will be compared to standard of care chemotherapy for first- and second-line treatment. However, the third-line cohort is a single arm with no comparator. Each cohort will be evaluated independently to provide more precise comparative data for each disease stage.

Trial Sites and Enrollment

There are presently three trial sites activated: Hoag Memorial Hospital Presbyterian in Orange County, Calif., The Chan Soon-Shiong Institute for Medicine in Los Angeles County, Calif., and Avera McKennan Hospital and University Health Center in Sioux Falls, South Dakota. The latter site will serve patients in the tri-state area (Iowa, Nebraska and South Dakota). Forty patients are currently enrolled in or being evaluated for the trial.

The Companies’ combination immunotherapy is designed to harness the body’s immune system to target, kill, and "remember" cancer cells. The agents being assessed in the study are designed to find pancreatic cancer cells and initiate a large immune response against them, which may allow the body to develop its own antibodies to fight the cancer.

Study Details

Each treatment setting, as well as each first- and second-line or later maintenance treatment, will be evaluated independently as Cohort A, Cohort B, and Cohort C, respectively, with Cohorts A and B having independent experimental and control arms. The study will initially enroll 298 subjects across all three cohorts. The primary objective of Cohorts A and B is progression-free survival (PFS) and the objective of Cohort C is overall survival (OS) per RECIST V1.1. Secondary objectives include initial safety and additional efficacy measures, including overall response rate (ORR), complete response (CR) rate, durability of response (DoR), disease control rate (DCR), and overall survival (OS).

"Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and requires significant advancements in treatment to improve outcomes for patients," said Steven A. Kriegsman, CytRx’s Chairman and Chief Executive Officer. "We commend the Companies for adding a third cohort and expanding this Phase 2 study of their combination immunotherapy that includes aldoxorubicin. We are encouraged that aldoxorubicin continues to play a role in their mission to recruit and amplify the power of the human body’s own immune system to target and destroy even the most difficult cancer cells."

CytRx out-licensed global development, manufacturing and commercialization rights for aldoxorubicin to ImmunityBio in 2017. The Company has an agreement with ImmunityBio that can yield up to $343 million in potential milestone payments as well as prospective royalties on sales of aldoxorubicin.

On October 13, 2020 Eureka Therapeutics, Inc., a clinical stage biotechnology company developing novel T cell therapies to treat solid tumors, reported that it will participate virtually in two upcoming conferences in October (Press release, Eureka Therapeutics, OCT 13, 2020, View Source [SID1234568418]):

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TCR-based Therapies Summit
Title: ARTEMIS Antibody TCR T Cell Therapies for Solid Tumors
Speaker: Cheng Liu, Ph.D., President and CEO
Date: Tuesday, October 27, 2020
Time: 9:00 a.m. EST
Cell & Gene Therapy Bioprocessing & Commercialization
Title: Optimizing Viral Vector Production
Speaker: Nicole Nunez, Ph.D., Process Development Scientist
Date: Thursday, October 22, 2020
Time: 8:00 a.m. EST

On October 13, 2020 BryoLogyx, Inc., reported that it has completed the synthesis of bryostatin-1 molecule, pursuant to FDA’s Good Manufacturing Practice (GMP) regulations (Press release, BryoLogyx, OCT 13, 2020, View Source [SID1234568416]). Bryostatin-1 is the company’s lead compound being developed to improve patient outcomes by amplifying the response and increasing the durability of targeted cancer immunotherapies. The GMP synthesis, accomplished in partnership with Albany Molecular Research Inc. (AMRI), a global contract research, development and manufacturing organization (CDMO), paves the way for BryoLogyx’s planned clinical program with bryostatin-1 in immuno-oncology, additional research on the compound’s potential in other therapeutic areas, and the development of next generation synthetic analogs.

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The GMP-manufactured compound is based on the landmark patented synthesis process for bryostatin-1 reported in Science (2017) and developed by Paul Wender, PhD, and colleagues at Stanford University and licensed to BryoLogyx. Bryostatin-1 is an extremely complex molecule, originally isolated from a marine organism more than 50 years ago that has generated extensive research interest based on its protein kinase C (PKC) – modulating activity that affects many cellular processes. Much of the world’s supply to date was produced years ago by the National Cancer Institute (NCI), through a costly extraction from its marine source organism which is impractical for commercial development; that supply is largely depleted.

"The Wender synthesis process, which has been compared to the conquest of Mt. Everest, is a foundational pillar of BryoLogyx," said Thomas Loarie, CEO of BryoLogyx. "The Wender method’s translation into a scalable and economical process to sustainably supply clinical grade bryostatin-1 is a key step towards defining the molecule’s potential in immuno-oncology through clinical trials and exploring additional therapeutic opportunities." He noted that synthetic bryostatin-1 will be integrated into the company’s clinical program, which is expected to begin early next year.

"There exists an extensive body of clinical and preclinical research from the NCI and other laboratories that suggests that bryostatin-1 has a broad range of potential therapeutic applications. Its development as a therapeutic has been limited until today by supply. The availability of bryostatin-1 provides an important avenue for continued exploration of this molecule in cancer, auto-immune diseases, anti-inflammatory diseases, and infectious diseases," said Dr. Wender, Bergstrom Professor of Chemistry at Stanford University; and cofounder and Board of Directors member at BryoLogyx.

BryoLogyx recently announced that the Company had entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) to conduct its first clinical trial with bryostatin-1 in patients with relapsing or refractory CD22 expressing acute lymphoblastic leukemia (ALL) and lymphoma. The study will evaluate bryostatin-1’s safety and tolerability, its ability to upregulate the CD22 antigen, an essential target of CD 22-directed antibody drug conjugates (ADCs) and CAR T cell therapies. Subsequent studies will evaluate bryostatin-1’s ability to upregulate target antigens in a variety of other B cell hematologic malignancies.

Underscoring the broad impact of this synthesis, earlier this year BryoLogyx announced an agreement with Neurotrope, to supply that company with synthetic bryostatin-1 for use in developing a treatment for Alzheimer’s disease and other neurological disorders.

Christopher Conway, President, AMRI, noted, "The GMP synthesis of this extraordinarily complex molecule took more than two years of work at our facilities in Hyderabad, India; Albany, NY, and Grafton, WI. The close collaboration on the project among our drug development team, BryoLogyx, and Dr. Wender, underscores how AMRI works with partners to produce complex pharmaceuticals and become integral to our partners’ supply chains."

On October 13, 2020 Kyowa Kirin International PLC (Kyowa Kirin), a wholly owned subsidiary of Kyowa Kirin Co., Ltd., reported data from a post hoc analysis of the MAVORIC trial. The analysis compared the efficacy and safety of POTELIGEO▼ (mogamulizumab) with vorinostat by patient blood classification in adult patients with mycosis fungoides (MF) and Sézary syndrome (SS), two types of CTCL.1 The data showed that higher levels of blood tumour involvement were associated with better patient outcomes in patients treated with mogamulizumab, compared to vorinostat.1

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MF and SS are subtypes of CTCL, a rare type of non-Hodgkin’s lymphoma that can affect the skin, blood, lymph nodes and internal organs.2 In MAVORIC, overall investigator-assessed progression-free survival (PFS) was significantly greater for patients treated with mogamulizumab compared to vorinostat, at 7.7 months and 3.1 months, respectively (P<0.0001).1 When data were stratified by blood classification, PFS was found to be significantly greater for mogamulizumab compared to vorinostat in patients with higher levels of blood involvement, known as B1 and B2 blood classifications.1

Professor Julia Scarisbrick, Consultant Dermatologist, lead author of this analysis from the study said: "In MF and SS, assessing the stage of the disease is key to prognosis, appropriate treatment and patient outcome. Assessment of blood involvement is part of this staging process. The data highlights that mogamulizumab is more effective in MF and SS patients who have blood involvement as part of their disease. Blood involvement is relatively common in the more advanced stages of CTCL and may be present in as many as 20% of less advanced cases.3 This new information could help improve the clinical management of MF and SS patients and highlights the need for blood monitoring."

Overall response rate (ORR) was also significantly greater for mogamulizumab than vorinostat in the MAVORIC trial at 28% and 5% respectively (P<0.0001).1 In this analysis, ORR was also found to be significantly greater for mogamulizumab than vorinostat in patients with B2 blood classification.1 Difference in ORR for patients with B1 blood classification was not significant between the two treatment groups.1 Difference in time-to-next-treatment (TTNT) was not significant for patients without blood involvement (B0 classification), but was significantly greater for mogamulizumab in patients with B1 or B2 blood involvement, 13.70 vs 3.30 months for mogamulizumab and vorinostat, respectively (P<0.0001).1 Drug-related treatment-emergent adverse events (TEAEs) were similar in patients regardless of blood involvement and were lower for mogamulizumab than vorinostat at each blood classification level.1

Danie du Plessis, Executive Vice President, Medical Affairs (EMEA) at Kyowa Kirin, commented: "We welcome the results of this analysis in furthering our understanding of the role of mogamulizumab in treating MF and SS patients. Research suggests that patients with B1 and B2 blood classifications may have reductions in median survival and an increased risk of disease progression, compared to those classified as B0.4 Through our work with this therapy, we are aiming to address the unmet needs in these patient populations and are dedicated to improving outcomes for people with MF and SS."

The data will be presented today in a poster session at the 16th European Association of Dermato Oncology (EADO) Congress.1

About Mycosis Fungoides (MF) and Sézary syndrome (SS)
MF and SS are subtypes of cutaneous T-cell lymphoma (CTCL), a rare type of non-Hodgkin’s lymphoma that can affect the skin, blood, lymph nodes and internal organs.2 CTCL is rare. For every 100,000 people in Europe, there are approximately 24 cases of CTCL.5 Together they represent approximately 65% of all cases of CTCL.2 Individuals with this disease often suffer from disfiguring, itchy, painful and unpredictable skin symptoms, which can lead to further complications that can impact their life expectancy.6,7

MF and SS are characterised by localisation of cancerous white blood cells called T lymphocytes (T cells), to the skin.8,9 These cancerous T cells consistently express a protein called CC-chemokine receptor 4 (CCR4), which enables them to move from the blood to the skin.10,11,12 When these cancerous T cells move to the skin, they can create a localised inflammatory immune skin response, commonly resulting in visible skin symptoms of red patches or plaques, 10,13,14,15,16 which can resemble psoriasis or eczema.8

MF and SS can affect the skin, blood, lymph nodes (part of the body’s immune system which is spread throughout the body) and internal organs.2 All four areas of the body are used to assess disease stage17,18 and clinically significant involvement of the blood, particularly in more advanced disease, is linked with increased morbidity and an overall reduction in patient survival.17,19,20

Due to its likeness to more common skin conditions such as eczema and psoriasis,8 CTCL can take, on average, between 2 and 7 years for individuals to receive a confirmed diagnosis.21 It is critical for doctors to diagnose CTCL as early as possible as the patient’s prognosis can be affected if the disease progresses to later stages.4 Whilst most individuals that present with early stage do not progress to a more advanced stage,22 patients with advanced disease have significantly poorer outcomes with only around half of patients (52%) surviving for just 5 years.17

About POTELIGEO (mogamulizumab)
POTELIGEO is a first-in-class humanised monoclonal antibody (mAb), designed to bind to CC chemokine receptor 4 (CCR4).7 After POTELIGEO binds to CCR4, it increases affinity of immune cells from the immune system to target the cancerous cells.23 POTELIGEO uses Kyowa Kirin’s proprietary POTELLIGENT technology.23

Following a positive opinion from Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), the European Commission (EC) granted marketing authorisation for POTELIGEO in November 2018 for the treatment of adult patients with MF or SS who have received at least one prior systemic therapy.24 The CHMP’s opinion was based on results of the MAVORIC trial, the largest randomised study of systemic therapy in MF and SS,7 and the first trial to compare systemic therapies using progression-free survival as a primary endpoint.7

About the MAVORIC Trial

The MAVORIC trial is the largest randomised study of systemic therapy conducted in MF and SS,7 and the first trial to compare systemic therapies using ‘progression-free survival’ (PFS) as a primary endpoint, which incorporates looking at disease progression in four different compartments of the body (skin, blood, lymph nodes and internal organs).7
Secondary endpoints were overall response rate; duration of response (time from first achievement of an overall response to progression or death); the proportion of patients with an overall response in the crossover portion of the trial; assessment of quality of life; immunogenicity (immune response) and safety.7
Results showed that:
In patients taking POTELIGEO disease was controlled for more than twice as long as in those taking the comparator treatment, vorinostat* (PFS of 7.7 mths vs 3.1 mths) (HR=0.53, 95% CI: 0.41–0.69; p<0.0001).7
Overall significantly more patients responded to POTELIGEO than vorinostat* (Overall Response Rate [ORR] 28% versus 5%; Risk Ratio [RR]: 23.1; 95% CI 12.8–33.1, P<0.0001).7
Response to treatment lasted 43% longer in people taking POTELIGEO versus those taking vorinostat* (14.1 months versus 9.1 months).7
More patients responded to POTELIGEO, across all studied MF/SS disease stages than with vorinostat.* 7
POTELIGEO has overall good tolerability with a manageable safety profile.7,25
The most common adverse reactions with POTELIGEO are constipation, diarrhoea, nausea, stomatitis, fatigue, oedema (peripheral), pyrexia, infections, infusion related reactions, headache and drug eruption (including skin rash).24
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*Vorinostat is a USA FDA-licensed existing treatment for MF and SS and is currently unlicensed in the EU