On August 25, 2020 Bristol Myers Squibb (NYSE:BMY) reported that the Phase 3 IDHENTIFY study evaluating IDHIFA (enasidenib) plus best supportive care (BSC) versus conventional care regimens, which include best supportive care (BSC) only, azacitidine plus BSC, low-dose cytarabine plus BSC or intermediate-dose cytarabine plus BSC, did not meet the primary endpoint of overall survival (OS) in patients with relapsed or refractory acute myeloid leukemia (R/R AML) with an isocitrate dehydrogenase-2 (IDH2) mutation (Press release, Bristol-Myers Squibb, AUG 25, 2020, View Source [SID1234563996]). The safety profile of IDHIFA was consistent with previously reported findings. The company will complete a full evaluation of the IDHENTIFY data and work with investigators to present detailed results at a future medical meeting.

"While we are disappointed by the outcome of the IDHENTIFY study, we remain confident in IDHIFA’s established role as a treatment option for patients with relapsed or refractory AML with an IDH2 mutation and are grateful to all those who participated in the study," said Noah Berkowitz, M.D., Ph.D., senior vice president, Global Clinical Development, Hematology, Bristol Myers Squibb. "AML is one of the most difficult-to-treat blood cancers, and we’re committed to furthering our research and improving on the standards of care for patients living with this aggressive disease."

In August 2017, Bristol Myers Squibb received full approval in the U.S. for IDHIFA for the treatment of adult patients with R/R AML with an IDH2 mutation as detected by a U.S. Food and Drug Administration (FDA)-approved test. IDHIFA is the first and only FDA-approved therapy for patients with R/R AML and positive for an IDH2 mutation, which represents up to 19 percent of AML patients. IDHIFA is also approved in Australia and Canada.

About IDHENTIFY

IDHENTIFY (NCT02577406) is an international, multicenter, open-label, randomized, Phase 3 study comparing the efficacy and safety of AG-221 versus conventional care regimens (CCRs), which include continuous 28-day cycles of best supportive care (BSC) only, azacitidine subcutaneously (SC) plus BSC, low-dose cytarabine SC plus BSC, or intermediate-dose cytarabine intravenously plus BSC, in subjects 60 years or older with acute myeloid leukemia (AML) refractory to or relapsed after second- or third-line AML therapy and positive for an isocitrate dehydrogenase (IDH2) mutation. The primary endpoint of the study was overall survival. Key secondary endpoints included overall response rate, event-free survival, duration of response and time to response.

About Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common type of acute leukemia. AML starts in the bone marrow but moves quickly into the blood. Unlike in normal blood cell development, in AML, the rapid buildup of abnormal white blood cells in the bone marrow may interfere with the production of normal blood cells, resulting in decreased healthy white blood cells, red blood cells and platelets. AML is a complex, diverse disease associated with multiple genetic mutations, such as the isocitrate dehydrogenase-2 (IDH2) mutation, and usually worsens quickly and can lead to death if not treated. IDH2 mutations are present in up to 19 percent of AML cases. AML has a high relapse rate, meaning following patients’ initial response to treatment, their disease is likely to return, signifying an unmet need for targeted therapy options. The worldwide incidence of AML is estimated to be over 350,000 cases. In the United States, there will be an estimated 21,450 new cases of AML this year, with an estimated 10,920 deaths resulting from the disease.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients’ quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About IDHIFA

IDHIFA (enasidenib) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation as detected by an FDA-approved test. IDHIFA is also approved in Australia and Canada.

Important Safety Information

BOXED WARNING: DIFFERENTIATION SYNDROME

Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the AG221-C-001 Phase 2 clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 1 day and at up to 5 months after IDHIFA initiation. Symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia and need for supplemental oxygen; pulmonary infiltrates and pleural effusion; renal impairment; fever; lymphadenopathy; bone pain; peripheral edema with rapid weight gain; and pericardial effusion. Hepatic, renal, and multi-organ dysfunction have also been observed. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.

Embryo-Fetal Toxicity: Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with IDHIFA and for at least 2 months after the last dose. Pregnant women, patients becoming pregnant while receiving IDHIFA, or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) included total bilirubin increased (81%), calcium decreased (74%), nausea (50%), diarrhea (43%), potassium decreased (41%), vomiting (34%), decreased appetite (34%), and phosphorus decreased (27%)
The most frequently reported ≥Grade 3 adverse reactions (≥5%) included total bilirubin increased (15%), potassium decreased (15%), phosphorus decreased (8%), calcium decreased (8%), diarrhea (8%), differentiation syndrome (7%), non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and nausea (5%)
Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%), tumor lysis syndrome (5%), and differentiation syndrome (8%). Differentiation syndrome events characterized as serious included pyrexia, renal failure acute, hypoxia, respiratory failure, and multi-organ failure
LACTATION

Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with IDHIFA and for at least 2 months after the last dose.

On August 25, 2020 Diaprost reported that it has signed an exclusive license agreement with Memorial Sloan Kettering Cancer Center for IP related to the use of PSA antibodies for therapeutic and diagnostic purposes for prostate cancer (Press release, Diaprost, AUG 25, 2020, View Source,ten%20pharmaceutical%20companies%20within%20oncology. [SID1234563994]). Diaprost is a private pharmaceutical research and development company based in Lund, Sweden and whose principle asset is h5A10, targeting PSA, a validated clinical biomarker. The h5A10 antibody combined with the appropriate payload offers the potential for highly specific therapeutic and diagnostic products, for example as a therapeutic product to deliver cytotoxic radionuclides. Diaprost’s h5A10 is already in pre-clinical development for the treatment of prostate cancer, the most common cancer in men and having a high unmet medical need. h5A10 displays high levels of specificity and affinity to PSA as well as successful tissue biodistribution and cellular internalization.

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"We believe this License Agreement complements the current IP-portfolio on the antibody h5A10 maximizing the potential of both Diaprost and the h5A10 program," said Johan Drott, the CEO of Diaprost. "We will now focus Diaprost’s efforts to deliver yet another important new oncology therapy to patients."

This h5A10 project follows in the footsteps of Diaprost’s successful earlier work in prostate cancer focusing on the hK2 antibody which led to a sale of the asset to a leading global oncology company.

On August 25, 2020 Groundbreaking cancer research by the University of South Australia reported that has identified an invasive protein molecule that could be responsible for some of the most aggressive breast cancers (Press release, University of South Australia, AUG 25, 2020, View Source [SID1234563993]).

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The never-before studied molecule (ZCCHC24) appears to change the structure of breast cancer cells to increase the aggressive nature of the deadly disease. Understanding how it works could stop the cancer from metastasizing to other sites in the body.

Lead researcher, and Laboratory Head at UniSA’s Centre of Cancer Biology, and recipient of the Cancer Council Beat Cancer Project grant, Associate Professor Philip Gregory, says the discovery could provide life-changing information to prevent the spread of breast cancer.

"Understanding why some forms of breast cancer spread and others don’t is vital in understanding how to treat breast cancer," Assoc Prof Gregory says.

"In this research, we’re drilling down to look at individual cancer cells and trying to find out what makes them turn from being benign to being aggressive. Once they become aggressive, these cells can go rogue, branching out across the body and making them very difficult to treat.

"What we’ve discovered is a molecule that appears to be strongly turned on in the most aggressive cancer cells. When we block the action of this molecule, the cells completely change and become far less aggressive.

"This molecule is particularly abundant in aggressive breast cancers, which can be extremely difficult to treat. By understanding how the molecule works, we could unlock new treatments for the disease."

breast cancer examinationBreast cancer is the most common cancer in women worldwide, with more than two million cases across the globe. In Australia, it is estimated that nearly 20,000 new cases of breast cancer will be diagnosed in 2020. It is the second leading cause of death from cancer among women.

Ahead of Daffodil Day on Friday 28 August, Cancer Council SA Chief Executive Lincoln Size says the findings are an exciting step forward in breast cancer research.

"This new discovery could transform treatments for breast cancer in the future and help thousands of Australian women," Size says.

"We’re incredibly proud to fund groundbreaking research such as Dr Gregory’s through Cancer Council’s Beat Cancer Project and encourage the community to show their support this Daffodil Day to enable us to continue to fund this critical work."

Daffodil Day is held across the country on Friday 28 August with donations funding vital cancer research projects across the country.

On August 25, 2020 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that it will give status updates and details on the recent clinical development plans for the clinical drug candidates mitazalimab, ATOR-1015 and ATOR-1017 on a virtual R&D Day on August 27 (Press release, Alligator Bioscience, AUG 25, 2020, View Source [SID1234563992]).

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"These clinical plans provide an excellent opportunity for Alligator to have two or even three competitive cancer therapeutics in clinical efficacy studies by the end of 2021", commented Per Norlén, CEO of Alligator Bioscience.

Mitazalimab is Alligator’s most advanced immunotherapy candidate intended for the treatment of different types of cancer. It activates CD40, a receptor on the dendritic cells which allows the immune system to selectively attack the cancer.

Next step in the development of mitazalimab is the submission of a Phase II clinical trial application (CTA) which is planned for December 2020. The study (OPTIMIZE-1) is an open-label, multi-center trial assessing the clinical efficacy of mitazalimab in combination with chemotherapy (mFolfirinox) in patients with metastatic pancreatic cancer. The OPTIMIZE study will be performed at several clinics in Europe, with inclusion of the first patient H1 2021.

Clinical data previously communicated from mitazalimab’s Phase I development program demonstrated that mitazalimab is safe and tolerated at clinically relevant dose levels, with early signs of clinical activity identified, including a partial response in a patient with renal cell cancer and prolonged stable disease ≥6 months in 10 patients. There is still one patient in the Phase I study, now treated with mitazalimab for more than 30 months.

ATOR-1015, wholly owned by Alligator, is a tumor-localizing, bispecific CTLA-4 and OX40 antibody developed for treatment of metastatic cancer. The first indication will be skin cancer (malignant melanoma) where the target molecule CTLA-4 has been proven effective but associated with significant toxicity.

Promising data from the ongoing ATOR-1015 Phase I clinical trial was presented in June 2020 and dose escalation has continued at high doses. The positive tolerability profile of ATOR-1015 has led to the frontloading of a Phase Ib study for demonstration of single-agent activity. This allows for an efficacy readout as early as H2 2021 in malignant melanoma. This could significantly increase the value of the concept and will be followed by a Phase II combination study with anti-PD-1.

The interim data include doses up to 600 mg (about 10 mg/kg) and show that ATOR-1015 is well tolerated, thus supporting for the concept. Dose-escalation is currently at 750 mg (12.5 mg/kg). The drug related adverse events in the study have generally been mild and transient. No dose-limiting toxicity or severe immune-related adverse events have been reported.

ATOR-1017 is Alligator’s wholly owned 4-1BB antibody in clinical Phase I development for the treatment of metastatic cancer. ATOR-1017 activates 4-1BB receptors on T cells which increases the ability of the immune system to detect and kill tumor cells. ATOR-1017 has a unique profile which creates an opportunity for a strong and tumor-directed immune activation that can increase efficacy and reduce side effects for the patient.

The ongoing Phase I study is a dose escalation study in patients with advanced cancer. The study is conducted at three different clinics in Sweden and is planned to include up to 50 patients. The objectives of the study are to assess the safety and tolerability of ATOR-1017, to determine the recommended dose for the subsequent Phase II studies, but also to assess initial signs of efficacy.

A more detailed invitation to the R&D Day on August 27 will be distributed shortly.

This information is such information as Alligator Bioscience AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 11:00 a.m. CEST on August 25, 2020.

On August 24, 2020 Cue Biopharma, Inc. (NASDAQ: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells within the body, reported a poster presentation featuring Neo-STAT, the Company’s next generation Immuno-STAT (Selective Targeting and Alteration of T cells) scaffold, at the 16th Annual PEGS Boston Essential Protein Engineering & Cell Therapy Summit (Press release, Cue Biopharma, AUG 24, 2020, View Source [SID1234608298]). Neo-STAT biologics are designed for targeted modulation of tumor-specific T cells with enhanced antigen modularity.

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Presentation Details
Title: Neo-STAT: A new biologics platform for selective targeting of tumor-specific T cells with enhanced antigen modularity
Presenter: Ahmet S. Vakkasoglu, Ph.D., senior scientist
Date: August 31-September 4, 2020

The poster highlights the engineering of the Neo-STAT platform, a scaffold with pocket-stabilized, peptide-free HLA molecules that enables enhanced antigen modularity through exogenous peptide loading. Compared to first generation scaffolds, the design of Neo-STAT improves the productivity and efficiency of scaffold production. Additionally, Neo-STAT biologics can incorporate diverse T cell epitopes, including peptides bearing post-translational modifications, peptide mixtures and peptides derived from tumor neo-antigens, thereby broadening the flexibility and therapeutic impact of the Immuno-STAT platform to target a wider spectrum of disease-associated epitopes.

"We are pleased to be presenting the Neo-STAT platform, which was developed to allow for the generation of therapeutic molecules incorporating diverse T cell epitopes," said Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma. "The Neo-STAT platform enables us to access a wider range of therapeutically relevant epitopes, including near-term applications in cancer immunotherapy with shared as well as personalized tumor antigens. In addition to cancer immunotherapy, we are also assessing the potential applications of Neo-STAT in infectious diseases, particularly against novel pathogens where immediate T cell responses could provide protective immunity before other prophylactic vaccination approaches are developed."

About Immuno-STAT
Immuno-STAT biologics are designed for targeted modulation of disease-associated T cells in the areas of immuno-oncology and autoimmune disease. Each of our biologic drugs is designed using our proprietary scaffold comprising: 1) a peptide-MHC complex (pMHC) to provide selectivity through interaction with the T cell receptor (TCR), and 2) a unique co-stimulatory signaling molecule to modulate the activity of the target T cells.

The simultaneous engagement of co-regulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells (APCs) to T cells during a natural immune response. This design enables Immuno-STAT biologics to engage with the T cell population of interest, resulting in highly targeted T cell modulation. Because our drugs are delivered directly in the patient’s body (in vivo), they are fundamentally different from other T cell therapeutic approaches that require the patients’ T cells to be extracted, modified outside the body (ex vivo), and reinfused.