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Immunotherapy Inches Forward in Development of Myeloid Malignancies – OncLive

Survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains poor, and although immunotherapy has been positioned as a holy grail, it would be preemptive to predict its future based on the number of small studies that have been performed to date, according to Amer Zeidan, MD, MHS.

Nonetheless, one of the first studies that showed the potential for checkpoint inhibition in hematologic malignances was a phase 1/1b study that evaluated ipilimumab (Yervoy) after allogeneic stem cell transplant. In the study, ipilimumab was administered at a dose of 3 mg/kg and 10 mg/kg every 3 weeks. The results demonstrated efficacy in patients who received the 10 mg/kg dose. Specifically, 5 of 13 patients with heavily pretreated AML achieved a complete response (CR).

Ipilimumab has also demonstrated activity in patients with relapsed/refractory MDS in a single-arm study of 29 patients. Although the marrow CR rate was only 3.4%, 7 patients experienced prolonged stable disease for 46 weeks or more, including 3 patients with stable disease surpassing 1 year. Moreover, the median survival was 9.8 months (295 days; 95% CI, 240-671+).

In correlative analysis, we observed that patients who had increased expression of the costimulatory marker ICOS seemed to have better disease stabilization, so the direction is clearly headed toward trying to select patients using biomarker-driven strategies, Zeidan, an associate professor of medicine in the Department of Internal Medicine and Section of Hematology at Yale University School of Medicine, Yale Cancer Center, said in a presentation during the5th Annual International Congress on Immunotherapies in Cancer.

In another phase 2 study that evaluated the combination of nivolumab (Opdivo) and azacitidine vs ipilimumab and azacitidine in MDS, a higher response rate was observed with either combination compared with ipilimumab alone, at 70% and 62% vs 30%, respectively. However, the median overall survival (OS) was similar, at 11.8 months, not reached, and 8.5 months, respectively, said Zeiden.

Pembrolizumab (Keytruda) is also being subject to research in myeloid malignancies. Specifically, in a phase 1b study in combination with entinostat in MDS after failure on hypomethylating agents (HMAs). Data from the study have yet to read out, but are highly anticipated, said Zeiden.

Findings from a phase 2 study (NCT02775903) however stunted some of the excitement that had been generated with immunotherapy, putting into perspective the work that had been done to date. When the combination of a checkpoint inhibitor and an HMA, specifically durvalumab (Imfinzi) and azacitidine, was taken into a randomized trial vs azacitidine alone in patients with high-risk MDS and older AML, no difference was seen in progression-free survival (PFS) or OS.

Bispecific antibodies are another treatment class under investigation as a potential avenue forward for immunotherapy. One such antibody is sabatolimab, which targets IgG4 and TIM-3, and is the focus of several ongoing studies in MDS and AML. Specifically, the phase 2 STIMULUS-MDS1 (NCT03946670) and phase 3 STIMULUS-MDS2 (NCT04266301) trials in MDS and phase 2 STIMULUS-AML1 trial (NCT04150029) in AML.

Another path that will be explored is that of checkpoint inhibition plus chemotherapy, explained Zeiden. In a phase 2 study, the combination of pembrolizumab and 7+3 chemotherapy will be evaluated as frontline therapy in fit patients with AML.

The combination of azacitidine and venetoclax (Venclexta) has become the standard of care for older patients with AML, and preclinical evidence suggests that the BCL-2 inhibitor can augment the antitumor response of PD-L1 inhibitors.

As such, investigators have launched the phase 2 BLAST AML 2 study in which unfit patients with AML will be randomized to azacitidine plus venetoclax vs azacitidine/venetoclax plus pembrolizumab as frontline therapy.

Anti-CD47 antibodies are also under study and have shown promising, though early, activity in AML and MDS. For example, in combination with azacitidine, magrolimab has shown objective responses exceeding 60% in untreated AML and 90% in untreated MDS, with CR rates of 41% and 50%, respectively.

Importantly, a lot of the responses seem to occur in patients who have TP53 mutations, which is one of the highest areas of unmet need in AML and MDS, because those patients do very poorly with conventional treatment, said Zeidan.

Although magrolimab will move forward in development, Zeidan cautioned that the antitumor effects of anti-CD47 antibodies may not be class specific. For example, in a phase 1 study, CC-90002 failed to demonstrate any benefit in patients with relapsed/refractory AML and higher-risk MDS.

In conclusion, Zeidan stated, Many of the studies that have been conducted are single-arm trials with small sample sizes. [However,] we are doing more and more randomized studies using novel inhibitors against TIM-3 and CD47. The field is definitely exciting for us, and we are hoping to see some clinical activity for our patients soon.

Reference

Zeidan A. Immunotherapy for treatment of myeloid malignancies: will it fill the promise? Presented at: 5thAnnualInternational Congress on Immunotherapies in Cancer; December 12, 2020; virtual. gotoper.com/go/ICIC20Virtual

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Immunotherapy Inches Forward in Development of Myeloid Malignancies - OncLive

Cytovia Therapeutics Partners with National Cancer Institute to Develop Novel Gene-Edited, iPSC-Derived GPC3 CAR NK Cells for the Treatment of Solid…

January 13, 2021 07:47 ET | Source: Cytovia Therapeutics

CAMBRIDGE, Mass., Jan. 13, 2021 (GLOBE NEWSWIRE) -- Cytovia Therapeutics, an emerging biopharmaceutical company focusing on Natural Killer cells in cancer, announced today that it has signed a licensing agreement with the National Cancer Institute (NCI), part of the National Institutes of Health, to apply its gene-edited iPSC-derived NK cell technology to develop GPC3 CAR NK cell therapeutics. Dr Mitchell Ho, PhD, Director of the Antibody Engineering Program and Deputy Chief of the Laboratory of Molecular Biology at the NCI Center for Cancer Research has developed novel antibodies and chimeric antigen receptors (CAR) binding to glypican-3 (GPC3) on liver cancer cells. Dr. Ho has published data on the humanized GPC3 antibody in scientific reports (nature research) in 2016 as well as on the GPC3 CAR in Gastroenterology in 2020.

GPC3 is an oncofetal antigen involved in Wnt-dependent cell proliferation. It is highly expressed in Hepatocellular Carcinoma tumor cells as well as multiple other solid tumors, including ovarian cancer and lung cancer, but not expressed in adult normal tissues.

Cytovia has also signed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute. Under the CRADA, Cytovia will collaborate with Dr. Hos laboratory to develop and evaluate gene-edited iPSC-derived GPC3 CAR NK cells. Cytovia expects to file an initial new drug application (IND) for its GPC3 CAR NK cells in the first half of 2022.

Dr. Daniel Teper, Chairman and CEO of Cytovia Therapeutics commented: GPC3 is an exciting new validated target for Hepatocellular Carcinoma, an area of major unmet medical need, as well as other solid tumors. We look forward to collaborating with Dr. Ho, a pioneer in GPC3 research, to develop a novel gene-edited, iPSC-derived GPC3 CAR NK that will advance toward a cure for liver cancer.

Dr. Ho added: Natural Killer cells play a major role in the immuno-surveillance of liver cancer. GPC3 is expressed in more than 70% of Hepatocellular Carcinoma cells but not on healthy cells. We look forward to investigating whether GPC3 CAR-NK therapy could provide a new safe and effective off-the-shelf option for patients with liver cancer.

ABOUT GENE-EDITED, IPSC-DERIVED NK CELLS Chimeric Antigen Receptors (CAR) are fusion proteins that combine an extracellular antigen recognition domain with an intracellular co-stimulatory signaling domain. Natural Killer (NK) cells are modified genetically to allow insertion of a CAR. CAR-NK cell therapy has demonstrated initial clinical relevance without the limitations of CAR-T, such as Cytokine Release Syndrome, neurotoxicity or Graft vs Host Disease (GVHD). In addition, CAR-NKs are naturally allogeneic, available off-the-shelf and may be able to be administered on an outpatient basis. Recent innovative developments with the induced pluripotent stem cell (iPSC)-derived CAR-NKs, an innovative technology, allow large quantities of homogeneous genetically modified CAR NK cells to be produced from a gene-edited iPSC master cell bank, and thus hold promise to expand access to cell therapy for many patients.

ABOUT HCC Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of death worldwide, with 800,000 new cases diagnosed globally every year. The incidence in Asia is amongst the highest in the world (75%) with 400,000 in China alone. In the US, it is estimated to reach upwards of 30,000 by the end of 2020 and continues to be on the rise. Despite advances in immunotherapy, with current treatment options including multi-kinase inhibitors (TKI) and checkpoint inhibitors, life expectancy for patients diagnosed with HCC remains very low. The disease is often diagnosed at an advanced stage, with a median survival of approximately 6 to 20 months following diagnosis, and a 5-year survival rate below 10% in the US. Fortunately, new options including cell therapy and bispecific antibodies offer promise towards a cure for liver cancer.

ABOUT GPC3 Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan expressed in the liver and the kidney of fetuses but is hardly expressed in adults, except in the placenta. However, it is highly expressed in HCC, ovarian clear cell carcinoma, squamous cell carcinoma of the lung, melanoma, hepatoblastoma, nephroblastoma (Wilms tumor), yolk sac tumor, and some pediatric cancers. GPC3 promotes Wnt-dependent cell proliferation and has been strongly suggested that it is related to the malignant transformation. Therefore, GPC3 is a promising target for cancer immunotherapy and can serve as a biomarker for predicting tumor recurrence and treatment efficacy.

About Cytovia TherapeuticsCytovia Therapeutics Inc is an emerging biotechnology company that aims to accelerate patient access to transformational immunotherapies, addressing several of the most challenging unmet medical needs in cancer. Cytovia focuses on Natural Killer (NK) cell biology and is leveraging multiple advanced patented technologies, including an induced pluripotent stem cell (iPSC) platform for CAR (Chimeric Antigen Receptors) NK cell therapy, next-generation precision gene-editing to enhance targeting of NK cells, and NK engager multi-functional antibodies. Our initial product portfolio focuses on both hematological malignancies such as multiple myeloma and solid tumors including hepatocellular carcinoma and glioblastoma. The company partners with the University of California San Francisco (UCSF), the New York Stem Cell Foundation (NYSCF), the Hebrew University of Jerusalem, INSERM, and CytoImmune Therapeutics.

Learn more atwww.cytoviatx.comand follow Cytovia Therapeutics on Social Media(Facebook,LinkedIn,Twitter,and Youtube).

Contact for investor enquiries:

Anna Baran-Djokovic Vice President, Investor Relations Anna@cytoviatx.com 1 (646) 355 1787

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Cytovia Therapeutics Partners with National Cancer Institute to Develop Novel Gene-Edited, iPSC-Derived GPC3 CAR NK Cells for the Treatment of Solid...

Kaleido Biosciences Announces Positive Interim Results of Controlled Study of KB109 in Patients with Mild-to-Moderate COVID-19 – BioSpace

Preliminary analysis (n=176) demonstrates favorable safety and tolerability; data provide a strong signal of clinical benefit for subjects reporting one or more comorbidities

Topline data from full study population of 350 patients and results of second study of KB109 are expected in the first quarter of 2021

LEXINGTON, Mass., Jan. 14, 2021 (GLOBE NEWSWIRE) -- Kaleido Biosciences Inc. (Nasdaq: KLDO), today announced positive interim results from the K031 non-IND controlled clinical study evaluating outpatients with mild to moderate COVID-19 disease. Patients in this non-IND clinical study were randomized within 48 hours of testing positive for COVID-19 to either receive Supportive Self Care (SSC) or SSC plus Microbiome Metabolic Therapy (MMT) candidate KB109 for two weeks and then followed for an additional three weeks. The planned interim analysis comprised approximately half of the total study population (n=176) and showed that KB109 was well tolerated, with a safety profile consistent with previous studies of MMT candidates and no unexpected treatment-related adverse events. For subjects reporting one or more comorbidities, the median time to resolution of the thirteen overall COVID-19 related symptoms was 18 days with KB109 plus SSC and 27 days with SSC alone.

This interim analysis, from the largest study conducted to date with an MMT candidate, reinforces the safety and tolerability previously observed with MMTs and provides a strong signal of clinical benefit for KB109, commented Dan Menichella, President and Chief Executive Officer of Kaleido. The study reveals that many patients with mild-to-moderate disease, and particularly those patients with a comorbidity, experience symptoms for a period of weeks. This study shows the significant burden experienced by these patients and we look forward to reporting the full dataset later this quarter.

These exciting and relevant data are in line with what we are seeing in the COVID-19 literature and suggests that the microbiome plays a role in this disease, said John P.Haran, M.D., Ph.D., associate professor of emergency medicine, microbiology &physiological systems and clinical director of the UMass Center for Microbiome Research at the University of Massachusetts Medical School. There is increasing evidence supporting the biological plausibility that microbiome restoration has a significant impact on different diseases and seeing an influence in COVID-19 patients with comorbidities aligns with this emerging science.

Summary of Interim Results

The K031 study of 350 subjects is fully enrolled with results expected in the first quarter of 2021. Topline data from a smaller 50 subject study of KB109 is also expected in the first quarter of 2021.

About the Potential Role of the Microbiome in COVID-19

COVID-19 infection has been associated with activation of an inappropriate inflammatory cascade, which in some patients can cause an abnormally aggressive immune response that can lead to pneumonia and respiratory failure. Metabolites such as short chain fatty acids (SCFAs) produced by the microbiome through utilization of glycans are modulators of the immune response and therefore could play a role in limiting this inflammatory cascade.

In preclinical models, increased SFCAs and/or SFCA-producing taxa, have been shown to influence immune pathways, mitigate immune pathology, and improve survival and morbidity associated with severe respiratory viral infections.1,2 Commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection.3

In-human data also support the role of SCFAs in reducing the impact of viral infections.In patients undergoing hematopoietic stem cell transplants who have contracted respiratory viral infections, including coronavirus, the presence of SCFA-producing taxa has been associated with a significantly reduced risk of progression to lower respiratory tract infections, which can have substantial morbidity in this patient population.4 KB109 is Generally Recognized as Safe (GRAS) and was selected for evaluation in these COVID-19 clinical studies based on its demonstrated ability to increase production of SCFAs as well as to promote commensal bacteria and reduce pathogenic bacteria ex vivo.

About Microbiome Metabolic Therapies (MMT)

Kaleidos Microbiome Metabolic Therapies, or MMTs, are designed to drive the function and distribution of the microbiomes existing microbes in order to decrease or increase the production of metabolites, or to advantage or disadvantage certain bacteria in the microbiome community. The Companys initial MMT candidates are targeted, synthetic glycans that are orally administered, have limited systemic exposure, and are selectively metabolized by enzymes in the microbiome.Kaleido utilizes its discovery and development platform to study MMTs in microbiome samples to rapidly advance MMT candidates rapidly into clinical studies in healthy subjects and patients. These human clinical studies are conducted under regulations supporting research with food, evaluating safety, tolerability and potential markers of effect. For MMT candidates that are further developed as therapeutics, the Company conducts clinical trials under an Investigational New Drug (IND) or regulatory equivalent outside the U.S., and in Phase 2 or later development.

AboutKaleido Biosciences

Kaleido Biosciencesis a clinical-stage healthcare company with a differentiated, chemistry-driven approach to targeting the microbiome to treat disease and improve human health. The Company has built a proprietary product platform to enable the rapid and cost-efficient discovery and development of novel Microbiome Metabolic Therapies (MMT).MMTs are designed to modulate the metabolic output and profile of the microbiome by driving the function and distribution of the guts existing microbes. Kaleido is advancing a broad pipeline of MMT candidates with the potential to address a variety of diseases and conditions with significant unmet patient needs. To learn more, visithttps://kaleido.com/.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the therapeutic potential of our MMT candidates, the timing of initiation, completion and reporting of results of clinical studies, and our strategy, business plans and focus. The words may, will, could, would, should, expect, plan, anticipate, intend, believe, estimate, predict, project, potential, continue, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on managements current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the breadth of our pipeline of product candidates, the strength of our proprietary product platform, the efficiency of our discovery and development approach, the fact that interim results from KB013 may not accurately predict final results from KB013 and that such final results may not support continued development of KB109, the clinical development and safety profile of our MMT candidates and their therapeutic potential, whether and when, if at all, our MMT candidates will receive approval from theU.S. Food and Drug Administration and for which, if any, indications, competition from other biotechnology companies, and other risks identified in ourSECfilings, including our most recent Form 10-Q, and subsequent filings with theSEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements.

Contacts Kaleido Biosciences William Duke, Jr. Chief Financial Officer 617-890-5772 william.duke@kaleido.com

Investors Mike Biega Solebury Trout 617-221-9660 mbiega@soleburytrout.com

Media Rich Allan Solebury Trout 646-378-2958 rallan@soleburytrout.com

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Kaleido Biosciences Announces Positive Interim Results of Controlled Study of KB109 in Patients with Mild-to-Moderate COVID-19 - BioSpace

Eton Pharmaceuticals Announces Acquisition of Canadian Rights for ALKINDI® SPRINKLE

DEER PARK, Ill., Jan. 14, 2021 (GLOBE NEWSWIRE) -- Eton Pharmaceuticals, Inc. (Nasdaq: ETON), a specialty pharmaceutical company focused on developing and commercializing innovative treatments for rare pediatric diseases, today announced that it has acquired Canadian rights to ALKINDI® SPRINKLE from Diurnal Group plc (LSE AIM: DNL). Eton Pharmaceuticals currently commercializes ALKINDI® SPRINKLE in the United States as a replacement therapy for Adrenocortical Insufficiency (AI) in children under 17 years of age.

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Eton Pharmaceuticals Announces Acquisition of Canadian Rights for ALKINDI® SPRINKLE

aTyr Pharma Announces Partner Kyorin Pharmaceutical, Co., Ltd. Completes Subject Visits for Phase 1 Trial of ATYR1923 in Japan

SAN DIEGO, Jan. 14, 2021 (GLOBE NEWSWIRE) -- aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, today announced that its partner Kyorin Pharmaceutical Co., Ltd., or Kyorin, a wholly owned subsidiary of Kyorin Holdings, Inc., has completed the last subject visit in its Phase 1 clinical trial of aTyr’s lead therapeutic candidate ATYR1923 (known as KRP-R120 in Japan). This achievement has triggered a milestone payment to aTyr.

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aTyr Pharma Announces Partner Kyorin Pharmaceutical, Co., Ltd. Completes Subject Visits for Phase 1 Trial of ATYR1923 in Japan

Cocrystal to Present at the 3rd Annual reimagine Health Research Symposium

BOTHELL, Wash., Jan. 14, 2021 (GLOBE NEWSWIRE) -- Cocrystal Pharma, Inc. (Nasdaq: COCP), (“Cocrystal” or the “Company”), a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication machinery of influenza viruses, the SARS-CoV-2 virus, hepatitis C viruses and noroviruses, announces that its President Sam Lee, Ph.D. will be making a presentation at the virtual 3rd Annual reimagine Health Research Symposium, University of Arizona College of Medicine, being held January 21, 2021.

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Cocrystal to Present at the 3rd Annual reimagine Health Research Symposium

Oncternal Therapeutics, Inc. Confirms Lentigen Technology, Inc. to Manufacture Lentiviral Vectors for Its ROR1-targeting CAR-T Cell Therapy Program

SAN DIEGO, Jan. 14, 2021 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced an agreement with Lentigen Technology, Inc. (“Lentigen”), a wholly-owned subsidiary of Miltenyi Biotec B.V. & Co. KG, to manufacture lentiviral vectors for Oncternal’s investigational ROR1-targeting CAR-T cell therapy program.

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Oncternal Therapeutics, Inc. Confirms Lentigen Technology, Inc. to Manufacture Lentiviral Vectors for Its ROR1-targeting CAR-T Cell Therapy Program

Lexicon Pharmaceuticals Provides Regulatory Update on Sotagliflozin in Heart Failure

THE WOODLANDS, Texas, Jan. 14, 2021 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced today that it has received U.S. Food and Drug Administration (FDA) regulatory feedback that the results of its SOLOIST and SCORED Phase 3 clinical studies can support a new drug application (NDA) submission for an indication to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure.

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Lexicon Pharmaceuticals Provides Regulatory Update on Sotagliflozin in Heart Failure

Grey Cloak Tech Fuel4Thought™ Migraine Formula Results Published in World Journal of Advanced Research and Reviews

Fuel4Thought™ proprietary formulation pilot study reduced the number of Migraine episodes by 39% and the average duration by 61% Fuel4Thought™ proprietary formulation pilot study reduced the number of Migraine episodes by 39% and the average duration by 61%

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Grey Cloak Tech Fuel4Thought™ Migraine Formula Results Published in World Journal of Advanced Research and Reviews

PDS Biotech Releases White Paper Detailing the Potential of the Versamune® Platform in Overcoming a Major Limitation of Immuno-Oncology

Promotes in-vivo tumor-attacking killer T-cells to facilitate cancer treatment Promotes in-vivo tumor-attacking killer T-cells to facilitate cancer treatment

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PDS Biotech Releases White Paper Detailing the Potential of the Versamune® Platform in Overcoming a Major Limitation of Immuno-Oncology