Events: ・・・ ※CICON 2019 Translating Science into Survival: MiNA Therapeutics. (9/25-28) ※Biotech in Europe Forum for Global Partnering & Investment: "Neuroscience - Development & Partnering Panel": (Panelists) Malcolm Weir, Sosei Heptares. (9/26 9:55-10:40) ※ESMO 2019: " First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 17:36 Presenting) ・Speakers: Debashis Sarker (Guy's and St. Thomas' Hospital NHS Trust, London, United Kingdom). ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 12:00 Presenting) ・Speakers: Mikael Sodergren (Imperial College London - Hammersmith Hospital, London, United Kingdom).
※ERS 2019: Industry Symposium (Organized by: Novartis): "Harnessing digital technology to improve the lives of patients with respiratory disease". (9/30 7:00-8:15) ※ERS 2019: "Late Breaking Abstract - Indacaterol/glycopyrronium versus salmeterol/fluticasone in chronic obstructive pulmonary disease: a meta-analysis on the protection against the risk of exacerbation". (9/30 Presenting) ※ERS 2019: "Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma". (9/30 Presenting) ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects". (9/30 Presenting) ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate as a fixed-dose combination in Japanese and Caucasian healthy subjects". (9/30 Presenting) ※ERS 2019: "Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study". (9/30 Presenting)
※ERS 2019: Industry Symposium (Organized by: Novartis): "The journey towards personalized medicine in asthma: where are we now? ". (9/30 17:15-19:15) ※ERS 2019: "Indacaterol/glycopyrronium/mometasone furoate combination consistently shows lung function benefits in patients with asthma". (10/1 Presenting) ※ERS 2019: "Efficacy and safety of once-daily low-dose indacaterol/mometasone via Breezhaler in symptomatic adult and adolescent patients with inadequately controlled asthma: Phase III randomised QUARTZ study". (10/1 Presenting) ※ERS 2019: "Mometasone furoate delivered via Breezhaler and Twisthaler in patients with asthma". (10/1 Presenting) ※ERS 2019: Industry Symposium (Organized by: Boehringer Ingelheim, GSK, Menarini Group, Mundipharma, Novartis, Teva, Vectura): "Joint ERS/Industry session: Time to be smarter about inhaler usage". (10/1 13:00-14:30)
※ClinicalTrials(NCT03100825): Phase 3, A Long-term Safety Study of QVM149 in Japanese Patients with Asthma. (8/26update, "Completed") ※ACS National Meeting："Discovery of HTL-0027772, their lead OX1 Receptor Antagonist for the Treatment of Addiction Disorders": Sosei Heptares. (8/28 Presented) ※Sosei Heptares：実験医学「コリン作動性ムスカリンM1およびM4受容体候補薬の精神・神経疾患における認知・行動・心理症状への作用」Drug Discovery Today誌(9/6)発表。(9/9) ※Vectura Interim Results 2019: QVM149(EU), Further Milestone of $5.0m on approval with low single-digit royalties from launch (2020). [2024 Consensus Sales]: Ultibro: $562m, Seebri: $122m, QVM149: $240m. (9/10) ※Sosei Heptares：インベスターR&D Day：英国から創薬研究の各部門の優秀な研究者たちが来日し熱く語りました。(動画) http://www.c-hotline.net/Viewer/Default/SOSE7e3faa78c98723a9b5c63252057bece1 (9/12)
※日刊薬業：「そーせい、収益性重視に転換 田村CEO」収益が見える形に経営戦略を切り替えた。現時点で自社創製品の販売は考えていない。リスクを一定程度抑えて、収益性が株主に評価されるよう努める考え。(9/12) ※ClinicalTrials(NCT03381274): Phase 1b/2, Oleclumab(MEDI9447) EGFRm NSCLC Novel Combination Study. (MEDI9447 with Osimertinib or AZD4635, AZD4635 with MEDI9447): Record Verification September 2019. (9/12update) ※Sosei Heptares：創薬「前臨床候補薬カルシトニン遺伝子関連ペプチド(CGRP)受容体拮抗薬HTL0022562の創薬」SCI/RSC Medicinal Chemistryシンポジウム(9/11)にて発表。(9/13) ※ClinicalTrials (NCT04089553): Phase 2, Study of AZD4635 in Patients with Prostate Cancer: Actual Start: August 29, 2019/8/29, Estimated Completion: 2021/3/18. ("New Trial Record", "Recruiting": 9/13up) ※ClinicalTrials (NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery. ("New Trial Record", "Recruiting": 9/13up)
※日刊薬業：「全ての開発品で導出交渉を行っている。もし全開発品を導出し尽くしたとしても、新規ターゲットを作れるので困らない」「当社の強みは低分子創薬だ。新規モダリティは提携すればいい」と述べた。(9/17) ※ClinicalTrials(NCT02740985): Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies: Record Verification September 2019. (9/17update) ※Discovery on Target: "Antagonists of the Adenosine 2a Receptor (AZD4635) to Reverse Tumor Suppression in the TME", "Targeting the Adenosine Pathway": Alwin Schuller, AstraZeneca. (9/17 Presented) ※Sosei Heptares Official Blog：「日刊薬業に当社会長兼社長CEO田村のインタビュー記事(9/17)が掲載」当社の強みであるGPCRをターゲットとした低分子創薬の可能性と今後の進捗を期待するパイプラインについて言及。(9/18up) ※ClinicalTrials(NCT03980821): Phase 1, Study of AZD4635 in Japanese Patients with Advanced Solid Malignancies: Research Site, Chuo-ku, Japan: "Recruiting". (9/18update)
※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Research Site, Texas: "Recruiting". (9/18 update) ※四季報：【急改善】マイルストーン収入に新規提携開始による一時金等収入も上乗せ。営業黒字転換。新規提携等牽引し収益改善持続。【進捗顕著】ジェネンテック、武田薬品と大型提携続く。新規提携さらに開拓。(9/19更新) ※ClinicalTrials(NCT03158311): Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (9/20update, " Completed ") ※ILCA 2019: "First-in-Human, First-in-Class Phase I Trial of MTL-CEBPA, a RNA Oligonucleotide Targeting the Transcription Factor C/EBP-α, Given as a Single Agent or in Combination with Sorafenib, in Patients with Advanced Hepatocellular Cance" (9/22 Presented) ・・・
※Sosei Heptares 5時間前：(9/24) “Prof. Pradeep Nathan and Dr. Geor Bakker from Sosei Heptares Experimental Medicine (Neuroscience) team were invited to be guest lecturers of an ExperimentalMedicine and Neuroimaging Course organized by the NIHRMaudsleyBRC”
Event update: ・・・ ※CICON 2019: CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, Translating Science into Survival: September 25th to 28th, 2019, Paris. Poster Session A "New Targets and Concepts": (9/26 18:30 Presenting ) “A213 / Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy”: ・Choon Ping TAN (MiNA Therapeutics Limited), Laura Sinigaglia (MiNA Therapeutics Limited), Siv A. Hegre (Norwegian University of Science and Technology, Trondheim, Norway), ・Alexandre Debacker (MiNA Therapeutics Limited), Albert Kwok (MiNA Therapeutics Limited), Pal Saetrom (Norwegian University of Science and Technology, Trondheim, Norway), ・Matthew Catley (MiNA Therapeutics Limited), David C Blakey (MiNA Therapeutics Limited), Nagy Habib (MiNA Therapeutics Limited).
Abstracts: Small activating RNAs (saRNAs) are short double-stranded oligonucleotides designed to upregulate target gene expression by transcriptional activation. saRNAs transfected into cells are loaded into Ago2 and translocate into the nucleus where they interact specifically at the target gene leading to recruitment and activation of RNA Polymerase II. This leads to new mRNA production resulting in upregulation of the target protein. We have developed a saRNA based therapeutic, MTL-CEBPA to target the expression of the CEBPA transcription factor. MTL-CEBPA has been shown to inhibit hepatocellular cancer tumor growth in preclinical models and to enhance the activity of immune checkpoint inhibitor drugs through impact on the tumor microenvironment. This is the first saRNA drug to enter clinical trials and we are investigating whether this technology could be applied to activate immune-stimulatory genes for utilization in cancer immunotherapy.
Using our proprietary algorithm we design saRNA sequences that bind to long non-coding RNA +2000 to -2000 nucleotides upstream or downstream from the transcriptional start site. saRNAs were designed and synthesized to target the IL23A, IL36g and OX40L transcripts. Double-stranded 19-nucleotide sequences from the algorithm for each target were added with mUmU overhangs at the 3’ ends of both strands to improve stability and reduce non-specific immunogenicity.
The saRNAs were screened in human (A549 and HepG2) or murine (CT26, BNL.1ME and RAW264.7) cells by transfection and mRNA levels of the target genes were measured by qPCR. The saRNA algorithm identified active saRNAs for all 3 targets leading to upregulation of target mRNA at 48 -72 hours post-transfection compared to oligonucleotide transfection controls. The levels of mRNA upregulation for each leading saRNA sequence from this screen were : IL23A (4.9 fold), IL36g (3.5 fold) and OX40L (6.7 fold). Sequence-dependent specificity of the lead saRNA were confirmed by switching the positions of 2 to 3 nucleotide residues in the seed portion of the sequences (nucleotides 2-8 in the anti-sense strand) which reduced induction of target mRNA compared to the parental saRNA sequence. The presence of increased target protein in saRNA transfected cells was confirmed either by immunofluorescence or ELISA. The heterodimeric IL23 cytokine is composed of the IL23A and IL12B subunit. We found that saRNA targeting IL23A expression increases IL12B expression indicating an increase of functional IL23. Furthermore, we observed that co-transfection of cells with a combination of IL23A and IL36g saRNA improved IL36g expression (from 3.5- fold with single IL36g saRNA to 13.1-fold with a combination of IL23A and IL36g saRNA). The induction of IL12B mRNA was also maintained using the combination of IL23A and IL36g saRNA.
In summary, we have demonstrated the ability of saRNA technology to upregulate immune-stimulatory targets for utilization in immunotherapy. We are currently optimizing formulation for delivery of the lead saRNAs for efficacy studies in preclinical tumor models.
※Molecular Pharmacology: "Modulators of CXCR4 and CXCR7/ACKR3 Function". (9/23 Published) ・Ilze Adlere 1, Birgit Caspar 2, Marta Arimont 3, Sebastian Dekkers 4, Kirsten Visser 3, Jeffrey Stuijt 3, Chris de Graaf 5, ・Michael Stocks 2, Barrie Kellam 2, Stephen Briddon 2, Maikel Wijtmans 3, Iwan de Esch 3, Stephen Hill 2, and Rob Leurs 3. 1. Griffin Discoveries BV; 2. University of Nottingham; 3. Vrije Universiteit Amsterdam; 4. School of Life Sciences, University of Nottingham; 5. Sosei Heptares Abstract: The two G protein-coupled receptors (GPCRs) C-X-C chemokine receptor type 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are part of the class A chemokine GPCR family and represent important drug targets for human immunodeficiency virus (HIV) infection, cancer and inflammation diseases. CXCR4 is one of only three chemokine receptors with an FDA approved therapeutic agent, the small molecule modulator AMD3100. In this review, known modulators of the two receptors are discussed in detail. Initially, the structural relationship between receptors and ligands is reviewed based on common structural motifs and available crystal structures. To this date, no atypical chemokine receptor has been crystallised making ligand design and predictions for these receptors more difficult. Next, the selectivity, receptor activation and the resulting ligand-induced signalling output of chemokines and other peptide ligands are reviewed. Binding of pepducins, a class of lipid-peptides based on the internal loop of a GPCR, to CXCR4 are also discussed. Finally, small-molecule modulators of CXCR4 and ACKR3 are reviewed. These modulators have furthermore led to the development of radio- and fluorescently labelled tool compounds, enabling the visualization of ligand binding and receptor characterisation, both in vitro and in vivo. Significance Statement: To investigate the pharmacological modulation of CXCR4 and ACKR3, significant effort has been focused on the discovery and development of a range of ligands, including small-molecule modulators, pepducins and synthetic peptides. Imaging tools, such as fluorescent probes, also play a pivotal role in the field of drug discovery. This review aims to provide an overview of the aforementioned modulators that facilitate the study of CXCR4 and ACKR3 receptors. ・・・
※Sosei Heptares：創薬「構造ベース創薬技術を用いたアロステリックな新規GLP-1受容体拮抗薬HTL26119の同定」Bioorganic & Medicinal Chemistry Letters誌(8/12)掲載。(8/13up) ※ClinicalTrials(NCT03100825): Phase 3, A Long-term Safety Study of QVM149 in Japanese Patients with Asthma. (8/26update, "Completed") ※ACS National Meeting："Discovery of HTL-0027772, their lead OX1 Receptor Antagonist for the Treatment of Addiction Disorders": Sosei Heptares. (8/28 Presented) ※Sosei Heptares：実験医学「コリン作動性ムスカリンM1およびM4受容体候補薬の精神・神経疾患における認知・行動・心理症状への作用」Drug Discovery Today誌(9/6)発表。(9/9) ※Vectura Interim Results 2019: QVM149(EU), Further Milestone of $5.0m on approval with low single-digit royalties from launch (2020). [2024 Consensus Sales]: Ultibro: $562m, Seebri: $122m, QVM149: $240m. (9/10) ※Sosei Heptares：インベスターR&D Day：英国から創薬研究の各部門の優秀な研究者たちが来日し熱く語りました。(動画) http://www.c-hotline.net/Viewer/Default/SOSE7e3faa78c98723a9b5c63252057bece1 (9/12) ※日刊薬業：「そーせい、収益性重視に転換 田村CEO」収益が見える形に経営戦略を切り替えた。現時点で自社創製品の販売は考えていない。リスクを一定程度抑えて、収益性が株主に評価されるよう努める考え。(9/12) ※ClinicalTrials(NCT03381274): Phase 1b/2, Oleclumab(MEDI9447) EGFRm NSCLC Novel Combination Study. (MEDI9447 with Osimertinib or AZD4635, AZD4635 with MEDI9447): Record Verification September 2019. (9/12update) ※Sosei Heptares：創薬「前臨床候補薬カルシトニン遺伝子関連ペプチド(CGRP)受容体拮抗薬HTL0022562の創薬」SCI/RSC Medicinal Chemistryシンポジウム(9/11)にて発表。(9/13)
※ClinicalTrials (NCT04089553): Phase 2, Study of AZD4635 in Patients with Prostate Cancer: Actual Start: August 29, 2019/8/29, Estimated Completion: 2021/3/18. ("New Trial Record", "Recruiting": 9/13up) ※ClinicalTrials (NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery. ("New Trial Record", "Recruiting": 9/13up) ※日刊薬業：「全ての開発品で導出交渉を行っている。もし全開発品を導出し尽くしたとしても、新規ターゲットを作れるので困らない」「当社の強みは低分子創薬だ。新規モダリティは提携すればいい」と述べた。(9/17) ※ClinicalTrials(NCT02740985): Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies: Record Verification September 2019. (9/17update) ※Discovery on Target: "Antagonists of the Adenosine 2a Receptor (AZD4635) to Reverse Tumor Suppression in the TME", "Targeting the Adenosine Pathway": Alwin Schuller, AstraZeneca. (9/17 Presented) ※Sosei Heptares Official Blog：「日刊薬業に当社会長兼社長CEO田村のインタビュー記事(9/17)が掲載」当社の強みであるGPCRをターゲットとした低分子創薬の可能性と今後の進捗を期待するパイプラインについて言及。(9/18up) ※ClinicalTrials(NCT03980821): Phase 1, Study of AZD4635 in Japanese Patients with Advanced Solid Malignancies: Research Site, Chuo-ku, Japan: "Recruiting". (9/18update) ※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Research Site, Texas: "Recruiting". (9/18 update) ※四季報：【急改善】マイルストーン収入に新規提携開始による一時金等収入も上乗せ。営業黒字転換。新規提携等牽引し収益改善持続。【進捗顕著】ジェネンテック、武田薬品と大型提携続く。新規提携さらに開拓。(9/19更新)
※ClinicalTrials(NCT03158311): Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (9/20update, " Completed ") ※ILCA 2019: "Phase I Trial of MTL-CEBPA, a RNA Oligonucleotide Targeting the Transcription Factor C/EBP-α, Given as a Single Agent or in Combination with Sorafenib, in Patients with Advanced Hepatocellular Cance" (9/22 Presented) ※Sosei Heptares：開発「国立衛生研究所(NIHR)モーズリーバイオメディカルリサーチセンターの実験医学および神経イメージングコースで、当社実験医学(神経科学)チームのPradeep Nathan教授とGeor Bakker博士が招かれ、特別講義(9/20)」(9/24up) ※Sosei Heptares：イベントカレンダー：今後のイベント：「2019年度第3四半期決算発表 2019/11/12」(9/24up) ・・・ ※Biotech in Europe Forum for Global Partnering & Investment: "Neuroscience - Development & Partnering Panel": (Panelists) Malcolm Weir, Executive Vice President & Chief R&D Officer, Sosei Heptares. (9/26 9:55-10:40) ※CICON 2019 Translating Science into Survival: "Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy", MiNA Therapeutics. (9/26 18:30 Presenting) ※ESMO 2019: " First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 17:36 Presenting) ・Speakers: Debashis Sarker (Guy's and St. Thomas' Hospital NHS Trust, London, United Kingdom). ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 12:00 Presenting) ・Speakers: Mikael Sodergren (Imperial College London - Hammersmith Hospital, London, United Kingdom). ・・・
※Biotech in Europe Forum for Global Partnering & Investment: "Neuroscience - Development & Partnering Panel": (Panelists) Malcolm Weir, Executive Vice President & Chief R&D Officer, Sosei Heptares. (9/26 9:55-10:40) ※European User Group Meeting: "Free Energy Perturbation for GPCR Structure-Based Drug Design": Francesca Deflorian and Chris de Graaf from Sosei Heptares. (9/26 14:00 Presenting) ※CICON 2019 Translating Science into Survival: "Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy", MiNA Therapeutics. (9/26 18:30 Presenting) ※ESMO 2019: " First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 17:36 Presenting) ・Speakers: Debashis Sarker (Guy's and St. Thomas' Hospital NHS Trust, London, United Kingdom). ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 12:00 Presenting) ・Speakers: Mikael Sodergren (Imperial College London - Hammersmith Hospital, London, United Kingdom). ※ERS 2019: "Lung Function Normalization with Indacaterol/Glycopyrronium/Mometasone Furoate in Patients with Asthma". (9/30 Presenting) ※ERS 2019: "Pharmacokinetics of Indacaterol, Glycopyrronium and Mometasone Furoate Following Once Daily Inhalation as a Fixed-Dose Combination in Healthy Subjects". (9/30 Presenting) ※ERS 2019: "Pharmacokinetics of Indacaterol, Glycopyrronium and Mometasone Furoate as a Fixed-Dose Combination in Japanese and Caucasian Healthy Subjects". (9/30 Presenting) ※ERS 2019: "Indacaterol/Glycopyrronium/Mometasone Furoate Combination Consistently Shows Lung Function Benefits in Patients with Asthma". (10/1 Presenting) ・・・
※Chris de Graaf 30分前: (9/25) "Rob Smith (Sosei Heptares) will present on 'Traversing and indexing chemically rich documentation with RDKit to aid GPCR-based Drug Discovery' at the RDKit UGM 2019 in Hamburg." ・RDKit UGM 2019: University of Hamburg, Faculty of Chemistry, Hamburg Germany, 25-27 September, 2019. ・(9/26 9:30-10:00 Presenting): "Traversing and indexing chemically rich documentation with RDKit to aid GPCR-based Drug Discovery": Rob Smith Sosei Heptares.
update: ・・・ ※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery. ("New Trial Record", "Recruiting": 9/13up) ※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Research Site, Texas: "Recruiting". (9/18 update)
※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery. (9/25 update) Brief Summary: (Change): 2 week after→"1 week after" This is a Phase 2a, 2-part study (designated Parts A and B) that will evaluate APP13007 dose strength and dosing frequency in a randomized double-masked fashion for comparison to the respective matching vehicle placebo. Part A will be conducted first to evaluate 0.05% APP13007 and matching vehicle placebo in an approximate 1:1 ratio in approximately 42 subjects who experience postoperative inflammation on the first day following routine, uncomplicated, cataract surgery and who meet all eligibility criteria. Based on the results of Part A, Part B of the study may be open for enrollment to evaluate 0.05% and/or 0.1% APP13007 at various dosing frequency in approximately 84 subjects, also in an approximate 1:1 ratio, active vs. placebo. In each Part, subjects will return periodically for study assessments during the treatment period and then for a follow-up visit approximately (2→"1")week after stopping the study drug. ・・・
※PharmaBiz, Argentina: "Novartis: Deal with Roemmers, Mature". (9/25) September 25, 2019 11:15 "The Swiss Novartis entrusted the Ultibro license to the national Roemmers group. The product, indicated for COPD, was renamed Enstrux and was under the umbrella of the Investi laboratory." The Swiss Novartis, which a semester ago had stopped promoting its Cardiometabolism portfolio in Argentina, continues to let go of its mature products. Now, as Pharmabiz learned, the multi licensed one of its medications enrolled in the Respiratory business to the Investi, owned by the Roemmers group. This is Ultibro, which is indicated for adults with COPD and after this deal was re-launched under the name of Enstrux. (View Site: https://enstrux.investi.com.ar ) The product had already been the protagonist of a similar agreement in Brazil. It was last June when Novartis sealed a partnership with the Indian Glenmark who granted the rights to sell Ultibro; Seebri; and Onbrize, in that country. In Argentina, Novartis also maintains an old-fashioned comarketing with the Gador who has Xoterna in its portfolio, a drug equivalent to Ultibro.
QVM149 update: ・・・ ※Vectura 2018 Preliminary Results：Ultibro in-Market Sales $512m(2018); EU Market Share 46%(2018). (3/26) ・QVM149 Filling H2 2019 (Submission Milestone $2.5m); QVM149 Launch 2020. ・[2024 Consensus Sales]: Ultibro: $632m, Seebri: $168m, QVM149: $238m. ※Novartis Q1 2019 Results: Ultibro BreezhalerSales"$104m", Seebr BreezhalerSales"$31m". (4/24) ・Expected Pipeline Milestones 2019: "QVM149 Asthma ( EU / JP ) Submissions: H2 2019"; Potential Blockbuster Launches 2020: "QVM149 Asthma". ※Sosei Heptares：喘息患者を対象として開発中の新規喘息治療配合吸入剤QVM149の第Ⅱ相臨床試験において新たに得られた有効性試験成績を発表。(5/22) ・新規の喘息治療配合吸入剤QVM149が既存の標準喘息治療吸入薬と比較し有意な改善を示した。・投与タイミングにかかわらない肺機能の改善も確認された。 ※Sosei Heptares：「新規の喘息治療配合吸入剤として開発中のQVM149について、医薬品販売承認を欧州医薬品庁へ申請」(5/24) ・医薬品販売承認申請の前倒し、当初2019年第4四半期に予定されていたこのMAA申請により、当社グループは、ノバルティス社より2.5百万米ドルのマイルストンを受領する。 ・QVM149は、現在、第Ⅲ/Ⅲb相臨床試験(IRIDIUMおよびARGON試験)を実施中であり、2019年第3四半期に完了する予定。 ※Vectura: ”Vectura receives $2.5m milestone payment for the European regulatory submission of QVM149”. (5/24) ・Further Milestone Payment of $5.0 million on European regulatory approval of the product and thereafter royalties on net sales from launch. ※Novartis: "Phase Ⅲ QUARTZ study of new investigational inhaled combination treatment QMF149 meets primary and key secondary endpoints in patients with inadequately controlled asthma" (5/30) ・QUARTZ is the first completed study of the phase III PLATINUM clinical development program which evaluates both QMF149 and QVM149. ・"The QMF149 results of the QUARTZ study complement the recently presented phase Ⅱ data of QVM149 at the ATS 2019, showing superiority of QVM149 to the current standard of care.
※ClinicalTrials(NCT03158311): Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (6/13update, "Active, No Longer Recruiting") ・Actual Enrollment: 1251→"1432 Participants", Estimated Primary Completion: 2019/6/21→"2019/6/28", Estimated Study Completion: 2019/6/28→"2019/7/5" ※ClinicalTrials(NCT02571777): Phase 3, Study to Compare the Efficacy and Safety of QVM149 With QMF149 in Patients With Asthma (IRIDIUM). ・Estimated Enrollment: 2980, Participants, Estimated Primary Completion: 2019/6/3, Estimated Study Completion: 2019/6/3.
※ClinicalTrials(NCT03100825): Phase 3, A Long-term Safety Study of QVM149 in Japanese Patients with Asthma. (8/26update, "Completed") ・Study Status: "Completed". Actual Enrollment: 94 → "96 Participants". Actual Study Completion: "2019/4/8". ※ClinicalTrials(NCT03100500): Phase 3, A Long-term Safety Study of QMF149 in Japanese Patients with Asthma. (8/26update, "Completed") ・Study Status: "Completed". Actual Enrollment: 51 Participants. Actual Study Completion: "2019/2/12". ※Trial Profile: Phase 3, study to compare the efficacy and safety of QVM149 with QMF149 in patients with asthma (IRIDIUM). (9/5update) ・05 Sep 2019, This study has been completed in Portugal. ※Trial Profile: Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (9/9update) ※Vectura Interim Results 2019: "Ultibro Maintaining Ex-US LAMA/LABA Class Leadership": EU Market Share: 44% (2Q19MAT). Ultibro in-Market Sales: $510m (2Q19MAT). [Potential Growth Catalysts]: China. (9/10) ・QVM149(EU), Further Milestone of $5.0m on Approval with low single-digit royalties from Launch (2020). [2024 Consensus Sales Estimates]: Ultibro: $562m, Seebri: $122m, QVM149: $240m. ※ClinicalTrials(NCT03158311): Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (9/20update, " Completed ") ・Overall Status: Active, not recruiting→"Completed". ・Primary Completion: 2019/6/28→"2019/7/12 [Actual]" ・Study Completion: 2019/7/5→"2019/7/19 [Actual]" ・Enrollment Patients: 1432→"1436 [Actual]"
↓ update: ※Trial Profile: Phase 3, study to compare the efficacy and safety of QVM149 with QMF149 in patients with asthma (IRIDIUM). (9/25update) ・24 Sep 2019, This trial has been completed in Slovenia.
※ERS (European Respiratory Society) International Congress 2019: Novartis. (9/30 Presenting, 10/1 Presenting) ※Novartis Q3 2019 Results: (10/22)
※Sosei Heptares：創薬「構造ベース創薬技術を用いたアロステリックな新規GLP-1受容体拮抗薬HTL26119の同定」Bioorganic & Medicinal Chemistry Letters誌(8/12)掲載。(8/13up) ※ClinicalTrials(NCT03100825): Phase 3, A Long-term Safety Study of QVM149 in Japanese Patients with Asthma. (8/26update, "Completed") ※ACS National Meeting："Discovery of HTL-0027772, their lead OX1 Receptor Antagonist for the Treatment of Addiction Disorders": Sosei Heptares. (8/28 Presented) ※RSC-BMCS / RSC-CICAG Artificial Intelligence in Chemistry: "Cheminformatics Driven GPCR Structure-Based Drug Design": Robert Smith and Chris de Graaf, Sosei Heptares. (9/2 Presented) ※Sosei Heptares：実験医学「コリン作動性ムスカリンM1およびM4受容体候補薬の精神・神経疾患における認知・行動・心理症状への作用」Drug Discovery Today誌(9/6)発表。(9/9) ※Sosei Heptares：創薬「GPCR構造ベース創薬における計算分子学的アプローチ」SCI/RSC Medicinal Chemistryシンポジウム(9/8)発表。(9/10up) ※Vectura Interim Results 2019: QVM149(EU), Further Milestone of $5.0m on approval with low single-digit royalties from launch (2020). [2024 Consensus Sales]: Ultibro: $562m, Seebri: $122m, QVM149: $240m. (9/10) ※Sosei Heptares：インベスターR&D Day：英国から創薬研究の各部門の優秀な研究者たちが来日し熱く語りました。(動画) http://www.c-hotline.net/Viewer/Default/SOSE7e3faa78c98723a9b5c63252057bece1 (9/12) ※日刊薬業：「そーせい、収益性重視に転換 田村CEO」収益が見える形に経営戦略を切り替えた。現時点で自社創製品の販売は考えていない。リスクを一定程度抑えて、収益性が株主に評価されるよう努める考え。(9/12) ※ClinicalTrials(NCT03381274): Phase 1b/2, Oleclumab(MEDI9447) EGFRm NSCLC Novel Combination Study. (MEDI9447 with Osimertinib or AZD4635, AZD4635 with MEDI9447): Record Verification September 2019. (9/12update) ※Sosei Heptares：創薬「前臨床候補薬カルシトニン遺伝子関連ペプチド(CGRP)受容体拮抗薬HTL0022562の創薬」SCI/RSC Medicinal Chemistryシンポジウム(9/11)にて発表。(9/13)
※ClinicalTrials (NCT04089553): Phase 2, Study of AZD4635 in Patients with Prostate Cancer: Actual Start: August 29, 2019/8/29, Estimated Completion: 2021/3/18. ("New Trial Record", "Recruiting": 9/13up) ※ClinicalTrials (NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery. ("New Trial Record", "Recruiting": 9/13up) ※日刊薬業：「全ての開発品で導出交渉を行っている。もし全開発品を導出し尽くしたとしても、新規ターゲットを作れるので困らない」「当社の強みは低分子創薬だ。新規モダリティは提携すればいい」と述べた。(9/17) ※ClinicalTrials(NCT02740985): Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies: Record Verification September 2019. (9/17update) ※Discovery on Target: "Antagonists of the Adenosine 2a Receptor (AZD4635) to Reverse Tumor Suppression in the TME", "Targeting the Adenosine Pathway": Alwin Schuller, AstraZeneca. (9/17 Presented) ※Sosei Heptares Official Blog：「日刊薬業に当社会長兼社長CEO田村のインタビュー記事(9/17)が掲載」当社の強みであるGPCRをターゲットとした低分子創薬の可能性と今後の進捗を期待するパイプラインについて言及。(9/18up) ※ClinicalTrials(NCT03980821): Phase 1, Study of AZD4635 in Japanese Patients with Advanced Solid Malignancies: Research Site, Chuo-ku, Japan: "Recruiting". (9/18update) ※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Research Site, Texas: "Recruiting". (9/18 update) ※四季報：【急改善】マイルストーン収入に新規提携開始による一時金等収入も上乗せ。営業黒字転換。新規提携等牽引し収益改善持続。【進捗顕著】ジェネンテック、武田薬品と大型提携続く。新規提携さらに開拓。(9/19更新) ※ClinicalTrials(NCT03158311): Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (9/20update, " Completed ") ※ILCA 2019: "Phase I Trial of MTL-CEBPA, a RNA Oligonucleotide Targeting the Transcription Factor C/EBP-α, Given as a Single Agent or in Combination with Sorafenib, in Patients with Advanced Hepatocellular Cance" (9/22 Presented)
※Sosei Heptares：開発「国立衛生研究所(NIHR)モーズリーバイオメディカルリサーチセンターの実験医学および神経イメージングコースで、当社実験医学(神経科学)チームのPradeep Nathan教授とGeor Bakker博士が招かれ、特別講義(9/20)」(9/24up) ※Sosei Heptares：イベントカレンダー：今後のイベント「2019年度第3四半期決算発表 (2019/11/12)」(9/24up) ※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Brief Summary (Change). (9/25 update) ・・・
Today Events: ※RDKit UGM 2019: "Traversing and Indexing Chemically Rich Documentation with RDKit to Aid GPCR-Based Drug Discovery": Rob Smith, Sosei Heptares. (9/26 Today 9:30-10:00 Presenting) ※Biotech in Europe Forum for Global Partnering & Investment: "Neuroscience - Development & Partnering Panel": (Panelists) Malcolm Weir, Executive Vice President & Chief R&D Officer, Sosei Heptares. (9/26 Today 9:55-10:40) ※European User Group Meeting: "Free Energy Perturbation for GPCR Structure-Based Drug Design": Francesca Deflorian and Chris de Graaf from Sosei Heptares. (9/26 Today 14:00 Presenting) ※CICON 2019 Translating Science into Survival: "Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy", MiNA Therapeutics. (9/26 Today 18:30 Presenting)
※ESMO 2019: " First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 17:36 Presenting) ・Speakers: Debashis Sarker (Guy's and St. Thomas' Hospital NHS Trust, London, United Kingdom). ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 12:00 Presenting) ・Speakers: Mikael Sodergren (Imperial College London - Hammersmith Hospital, London, United Kingdom).
※ERS 2019: Industry Symposium (Organized by: Novartis): "Harnessing digital technology to improve the lives of patients with respiratory disease". (9/30 7:00-8:15) ※ERS 2019: "Late Breaking Abstract - Indacaterol/glycopyrronium versus salmeterol/fluticasone in chronic obstructive pulmonary disease: a meta-analysis on the protection against the risk of exacerbation". (9/30 Presenting) ※ERS 2019: "Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma". (9/30 Presenting) ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects". (9/30 Presenting) ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate as a fixed-dose combination in Japanese and Caucasian healthy subjects". (9/30 Presenting) ※ERS 2019: "Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study". (9/30 Presenting) ※ERS 2019: Industry Symposium (Organized by: Novartis): "The journey towards personalized medicine in asthma: where are we now? ". (9/30 17:15-19:15) ※ERS 2019: "Indacaterol/glycopyrronium/mometasone furoate combination consistently shows lung function benefits in patients with asthma". (10/1 Presenting) ※ERS 2019: "Efficacy and safety of once-daily low-dose indacaterol/mometasone via Breezhaler in symptomatic adult and adolescent patients with inadequately controlled asthma: Phase III randomised QUARTZ study". (10/1 Presenting) ※ERS 2019: "Mometasone furoate delivered via Breezhaler and Twisthaler in patients with asthma". (10/1 Presenting) ※ERS 2019: Industry Symposium (Organized by: Boehringer Ingelheim, GSK, Menarini Group, Mundipharma, Novartis, Teva, Vectura): "Joint ERS/Industry session: Time to be smarter about inhaler usage". (10/1 13:00-14:30) ・・・
※RDKit UGM 2019: "Traversing and Indexing Chemically Rich Documentation with RDKit to Aid GPCR-Based Drug Discovery": Rob Smith, Sosei Heptares. (9/26 Today 9:30-10:00 Presented) ↓ ※RSC CICAG (Royal Society of Chemistry Chemical Information and Computer Applications Group) 1時間前: (9/26) "Next up today is Rob Smith talking on Traversing and Indexing Chemically Rich Documentation with RDKit to Aid GPCR-based Drug Discovery RDKitUGM2019."
※European User Group Meeting: "Free Energy Perturbation for GPCR Structure-Based Drug Design": Francesca Deflorian and Chris de Graaf from Sosei Heptares. (9/26 Today 14:00 Presenting) ↓ ※Chris de Graaf 24分前: (9/26) "Francesca Deflorian (Sosei Heptares) will present on 'Free Energy Perturbation for GPCR Structure-Based Drug Design' GPCR SBDD Schrodinger EUGM2019." ・19th Annual European User Group Meeting, Berlin, Germany, September 25-27, 2019. ・(9/26 14:00-14:30 Presenting): "Free Energy Perturbation for GPCR Structure-Based Drug Design": Francesca Deflorian and Chris de Graaf from Sosei Heptares.
MTL-CEBPA New Trial up: ・・・ ※ClinicalTrials (NCT04105335: MNA-3521-012): Phase 1, "A Study of MTL-CEBPA in Combination with a PD-1 Inhibitor in Patients with Advanced Solid Tumours (TIMEPOINT)". ("New Trial Record": 9/26up) [Official Title]: ・"An Open Label Phase 1a/b Study of MTL-CEBPA in Combination With a PD-1 Inhibitor (Pembrolizumab) in Adult Patients with Advanced Solid Tumours". [Intervention Model Description]: ・The principal objective of the first part of the study (Phase 1a) is to establish if a combination of an experimental drug (MTL-CEBPA) with pembrolizumab (PD-1 inhibitor) is safe and well-tolerated in patients with advanced solid tumours. ・Phase 1b will aim to confirm the doses of the drugs obtained in Phase 1a in a larger population and if it has potential to reduce the size of the tumour and/or extend the life of participants. [Study Status]: ・Record Verification: September 2019 ・Overall Status: "Not yet recruiting" ・Estimated Study Start: 2019/11/1 ・Estimated Primary Completion: 2021/12/31 ・Estimated Study Completion: 2022/6/30 ・Estimated Enrollment: 108 Participants. ・Last Update Posted: September 26, 2019
[Brief Summary]: This is an open label Phase 1a/1b study in patients who have advanced solid cancer tumours. Patients will receive MTL-CEBPA (an experimental drug) in combination with pembrolizumab (a drug which has been given approval for use for some tumour types). The Phase 1a dose escalation part of the study is designed to establish which doses of MTL-CEBPA are safe and well-tolerated when combined with the standard dose of pembrolizumab. Patients recruited to this part of the study will be those whose cancer progressed on standard treatment(s) or for whom no treatments are available. Phase 1b the dose expansion part of the study will further explore how safe and well-tolerated these two drugs are when combined and will assess if the combination of drugs could potentially reduce the size of tumours. Participants in this part of the study will receive the experimental drug (MTL-CEBPA) at a dose which is considered safe and well-tolerated based on data from the first part of the study (Phase 1a). Participants will remain in the study taking study drugs until either death, or they choose to withdraw from the study. [Detailed Description]: Phase 1a comprises three planned dose cohorts (ascending dose, 3+3 design, at the following dose levels: 70 mg/m2 QW, 98 mg/m2 QW, and 130 mg/m2 QW) of MTL-CEBPA combined with standard dose of pembrolizumab (given every 3 weeks). The aim is to assess the safety and tolerability of MTL-CEBPA in combination with pembrolizumab, recruiting patients whose disease progressed on standard of care therapy or for whom no therapy is available. In the first dose cohort the first participant enrolled will receive MTL-CEBPA treatment at the 70mg/m2 QW dose level. Pembrolizumab (200mg) will be administered on Day 2 of the first cycle and subsequently every 3 weeks whilst participant is on treatment. MTL-CEBPA and pembrolizumab will not be administered on the same day. Phase 1b of the study will further evaluate safety, tolerability, and assess the clinical activity of MTL-CEBPA and a PD-1 inhibitor (pembrolizumab) in combination. Participants will receive MTL-CEBPA at a dose considered most appropriate, with regards to safety, tolerability, and efficacy, for further development (based on data from Phase 1a of the study). Patients with the following (but not limited to) solid tumours will be specifically targeted: breast, lung, ovarian, pancreatic, gall bladder, HCC, neuroendocrine, and cholangiocarcinoma. ・・・
update: ・・・ ※Molecular Therapy: Nucleic Acids Vol. 18 December 2019: "Targeted Delivery of C/EBPα-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC". (8/22) ・Sorah Yoon 1, Kai-Wen Huang 2 3, Pinelopi Andrikakou 4, Daniel Vasconcelos 5, Piotr Swiderski 6, Vikash Reebye 5, Mikael Sodergren 4, Nagy Habib 4, John J.Rossi 1. 1. Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope. 2. Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital,. 3. Graduate Institute of Clinical Medicine, National Taiwan University. 4. Department of Surgery and Cancer, Imperial College London,. 5. MiNA Therapeutics, Ltd.. 6. DNA/RNA Synthesis Core Facility, Department of Molecular Medicine, Beckman Research Institute of City of Hope. ↓
※MiNA Therapeutics PUBLICATIONS: "Targeted Delivery of C/EBPa-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC". (9/26up) (Molecular Therapy: Nucleic Acids (2019) 18:143) Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies; it preferentially metastasizes to the liver and is the main cause of death from this disease. In previous studies, small activating RNA against CCAAT/enhancer-binding protein-α (C/EBPα-saRNA) demonstrated efficacy of PDAC in a local subcutaneous tumor model. In this study, we focused on the efficacy of C/EBPα-saRNA in advanced stage PDAC. For targeted delivery, we selected a new anti-transferrin receptor aptamer (TR14), which demonstrated a high binding affinity to target proteins. The TR14 aptamer was internalized with clathrin-mediated endocytosis, distributed in early endosome, late endosome, and lysosome subcellularly. To investigate its anti-tumor effects to advanced PDAC, we conjugated C/EBPα-saRNA to TR14. Treatment of pancreatic cancer cells with the conjugates upregulated expression of C/EBPα and its downstream target p21, and inhibited cell proliferation. For in vivo assays, we established an advanced PDAC mouse model by engrafting luciferase reporter-PANC-1 cells directly into the livers of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After treatment of aptamer-C/EBPα conjugates, we observed significant reduction of tumor growth in this advanced PDAC mouse model. Combinational treatment of the conjugates with gemcitabine also demonstrated enhanced anti-tumor effects in advanced PDAC. This suggests that aptamer-C/EBPα conjugates could be used as an adjuvant, along with other conventional anti-cancer drugs in advanced PDAC. In conclusion, targeted delivery of C/EBPα-saRNAs by aptamers might have potential therapeutic effects in advanced PDAC. ・・・ https://www.cell.com/action/showPdf?pii=S2162-2531%2819%2930230-6
ちなみに ※ERS Publications: "ERS International Congress 2019", Programme update. (8/10up) ・ERS 2019: Industry Symposium (Organized by: Novartis): "Harnessing digital technology to improve the lives of patients with respiratory disease". (9/30 7:00-8:15) ・ERS 2019: "Late Breaking Abstract - Indacaterol/glycopyrronium versus salmeterol/fluticasone in chronic obstructive pulmonary disease: a meta-analysis on the protection against the risk of exacerbation". (9/30 Presenting) ・ERS 2019: "Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma". (9/30 Presenting) ・ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects". (9/30 Presenting) ・ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate as a fixed-dose combination in Japanese and Caucasian healthy subjects". (9/30 Presenting) ・ERS 2019: "Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study". (9/30 Presenting) ・ERS 2019: Industry Symposium (Organized by: Novartis): "The journey towards personalized medicine in asthma: where are we now? ". (9/30 17:15-19:15) ・ERS 2019: "Indacaterol/glycopyrronium/mometasone furoate combination consistently shows lung function benefits in patients with asthma". (10/1 Presenting) ・ERS 2019: "Efficacy and safety of once-daily low-dose indacaterol/mometasone via Breezhaler in symptomatic adult and adolescent patients with inadequately controlled asthma: Phase III randomised QUARTZ study". (10/1 Presenting) ・ERS 2019: "Mometasone furoate delivered via Breezhaler and Twisthaler in patients with asthma". (10/1 Presenting) ・ERS 2019: Industry Symposium (Organized by: Boehringer Ingelheim, GSK, Menarini Group, Mundipharma, Novartis, Teva, Vectura): "Joint ERS/Industry session: Time to be smarter about inhaler usage". (10/1 13:00-14:30) ・・・ ↓
※Fraunhofer ITEM: Events up: "ERS International Congress 2019". (9/26up) ・Congress 2019/9/28-10/02. ・Congress of the European Respiratory Society.
This year’s international congress of the European Respiratory Society will be held in Madrid (Spain) from September 28 to October 2, 2019. Over 20,000 respiratory professionals from all over the world meet at this congress each year. In a broad range of oral and poster presentations, Fraunhofer ITEM will present selected projects from its respiratory research.
Our poster presentations: "Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma" ・Authors: Kenneth R. Chapman, Henrik Watz, Jutta Beier, Dave Singh, Jens Hohlfeld, Zuzana Diamant, Veronika Scholz, Ieuan Jones, Ruobing Li, Pascale Pinot, Hanns-Christian Tillmann. ・Session: Clinical studies of asthma treatments (thematic poster) ・Date and time: September 30, 2019, 12.50 AM-2.40 PM ・Location: TP-15
"Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: the CLAIM study“ ・Authors: Andreas Voskrebenzev, Till Kaireit, Filip Klimeš, Gesa Pöhler, Lea Behrendt, Korbinian Berschneider, Frank Wacker, Tobias Welte, Jens Hohlfeld, Jens Vogel-Claussen. ・Session: COPD clinical studies: bronchodilators, corticosteroids and more (poster discussion) ・Date and time: September 30, 2019, 2.45-4.45 PM ・Location: 6D
Today Event: ※ESMO 2019: " First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 17:36 Presenting) ・Speakers: Debashis Sarker (Guy's and St. Thomas' Hospital NHS Trust, London, United Kingdom).
Abstract up ※ESMO 2019 Presentation Number: 455PD: "First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)" ・Speakers: Debashis Sarker (Guy's and St. Thomas' Hospital NHS Trust, London, United Kingdom). ・(9/28 17:36 Presenting) Background: MTL-CEBPA is a first-in-class small activating RNA (saRNA) oligonucleotide which specifically up-regulates the myeloid cell master regulator, C/EBP-α (CCAAT/enhancer-binding protein alpha). Methods We conducted a phase I, 3 + 3 dose escalation and dose expansion trial of MTL-CEBPA in adults with HCC or secondary liver cancer. Patients received intravenous MTL-CEBPA at 28-160 mg/m2 for 3 weeks either QW, BIW at d1 and d2, BIW at d1 and d3, or TIW at d1, d2, and d3 followed by a rest period of 1 week. Adverse events (AEs), serum PK, WBC biomarkers and anti-tumour activity were assessed. Results: 38 participants (31 HCC, 4 colorectal, 2 fibrolamellar, 1 ampullary) have been treated across 6 dose levels (28-160 mg/m2) and 3 dosing schedules: 29M/9F, median age 66 years (range 27 - 80), ECOG PS 0/1: 16/22. In 28 HCC patients evaluable for efficacy, PR was achieved in 1 pt, SD > 1 year in 1 patient and SD < 1 year in 11 pts. After discontinuation of MTL-CEBPA, four sorafenib- naïve HCC patients were treated with sorafenib; 3/4 had durable CR (14, 12 and 9 months) and 1/4 had PR [6 months] by RECIST 1.1. Treatment-related adverse events (all grades) that occurred in more than 10% of patients were fatigue (23.7%), thrombocytopaenia (13.2%), anaemia (13.2%), elevated AST (13.2%), elevated ALP (10.5%), hypoalbuminaemia (10.5%), increased ALT (10.5%) and increased bilirubin (10.5%); no maximum dose was reached in any dosing cohorts. Target engagement was evidenced in evaluable patients by a significant 1.5 fold increase in CEBPA mRNA in WBC and a significant increase in WBC count consistent with C/EBP-α dependent granulopoiesis. Altered immunological markers were observed in WBC of one patient including decreased levels of ADA, PD-L1 and CXCR4 mRNA. Conclusions: MTL-CEBPA is a first-in-class therapy targeting the myeloid cell master regulator C/EBP-α. In HCC patients MTL-CEBPA demonstrated a good safety profile, induced altered gene expression in WBC and as well as anti-tumour activity. These encouraging phase I data validate targeting of CEBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC. Clinical trial identification: NCT02716012. Legal entity responsible for the study: MiNA Therapeutics. Funding: MiNA Therapeutics.
・・・ ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 12:00 Presenting) ・Speakers: Mikael Sodergren (Imperial College London - Hammersmith Hospital, London, United Kingdom). Presentation Number: 1230P. Abstract: Background: MTL-CEBPA is a myeloid modifier saRNA therapy which upregulates CEBPalpha and is the first saRNA therapy to enter clinical trials. We hypothesise that targeting myeloid-derived suppressor cells (MDSCs) with MTL-CEBPA and T cells with PD-1 antibody may enhance the therapeutic efficacy of each individual therapy. Methods: CT26 syngeneic mice were randomised into 4 groups (n = 10) and treated with vehicle control, PD-1 antibody (10mg/kg, i.p., d1/d4 schedule, 7 doses), MTL-CEBPA (5mg/kg, i.v, d1/d3 schedule, 7 doses) or a combination of both compounds. RNA extracted from tumours at termination were analysed by Nanostring IO360 and myeloid innate immunity codeset. Results: At 21 days of treatment, the average tumonur volumes in the MTL-CEBPA/PD-1 treated group were smallest and 3.0-fold smaller (p < 0.05) than the closest group. Nanostring analysis shows that only tumours from the combination group display significant increase in tumour infiltrating lymphocytes (2.4-fold versus control, p < 0.05) and pathway analysis reveals that 5 of the 6 tumours in this group have the highest increase in expression of genes for various immune pathways including lymphoid compartment, antigen presentation and cytotoxicity when compared against all tumour samples. At the level of individual genes, we observed synergy in gene expression changes in combination of PD-1 antibody and MTL-CEBPA as illustrated in table.Table: 1230P Individual genes that show synergistic effect. Calcilated as fold versus vehicle control. p < 0.05 and ** p < 0.01. PD-1 mAb MTL-CEBPA Combination ･･･ Conclusions: The study indicates enhanced anti-tumour activity when combining MTL-CEBPA with PD-1 antibody in the immunocompetent mouse CT26 colorectal cancer model. The combination treatment appears to result in increased penetration of TILs through modulation of immune activity in the tumour microenvironment. Legal entity responsible for the study: MiNA Therapeutics. Funding: MiNA Therapeutics.
Events update: ※RNA Therapeutics Conference: "SMi Group announces the 11th Annual RNA Therapeutics Conference in London on February 19th - 20th 2020". (9/27up) The field of RNA therapeutics is rapidly expanding, and the potential for using RNA drugs for personalised medicines and immunotherapy, as well as to address genetic, infectious and chronic diseases will ensure the continued development of RNA therapeutics for years to come. The global antisense and RNA therapeutics market size is expected to expand at a compound annual growth rate (CAGR) of 8.6% between 2019 and 2025, when it is projected to reach $1.81 billion. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. ・・・ David Blakey, Chief Scientific Officer, MiNA Therapeutics: (2020/2/19 13:20-14:00 Presenting) "SMALL ACTIVATING RNAS(SARNAS) - A NOVEL THERAPEUTIC CLASS OF OLIGONUCLEOTIDES WITH BROAD THERAPEUTIC POTENTIAL": ・Description of saRNA technology and broad applicability to a range of therapeutic targets. ・Update on MiNA’s lead saRNA product MTL-CEBPA - preclinical and clinical data. ・Emerging data on new therapeutic strategies with saRNAs.
※Sosei Heptares：創薬「構造ベース創薬技術を用いたアロステリックな新規GLP-1受容体拮抗薬HTL26119の同定」Bioorganic & Medicinal Chemistry Letters誌(8/12)掲載。(8/13up) ※ClinicalTrials(NCT03100825): Phase 3, A Long-term Safety Study of QVM149 in Japanese Patients with Asthma. (8/26update, "Completed") ※ACS National Meeting："Discovery of HTL-0027772, their lead OX1 Receptor Antagonist for the Treatment of Addiction Disorders": Sosei Heptares. (8/28 Presented) ※Sosei Heptares：実験医学「コリン作動性ムスカリンM1およびM4受容体候補薬の精神・神経疾患における認知・行動・心理症状への作用」Drug Discovery Today誌(9/6)発表。(9/9) ※Vectura Interim Results 2019: QVM149(EU), Further Milestone of $5.0m on approval with low single-digit royalties from launch (2020). [2024 Consensus Sales]: Ultibro: $562m, Seebri: $122m, QVM149: $240m. (9/10) ※Sosei Heptares：インベスターR&D Day：英国から創薬研究の各部門の優秀な研究者たちが来日し熱く語りました。(動画) http://www.c-hotline.net/Viewer/Default/SOSE7e3faa78c98723a9b5c63252057bece1 (9/12) ※日刊薬業：「そーせい、収益性重視に転換 田村CEO」収益が見える形に経営戦略を切り替えた。現時点で自社創製品の販売は考えていない。リスクを一定程度抑えて、収益性が株主に評価されるよう努める考え。(9/12) ※ClinicalTrials(NCT03381274): Phase 1b/2, Oleclumab(MEDI9447) EGFRm NSCLC Novel Combination Study. (MEDI9447 with Osimertinib or AZD4635, AZD4635 with MEDI9447): Record Verification September 2019. (9/12update)
※Sosei Heptares：創薬「前臨床候補薬カルシトニン遺伝子関連ペプチド(CGRP)受容体拮抗薬HTL0022562の創薬」SCI/RSC Medicinal Chemistryシンポジウム(9/11)にて発表。(9/13) ※ClinicalTrials (NCT04089553): Phase 2, Study of AZD4635 in Patients with Prostate Cancer: Actual Start: August 29, 2019/8/29, Estimated Completion: 2021/3/18. ("New Trial Record", "Recruiting": 9/13up) ※ClinicalTrials (NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery. ("New Trial Record", "Recruiting": 9/13up) ※日刊薬業：「全ての開発品で導出交渉を行っている。もし全開発品を導出し尽くしたとしても、新規ターゲットを作れるので困らない」「当社の強みは低分子創薬だ。新規モダリティは提携すればいい」と述べた。(9/17) ※ClinicalTrials(NCT02740985): Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies: Record Verification September 2019. (9/17update) ※Discovery on Target: "Antagonists of the Adenosine 2a Receptor (AZD4635) to Reverse Tumor Suppression in the TME", "Targeting the Adenosine Pathway": Alwin Schuller, AstraZeneca. (9/17 Presented) ※Sosei Heptares Official Blog：「日刊薬業に田村CEOのインタビュー記事(9/17)が掲載」低分子創薬の可能性と今後の進捗を期待するパイプラインについて言及。https://drive.google.com/file/d/14EeBcYMnB1EsRbrwsaLzxzZLzDTQdDrH (9/18up) ※ClinicalTrials(NCT03980821): Phase 1, Study of AZD4635 in Japanese Patients with Advanced Solid Malignancies: Research Site, Chuo-ku, Japan: "Recruiting". (9/18update)
※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Research Site, Texas: "Recruiting". (9/18 update) ※四季報：【急改善】マイルストーン収入に新規提携開始による一時金等収入も上乗せ。営業黒字転換。新規提携等牽引し収益改善持続。【進捗顕著】ジェネンテック、武田薬品と大型提携続く。新規提携さらに開拓。(9/19更新) ※ClinicalTrials(NCT03158311): Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (9/20update, " Completed ") ※ILCA 2019: "Phase I Trial of MTL-CEBPA, a RNA Oligonucleotide Targeting the Transcription Factor C/EBP-α, Given as a Single Agent or in Combination with Sorafenib, in Patients with Advanced Hepatocellular Cance" (9/22 Presented) ※Sosei Heptares：開発「国立衛生研究所(NIHR)モーズリーバイオメディカルリサーチセンターの実験医学および神経イメージングコースで、当社実験医学(神経科学)チームのPradeep Nathan教授とGeor Bakker博士が招かれ、特別講義(9/20)」(9/24up) ※Sosei Heptares：イベントカレンダー：今後のイベント：「2019年度第3四半期決算発表 2019/11/12」(9/24up) ※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Brief Summary (Change). (9/25 update) ※RDKit UGM 2019: "Traversing and Indexing Chemically Rich Documentation with RDKit to Aid GPCR-Based Drug Discovery": Rob Smith, Sosei Heptares. (9/26 Presented)
※European User Group Meeting: "Free Energy Perturbation for GPCR Structure-Based Drug Design": Francesca Deflorian and Chris de Graaf from Sosei Heptares. (9/26 Presented) ※Biotech in Europe Forum for Global Partnering & Investment: "Neuroscience - Development & Partnering Panel": (Panelists) Malcolm Weir, Executive Vice President & Chief R&D Officer, Sosei Heptares. (9/26) ※CICON 2019 Translating Science into Survival: "Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy", MiNA Therapeutics. (9/26 Presented) ※ClinicalTrials (NCT04105335: MNA-3521-012): Phase 1, "A Study of MTL-CEBPA in Combination with a PD-1 Inhibitor in Patients with Advanced Solid Tumours (TIMEPOINT)". ("New Trial Record", "Not yet recruiting": 9/26up) ※MiNA Therapeutics PUBLICATIONS: "Targeted Delivery of C/EBPa-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC". (9/26up) ※薬事日報：【そーせいグループ】GPCR創薬で他社導出し、製薬大手が行う創薬にも手を貸す。「26年までに次の収入源を、次の収入源を作っていきたい」と目標を掲げた。(9/27) ※ESMO 2019: " First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 Presented) ・・・
First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 Presented)
After discontinuation of MTL-CEBPA, HCC patients were treated with sorafenib; 3/4 had durable CR (14, 12 and 9 months) and 1/4 had PR [6 months] by RECIST 1.1.
・・・ ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 12:00 Presenting) ※ERS 2019: Industry Symposium (Organized by: Novartis): "Harnessing digital technology to improve the lives of patients with respiratory disease". (9/30 7:00-8:15) ※ERS 2019: "Late Breaking Abstract - Indacaterol/glycopyrronium versus salmeterol/fluticasone in chronic obstructive pulmonary disease: a meta-analysis on the protection against the risk of exacerbation". (9/30 Presenting) ※ERS 2019: "Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma". (9/30 Presenting) ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects". (9/30 Presenting) ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate as a fixed-dose combination in Japanese and Caucasian healthy subjects". (9/30 Presenting) ※ERS 2019: "Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study". (9/30 Presenting) ※ERS 2019: Industry Symposium (Organized by: Novartis): "The journey towards personalized medicine in asthma: where are we now? ". (9/30 17:15-19:15) ※ERS 2019: "Indacaterol/glycopyrronium/mometasone furoate combination consistently shows lung function benefits in patients with asthma". (10/1 Presenting) ※ERS 2019: "Efficacy and safety of once-daily low-dose indacaterol/mometasone via Breezhaler in symptomatic adult and adolescent patients with inadequately controlled asthma: Phase III randomised QUARTZ study". (10/1 Presenting) ※ERS 2019: "Mometasone furoate delivered via Breezhaler and Twisthaler in patients with asthma". (10/1 Presenting) ※ERS 2019: Industry Symposium (Organized by: Boehringer Ingelheim, GSK, Menarini Group, Mundipharma, Novartis, Teva, Vectura): "Joint ERS/Industry session: Time to be smarter about inhaler usage". (10/1 13:00-14:30)
※EMBO Workshop Tools for Structural Biology of Membrane Proteins: Jana Broecker, Sosei Heptares. (10/7 14:30-15:00 Presenting) ※BioJapan2019：JITSUBO出展：最先端ペプチド合成技術、Molecular Hivingの最新情報を紹介。(10/9-11) ※OTS 2019: "Late Breaking Talk: Activation of CEBPA in Myeloid Cells by saRNA in HCC Patients: The Emergence of an Immunomodulatory Switch for Anti-Cancer Therapy": Nagy Habib. (10/16 16.25-16.40 Presenting) ※Novartis Q3 2019 Results. (10/22) ※AstraZeneca Q3 2019 Results. (10/24) ※AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics: "Identification of Small Activating RNAs that can Upregulate Immune Activation Tagets for Cancer Immunotherapy": David Blakey, MiNA Therapeutics. (10/2912:30 Presenting) ※Medicinal Chemistry & Protein Degradation Summit: "RI Revitalises Drug Discovery & Drives AI": Jonthan Mason, Sosei Heptares. (10/28 15:00-16:00 Presenting) ※ERNEST First Meeting GPCR Pharmacology: Activation, Signalling and Drug Design: Invited Speakers: Chris Tate (MRC); Chris De Graaf (Sosei Heptares). Meeting Sponsored: Sosei Heptares. (10/28-30) ※DIA Oligonucleotide-Based Therapeutics Conference: "MTL-CEBPA, The First Small Activating RNA Therapy in Clinical Development": Nagy Habib, MiNA Therapeutics. (10/29 11:30-12:00 Presenting) ※Pfizer Q3 2019 Results. (10/29) ※MorphoSys Q3 2019 Interim Statement. (10/29)
※ERS 2019: "Late Breaking Abstract - Indacaterol/glycopyrronium versus salmeterol/fluticasone in chronic obstructive pulmonary disease: a meta-analysis on the protection against the risk of exacerbation". (9/30 12:50 Presenting) Abstract: Background: FLAME and other trials evaluated the effect of indacaterol/glycopyrronium (IND/GLY) vs salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD). Aims and objectives: A meta-analysis (MA) to assess the efficacy of IND/GLY vs SFC in reducing the risk of acute COPD exacerbation (AECOPD) was performed and the impact of some variables was evaluated by meta-regression. Methods: Primary outcome of the MA was the effect of IND/GLY vs SFC on the risk of AECOPD. OpenMetaAnalyst was used to perform pair-wise MA and meta-regression analysis; the statistical significance was set at p<0.05. Results: Four randomized clinical trials comparing IND/GLY 50/110 ug QD vs SFC 50/500 ug BID in COPD were identified. IND/GLY was significantly more effective than SFC in reducing the risk of AECOPD (RR 0.84 95%CI 0.72–0.99) (figure 1). Study duration (coefficient 0.008 95%CI 0.001–0.014), history of AECOPD (coefficient 0.320 95%CI 0.044–0.595), and duration of run-in period (coefficient 0.086 95%CI 0.009–0.164) significantly modulated the protective effect, but only considering all AECOPD combined. Conclusions: The MA showed that IND/GLY was significantly more effective than SFC in reducing the overall risk of AECOPD. Run-in period in the FLAME study did not improve the effect of IND/GLY compared with shorter or no run-in studies.
※ERS 2019: "Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma". (9/30 12:50 Presenting) Abstract: Introduction: Indacaterol (IND, LABA), glycopyrronium (GLY, LAMA) and mometasone furoate (MF, ICS) have been formulated as a once-daily (o.d.) fixed-dose combination therapy (IND/GLY/MF) delivered via the Breezhaler device for the treatment of asthma. We report data from two Phase II studies (B2208 and B2209). Methods: Both studies had a randomized, double-blind, 3-period crossover design. B2208 included 116 adult patients with moderate-to-severe asthma (on LABA/ICS, FEV1 %predicted <80%), comparing IND/GLY/MF o.d. 150/50/160 μg (high-dose ICS) and 150/50/80 μg (medium-dose ICS) with twice-daily high-dose salmeterol/fluticasone (S/F [LABA/ICS], 50/500 μg) over 21 days. B2209 included 37 adult patients with mild-to-moderate asthma (on low- or medium-dose ICS, FEV1 %predicted ≥60－<100%), comparing medium-dose IND/GLY/MF with placebo over 14 days. Results: In B2208, 44.6% and 47.3% of patients on high- or medium-dose IND/GLY/MF, respectively, achieved near-normal lung function (FEV1 [AUC0–24h] ≥80% of predicted normal) compared with 34.4% with S/F (p<0.05 for both comparisons). In B2209, 48.4% of patients on medium-dose IND/GLY/MF achieved normal lung function (FEV1 [AUC0–24h] ≥90% of predicted normal) vs 6.7% on placebo. The odds ratio (OR) (95% CI) of being rescue medication free was 1.87 (1.03, 3.41) and 1.44 (0.80, 2.59) when treated with high- or medium-dose IND/GLY/MF, respectively, compared with S/F (B2208). The OR (95% CI) was 11.51 (3.77, 35.14) for medium-dose IND/GLY/MF vs placebo (B2209). Conclusion: Patients with asthma are more likely to achieve normal or near-normal lung function and to remain rescue medication free with IND/GLY/MF compared with high-dose S/F or placebo. Poster: https://ers-eposter.key4events.com/145/66458.pdf
※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects". (9/30 12:50 Presenting) Abstract: Background: Indacaterol (IND [LABA]), is co-formulated with glycopyrronium (GLY [LAMA]), and mometasone furoate (MF [ICS]) as a once daily (o.d.) fixed dose combination (IND/GLY/MF) delivered with the Breezhaler device for maintenance treatment of asthma. We evaluated the steady-state plasma pharmacokinetics (PK) of IND, GLY and MF following inhalation of IND/GLY/MF o.d. Methods: This was a randomised, open-label, four-way crossover study. Subjects received IND/GLY/MF 150/50/160 μg (high-dose ICS), IND 150 µg, GLY 50 µg or MF 190 µg (in vitro fine particle mass comparable to 160 μg MF in IND/GLY/MF) via the Breezhaler device, o.d. for 14 days in each period, with a washout of at least 7 days. PK was characterised on Day 14 up to 24h post-dose. Results: In total 36 healthy subjects were randomised. For IND, the geometric mean ratios (GMR) [90% CI] for AUC0-24h,ss and Cmax,ss were 0.922 [0.878, 0.969] and 1.02 [0.967, 1.08], respectively, for IND/GLY/MF vs IND monotherapy. For GLY, the GMR [90% CI] for AUC0-24h,ss and Cmax,ss were 0.986 [0.944, 1.03] and 1.21 [1.09, 1.34], respectively for IND/GLY/MF vs. GLY. For MF, the GMR [90% CI] for AUC0-24h,ss and Cmax,ss were 1.16 [1.09, 1.24] and 1.17 [1.09, 1.25], respectively for IND/GLY/MF vs. MF. Similar systemic exposure was noted for IND/GLY/MF vs. monotherapy comparison for all monocomponents, indicating a lack of PK interaction. Multiple inhaled doses of IND, GLY and MF were safe and well tolerated, when administered alone or in combination. Conclusion: There was no clinically relevant pharmacokinetic interaction between IND, GLY and MF when administered as IND/GLY/MF. Poster: https://ers-eposter.key4events.com/145/66946.pdf
※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate as a fixed-dose combination in Japanese and Caucasian healthy subjects". (9/30 12:50 Presenting) Abstract: Background: A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler device (IND/GLY/MF) is being developed for treatment of asthma. We compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d. Methods: This was a single-centre, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 μg (medium-dose ICS) or 150/50/160 μg o.d. (high-dose ICS) for 14 days in each period. Pharmacokinetics were characterised for 24h post-dose on Days 1 and 14. Results: In total, 16 Japanese (median age 31 years [range:20-40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range:21-43 years], mean weight 75.0 kg) were randomised. Geometric mean ratios (Japanese/Caucasian) for Cmax for IND, GLY and MF at the high dose on Day 14 were 1.31, 1.38 and 1.07, respectively. Those for AUC0-24h on Day 14 for IND, GLY and MF (Japanese/Caucasian) at the high dose were 1.17, 1.05 and 1.15, respectively. Similar trends were noted for all mono-components for the medium-dose treatment. IND/GLY/MF was safe and well tolerated; no study drug-related AEs were observed. Conclusion: Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as fixed-dose combination were comparable between Japanese and Caucasian subjects. IND/GLY/MF was safe and well tolerated in both ethnic groups. These results confirm that no dose adjustment for IND/GLY/MF is required in Asian population. Poster: https://ers-eposter.key4events.com/145/66928.pdf
※ERS 2019: "Lung function, pharmacokinetics, and tolerability of indacaterol maleate and acetate in asthma patients". (9/30 12:50 Presenting) Abstract: Background: In the development of indacaterol (IND)/glycopyrronium/mometasone FDC for asthma, the maleate salt of IND was replaced by acetate to avoid post-inhalation cough. We investigated lung function, PK, and safety/tolerability of the two IND salt forms in patients with asthma. Methods: This was a randomized, double-blind, three-period cross-over study. Adult asthma patients with percentage predicted pre-bronchodilator FEV1 ≥50% and ≤90% received IND maleate 150µg od, IND acetate 150µg od and placebo on top of stable background ICS in randomised sequence. Primary endpoint was trough FEV1 after 14 days of treatment. Plasma PK were assessed at steady state after 14 days, while AEs were collected throughout the study. Results: In total, 51 patients (median age, 48 yrs) completed the study. Both IND salts significantly improved lung function vs placebo (Table). Systemic exposure to IND after inhalation of IND acetate and IND maleate were comparable (Table). Both salt forms were safe and well tolerated, with considerable difference in incidence of post-inhalation cough with IND acetate (maleate, 23.5%; acetate, 0%). Conclusions: In patients with asthma, indacaterol acetate and maleate elicited comparable and significant improvements in lung function and achieved comparable systemic exposure. Both indacaterol salts were safe and well tolerated. Indacaterol acetate was not associated with any post-inhalation cough. Poster: https://ers-eposter.key4events.com/145/66942.pdf
※ERS 2019: "Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study". (9/30 14:45 Presenting) Abstract: Background: Reduction of hyperinflation and improvement of heart function, regional lung ventilation and pulmonary microvascular blood flow after indacaterol/glycopyrronium (IND/GLY) treatment was demonstrated in COPD. Objectives: The objective of this analysis was to analyze treatment effects of indacaterol/glycopyrronium (IND/GLY) on pulmonary ventilation/perfusion match (VQM) and regional ventilation dynamics. Methods: CLAIM was a randomized, double-blind, single-center, placebo-controlled, 2 period cross-over trial. 62 hyperinflated COPD patients were enrolled to receive IND/GLY (110/50 μg q.d.) for 14 days followed by placebo or vice versa. Regional lung ventilation dynamics and perfusion was measured in three coronal slices using phase-resolved functional lung (PREFUL)-MRI. The regional MRI flow-volume curves during continuous tidal volume breathing were rated from 0% to 100% by a correlation metric (CM) based on an intra-subject healthy reference. A threshold of 20 ml/min/100ml (perfusion) and 90% (CM) were used to calculate VQM. Results: Treatment with IND/GLY increased CM in the lung by a relative LS Mean difference vs. placebo of 6.2% (p<0.0001) at day 14. Furthermore, the treatment was associated with an increase of perfusion by 8.2% (p=0.0489) and an increase in VQM by 9.7% (p<0.0001) vs. placebo. VQM changes correlate with the changes of LV EDV (p=0.015), FEV1 (p<0.0001) and FVC (p=0.004). Conclusion: IND/GLY leads to improved VQM and regional ventilation dynamics in hyperinflated COPD patients. This in turn likely leads to better oxygenation resulting in improved microvascular function, which results in improved ventricular filling.
※ERS 2019: "Indacaterol/glycopyrronium/mometasone furoate combination consistently shows lung function benefits in patients with asthma". (10/1 8:30 Presenting) Abstract: Introduction: Indacaterol (IND, LABA), glycopyrronium (GLY, LAMA) and mometasone furoate (MF, ICS) have been formulated as a once-daily (o.d.) fixed-dose combination therapy (IND/GLY/MF) delivered via the Breezhaler device for treatment of asthma. We report data from an active-comparator-controlled (B2208) and a placebo-controlled (B2209) study. Methods: Both studies had a randomized, double-blind, 3-period crossover design. B2208 included 116 adult patients with moderate-to-severe asthma (on LABA and medium- or high-dose ICS, FEV1 %predicted <80%), comparing IND/GLY/MF o.d. 150/50/160 μg (high-dose ICS) and 150/50/80 μg (medium-dose ICS) with twice-daily (b.i.d.) high-dose salmeterol/fluticasone (S/F [LABA/ICS], 50/500 μg) over 21 days. B2209 included 37 adult patients with mild-to-moderate asthma (on low- or medium-dose ICS, FEV1 %predicted ≥60－<100%), comparing medium-dose IND/GLY/MF with placebo over 14 days. Results: In B2208, both high- and medium-dose IND/GLY/MF showed superior treatment effect (mean difference) vs S/F on trough FEV1 (124 mL [95%CI: 86, 161] and 105 mL [95% CI: 67, 143], respectively) and FVC (AUC0-24h) (104 mL [95%CI: 66, 142] and 86 mL [95% CI: 48, 125], respectively [all p<0.0001]). In B2209, mean improvement in trough FEV1 by IND/GLY/MF was 544 mL vs. placebo (95% CI: 460, 628 mL; p<0.0001), with a mean increase of 304 mL in FVC (AUC0-24h) vs. placebo (95% CI: 243, 364 mL; p<0.0001). Conclusion: IND/GLY/MF o.d. consistently demonstrates clinically and statistically significant improvements in lung function compared with high-dose S/F b.i.d. and placebo in patients with mild, moderate and severe asthma in two separate Phase II studies. Poster: https://ers-eposter.key4events.com/145/66456.pdf
※ERS 2019: "Efficacy and safety of once-daily low-dose indacaterol/mometasone via Breezhaler in symptomatic adult and adolescent patients with inadequately controlled asthma: Phase III randomised QUARTZ study". (10/1 10:55 Presenting) Abstract: Introduction: GINA recommends ICS/LABA as initial controller therapy in inadequately controlled asthma patients (pts) on low-dose ICS. We evaluated efficacy and safety of low-dose indacaterol acetate/mometasone furoate (IND/MF) 150/80 µg once daily (o.d.) via Breezhaler versus MF 200 µg o.d. via Twisthaler in symptomatic asthma pts Methods: This Phase III, 12-week, double-blind study randomised (1:1) asthma pts (≥12yrs) receiving low-dose ICS prior to study, to IND/MF or MF (Figure). Pts were symptomatic (ACQ-7 ≥1.5) prior to randomisation. Primary endpoint: trough FEV1 at Week 12. Key secondary endpoint: change in ACQ-7 score. Other secondary endpoints: ACQ-7 responders, AM and PM peak expiratory flow (PEF), rescue medication use, AQLQ and daily symptom score. We also assessed safety Results: Of 802 pts randomised, 768 completed study. IND/MF significantly improved trough FEV1 (least squares mean treatment difference [LSMTD]: 0.182L; P < 0.001) and ACQ-7 (LSMTD: －0.218; P < 0.001) versus MF at Week 12. ACQ-7 responder rate, rescue medication use, PEF and AQLQ favoured IND/MF. Safety was comparable Conclusion: In symptomatic asthma pts, IND/MF significantly improved lung function and asthma control versus MF. This supports IND/MF as efficacious maintenance therapy for asthma Poster: https://ers-eposter.key4events.com/145/70471.pdf
※ERS 2019: "Mometasone furoate delivered via Breezhaler and Twisthaler in patients with asthma". (10/1 12:50 Presenting) Abstract: Introduction: Mometasone furoate (MF), an inhaled corticosteroid (ICS), is approved for the treatment of asthma. Previous studies suggest that MF Twisthaler doses of 800 and 200 µg and MF Breezhaler doses of 320 and 80 µg would elicit similar lung function effects, respectively. These MF doses are also used in an indacaterol/MF combination in development for asthma. Since sensitivity to ICS is variable, individual patients’ ICS sensitivity (as measured by FEV1 decline on ICS weaning) was used to build a robust analysis model for the study data. Methods: This was a randomized, double-blind, double-dummy, parallel-group, non-inferiority study of 739 adolescents and adults with asthma. MF was delivered with Breezhaler at daily doses of 80 and 320 µg and corresponding Twisthaler® doses of 200 and 800 µg. The primary endpoint was trough FEV1 on Day 29 (non-inferiority margin: -90 mL). Models with and without ICS sensitivity at baseline were used to analyze the data. Results: In the model with ICS sensitivity the least squares (LS) mean difference (Δ) in trough FEV1 between MF 80 µg Breezhaler and MF 200 µg Twisthaler was 27 mL (95% CI –34, 89); for MF 320 µg Breezhaler and MF 800 µg Twisthaler Δ was 0 mL (95% CI –60, 61). In the model without ICS sensitivity Δ between MF 80 μg Breezhaler and MF 200 μg Twisthaler patients was 68 mL (0, 137) and 25 mL (-43, 92) between MF 320 μg Breezhaler and MF 800 μg Twisthaler. Model diagnostics showed that using ICS sensitivity as a covariate improved the model. Conclusion: MF 80 and 320 μg, delivered via Breezhaler, is non-inferior to MF at 200 and 800 μg, delivered via Twisthaler. Including ICS sensitivity in the model improves model robustness. Poster: https://ers-eposter.key4events.com/145/66452.pdf
次なる飛躍へ。着実な進捗と共に更なる成長の黎明期にて振るい育ちゆく相場。控える材料と共に水準訂正。笑。 成長期。予定されていた業績の急成長と共に更なる成長戦略が進展。順調なR&D・PL等の拡充・拡大の加速。笑。 ・・・ ※ILCA Annual Conference 2019: Session, Novel Targetsnd Prognostics Markers: (Speakers) Debashis Sarker, Guy's and St. Thomas' Hospital NHS Trust, London, United Kingdom: (9/22 Presented) ・"First-in-Human, First-in-Class Phase I Trial of MTL-CEBPA, a RNA Oligonucleotide Targeting the Transcription Factor C/EBP-α, Given as a Single Agent or in Combination with Sorafenib, in Patients with Advanced Hepatocellular Cancer (HCC)" ※RDKit UGM 2019: "Traversing and Indexing Chemically Rich Documentation with RDKit to Aid GPCR-Based Drug Discovery": Rob Smith, Sosei Heptares. (9/26 Presented) ※European User Group Meeting: "Free Energy Perturbation for GPCR Structure-Based Drug Design": Francesca Deflorian and Chris de Graaf from Sosei Heptares. (9/26 Presented) ※Biotech in Europe Forum for Global Partnering & Investment: "Neuroscience - Development & Partnering Panel": (Panelists) Malcolm Weir, Executive Vice President & Chief R&D Officer, Sosei Heptares. (9/26) ※CICON 2019 Translating Science into Survival: "Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy", MiNA Therapeutics. (9/26 Presented) ・Demonstrated the ability of saRNA technology to upregulate immune-stimulatory targets for utilization in immunotherapy. We are currently optimizing formulation for delivery of the lead saRNAs for efficacy studies in preclinical tumor models. ※ClinicalTrials (NCT04105335: MNA-3521-012): Phase 1, "A Study of MTL-CEBPA in Combination with a PD-1 Inhibitor in Patients with Advanced Solid Tumours (TIMEPOINT)". ("New Trial Record": 9/26up) ・Estimated Study Start: 2019/11/1. ・Estimated Primary Completion: 2021/12/31. ・Estimated Study Completion: 2022/6/30. ・Estimated Enrollment: 108 Participants.
※MiNA Therapeutics Publications: "Targeted Delivery of C/EBPa-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC". (9/26up) ・In conclusion, targeted delivery of C/EBPα-saRNAs by aptamers might have potential therapeutic effects in advanced PDAC. ※Fraunhofer ITEM: "ERS International Congress 2019". Poster Presentations, Fraunhofer ITEM will Present Selected Projects from its Respiratory Research. (9/26up) ・"Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma" ・"Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: the CLAIM study“ ※RNA Therapeutics Conference: "SMi Group announces the 11th Annual RNA Therapeutics Conference in London on February 19th - 20th 2020". (9/27up) ・"Small Activating RNAs(saRNAs) - A Novel Therapeutic Class of Oligonucleotides with Broad Therapeutic Potential": David Blakey, MiNA Therapeutics: 2020/2/19 13:20-14:00 Presenting. ・Description of saRNA technology and broad applicability to a range of therapeutic targets.・Update on MiNA’s lead saRNA product MTL-CEBPA - preclinical and clinical data.・Emerging data on new therapeutic strategies with saRNAs. ※ESMO 2019: "First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)". (9/28 Presented) ・MTL-CEBPA is a first-in-class therapy targeting the myeloid cell master regulator C/EBP-α. In HCC patients MTL-CEBPA demonstrated a good safety profile, induced altered gene expression in WBC and as well as anti-tumour activity. ・These encouraging phase I data validate targeting of CEBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC. ・・・
9/30 Today Events： ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 12:00 Presenting) ・The study indicates enhanced anti-tumour activity when combining MTL-CEBPA with PD-1 antibody in the immunocompetent mouse CT26 colorectal cancer model. ・The combination treatment appears to result in increased penetration of TILs through modulation of immune activity in the tumour microenvironment. ※ERS 2019: Industry Symposium (Organized by: Novartis): "Harnessing digital technology to improve the lives of patients with respiratory disease". (9/30 7:00-8:15) ・Are we ready for the digital revolution? ・Using mobile spirometry to bring benefits to patients. ・Automated inhaler tracking for improved respiratory care. ・Can AI and machine learning already beat physicians? ※ERS 2019: "Late Breaking Abstract - Indacaterol/glycopyrronium versus salmeterol/fluticasone in chronic obstructive pulmonary disease: a meta-analysis on the protection against the risk of exacerbation". (9/30 12:50 Presenting) ・The MA showed that IND/GLY was significantly more effective than SFC in reducing the overall risk of AECOPD. ・Run-in period in the FLAME study did not improve the effect of IND/GLY compared with shorter or no run-in studies.
※ERS 2019: "Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma". (9/30 12:50 Presenting) ・Patients with asthma are more likely to achieve normal or near-normal lung function and to remain rescue medication free with IND/GLY/MF compared with high-dose S/F or placebo. ・https://ers-eposter.key4events.com/145/66458.pdf ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects". (9/30 12:50 Presenting) ・There was no clinically relevant pharmacokinetic interaction between IND, GLY and MF when administered as IND/GLY/MF. ・https://ers-eposter.key4events.com/145/66946.pdf ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate as a fixed-dose combination in Japanese and Caucasian healthy subjects". (9/30 12:50 Presenting) ・Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as fixed-dose combination were comparable between Japanese and Caucasian subjects. ・IND/GLY/MF was safe and well tolerated in both ethnic groups. These results confirm that no dose adjustment for IND/GLY/MF is required in Asian population. ・https://ers-eposter.key4events.com/145/66928.pdf
※ERS 2019: "Lung function, pharmacokinetics, and tolerability of indacaterol maleate and acetate in asthma patients". (9/30 12:50 Presenting) ・In patients with asthma, indacaterol acetate and maleate elicited comparable and significant improvements in lung function and achieved comparable systemic exposure. ・Both indacaterol salts were safe and well tolerated. Indacaterol acetate was not associated with any post-inhalation cough. ・https://ers-eposter.key4events.com/145/66942.pdf ※ERS 2019: "Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study". (9/30 14:45 Presenting) ・IND/GLY leads to improved VQM and regional ventilation dynamics in hyperinflated COPD patients. ・This in turn likely leads to better oxygenation resulting in improved microvascular function, which results in improved ventricular filling. ※ERS 2019: Industry Symposium (Organized by: Novartis): "The journey towards personalized medicine in asthma: where are we now? ". (9/30 17:15-19:15) ・In the era of personalized medicine, what are the current unmet needs in asthma? ・Inhaled therapies: can they breathe new life into asthma? ・・・
※Novartis: "Novartis announces positive results from Phase III PALLADIUM study of inhaled combination QMF149 in patients with uncontrolled asthma" (9/30) ・Once-daily QMF149 demonstrated superior improvement in lung function versus mometasone furoate, meeting primary endpoint. ・PALLADIUM is part of Phase III PLATINUM clinical development program, which evaluates inhaled combinations QMF149 and QVM149. ・Novartis is aiming to reimagine inhaled asthma care by developing once-daily fixed-dose combination treatments to help patients achieve better asthma control. Basel, September 30, 2019 Novartis today announced that investigational, once-daily, fixed-dose inhaled QMF149 (indacaterol acetate and mometasone furoate or IND/MF) was superior to mometasone furoate (MF) in improving trough forced expiratory volume in one second (FEV1) after 26 weeks, meeting the primary endpoint of the Phase III PALLADIUM clinical trial. This superior improvement in lung function was achieved in patients with asthma who remain uncontrolled on treatment with inhaled corticosteroid (ICS) at medium or high dose, or long-acting beta agonist (LABA)/ICS at low dose. ・・・
※Novartis: "Novartis announces positive results from Phase III IRIDIUM study of inhaled combination QVM149 in patients with uncontrolled asthma"(9/30) Sep 30, 2019 ・Once-daily QVM149 demonstrated statistically significant improvement in lung function versus QMF149, meeting primary endpoint[1],[2] ・IRIDIUM is largest study in Phase III PLATINUM clinical development program, which evaluates inhaled combinations QVM149 and QMF149 ・Novartis is aiming to reimagine inhaled asthma care by developing once-daily fixed-dose combination treatments to help patients achieve better asthma control Basel, September 30, 2019 Novartis today announced that investigational, once-daily, inhaled QVM149 (indacaterol acetate, glycopyrronium bromide and mometasone furoate or IND/GLY/MF) was superior to QMF149 (indacaterol acetate and mometasone furoate or IND/MF) in improving trough forced expiratory volume in one second (FEV1) after 26 weeks, meeting the primary endpoint of the Phase III IRIDIUM clinical trial. This superior improvement in lung function was achieved in asthma patients who were uncontrolled on treatment with a long-acting beta agonist/inhaled corticosteroid (LABA/ICS). IND/GLY/MF was generally well tolerated and safety was comparable across treatment arms.
The key secondary endpoint was improvement in Asthma Control Questionnaire (ACQ-7) score for IND/GLY/MF versus IND/MF. Tested treatments delivered clinically meaningful improvements in this measure of symptoms from baseline at Week 26, but the key secondary endpoint was not met. Among other secondary endpoints, IRIDIUM explored reduction of asthma exacerbation rates, where a substantial reduction was observed in moderate-to-severe and severe asthma exacerbation rates with IND/GLY/MF compared with an established LABA/ICS standard of care (twice-daily salmeterol xinafoate/fluticasone propionate 50/500 µg). The IRIDIUM study was conducted to evaluate the efficacy and safety of medium and high doses of IND/GLY/MF (150/50/80 µg and 150/50/160 µg) versus respective medium and high doses of IND/MF (150/160 µg and 150/320 µg) delivered via the dose-confirming Breezhaler device, as well as versus twice-daily salmeterol/fluticasone (50/500 µg) delivered via the Accuhaler. Patients with uncontrolled asthma on medium and high doses of LABA/ICS (as determined by pulmonary function testing and effects on asthma control) were included.
“Despite being on treatment with LABA/ICS, nearly half of all patients with moderate-to-severe asthma are uncontrolled and at a higher risk of exacerbations, hospitalization or even death,” said Dr. Huib Kerstjens, University Medical Center Groningen, The Netherlands. “For these patients, it is important to explore additional options to improve treatment outcomes and quality of life. The initial results of IRIDIUM show us that QVM149 can improve lung function in these patients and potentially deliver substantial reduction in exacerbation rates, which can have a significant impact on the daily lives of people with uncontrolled asthma.”
“Today’s news represents a key milestone in the ongoing Novartis effort to reimagine asthma care for patients,” said Linda Armstrong, MD, Respiratory Development Unit Head, Novartis Pharmaceuticals. “These positive initial IRIDIUM results are consistent with the Phase II outcomes presented at ATS earlier this year and strengthen the evidence to suggest that, if approved, medium and high dose QVM149 could be beneficial for people with asthma who are still uncontrolled after being treated with medium and high dose LABA/ICS.”
The overall incidence of adverse events (AEs) and serious AEs in IRIDIUM was comparable among treatment groups and consistent with the known safety profile of the monocomponents. Detailed results from the IRIDIUM trial will be presented at upcoming medical congresses. As previously announced, the regulatory submission for QVM149 was accepted for review by the European Medicines Agency earlier this year.
※Sosei Heptares 20分前：(9/30) "Chairman, President and CEO Shinichi Tamura sat down with yakuji_nippo, Japan's long-established pharma news service, to talk about our sustainable business model based on unique and powerful platform capabilities." (The article only available in Japanese)
※Pharma News: "Novartis Scores with Two Asthma Candidates". (9/30) Novartis has achieved its goals in the treatment of asthma patients with two product candidates. As the group announced on Monday, the inhalable combination QVM149 proved effective in patients with uncontrolled asthma. In turn, the candidate QMF149 achieved superior lung function improvement over mometasone furoate. Both studies are part of the large-scale Phase III Platinum Program that Novartis is currently conducting with the two candidates. For example, QVM149, when inhaled once daily, has proved superior to QMF149 in terms of improving expiratory volume. This superior improvement in lung function was achieved in asthmatic patients who were uncontrolled when treated with LABA / ICS. ・Novartis pharmaceutical group has seen encouraging results for asthma treatments in phase III clinical trials, he said Monday. ・The QVM149 therapy, or inhalation once a day the drug "significantly" improves the respiratory capacity. ・The Phase III study of Iridium showed that after 26 weeks of treatment, respiratory function improved in patients. ・The QMF149 treatment demonstrated a "superior improvement" in respiratory capacity compared to mometasone furoate after 26 weeks of treatment. ・According to the details of the Phase III Paladium clinical study published in a separate version.
※MiNA Therapeutics: "MiNA Therapeutics Presents Clinical and Pre-Clinical Data at ESMO Supporting MTL-CEBPA as Immunological Combination Treatment" (9/30) --Final results from Phase 1 study of MTL-CEBPA in advanced liver cancer patients demonstrate clinical activity and attractive safety profile-- --Results from pre-clinical study highlight synergistic benefit of combining MTL‑CEBPA with anti-PD1 checkpoint inhibitors-- September 30, 2019 LONDON--MiNA Therapeutics, the pioneer in RNA activation (RNAa) therapeutics, today announced final Phase 1 clinical data of MTL-CEBPA as a single agent in patients with advanced liver cancer as well as pre-clinical data demonstrating synergistic immunological and anti-tumour activity of MTL-CEBPA in combination with anti-PD1 checkpoint inhibition. The data will be presented in two posters at the European Society for Medical Oncology (ESMO) 2019 Congress taking place in Barcelona, Spain on September 28th and September 30th.
"The Phase 1 study, in which immunological activity and tolerability of MTL-CEBPA as a single agent was observed, provides an excellent foundation on which to advance MTL‑CEBPA in combination with other cancer therapies and serves as a strong, general validation of our novel approach to targeting cancer," said Robert Habib, CEO of MiNA Therapeutics. "In addition to the ongoing evaluation of MTL-CEBPA in combination with sorafenib in patients with advanced liver cancer, the new pre-clinical findings support investigating MTL‑CEBPA and anti-PD1 checkpoint combination therapy in patients with other solid tumour cancers."
Final results of the first-in-human evaluation of MTL-CEBPA as a single agent demonstrated MTL-CEBPA to be well tolerated at all dose levels with clear pharmacological activity. In the study, MTL-CEBPA was evaluated as a single agent in 39 patients with advanced liver cancer and liver disease across escalating dose levels and dose frequencies in which no maximum tolerated dose was identified. Pharmacological activity was observed in patients with significant activation of CEBPA target gene and subsequent changes in white blood cell count. Analysis of paired biopsies indicated repopulation of the tumour microenvironment from immuno-suppressive to mature myeloid cells. In 35 patients evaluable for efficacy, partial tumour response was achieved in 1 patient, and stable disease was achieved in 15 patients. Following discontinuation of MTL‑CEBPA, 8 patients received subsequent tyrosine kinase inhibitor therapy. Of 5 patients treated with sorafenib, 4 experienced durable, objective tumour responses including 3 complete tumour responses durable for over 1 year. The ongoing OUTREACH Phase 1b study continues to evaluate MTL-CEBPA in combination with sorafenib standard of care.
Separately, a new pre-clinical study described the synergistic benefits of combining MTL‑CEBPA with anti-PD1 checkpoint inhibition in an immunocompetent mouse model of colon cancer. Compared to single agent treatments, the combination treatment resulted in synergistic improvements in tumour growth inhibition. Synergistic increases in infiltration of cytotoxic T lymphocytes (TILs) evidenced the immunological role of MTL-CEBPA in the tumour microenvironment.
The posters will be made available on the Company's website in the Publications section under "RNA Activation".
Title: Targeting myeloid-derived suppressor cells and T cells: combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model Poster no: 1230P (Abstract 3089) Session: Poster Display Session 3, Immunotherapy of cancer Date / time: 12:00 – 13:00 CET, Monday 30 September 2019 Location: Poster Area (Hall 4) ※MiNA Therapeutics Publications: (9/30up): https://minatx.com/wp-content/uploads/2019/09/ESMO_MTL-CEBPA-and-PD-1-antibody-in-a-mouse-syngeneic-CT26-model.pdf
About MTL-CEBPA: MTL-CEBPA is the first therapy to specifically up-regulate CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and identified as a critical barrier for many therapies to induce clinical responses in solid tumour cancers. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppression in the tumour microenvironment.
About MiNA Therapeutics: Harnessing an innate mechanism of gene activation, MiNA Therapeutics' platform enables the development of new medicines that restore normal function to patients’ cells. We are applying our technology and clinical know-how to transform the therapy landscape of cancer and other severe diseases.
※Endpoints News: "Charging at blockbuster Advair, Novartis boasts topline victories for asthma drugs in twin PhIII studies." (9/30) September 30, 2019
In a bit of a Russain nesting doll moment, Novartis says that its potential blockbuster asthma drug has beat another treatment from its portfolio, which in turn performed better than a corticosteroid in another Phase III study. Announced simultaneously, the studies both enrolled patients whose disease remained uncontrolled despite treatment and employ improvement in trough forced expiratory volume in one second - a standard measure of lung function - after 26 weeks as the primary endpoint. That was met, though QVM149 didn’t hit the key secondary endpoint regarding the Asthma Control Questionnaire (ACQ-7) while QMF149 did. QVM149 differs from QMF149 by a key ingredient: glycopyrronium bromide, a long-acting muscarinic receptor antagonist (LAMA). The long-acting beta-agonist (LABA) indacaterol acetate and corticosteroid, mometasone furoate, are present in both therapies.
Novartis CEO Vas Narasimhan has billed QVM149 as one of 25 drugs that have the potential to earn $1 billion or more in annual sales after it demonstrated better outcomes than GlaxoSmithKline’s Advair in a Phase II trial. Advair, the current standard of care, consists of a LABA and a steroid. Nearly half of all patients with moderate-to-severe asthma are uncontrolled and thus at a higher risk of exacerbations, hospitalization or death, Novartis emphasized in its announcements. In the IRIDIUM study - which compared QVM149 to QMF149 as well as Advair - investigators observed “a substantial reduction” in exacerbation rates, meeting a secondary endpoint. Meanwhile, the PALLADIUM study, starring QMF149, suggested that QMF149 induced a statistically significant improvement in scores on the ACQ-7 compared to mometasone furoate alone. Comparisons against a version of Advair were also made, but we’ll have to wait until a future medical conference for the data.
Both drugs are delivered via the Breezhaler device. Linda Armstrong, Novartis’ head of respiratory development, said the results confirm outcomes from previously reported trials - including the Phase III QUARTZ study for QMF149 - and deepen their understanding about different doses of the drugs. “Today’s news represents a key milestone in the ongoing Novartis effort to reimagine asthma care for patients,” she said in a statement.
※Pharma Phorum News: "Novartis announces positive results from asthma combination therapiesRichard Staines." (9/30) September 30, 2019
Novartis has announced positive results from trials testing its daily fixed dose treatment two-drug combination for people with uncontrolled asthma, QMF149, and its triple combination QVM149. Both drugs are under review by the European Medicines Agency after more than a decade of clinical development at Novartis, which acquired rights to QMF149 in 2009 from Schering-Plough. Novartis and S-P had been collaborating on respiratory drugs since the early noughties and decided to restructure the deal so that the Swiss pharma had rights to QMF149 a few months before the latter’s merger with Merck & Co. Results from the PALLADIUM and IRIDIUM trials are part of a clinical development programme called PLATINUM, and build on results from the successful QUARTZ study announced earlier this year. Both trials announced today tested QMF149, a combination of indacaterol acetate and mometasone furoate in patients whose asthma was uncontrolled on standard therapy such as a long-acting beta agonist (LABA) and inhaled corticosteroid (ICS). The new drugs are delivered through Novartis’ dose confirming device known as Breezhaler.
In PALLADIUM QMF149 improved lung function compared with mometasone furoate alone, measured using trough forced expiratory volume in one second (FEV1). It also improved symptoms assessed with a questionnaire in the 26-week trial, with a statistically significant improvement in asthma control at the end of the study compared with baseline. IRIDIUM tested a slightly different combination - QVM149, which consists of indacaterol acetate, glycopyrronium bromide and mometasone furoate. The trial tested QVM149 against QMF149 and found the triple therapy improved FEV1 compared with the two-drug combination, meeting its primary endpoint. However Novartis said the triple therapy produced a “clinically meaningful” improvement in symptoms measured with the questionnaire, but this was not statistically significant. Detailed results will be announced at forthcoming medical conferences.
Dr Richard van Zyl-Smit, associate professor, head of the Lung Clinical Research Unit, University of Cape Town Lung Institute, and consultant pulmonologist, Groote Schuur Hospital, Cape Town, South Africa, said: “Promising results from PALLADIUM in both doses of the indacaterol and mometasone furoate combination provide evidence for the efficacy and safety profile of QMF149 for the treatment of asthma. “If approved, the easy-to-use, dose-confirming, once-daily device adds an additional and important option for clinicians treating asthma. I believe that this new fixed-dose combination has the potential to improve and simplify the lives of many patients with uncontrolled asthma.
Commenting on IRIDIUM, Dr Huib Kerstjens, University Medical Center Groningen, The Netherlands said: “The initial results of IRIDIUM show us that QVM149 can improve lung function in these patients and potentially deliver a substantial reduction in exacerbation rates, which can have a significant impact on the daily lives of people with uncontrolled asthma.”
次なる飛躍へ。着実な進捗と共に更なる成長の黎明期にて振るい育ちゆく相場。控える材料と共に水準訂正。笑。 成長期。予定されていた業績の急成長と共に更なる成長戦略が進展。順調なR&D・PL等の拡充・拡大の加速。笑。 ・・・ ※ILCA Annual Conference 2019: Session, Novel Targetsnd Prognostics Markers: (Speakers) Debashis Sarker, Guy's and St. Thomas' Hospital NHS Trust, London, United Kingdom: (9/22 Presented) ・"First-in-Human, First-in-Class Phase I Trial of MTL-CEBPA, a RNA Oligonucleotide Targeting the Transcription Factor C/EBP-α, Given as a Single Agent or in Combination with Sorafenib, in Patients with Advanced Hepatocellular Cancer (HCC)" ※RDKit UGM 2019: "Traversing and Indexing Chemically Rich Documentation with RDKit to Aid GPCR-Based Drug Discovery": Rob Smith, Sosei Heptares. (9/26 Presented) ※European User Group Meeting: "Free Energy Perturbation for GPCR Structure-Based Drug Design": Francesca Deflorian and Chris de Graaf from Sosei Heptares. (9/26 Presented) ※Biotech in Europe Forum for Global Partnering & Investment: "Neuroscience - Development & Partnering Panel": (Panelists) Malcolm Weir, Executive Vice President & Chief R&D Officer, Sosei Heptares. (9/26) ※CICON 2019 Translating Science into Survival: "Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy", MiNA Therapeutics. (9/26 Presented) ・Demonstrated the ability of saRNA technology to upregulate immune-stimulatory targets for utilization in immunotherapy. We are currently optimizing formulation for delivery of the lead saRNAs for efficacy studies in preclinical tumor models. ※ClinicalTrials (NCT04105335: MNA-3521-012): Phase 1, "A Study of MTL-CEBPA in Combination with a PD-1 Inhibitor in Patients with Advanced Solid Tumours (TIMEPOINT)". ("New Trial Record": 9/26up) ・Estimated Study Start: 2019/11/1. ・Estimated Primary Completion: 2021/12/31. ・Estimated Study Completion: 2022/6/30. ・Estimated Enrollment: 108 Participants.
※MiNA Therapeutics Publications: "Targeted Delivery of C/EBPa-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC". (9/26up) ・In conclusion, targeted delivery of C/EBPα-saRNAs by aptamers might have potential therapeutic effects in advanced PDAC. ※Fraunhofer ITEM: "ERS International Congress 2019". Poster Presentations, Fraunhofer ITEM will Present Selected Projects from its Respiratory Research. (9/26up) ・"Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma" ・"Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: the CLAIM study“ ※RNA Therapeutics Conference: "SMi Group announces the 11th Annual RNA Therapeutics Conference in London on February 19th - 20th 2020". (9/27up) ・"Small Activating RNAs(saRNAs) - A Novel Therapeutic Class of Oligonucleotides with Broad Therapeutic Potential": David Blakey, MiNA Therapeutics: 2020/2/19 13:20-14:00 Present. ・Description of saRNA technology and broad applicability to a range of therapeutic targets.・Update on MiNA’s lead saRNA product MTL-CEBPA - preclinical and clinical data.・Emerging data on new therapeutic strategies with saRNAs. ※ESMO 2019: "First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)". (9/28 Presented) ・MTL-CEBPA is a first-in-class therapy targeting the myeloid cell master regulator C/EBP-α. In HCC patients MTL-CEBPA demonstrated a good safety profile, induced altered gene expression in WBC and as well as anti-tumour activity. ・These encouraging phase I data validate targeting of CEBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.
※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 Presented) ・The study indicates enhanced anti-tumour activity when combining MTL-CEBPA with PD-1 antibody in the immunocompetent mouse CT26 colorectal cancer model. ・The combination treatment appears to result in increased penetration of TILs through modulation of immune activity in the tumour microenvironment. ※ERS 2019: Industry Symposium (Organized by: Novartis): "Harnessing digital technology to improve the lives of patients with respiratory disease". (9/30) ・Are we ready for the digital revolution? ・Using mobile spirometry to bring benefits to patients. ・Automated inhaler tracking for improved respiratory care. ・Can AI and machine learning already beat physicians? ※ERS 2019: "Late Breaking Abstract - Indacaterol/glycopyrronium versus salmeterol/fluticasone in chronic obstructive pulmonary disease: a meta-analysis on the protection against the risk of exacerbation". (9/30 Presented) ・The MA showed that IND/GLY was significantly more effective than SFC in reducing the overall risk of AECOPD. ・Run-in period in the FLAME study did not improve the effect of IND/GLY compared with shorter or no run-in studies.
※ERS 2019: "Lung function normalization with indacaterol/glycopyrronium/mometasone furoate in patients with asthma". (9/30 Presented) ・Patients with asthma are more likely to achieve normal or near-normal lung function and to remain rescue medication free with IND/GLY/MF compared with high-dose S/F or placebo. ・https://ers-eposter.key4events.com/145/66458.pdf ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate following once daily inhalation as a fixed-dose combination in healthy subjects". (9/30 Presented) ・There was no clinically relevant pharmacokinetic interaction between IND, GLY and MF when administered as IND/GLY/MF. ・https://ers-eposter.key4events.com/145/66946.pdf ※ERS 2019: "Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate as a fixed-dose combination in Japanese and Caucasian healthy subjects". (9/30 Presented) ・Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as fixed-dose combination were comparable between Japanese and Caucasian subjects. ・IND/GLY/MF was safe and well tolerated in both ethnic groups. These results confirm that no dose adjustment for IND/GLY/MF is required in Asian population. ・https://ers-eposter.key4events.com/145/66928.pdf
※ERS 2019: "Lung function, pharmacokinetics, and tolerability of indacaterol maleate and acetate in asthma patients". (9/30 Presented) ・In patients with asthma, indacaterol acetate and maleate elicited comparable and significant improvements in lung function and achieved comparable systemic exposure. ・Both indacaterol salts were safe and well tolerated. Indacaterol acetate was not associated with any post-inhalation cough. ・https://ers-eposter.key4events.com/145/66942.pdf ※ERS 2019: "Effect of indacaterol/glycopyrronium on ventilation/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study". (9/30 Presented) ・IND/GLY leads to improved VQM and regional ventilation dynamics in hyperinflated COPD patients. ・This in turn likely leads to better oxygenation resulting in improved microvascular function, which results in improved ventricular filling. ※ERS 2019: Industry Symposium (Organized by: Novartis): "The journey towards personalized medicine in asthma: where are we now? ". (9/30) ・In the era of personalized medicine, what are the current unmet needs in asthma? ・Inhaled therapies: can they breathe new life into asthma?
※Novartis: "Novartis announces positive results from Phase III IRIDIUM study of inhaled combination QVM149 in patients with uncontrolled asthma" (9/30 Press Release) ・Once-daily QVM149 demonstrated statistically significant improvement in lung function versus QMF149, meeting primary endpoint. ・IRIDIUM is largest study in Phase III PLATINUM clinical development program, which evaluates inhaled combinations QVM149 and QMF149. ・Novartis is aiming to reimagine inhaled asthma care by developing once-daily fixed-dose combination treatments to help patients achieve better asthma control. ※Novartis: "Novartis announces positive results from Phase III PALLADIUM study of inhaled combination QMF149 in patients with uncontrolled asthma" (9/30 Press Release) ・PALLADIUM is part of Phase III PLATINUM clinical development program, which evaluates inhaled combinations QMF149 and QVM149. ※MiNA Therapeutics: "MiNA Therapeutics Presents Clinical and Pre-Clinical Data at ESMO Supporting MTL-CEBPA as Immunological Combination Treatment" (9/30 Press Release) ・Final results from Phase 1 study of MTL-CEBPA in advanced liver cancer patients demonstrate clinical activity and attractive safety profile. ・Results from pre-clinical study highlight synergistic benefit of combining MTL‑CEBPA with anti-PD1 checkpoint inhibitors. ※MiNA Therapeutics Publications: First-in-human, first-in-class phase I study of MTL-CEBPA, a RNA oligonucleotide targeting the myeloid cell master regulator C/EBP-α, in patients with advanced hepatocellular cancer. (9/30up) ・https://minatx.com/wp-content/uploads/2019/09/ESMO-Poster-OUTREACH-Study-190911-FINAL2.pdf ※MiNA Therapeutics Publications: Targeting myeloid-derived suppressor cells and T cells: combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model. (9/30up) ・https://minatx.com/wp-content/uploads/2019/09/ESMO_MTL-CEBPA-and-PD-1-antibody-in-a-mouse-syngeneic-CT26-model.pdf
10/1 Today Events: ・・・ ※ERS 2019: "Indacaterol/glycopyrronium/mometasone furoate combination consistently shows lung function benefits in patients with asthma". (10/1 8:30 Presenting) ・IND/GLY/MF o.d. consistently demonstrates clinically and statistically significant improvements in lung function compared with high-dose S/F b.i.d. and placebo in patients with mild, moderate and severe asthma in two separate Phase II studies. ・https://ers-eposter.key4events.com/145/66456.pdf ※ERS 2019: "Efficacy and safety of once-daily low-dose indacaterol/mometasone via Breezhaler in symptomatic adult and adolescent patients with inadequately controlled asthma: Phase III randomised QUARTZ study". (10/1 10:55 Presenting) ・In symptomatic asthma pts, IND/MF significantly improved lung function and asthma control versus MF. ・This supports IND/MF as efficacious maintenance therapy for asthma ・https://ers-eposter.key4events.com/145/70471.pdf ※ERS 2019: "Mometasone furoate delivered via Breezhaler and Twisthaler in patients with asthma". (10/1 12:50 Presenting) ・MF 80 and 320 μg, delivered via Breezhaler, is non-inferior to MF at 200 and 800 μg, delivered via Twisthaler. ・Including ICS sensitivity in the model improves model robustness. ・https://ers-eposter.key4events.com/145/66452.pdf ※ERS 2019: Industry Symposium (Organized by: Boehringer Ingelheim, GSK, Menarini Group, Mundipharma, Novartis, Teva, Vectura): "Joint ERS/Industry session: Time to be smarter about inhaler usage". (10/1 13:00-14:30) ・SCIENCE: The Essential Knowledge for Clinical Practice. ・TECHNOLOGY: Inhaler Usage - Is It Time To Get Smarter? ・PATIENTS: Does Supporting Adherence Improve Clinical Outcomes? ・・・
※米国特許(Heptares)：Bicyclic AZA Compounds as Muscarnic M1 Receptor and/or M4 Receptor Antagonists (US Patent 10385039 B2). (8/20公開) ※欧州特許出願(Heptares)：Heterocyclic Compounds Having Activity as Modulators of Muscarinic M1 Receptor and/or M4 Receptors in the Treatment of CNS Diseases and Pains (EP3526207 A1). (8/21公開) ※日本特許(Heptares)：「変異体タンパク質とその製造方法」(特許第6567291号 B2) (8/9登録、8/28公開) ※米国特許出願(Heptares)：Muscarinic Agonists (US 20190270718 A1). (9/5公開) ※米国特許出願(Heptares)：Pharmaceutical Compounds (US 20190276437 A1). (9/12公開) ※米国特許(Heptares)：Muscarinic M1 Receptor Agonists (US Patent 10413553 B2). (9/17公開)
↓ ※米国特許(Heptares)："Muscarinic Receptor Agonists". (10/1公開) ・Document Type and Number: United States Patent 10428088 B2 ・Publication Date: 2019/10/01 ・Assignee: Heptares Therapeutics Limited. Abstract: This invention relates to compounds that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where m, p, q, W, Z, Y, X1, X2, R1, R2, R3 and R4 are as defined herein. http://www.freepatentsonline.com/10428088.pdf
次なる飛躍へ。着実な進捗と共に更なる成長の黎明期にて振るい育ちゆく相場。控える材料と共に水準訂正。笑。 成長期。予定されていた業績の急成長と共に更なる成長戦略が進展。順調なR&D・PL等の拡充・拡大の加速。笑。 ・・・ ※Sosei Heptares：｢喘息患者を対象として開発中のQVM149の第Ⅱ相臨床試験において新たに得られた有効性試験成績を発表」有意な改善を示し、投与タイミングにかかわらない肺機能の改善も確認。(5/22) ※Sosei Heptares：｢喘息治療配合吸入剤QVM149、医薬品販売承認を欧州医薬品庁へ申請、前倒し」現在、第Ⅲ/Ⅲb相IRIDIUMおよびARGON試験を実施中であり、2019年第3四半期に完了予定。(5/24) ※Novartis Q2 2019 Results: 2019 Expected Pipeline Milestones: [QVM149 Asthma ( EU / JP ) Submissions: H2 2019]: "EU Achieved (Q2, QVM149 Submitted in EU) ". (7/18) ※Trial Profile: Phase 3, study to compare the efficacy and safety of QVM149 with QMF149 in patients with Asthma (IRIDIUM). This Trial has been Completed. (7/25, 9/5, 9/25update,) ※ClinicalTrials(NCT03100825): Phase 3, A Long-term Safety Study of QVM149 in Japanese Patients with Asthma. (8/26update, "Completed") ※ClinicalTrials(NCT03158311): Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (9/20update, " Completed ") ※ERS International Congress 2019: "PALLADIUM Study Results", "IRIDIUM Study Results", "JAPANESE Study Results". (9/30 Novartis Presented) ※Novartis: "Novartis Announces Positive Results from Phase III PALLADIUM Study of Inhaled Combination QMF149 in Patients with Uncontrolled Asthma" (9/30 Press Release) ※Novartis: "Novartis Announces Positive Results from Phase III IRIDIUM Study of Inhaled Combination QVM149 in Patients with Uncontrolled Asthma" (9/30 Press Release) ※Sosei Heptares：｢開発中の配合吸入剤QVM149がコントロール不良の喘息患者を対象とした第Ⅲ相IRIDIUM試験において良好な治療結果を示した」ARGON試験の結果は、データ分析後に発表予定。(10/1 Press Release) ・・・
※ILCA 2019: " First-in-Class Phase I Trial of MTL-CEBPA, a RNA Oligonucleotide Targeting the Transcription Factor C/EBP-α, Given as a Single Agent or in Combination with Sorafenib, in Patients with Advanced Hepatocellular Cance" (9/22 Presented) ※CICON 2019 Translating Science into Survival: "Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy", MiNA Therapeutics. (9/26 Presented) ※ClinicalTrials (NCT04105335: MNA-3521-012): Phase 1, "A Study of MTL-CEBPA in Combination with a PD-1 Inhibitor in Patients with Advanced Solid Tumours (TIMEPOINT)". ("New Trial Record", "Not yet recruiting": (9/26up) ※MiNA Therapeutics Publications: "Targeted Delivery of C/EBPa-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC". (9/26up) ※ESMO 2019: "First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 Presented) ・https://minatx.com/wp-content/uploads/2019/09/ESMO-Poster-OUTREACH-Study-190911-FINAL2.pdf ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 Presented) ・https://minatx.com/wp-content/uploads/2019/09/ESMO_MTL-CEBPA-and-PD-1-antibody-in-a-mouse-syngeneic-CT26-model.pdf ※MiNA Therapeutics: "MiNA Therapeutics Presents Clinical and Pre-Clinical Data at ESMO Supporting MTL-CEBPA as Immunological Combination Treatment" (9/30 Press Release) ・https://minatx.com/wp-content/uploads/2019/09/20190930_MiNA_ESMO-Posters-Announcement_Final.pdf ・・・
※EMBO Workshop Tools for Structural Biology of Membrane Proteins: "Structure based Drug Design for GPCRs": Jana Broecker, Sosei Heptares. (10/7 14:30-15:00 Presenting) ※OTS 2019: "Late Breaking Talk: Activation of CEBPA in Myeloid Cells by saRNA in HCC Patients: The Emergence of an Immunomodulatory Switch for Anti-Cancer Therapy": Nagy Habib, MiNA Therapeutics. (10/16 16.25 Presenting) ※Novartis Q3 2019 Results. (10/22) ※AstraZeneca Q3 2019 Results. (10/24) ※AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics: "Identification of Small Activating RNAs that can Upregulate Immune Activation Tagets for Cancer Immunotherapy": David Blakey, MiNA Therapeutics. (10/29 12:30 Presenting) ※Medicinal Chemistry & Protein Degradation Summit: "RI Revitalises Drug Discovery & Drives AI": Jonthan Mason, Sosei Heptares. (10/28 15:00-16:00 Presenting) ※ERNEST First Meeting GPCR Pharmacology: Activation, Signalling and Drug Design: Invited Speakers: Chris Tate (MRC); Chris De Graaf (Sosei Heptares). Meeting Sponsored: Sosei Heptares. (10/28-30) ※DIA Oligonucleotide-Based Therapeutics Conference: "MTL-CEBPA, The First Small Activating RNA Therapy in Clinical Development": Nagy Habib, MiNA Therapeutics. (10/29 11:30-12:00 Presenting) ※Pfizer Q3 2019 Results. (10/29) ※MorphoSys Q3 2019 Interim Statement. (10/29) ※Allergan Q3 2019 Results. (10/30 Projected) ※武田薬品工業 2019年度 第2四半期決算 (10/31) ※第一三共 2020年3月期 第2四半期決算 (10/31) ※ペプチドリーム 2019年6月期第1四半期決算 (11/7) ※Sosei Group 2019年12月期第3四半期決算発表 (11/12) ・・・
※Sosei Heptares：創薬「構造ベース創薬技術を用いたアロステリックな新規GLP-1受容体拮抗薬HTL26119の同定」Bioorganic & Medicinal Chemistry Letters誌(8/12)掲載。(8/13up) ※ClinicalTrials(NCT03100825): Phase 3, A Long-term Safety Study of QVM149 in Japanese Patients with Asthma. (8/26update, "Completed") ※ACS National Meeting："Discovery of HTL-0027772, their lead OX1 Receptor Antagonist for the Treatment of Addiction Disorders": Sosei Heptares. (8/28 Presented) ※Sosei Heptares：実験医学「コリン作動性ムスカリンM1およびM4受容体候補薬の精神・神経疾患における認知・行動・心理症状への作用」Drug Discovery Today誌(9/6)発表。(9/9) ※Vectura Interim Results 2019: QVM149(EU), Further Milestone of $5.0m on approval with low single-digit royalties from launch (2020). [2024 Consensus Sales]: Ultibro: $562m, Seebri: $122m, QVM149: $240m. (9/10) ※Sosei Heptares：インベスターR&D Day：英国から創薬研究の各部門の優秀な研究者たちが来日し熱く語りました。(動画) http://www.c-hotline.net/Viewer/Default/SOSE7e3faa78c98723a9b5c63252057bece1 (9/12) ※日刊薬業：「そーせい、収益性重視に転換 田村CEO」収益が見える形に経営戦略を切り替えた。現時点で自社創製品の販売は考えていない。リスクを一定程度抑えて、収益性が株主に評価されるよう努める考え。(9/12) ※ClinicalTrials(NCT03381274): Phase 1b/2, Oleclumab(MEDI9447) EGFRm NSCLC Novel Combination Study. (MEDI9447 with Osimertinib or AZD4635, AZD4635 with MEDI9447): Record Verification September 2019. (9/12update)
※Sosei Heptares：創薬「前臨床候補薬カルシトニン遺伝子関連ペプチド(CGRP)受容体拮抗薬HTL0022562の創薬」SCI/RSC Medicinal Chemistryシンポジウム(9/11)にて発表。(9/13) ※ClinicalTrials (NCT04089553): Phase 2, Study of AZD4635 in Patients with Prostate Cancer: Actual Start: August 29, 2019/8/29, Estimated Completion: 2021/3/18. ("New Trial Record", "Recruiting": 9/13up) ※ClinicalTrials (NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery. ("New Trial Record", "Recruiting": 9/13up) ※日刊薬業：「全ての開発品で導出交渉を行っている。もし全開発品を導出し尽くしたとしても、新規ターゲットを作れるので困らない」「当社の強みは低分子創薬だ。新規モダリティは提携すればいい」と述べた。(9/17) ※ClinicalTrials(NCT02740985): Phase 1 Clinical Study of AZD4635 in Patients With Advanced Solid Malignancies: Record Verification September 2019. (9/17update) ※Discovery on Target: "Antagonists of the Adenosine 2a Receptor (AZD4635) to Reverse Tumor Suppression in the TME", "Targeting the Adenosine Pathway": Alwin Schuller, AstraZeneca. (9/17 Presented) ※Sosei Heptares Official Blog：「日刊薬業に田村CEOのインタビュー記事(9/17)が掲載」低分子創薬の可能性と今後の進捗を期待するパイプラインについて言及。https://drive.google.com/file/d/14EeBcYMnB1EsRbrwsaLzxzZLzDTQdDrH (9/18up) ※ClinicalTrials(NCT03980821): Phase 1, Study of AZD4635 in Japanese Patients with Advanced Solid Malignancies: Research Site, Chuo-ku, Japan: "Recruiting". (9/18update)
※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Research Site, Texas: "Recruiting". (9/18 update) ※四季報：【急改善】マイルストーン収入に新規提携開始による一時金等収入も上乗せ。営業黒字転換。新規提携等牽引し収益改善持続。【進捗顕著】ジェネンテック、武田薬品と大型提携続く。新規提携さらに開拓。(9/19更新) ※ClinicalTrials(NCT03158311): Phase 3, Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (ARGON). (9/20update, " Completed ") ※ILCA 2019: "Phase I Trial of MTL-CEBPA, a RNA Oligonucleotide Targeting the Transcription Factor C/EBP-α, Given as a Single Agent or in Combination with Sorafenib, in Patients with Advanced Hepatocellular Cance" (9/22 Presented) ※Sosei Heptares：開発「国立衛生研究所(NIHR)モーズリーバイオメディカルリサーチセンターの実験医学および神経イメージングコースで、当社実験医学(神経科学)チームのPradeep Nathan教授とGeor Bakker博士が招かれ、特別講義(9/20)」(9/24up) ※Sosei Heptares：イベントカレンダー：今後のイベント：「2019年度第3四半期決算発表 2019/11/12」(9/24up) ※ClinicalTrials(NCT04089735): Phase 2, Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery: Brief Summary (Change). (9/25 update) ※RDKit UGM 2019: "Traversing and Indexing Chemically Rich Documentation with RDKit to Aid GPCR-Based Drug Discovery": Rob Smith, Sosei Heptares. (9/26 Presented)
※European User Group Meeting: "Free Energy Perturbation for GPCR Structure-Based Drug Design": Francesca Deflorian and Chris de Graaf from Sosei Heptares. (9/26 Presented) ※Biotech in Europe Forum for Global Partnering & Investment: "Neuroscience - Development & Partnering Panel": (Panelists) Malcolm Weir, Executive Vice President & Chief R&D Officer, Sosei Heptares. (9/26) ※CICON 2019 Translating Science into Survival: "Novel Therapeutic Approach to Upregulate Immunostimulatory Targets for Cancer Therapy", MiNA Therapeutics. (9/26 Presented) ※ClinicalTrials (NCT04105335: MNA-3521-012): Phase 1, "A Study of MTL-CEBPA in Combination with a PD-1 Inhibitor in Patients with Advanced Solid Tumours (TIMEPOINT)". ("New Trial Record", "Not yet recruiting": 9/26up) ※MiNA Therapeutics PUBLICATIONS: "Targeted Delivery of C/EBPa-saRNA by RNA Aptamers Shows Anti-tumor Effects in a Mouse Model of Advanced PDAC". (9/26up) ※Fraunhofer ITEM: "ERS International Congress 2019". Poster Presentations, Fraunhofer ITEM will Present Selected Projects from its Respiratory Research. (9/26up) ※薬事日報：【そーせいグループ】GPCR創薬で他社導出し、製薬大手が行う創薬にも手を貸す。「26年までに次の収入源を、次の収入源を作っていきたい」と目標を掲げた。(9/27) ※ESMO 2019: "First-in-Human, First-in-Class Phase I Study of MTL-CEBPA, a RNA Oligonucleotide Targeting the Myeloid Cell Master Regulator C/EBP-α, in Patients with Advanced Hepatocellular Cancer (HCC)": (9/28 Presented)
※Sosei Heptares Official Blog：「薬事日報に当社会長兼社長CEO田村眞一のインタビュー記事(9/27)が掲載されました」当社独自のGPCR創薬基盤技術を柱とした、持続可能なビジネスモデルについて言及しています。(9/30up) ※ESMO 2019: "Targeting Myeloid-Derived Suppressor Cells and T Cells: Combination Treatment with MTL-CEBPA and PD-1 Antibody in a Mouse Syngeneic CT26 Model": (9/30 Presented) ※ERS International Congress 2019: "PALLADIUM Study Results", "IRIDIUM Study Results", "JAPANESE Study Results", "QUARTZ Study Results ". (9/30-10/1 Novartis Presented) ※Novartis: "Novartis announces positive results from Phase III IRIDIUM study of inhaled combination QVM149 in patients with uncontrolled asthma" (9/30 Press Release) ※MiNA Therapeutics: "MiNA Therapeutics Presents Clinical and Pre-Clinical Data at ESMO Supporting MTL-CEBPA as Immunological Combination Treatment" (9/30 Press Release) ※Sosei Heptares：「開発中の配合吸入剤QVM149がコントロール不良の喘息患者を対象とした第Ⅲ相IRIDIUM試験において良好な治療結果を示した」(10/1 Press Release) ※JapicCTI-183989(NCT03592862)：フェーズ2、レビー小体型認知症患者を対象としたHTL0018318の安全性、忍容性及び有効性を評価する無作為化二重盲検プラセボ対照用量範囲探索試験："試験中止(恒久的)" (9/27改訂, 10/1up) ※ClinicalTrials(NCT03592862): Phase 2, A Study to Assess Safety, Tolerability, and Efficacy of HTL0018318 in Patients With Dementia With Lewy Bodies (DLB). (10/1update, "Withdrawn") ※日本経済新聞夕刊：日本株番付「大幅高のマザーズ銘柄 業績好調組が上位に」2位のそーせいグループは1月の社長交代以降、東証1部上場を目指して黒字化路線にカジを切った。製薬大手との共同開発を進める点にも評価が高い。(10/2)
・・・ ※EMBO Workshop Tools for Structural Biology of Membrane Proteins: "Structure based Drug Design for GPCRs": Jana Broecker, Sosei Heptares. (10/7 14:30-15:00 Presenting) ※BioJapan2019：JITSUBO出展：最先端ペプチド合成技術、Molecular Hivingの最新情報を紹介。(10/9-11) ※OTS 2019: "Late Breaking Talk: Activation of CEBPA in Myeloid Cells by saRNA in HCC Patients: The Emergence of an Immunomodulatory Switch for Anti-Cancer Therapy": Nagy Habib. (10/16 16.25-16.40 Presenting) ※Novartis Q3 2019 Results. (10/22) ※AstraZeneca Q3 2019 Results. (10/24) ※AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics: "Identification of Small Activating RNAs that can Upregulate Immune Activation Tagets for Cancer Immunotherapy": David Blakey, MiNA Therapeutics. (10/2912:30 Presenting) ※Medicinal Chemistry & Protein Degradation Summit: "RI Revitalises Drug Discovery & Drives AI": Jonthan Mason, Sosei Heptares. (10/28 15:00-16:00 Presenting) ※ERNEST First Meeting GPCR Pharmacology: Activation, Signalling and Drug Design: Invited Speakers: Chris Tate (MRC); Chris De Graaf (Sosei Heptares). Meeting Sponsored: Sosei Heptares. (10/28-30) ※DIA Oligonucleotide-Based Therapeutics Conference: "MTL-CEBPA, The First Small Activating RNA Therapy in Clinical Development": Nagy Habib, MiNA Therapeutics. (10/29 11:30-12:00 Presenting) ※Pfizer Q3 2019 Results. (10/29) ※MorphoSys Q3 2019 Interim Statement. (10/29) ※Allergan Q3 2019 Results. (10/30 Projected) ※武田薬品工業 2019年度 第2四半期決算 (10/31) ※第一三共 2020年3月期 第2四半期決算 (10/31) ※Protein Structure Determination in Industry Meeting (PSDI 2019): Richard Henderson (MRC-LMB); Stacey Southall (Sosei Heptares). (11/3-5) ※ペプチドリーム 2019年6月期第1四半期決算 (11/7) ※Sosei Group 2019年12月期第3四半期決算発表 (11/12) ・・・
※Sosei Heptares 2時間前：(10/4) "Dr. Rie Suzuki, along with former and present peers from Sosei Heptares , recently published a Review article titled “Recent Developments in Therapeutic Peptides for the Glucagon-like Peptide 1 and 2 Receptors” in the Journal of Medicinal Chemistry."
※Sosei Heptares：知識：創薬「グルカゴン様ペプチド1および2受容体に関するペプチド医薬品開発の進捗」(10/4) By Rie Suzuki, Giles Brown, John Christopher, Conor Scully and Miles Congreve | Oct 4, 2019 サマリー： トランスレーショナル・サイエンス部門ディレクターの鈴木理愛博士が、OMass社のGiles Brown、ならびに当社研究員の John Christopher、Conor Scully、Miles Congreveとの共著で、 『グルカゴン様ペプチド1および2受容体に関するペプチド医薬品開発の進捗』と題した論文をJournal of Medicinal Chemistry誌で発表しました。 概要： グルカゴン様ペプチド-1（GLP-1）およびグルカゴン様ペプチド-2（GLP-2）は、プログルカゴン由来のペプチドであり、栄養素摂取に呼応して消化管内分泌細胞から分泌される。 これらの分子はジぺプチジルペプチターゼ-Ⅳにより速やかに不活化されるため、治療薬としての可能性が制限されている。 最近、GLP-1Rやグルカゴン受容体といったGPCRの立体構造が明らかになったことで、新規ペプチド医薬品として有望で革新的なペプチド分子の合理的設計が進んでいる。 新興領域の一つが、治療有効性を高めるため、2つ以上の薬理作用をもつ多機能型分子の創製である。 さらに、創薬では、ペプチドの送達ルートに代替性をもたせることで、患者の便宜性を高めるような戦略にも注力している。 こうした新たな戦略は、未だアンメットニーズの存在するヒトの疾患領域における、ペプチドをベースとした治療薬の広範な有用性を強く示している。 論文を読む（英語のみ）： ※Journal of Medicinal Chemistry: "Recent Developments in Therapeutic Peptides for the Glucagon-like Peptide 1 and 2 Receptors". ・Rie SuzukiGiles BrownJohn A. ChristopherConor ScullyMiles Congreve. ・Publication Date:October 2, 2019 https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b00835
Event update; ・・・ ※EMBO Workshop Tools for Structural Biology of Membrane Proteins: "Structure based Drug Design for GPCRs": Jana Broecker, Sosei Heptares. (10/7 14:30-15:00 Presenting) ※BioJapan2019：JITSUBO出展：最先端ペプチド合成技術、Molecular Hivingの最新情報を紹介。(10/9-11) ※OTS 2019: "Late Breaking Talk: Activation of CEBPA in Myeloid Cells by saRNA in HCC Patients: The Emergence of an Immunomodulatory Switch for Anti-Cancer Therapy": Nagy Habib. (10/16 16.25-16.40 Presenting) ※Novartis Q3 2019 Results. (10/22) ※AstraZeneca Q3 2019 Results. (10/24) ※AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics: "Identification of Small Activating RNAs that can Upregulate Immune Activation Tagets for Cancer Immunotherapy": David Blakey, MiNA Therapeutics. (10/2912:30 Presenting) ※Medicinal Chemistry & Protein Degradation Summit: "RI Revitalises Drug Discovery & Drives AI": Jonthan Mason, Sosei Heptares. (10/28 15:00-16:00 Presenting) ※ERNEST First Meeting GPCR Pharmacology: Activation, Signalling and Drug Design: Invited Speakers: Chris Tate (MRC); Chris De Graaf (Sosei Heptares). Meeting Sponsored: Sosei Heptares. (10/28-30)
※Sosei Heptares：「ジェネンテック社との提携」契約一時金と初期マイルストン合計で26百万米ドル(約28億円)受領。総額1,000百万米ドル(約1,085億円)超マイルストンや販売ロイヤルティ受領権利。(7/16) ※Sosei Heptares：「Formosa社より2.5百万米ドル(約2.7億円)のマイルストン受領」Formosa社が開発中のAPP13007の臨床試験実施申請が承認されマイルストンを達成。(7/18) ※Sosei Heptares：「シーブリおよびウルティブロの2019年第2四半期(2019年4月～6月)の業績」：ウルティブロ(売上112百万ドル)、シーブリ(売上34百万ドル)。(7/18) ※Sosei Heptares：「武田薬品との新規戦略提携」契約一時金と初期マイルストン合計で最大26百万米ドル(約28億円)を受領。総額1,200百万米ドル(約1,286億円)超のマイルストンやロイヤルティを受領する権利。(8/5) ※Sosei Group 2019年12月期第2四半期決算：売上収益5,056百万円、営業利益731百万円、税引前利益292百万円、純利益395百万円。業績見込みは据置。R&D・パイプライン等を引き続き拡充。(8/13) ※Sosei Group 2019年12月期上期ビジネスハイライト：-全事業分野において力強いモメンタムを継続-。事業の強化の点で格段の進捗が見られ、多くの戦略機会を十分に活用していくための体制を整えた。(8/13) ※Sosei Group 2019年12月期第2四半期決算説明会 ：全社的なビジネスの強化が進展：2019年度の戦略見通しに対する着実な進捗：黒字化へ向けて着実に進展：GPCRリーダーシップ拡大。(8/13) ※Sosei Heptares：創薬「構造ベース創薬技術を用いたアロステリックな新規GLP-1受容体拮抗薬HTL26119の同定」Bioorganic & Medicinal Chemistry Letters誌(8/12)掲載。(8/13up) ※ACS National Meeting："Discovery of HTL-0027772, their lead OX1 Receptor Antagonist for the Treatment of Addiction Disorders": Sosei Heptares. (8/28 Presented)
