On November 30, 2020 Imago BioSciences, Inc., ("Imago") a clinical-stage biotechnology company developing innovative treatments for myeloid diseases, reported the expansion of its global Phase 2b clinical study evaluating bomedemstat (IMG-7289) for the treatment of advanced myelofibrosis (MF) into Hong Kong, where the first patient has now been enrolled and dosed at the Department of Medicine, Queen Mary Hospital and the University of Hong Kong (Press release, Imago BioSciences, NOV 30, 2020, View Source [SID1234571943]). Myelofibrosis is a rare bone marrow cancer that interferes with the production of blood cells.

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In addition to Hong Kong, the Phase 2b study continues to actively enroll patients in the U.S., U.K., and E.U. The study is in the final stages of completing enrollment and continues to dose patients to evaluate safety, tolerability and efficacy.

"Patients with myelofibrosis around the world are still in need of new treatment options," said Hugh Young Rienhoff, Jr. M.D., Chief Executive Officer, Imago BioSciences. "We are progressing well with enrollment and are pleased to continue expanding our global Phase 2 study into new geographies like Hong Kong. We are encouraged by the signs of clinical activity and safety of bomedemstat as a treatment alternative for patients who do not benefit from the current standards of care."

Bomedemstat is an inhibitor of lysine-specific demethylase 1 (LSD1), an epigenetic regulator critical for self-renewal of malignant myeloid cells and the differentiation of myeloid progenitors. Data presented at the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in June demonstrated that the first-in-class LSD1 inhibitor was well tolerated with no dose-limiting toxicities or safety signals. Furthermore, recent data demonstrates the potential of bomedemstat as a monotherapy in intermediate-2 and high-risk patients with myelofibrosis who have become intolerant of, resistant to or are ineligible for a Janus Kinase (JAK) inhibitor.

Bomedemstat was recently granted PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA) for the treatment of MF. The EMA reviewed bomedemstat non-clinical and clinical data from the ongoing Phase 2 study. The PRIME initiative was launched by the EMA in 2016 to provide proactive and enhanced support to the developers of promising medicines with the view of accelerating their evaluation to reach patients faster.

About Bomedemstat (IMG-7289)

Bomedemstat is an orally available small molecule discovered and developed by Imago BioSciences that inhibits lysine-specific demethylase 1 (LSD1 or KDM1A), an enzyme shown to be vital in cancer stem/progenitor cells, particularly neoplastic bone marrow cells. In non-clinical studies, bomedemstat demonstrated robust in vivo anti-tumor efficacy across a range of myeloid malignancies as a single agent and in combination with other therapeutic agents. Bomedemstat is an investigational agent currently being evaluated in ongoing clinical trials (ClinicalTrials.gov Identifier:
NCT03136185, NCT04262141, NCT04254978 and NCT04081220).

Bomedemstat has U.S. FDA Orphan Drug and Fast Track Designation for the treatment of myelofibrosis and essential thrombocythemia, Orphan Drug Designation for treatment of acute myeloid leukemia and PRIME designation by the European Medicines Agency for the treatment of MF.

Bomedemstat is being evaluated in two open-label Phase 2 clinical trials for the treatment of advanced myelofibrosis (MF) and essential thrombocythemia (ET), bone marrow cancers that interfere with the production of blood cells. MF patients who are resistant to a Janus Kinase (JAK) inhibitor are eligible for the study of bomedemstat. ET patients who have failed one standard of care treatment are eligible for the bomedemstat ET study.

On November 30, 2020 Celleron Therapeutics, the UK-based company developing personalised medicines for cancer patients, reported the formation of a new spin out, SynOx Therapeutics, as a vehicle for the continued development of emactuzumab as an effective treatment for tenosynovial giant cell tumours (Press release, Celleron, NOV 30, 2020, View Source [SID1234571942]).

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Celleron established SynOx Therapeutics to complete clinical development and obtain marketing approval for emactuzumab. SynOx Therapeutics has attracted €37M venture funding co-led by life science investors HealthCap and Medicxi, joined by Forbion and Gimv. The investment allows SynOx to complete the development of emactuzumab for the treatment of diffuse tenosynovial giant cell tumours (dTGCT).

Emactuzumab is a clinical-stage humanised CSF-1R targeted antibody designed to deplete macrophages in tumour tissue. It has shown a favourable safety profile in patients and encouraging efficacy for TGCT, a rare disease characterised by the proliferation of macrophages in the synovial tissue of the joint and tendon sheath.

Professor Nick La Thangue, Chief Executive Officer of Celleron and SynOx commented: "We are very excited to be working on emactuzumab and feel privileged to be supported by a strong syndicate of leading investors. The successful launch of SynOx, as a single asset company with dedicated funding, reflects Celleron’s business model of spinning-out new assets and securing independent funding".

Professor David Kerr, Chief Medical Officer of Celleron and SynOx commented: "SynOx’s focus is on developing emactuzumab to provide the best possible therapeutic agent for patients suffering from TGCT, which remains a very debilitating disease with limited clinical options. I am sure that our deep understanding of emactuzumab’s mechanism of action will yield other tractable disease targets"

On November 30, 2020 Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY) reported that it has completed its conversion into an N.V., a public company under the laws of the Netherlands (naamloze vennootschap, "N.V.") effective from 28 November 2020 (Press release, Vivoryon Therapeutics, NOV 30, 2020, View Source [SID1234571935]). The Company will from that moment operate under the registered name Vivoryon Therapeutics N.V. and its statutory seat will be in Amsterdam, the Netherlands, while the administrative headquarters and the business operations will remain in Germany with locations in Halle (Saale) and Munich. The new legal form has no impact on the Company’s day-to-day operations.

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As a consequence of the conversion, the shareholders of Vivoryon Therapeutics AG will automatically become shareholders of Vivoryon Therapeutics N.V.. The shares will be trading under a new ISIN NL00150002Q7. The last trading date of the shares under the ISIN DE0007921835 and the first trading day of the shares under the new ISIN NL00150002Q7 will be announced as soon as possible by a press release . The central securities depository for the shares under ISIN NL00150002Q7 will be Euroclear Nederland (Nederlands Centraal Instituut voor Giraal Effectenverkeer B.V.). Trading in Vivoryon Therapeutics shares will not be affected by the conversion.

Dr. Ulrich Dauer, Chief Executive Officer of Vivoryon Therapeutics N.V., commented: "This conversion into anN.V. reflects the continued international focus of Vivoryon Therapeutics. We are convinced that this corporate transformation will be a gateway to new international investors and may also provide access to additional capital markets, such as the US stock market via an ADR program or a full NASDAQ listing, even though there are currently no specific plans in this regard. We look forward to continuing to execute on our growth strategy with additional opportunities gained by this corporoate conversion."

On November 29, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported it has entered into an agreement with the University of Michigan, through which the company may obtain the exclusive global rights to a MDM2 protein degrader developed using the Proteolysis-Targeting Chimeras (PROTACs) technology (Press release, Ascentage Pharma, NOV 29, 2020, View Source [SID1234571915]). The drug candidate is currently entering IND-enabling studies.

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MDM2 is a key regulator of the tumor suppressor p53 and one of the most potent inhibitors of apoptosis discovered thus far. It has high expression in tumors and plays a key role in the occurrence and development of tumors. Binding to the MDM2 protein with high affinity, MDM2 inhibitor blocks the MDM2-p53 interactions and restore the tumor-suppressing activity of p53.1 Meanwhile, these MDM2 inhibitors present some challenges, including dose-limiting hematological toxicities, thus the urgent need to develop new generation of MDM2-targeting therapies in the treatment of cancer. The PROTAC technology has emerged as a new and promising approach that induces the degradation of targeted proteins through the ubiquitin-proteasome system (UPS), and it has received widespread interest from both the scientific community and industries since its introduction. Compared to conventional "occupancy-driven" pharmacological modality, the "event-driven" PROTAC technology has many advantages, such as high potency, high selectivity, with catalytic mode of action, and the ability to target undruggable proteins.2

Prof. Shaomeng Wang, Ph.D., C-Founder of Ascentage Pharma and Chairman of its Scientific Advisory Board, and Warner-Lambert/Parke-Davis Professor in Medicine, Professor of Internal Medicine, Pharmacology and Medicinal Chemistry, Director of Michigan Center for Therapeutic Innovation, University of Michigan, is a leading researcher in the field. Through structure-function studies of their previously discovered MDM2 inhibitors using the PROTAC technology, Dr. Wang’s research team has obtained potent and efficacious MDM2 degraders that could effectively induce rapid degradation of MDM2. The lead MDM2 degrader has achieved complete and durable tumor regression in a xenograft tumor model in mice3.

"As a new strategy to induce protein degradation, PROTAC has emerged as a novel modality in drug discovery," said Dr. Wang. "Studies showed, PROTAC-induced MDM2 degradation can not only enhance the potency of MDM2 inhibitors, but also maintain a long-lasting suppression of MDM2 protein levels, providing a new strategy to the treatment of MDM2-driven tumors such as leukemia. We look forward to the further development of the asset by Ascentage Pharma."

"The emergence of the PROTAC technology represents another breakthrough in the identification of small molecule drugs. The technology has received tremendous interest for its ability to target undruggable proteins," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "We are very pleased to reach this agreement with the University of Michigan, to begin the assessment of this PROTAC-based MDM2 degrader and potentially bring this important addition to our existing pipeline. Through the assessment and potential development of the MDM2 degrader, we hope soon that it will offer an effective therapy for serious unmet medical needs."

References:

Zhao, Y.; Aguilar, A.; Bernard, D.; Wang, S. Small-molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 inhibitors) in clinical trials for cancer treatment. J. Med. Chem. 2015, 58, 1038−1052.
Lai, A. C.; Crews, C. M. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev. Drug Discov. 2017, 16, 101-114.
Ryan P. Wurz and Victor J. Cee. Targeted Degradation of MDM2 as a New Approach to Improve the Efficacy of MDM2-p53 Inhibitors. J. Med. Chem. 2019, 62, 445−447.

On November 29, 2020 Sorrento Therapeutics, Inc. (NASDAQ: SRNE, "Sorrento"), reported that Dr. Henry Ji, Chairman and CEO, will be participating in the Piper Sandler 32nd Annual Virtual Healthcare Conference (Press release, Sorrento Therapeutics, NOV 29, 2020, View Source [SID1234571914]).

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A pre-recorded presentation is made available to participants and the public, in addition to 1 on 1 virtual meetings with selected investors taking place between 11/30/20 and 12/03/20.