On April 6, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, reported that the National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for a Phase I clinical trial to evaluate safety and tolerability of ATG-019 (monotherapy or combined with niacin ER) in patients with advanced solid tumors or non-Hodgkin’s lymphoma (NHL) in China (Press release, Antengene, APR 6, 2021, View Source [SID1234577709]).

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As an orally bioavailable dual PAK4/NAMPT inhibitor, ATG-019 can lead to antitumor effects through energy depletion, inhibition of DNA repair, cell cycle arrest, inhibition of proliferation, and ultimately cell apoptosis. Hematological and solid tumor cells that are dependent on both PAK4 and NAMPT pathways may be susceptible to single-agent anti-tumor activity by ATG-019. ATG-019 has clear preclinical anti-tumor activity and a superior pharmacokinetics (PK) and safety profile making it an attractive novel drug candidate. Antengene has recently been conducting a Phase I clinical trial (TEACH) of ATG-019 in advanced solid tumors and NHL in Taiwan.

"The NMPA‘s approval of the IND application for ATG-019 indicates the potential of this drug to be applied to Chinese patients. We look forward to initiating the first clinical trial of ATG-019 in mainland China," said Dr. Jay Mei, Founder, Chairman and CEO of Antengene. "ATG-019 is an orally available dual PAK4/NAMPT inhibitor that achieves synergistic antitumor effects through the co-inhibition of the two pathways. We believe that ATG-019, as a novel agent under investigation, can potentially provide an additional treatment option for patients with advanced solid tumor and NHL."

About ATG-019
ATG-019 is a global first-in-class oral dual PAK4/NAMPT inhibitor developed by Karyopharm Therapeutics Inc. (NASDAQ: KPTI). Antengene reached an exclusive agreement of cooperation and authorization with Karyopharm and obtained the exclusive development and commercialization rights of ATG-019 in multiple Asia-Pacific markets, including Greater China, South Korea, Australia, New Zealand and ASEAN countries.

PAK4 is a signaling protein regulating numerous fundamental cellular processes, including intracellular transport, cellular division, cell shape and motility, cell survival, immune defense and the development of cancer. PAK4 interacts with many key signaling molecules involved in cancer development such as beta-catenin, CDC42, Raf-1, BAD and myosin light chain. NAMPT is a pleiotropic protein with intra- and extra-cellular functions as an enzyme, cytokine, growth factor, and hormone that can be found in a complex with PAK4 in the cell. In preclinical mouse models, ATG-019 in combination with anti-PD-1 therapies showed improved antitumor efficacy over anti-PD-1 monotherapy, indicating the potential of the combined therapy to treat anti-PD-1 resistant patients.

Antengene is conducting a Phase I clinical trial of ATG-019 in Taiwan in patients with advanced NHL and solid tumors and are planning to conduct clinical trials exploring its combination potential with other agents.

On April 6, 2021 I-Mab (the "Company") (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, and ABL Bio, Inc. (Kosdaq:298380, hereafter "ABL"), a South Korean biotech specializing in bispecific antibody technology, reported that the first patient has been dosed in a phase 1 trial for bispecific antibody TJ-L14B/ABL503 (Press release, I-Mab Biopharma, APR 6, 2021, View Source [SID1234577685]). The phase 1 clinical trial is an open-label, multi-center, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), preliminary antitumor activity, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of TJ-L14B/ABL503 in locally advanced or metastatic solid tumors (NCT04762641).

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Being developed jointly with ABL, TJ-L14B/ABL503 is a differentiated PD-L1-based bispecific antibody with the PD-L1 arm as the tumor-dependent T-cell activator and the 4-1BB arm as the conditional T cell activator upon tumor engagement. Using ABL’s ‘Grabody-T’ bispecific antibody platform technology, TJ-L14B/ABL503 stimulates 4-1BB activation only in the presence of PD-L1 expressing tumor cells to minimize the risk of off-tumor toxicity. Preclinical studies have demonstrated that the bispecific antibody shows better anti-tumor activity than equimolar doses of single agents alone or in combination.

"Immune checkpoint inhibitors, such as PD-L1, have created a new paradigm for cancer treatment; however, they have limitations in their efficacy and response rates," said Dr. Joan Shen, CEO of I-Mab. "Co-targeting of PD-L1 with a bispecific antibody molecule using this particular platform is postulated to enhance antitumor activity while ensuring the safety of the patients. It may provide an alternative therapeutic approach for patients who have not responded to existing treatments."

"We are very pleased to advance the clinical development of TJ-L14B/ABL503 as planned.," said Dr. Sang Hoon Lee, CEO of ABL. "With phase 1 trial for TJ-L14B/ABL503 being the first testbed for our Grabody-T bispecific antibody platform, we look forward to validating our company’s technology in the field of cancer immunotherapy."

"We are excited to be the first center to conduct this study for TJ-L14B/ABL503," said Dr. Anthony W. Tolcher, FRCPC, FACP, CEO and director of clinical research at NEXT Oncology. "TJ-L14B/ABL503 has demonstrated potential to overcome the adverse toxicity issues of anti-4-1BB antibodies. In collaboration with I-Mab and ABL, we hope for a thorough evaluation to deliver a highly promising treatment for the benefit of cancer patients." NEXT Oncology is a phase 1 center in the U.S. dedicated to providing patients with advance cancer access to the newest cancer treatments available.

On April 6, 2021 HiFiBiO Therapeutics reported that it will share with the scientific community preclinical data for novel monoclonal antibodies for clinical development as new cancer immunotherapeutic options (Press release, HiFiBiO Therapeutics, APR 6, 2021, View Source [SID1234577676]). Two of these programs, HFB3010 and HFB2003, are slated to enter Phase I clinical trials later this year.

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The team will present highlights in four poster sessions at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting, April 10-15 and May 17-21, 2021. These four programs highlight the continual evolution of HiFiBiO Therapeutic’s robust pipeline and unique capability to develop novel antibodies to address unmet medical needs.

"We are excited to share the latest data from four of our programs with the oncology research community at AACR (Free AACR Whitepaper). These include our two most advanced oncology antibodies, HFB301001, a highly differentiated second-generation OX40 agonist, and HFB200301, a novel anti-TNFR2 agonist bridging innate and adaptive immunity. We also share the profile of antibody candidates against CXCR5 and Galectin-9 that hold exceptional promise for the treatment of hematological malignancies and solid tumors," said Francisco Adrian, Global Head of Research.

"Applying single-cell immuno-profiling insights from our groundbreaking DIS platform to our oncology trials is a step towards realizing one of greatest ambitions; to deliver significant benefit to patients through targeted immunotherapies. Our novel biomarker strategy by analyzing tumor immune profiles at the single cell level aims to enrich for responding patients in our upcoming HFB3010 and HFB2003 clinical studies," said Andreas Raue, PhD, Global Head of Drug Intelligent Science.

The four HiFiBiO Therapeutics pipeline programs being presented at AACR (Free AACR Whitepaper) are:

HFB3010 (OX40)

HFB301001 is a second-generation novel, fully human IgG1 class OX-40 agonistic antibody with an optimized pharmacological profile. In contrast to previous anti-OX-40 antibodies, the agonistic activity of HFB301001 is further enhanced in the presence of the endogenous ligand OX-40L, does not result in reduced levels of OX-40 on T-cells, and leads to superior anti-tumor activity in a human OX-40 knock-in mouse model compared to a benchmark antibody. HiFiBiO is also applying a biomarker strategy by leveraging its DIS platform to select patients who may benefit the most from treatment.

HFB2003 (TNFR2)

HFB200301 is a first-in-class agonistic anti-TNFR2 candidate antibody that binds potently and selectively to TNFR2, recognizes cyno TNFR2, and induces CD4 and CD8 T-cell activation and proliferation cooperatively with TNFα without requiring crosslinking. In vivo, HFB200301 demonstrates potent antitumor activity alone and combined with anti-PD-1. It is also well tolerated in mice and NHPs. HiFiBiO is also utilizing its DIS platform to implement a biomarker strategy for HFB2003.

HFB2009 (Gal-9)

Galactoside-binding lectin Galectin 9 (Gal-9) is a key pleiotropic immunosuppressive modulator present in the tumor microenvironment. HFB9-2, an anti-Gal-9 blocking antibody with demonstrated single agent anti-tumor activity in a mouse cancer model, offers improved survival in combination with anti-PD-1 therapy as compared to anti-PD-1 alone, and shows good tolerability in NHPs.

HFB1002 (GPCR)

CXCR5 is a GPCR expressed on B cells, as well as on follicular helper T cells. CXCR5 plays a key role in the migration of B cells to germinal centers and the production of autoantibodies. CXCR5 is implicated in autoimmune diseases, such as Sjögren syndrome, and in cancers such as B cell lymphomas and solid tumors, where it has been associated with metastasis and poor prognosis. HiFiBiO generated and characterized a novel anti-hCXCR5 blocker with potent ADCC activity to treat tumor and autoimmune diseases.

On April 7, 2021 PsiOxus Therapeutics, Ltd. (PsiOxus) reported an updated agreement to advance its clinical collaboration with Bristol Myers Squibb (NYSE: BMY) to evaluate the safety, tolerability, and preliminary efficacy of PsiOxus’ tumor re-engineering platform, in combination with Bristol Myers Squibb’s PD-1 immune checkpoint inhibitor Opdivo (nivolumab) to treat a range of tumor types in late-stage cancer patients (Press release, PsiOxus Therapeutics, APR 7, 2021, View Source [SID1234577657]).

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The first stage of this collaboration combined Bristol Myers Squibb’s Opdivo with PsiOxus’ enadenotucirev in the Phase 1 SPICE study to determine the safety and tolerability of combining these two agents, and to optimise the combination intravenous dosing regimen. The revised collaboration announced today will build upon the initial study data and will combine Opdivo with PsiOxus’ NG-641.

NG-641, is a tumor re-engineering product using PsiOxus’ proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn) platform based upon the enadenotucirev vector. NG-641 is a systemically administered product that encodes for the tumor selective delivery of an anti-FAP / anti-CD3 bispecific, interferon alpha, CXCL9 and CXCL10. Fibroblast Activating Protein (FAP) is selectively upregulated on the cancer associated fibroblasts (CAF) that play an important role in the immune suppressive tumor microenvironment found in many stromally dense tumors that are refractory to checkpoint inhibitors. Using a bispecific to drive T-cell mediated killing of CAF is designed to remove stroma and thereby reduce immune suppression within the tumor. A combination of NG-641 and a checkpoint inhibitor such as Opdivo may thus provide an optimal treatment strategy for certain stromally dense tumors.

"We are delighted to continue our collaboration with Bristol Myers Squibb and to investigate the clinical combination of NG-641 with Opdivo in several tumor types," stated John Beadle, M.D., Chief Executive Officer, PsiOxus. "We believe that NG-641 provides a unique combination of tumor modulatory elements that may synergise with the known efficacy of Opdivo to bring patient benefits for a wide range of tumor types."

Opdivo is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. Opdivo is a registered trademark of Bristol Myers Squibb.

Under the terms of this agreement, PsiOxus will be responsible for conducting the Phase 1 study with patient recruitment expected to start in the third quarter of 2021.

On April 6, 2021 Gan & Lee Pharmaceuticals Co., Ltd. (hereinafter referred to as Gan & Lee, stock code: 603087.SH), a global biopharmaceutical company, reported that the European Medicine Agency (EMA) Committee for Orphan Medicinal Products granted orphan drug designation for the investigational compound GLR2007, for the treatment of glioma (Press release, Gan and Lee Pharmaceuticals, APR 6, 2021, View Source [SID1234577644]).

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Glioma is a broad term describing neuroepithelial tumors originating from glial cells of the central nervous system, including astrocytic tumors such as glioblastomas (GBM). GBM is one of the most aggressive primary brain tumors and has median survival of 12 to 15 months, despite advances in surgery, chemotherapy, and radiation therapy1. Gan & Lee’s current clinical development program for GLR2007, a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor, is investigating the treatment of advanced solid tumors which has the potential to provide physicians and patients with a much-needed treatment option.

"The EMA’s positive decision for GLR2007’s orphan drug designation is another milestone in the clinical development program as this compound was also recently granted ODD by the FDA," Dr. Michelle Mazuranic, Head of Global Medical Affairs, Gan & Lee. The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining market approval.

Orphan drug designation in the European Union (EU) is granted by the European Commission based on a positive opinion issued by the EMA Committee for Orphan Medicinal Products. To qualify, an investigational medicine must be intended to treat a seriously debilitating or life-threatening condition that affects fewer than five in 10,000 people in the EU, and there must be sufficient non-clinical or clinical data to suggest the investigational medicine may produce clinically relevant outcomes and the potential for significant benefit over currently approved products. The EMA orphan drug designation can provide companies with clinical protocol assistance, differentiated evaluation procedures for Health Technology Assessments in certain countries, access to a centralized marketing authorization procedure valid in all EU member states, and reduced regulatory fees. After being granted marketing approval, compounds with orphan designation are eligible for 10 years of market exclusivity.