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.

On April 6, 2021 MyBiotics Pharma Ltd., a microbiome therapeutics company, and Hadasit Medical Research Services and Development Ltd., the technology transfer office of Hadassah Medical Center, reported that they have entered into a research collaboration and licensing agreement for the identification of microbiome-based therapeutics that will enhance the response to and reduce adverse effects of anti-PD-1 and anti-PD-L1 in melanoma patients (Press release, MyBiotics, APR 6, 2021, View Source [SID1234577652]).

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The collaboration will combine Hadassah’s knowhow and expertise in immunotherapy treatment of melanoma patients with MyBiotics’ proprietary microbiome technologies enabling development of novel therapeutics. The two-year joint research project will be conducted by researchers from MyBiotics together with a team of researchers at Hadassah Cancer Research Institute headed by Prof. Michal Lotem, MD., Head of the Center for Melanoma and Cancer Immunotherapy, Department of Oncology at Hadassah Medical Center. It will be funded by MyBiotics, which has an exclusive license for all data and inventions stemming from the collaboration.

The research is aimed at assessing the composition of the gut microbiome and secondary metabolites (organic compounds produced by the gut bacteria) in up to 100 melanoma patients treated with PD-1/PD-L1 checkpoint inhibitors, some of which already exhibited long-term response to the treatment. Stool and blood samples will be collected at various time points along the treatment, for the purpose of identifying microbiome components that promote treatment success.

"Recent research supports the important role played by the microbiome in promoting the success of cancer immunotherapies, and points to the possibility of influencing the composition of the microbiome as an adjunct treatment," stated David Daboush, CEO of MyBiotics Pharma. "In this collaboration with Hadassah we will leverage Mybiotics’ SuperDonor whole microbiome recovery technology in combination with the MyLiveIn computational and predictive tools to advance research in order to unravel new layers of understanding and findings that will enable the design of effective microbiome-based therapeutics."

"We look forward to the joint research with the team at Hadassah Cancer Research Institute, who bring excellent clinical capabilities combined with innovative thinking and expect this will be a significant partnership that will lead to better treatment options for oncology patients within the next few years," Daboush added.

"For years I have strived to study what was driving long-term survival of melanoma patients who did well beyond expectations," stated Prof Michal Lotem, and added, "This collaboration gives us advanced molecular and genomic tools to analyze treatment success. After years of studying how cancer deceives us, I cannot wait to translate lessons of the past to therapies of the future."

"This collaboration is an excellent example of the kind of partnerships we strive to create between medical companies and hospital-based research centers. I trust that the unique combination of scientific excellence and clinical expertise will work for the benefit of patients in Israel and worldwide", stated Dr. Tamar Raz, the CEO of Hadasit.

MyBiotics has developed breakthrough and robust culturing, fermentation and delivery technologies for generating a highly stable and diverse bacterial community that can be efficiently delivered to the gut and can reliably restore microbiome equilibrium. These technologies are effective for single microbes, complex microbial consortia and whole microbiome products, and are integrated with a computational AI platform which enables the design of unique microbial consortia and whole microbiome profiles. The technologies are highly potent and suitable for patients with microbiome-related medical conditions or for those who use antibiotics. Preclinical studies have shown that MyBiotics’ products deliver enhanced durability in various gastrointestinal and manufacturing conditions, enable targeted release in different gastrointestinal locations and exhibit robust colonization in the gut.

About the Microbiome and Cancer Immunotherapy

In the last 5 years, studies elucidating the possible contribution of the microbiome to cancer development and response to treatments has been at the forefront of scientific research. Findings have shown, for example, that broad-spectrum antibiotics can reduce the efficiency of checkpoint inhibitors. In addition, studies have pointed to differences between microbiomes of patients responding to immunotherapy and those who do not respond to treatment. In animal models, tweaking the microbiome or adding secondary metabolites thereof, influenced the efficiency of cancer immunotherapy. These findings and others support the potential of changing the microbiome composition as a tool for improving the efficacy and reducing the toxicity of checkpoint inhibitor immunotherapy in cancer patients.

On April 6, 2021 OBI Pharma, Inc. (TPEx: 4174) reported the data highlighting the characteristics and antitumor efficacy of OBI-3424 and animal studies of OBI-998, as well as the T-cell inhibitory roles of Globo-H and SSEA-4 in the tumor microenvironment, will be presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting from April 10–15, 2021 (Press release, OBI Pharma, APR 6, 2021, View Source [SID1234577650]).

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OBI’s Chief Scientific Officer, Ming-Tain Lai, Ph. D stated that "OBI Pharma is proud to present at the AACR (Free AACR Whitepaper) Annual Meeting our latest findings on our Cancer portfolio products, OBI-3424 and OBI-998. OBI-3424’s impressive anti-AKR1C3 tumor activities in various cancer models, and enhanced efficacy when used in combination with standard-of-care chemotherapy. We are also excited to share, for the first-time, results from our early development program of OBI-998, an SSEA-4 antibody-drug conjugate." "Our research team have revealed interesting T-Cell inhibitory activities of Globo H and SSEA-4 in the tumor microenvironment. We will continue our investigation on the immunosuppressive activities of Globo H and SSEA-4, and the potential combination uses of anti-Globo H and Anti-SSEA-4 products with other cancer immunotherapeutic agents," added Dr. Lai.

The e-posters will be available for browsing at the virtual AACR (Free AACR Whitepaper) Annual Meeting from 8:30 a.m. ET on April 10–June 21 and on the OBI Pharma website (www.obipharma.com) on April 11.

Title: Selective and Broad Anti-tumor Activity of AKR1C3-activated Prodrug AST-3424/OBI-3424

Poster Number: 1220 / Abstract number: 1062

Authors: Fanying Meng 1, Wan-Fen Li 2, Donald Jung 1, Chun-Chung Wang 2, Tianyang Qi 1, Chi-Sheng Shia 2, Ren-Yu Hsu 2, Yin-Cheng Hsieh 2, Jianxin Duan 1.

(1) Ascentawits Pharmaceuticals, Ltd., Shenzhen, China.

(2) OBI Pharma, Inc., Taipei, Taiwan.

Title: Preclinical characterization of a novel SSEA4-targeting antibody drug conjugate, OBI-998

Poster number: 955 / Abstract number: 1238

Authors: I-Ju Chen, Chun-Chung Wang, Chi-Sheng Shia, Chung-Chen Su, Chi-Huan Lu, Hui-Wen Chang, Ping-Tzu Chiu, Yueh-Chin Wu, Ming-Tain Lai, Wei-Chien Tang, Hsin-Yi Tung, Ren-Yu Hsu.

(OBI Pharma, Inc., Taipei, Taiwan)

Title: Inhibitory activity of Globo-H and SSEA-4 on activated T cells

Poster number: 3176 / Abstract number: 1294

Authors: Tzer-Min Kuo, Chin-Chan Lee, Jiann-Shiun Lai, Chung-Chen Su and Ming-Tain Lai.

(OBI Pharma, Inc., Taipei, Taiwan)

About OBI-3424

OBI-3424 is a first-in-class novel small-molecule prodrug that selectively targets cancers overexpressing the enzyme aldo-keto reductase 1C3 (AKR1C3), and selectively releases a potent DNA alkylating agent in the presence of the AKR1C3 enzyme. This selective mode of activation distinguishes OBI-3424 from traditional alkylating agents, such as cyclophosphamide and ifosfamide, which are non-selective.

AKR1C3 overexpression has been documented in a number of treatment-resistant and difficult-to-treat cancers including hepatocellular carcinomas (HCC), castrate-resistant prostate cancer (CRPC), and T-cell acute lymphoblastic leukemia (T-ALL). AKR1C3 is highly expressed in up to 15 solid and liquid tumors.

Furthermore, individualized patient selection by staining for AKR1C3 overexpression by immunohistochemistry can be performed based on tumor biopsies or circulating tumor cells to identify patients with other tumor types most likely to respond to treatment with OBI-3424, and thus offering the possibility for a streamlined clinical development strategy.

About OBI-998

OBI-998 is a novel ADC comprising a humanized anti-SSEA4 antibody that is conjugated to the highly potent microtubule-disrupting agent monomethyl auristatin E (MMAE). It possesses desired properties such as high target specificity, rapid internalization, potent cytotoxicity, and significant bystander effects. OBI-998 showed high level of deposition and persistent presence of MMAE in tumors and significant anti-tumor efficacy in variety of animal models. OBI-998 is currently in preclinical research and development.