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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

On April 6, 2021 Genmab reported the initiation of a share buy-back program to mitigate dilution from warrant exercises and to honor our commitments under our Restricted Stock Units program (Press release, Genmab, APR 6, 2021, View Source [SID1234577602]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The share buy-back program is expected to be completed no later than June 30, 2021 and comprises up to 200,000 shares.

The following transactions were executed under the program from March 29, 2021 to March 31, 2021:

Details of each transaction are included as an appendix to this announcement.

Following these transactions, Genmab holds 202,977 shares as treasury shares, corresponding to 0.31% of the total share capital and voting rights.

The share buy-back program is undertaken in accordance with Regulation (EU) No. 596/2014 (‘MAR’) and the Commission Delegated Regulation (EU) 2016/1052, also referred to as the "Safe Harbour Regulation." Further details on the terms of the share buy-back program can be found in our company announcement no. 11 dated February 23, 2021.

On April 6, 2021 Ribon Therapeutics, a clinical stage oncology company developing therapeutics targeting stress support pathways, reported that it will present one oral and four poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Virtual Annual Meeting (Week 1), taking place from April 10 to 15, 2021 (Press release, Ribon Therapeutics, APR 6, 2021, View Source [SID1234577618]). Abstracts are available at: www.aacr.org.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The breadth of new pre-clinical data that we are presenting this year at AACR (Free AACR Whitepaper) further validates our BEACON+ platform targeting novel cellular stress pathways," said Heike Keilhack, Ph.D., Senior Vice President of Biological Sciences, Ribon Therapeutics. "We are particularly encouraged by our research further elucidating the mechanism of action of our PARP7 inhibitor and lead asset, RBN-2397, and its potential for efficacy in numerous types of cancer."

Ribon Therapeutics will present the following from its development program and platform:

Abstract Title: RBN-2397: A potent and selective small molecule inhibitor of PARP7 that induces tumor-derived antitumor immunity dependent on CD8 T cells
Presenter: Joseph M. Gozgit, Ph.D., Director, Biological Sciences, Ribon Therapeutics
Date & Time: Sunday, April 11, 2021 at 2:00 PM ET
Session Type: Minisymposium
Session Title: New Therapeutics Targeting Molecular Drivers in Cancer
Abstract ID: 48
Summary:

RBN-2397 restores Type I interferon (IFN) signaling in cancer cells and researchers demonstrate that this is an on-target effect of inhibiting the catalytic activity of PARP7 and not PARP1. Researchers further show that the adaptive immune response was required for the antitumor effects of RBN-2397.
Abstract Title: Elevated PARP7 expression in select cancers identifies a target population for RBN-2397 therapy
Presenter: Jodie Wong, Research Associate, Ribon Therapeutics
Date & Time: Available for online viewing starting at 8:30 AM on Saturday, April 10
Session Type: E-Poster Session
Session Title: Biomarkers Predictive of Therapeutic Benefit
Abstract ID: 381
Summary:

RBN-2397 is a PARP7 inhibitor that induces cancer cell autonomous and immune stimulatory effects in preclinical models through enhanced Type I IFN signaling in cancer cells. Elevated PARP7 expression or amplification may identify cancer patients who could derive benefit from treatment with RBN-2397. Researchers showed the presence of PARP7 amplifications as well as high expression levels in several tumor types including non-small cell lung carcinoma, breast, and pancreatic ductal adenocarcinoma, providing evidence for the therapeutic relevance of PARP7 inhibition and highlighting potential patient selection strategies to identify those patients more likely to benefit from RBN-2397 treatment.
Abstract Title: Investigating the mechanism of PARP7 inhibition in Type I interferon signaling by arrayed CRISPR screening
Presenter: Bin Gui, Ph.D., Senior Scientist, Ribon Therapeutics
Date & Time: Available for online viewing starting at 8:30 AM on Saturday, April 10
Session Type: E-Poster Session
Session Title: Cellular Responses to Anticancer Drugs
Abstract ID: 1021
Summary:

To investigate the underlying mechanism of PARP7 inhibition and to determine the drivers of the differential sensitivity across cell lines, researchers performed arrayed CRISPR knockout screens, targeting approximately 240 genes in the nucleic acid sensing and IFN signaling pathways, in the presence and absence of PARP7 inhibition. The arrayed screens confirmed multiple hits from a previous genome-wide pooled synthetic/lethal CRISPR dropout screen, shedding light on the mechanism by which PARP7 acts as a critical suppressor of the innate immune response in tumor cells and demonstrating both redundancy and crosstalk between different nucleic acid-sensing pathways.
Abstract Title: Targeted Degradation of PARP14 Using a Heterobifunctional Small Molecule
Presenter: Tim J. Wigle, Ph.D., Senior Director, Biochemical & Cellular Pharmacology, Ribon Therapeutics
Date & Time: Available for online viewing starting at 8:30 AM on Saturday, April 10
Session Type: E-Poster Session
Session Title: Novel Targets and Pathways
Abstract ID: 1348
Summary:

RBN012811 is a heterobifunctional small molecule based on a catalytic inhibitor of PARP14 that binds in the enzyme’s NAD+-binding site and recruits the E3 ligase cereblon to ubiquitinate PARP14 and selectively target it for degradation. Researchers found that in PARP14 expressing cells, RBN012811 has a half-maximal degradation concentration (DC50) of 0.005 μM and it does not cause degradation of other PARP enzymes. In human primary macrophages, PARP14 degradation by RBN012811 led to a dose-dependent decrease of IL-10 release induced by IL-4 stimulation.
Abstract Title: Small molecule inhibitor of CD38 modulates its intra- and extracellular functions leading to antitumor activity
Presenter: Prashant B. Shambharkar, Ph.D., Senior Scientist, Ribon Therapeutics
Date & Time: Available for online viewing starting at 8:30 AM on Saturday, April 10
Session Type: E-Poster Session
Session Title: Novel Targets and Pathways
Abstract ID: 1344
Summary:

Inhibition of CD38 with a small molecule affects both intra- and extra-cellular CD38 activity and modulates key metabolites playing an important role in immunomodulation. Further, data indicate that CD38 is expressed at baseline in cancer and further increased by immune checkpoint inhibitor treatment. Finally, catalytic inhibition of CD38 can lead to antitumor activity in mouse cancer models.
Following its AACR (Free AACR Whitepaper) presentations, Ribon Therapeutics expects to make the poster presentations available on its corporate website via the following link: View Source

About RBN-2397

RBN-2397, is an orally available small molecule inhibitor of PARP7 that we are developing for the treatment of solid tumors. PARP7 is upregulated in response to cellular stress, including genomic instability in cancers, and acts as a brake on the cellular stress response by negatively regulating the Type I interferon response. By inhibiting PARP7 in tumor cells, RBN-2397 has been shown to directly inhibit cellular proliferation and restore interferon signaling to stimulate an innate and adaptive antitumor immune response. RBN-2397 is currently in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors. PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung, or SCCL, which represents approximately 30% of all non-small cell lung cancers.

On April 6, 2021 Volastra Therapeutics reported it will collaborate with Microsoft to develop tools that help detect drivers of cancer metastasis (Press release, Volastra Therapeutics, APR 6, 2021, View Source [SID1234577634]). These unique digital pathology tools will accelerate the development of promising new therapies for cancer and help identify the patients most likely to benefit.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Metastasis is one of the biggest unsolved challenges in cancer treatment, but new insights into tumor biology from our founders have laid the groundwork for major advancements in this field," said Charles Hugh-Jones, M.D., Chief Executive Officer at Volastra. "We are excited to work with Microsoft to apply data science to the challenges of cancer research. The digital tools we develop will fuel our drug discovery efforts and bring new hope to people living with cancer."

"We have seen the tremendous promise of advanced computation in the fields of medical diagnostics and drug discovery," said Desney Tan, Ph.D., Managing Director, Microsoft Health Futures. "The collaboration with Volastra will lead to potential advances in the development of therapies to prevent and treat cancer metastasis. We look forward to continued collaboration with Volastra to deliver solutions for the computational life sciences community."

The teams will work together on algorithms to identify markers that correlate with tumor metastatic behaviors. The collaboration will develop automated machine learning tools capable of rapidly and accurately integrating insights across multiple datasets, including pathology slides and three-dimensional tumor-derived organoids.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.