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.

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"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 SQZ Biotechnologies (NYSE:SQZ), a cell therapy company developing novel treatments for multiple therapeutic areas, reported that management will be participating in multiple investor conferences in April 2021 (Press release, SQZ Biotech, APR 6, 2021, View Source [SID1234577633]). Armon Sharei, PhD, chief executive officer, will present a corporate overview at the 20th Annual Needham Virtual Healthcare Conference taking place April 12-15, 2021 and will participate in a cell therapy focused panel at the Canaccord Horizons in Oncology Virtual Conference on April 15, 2021. The company will also be hosting one on one meetings at both conferences.

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Needham Virtual Healthcare Conference
Presentation: Tuesday, April 13, 2021, 3:45pm EDT

Canaccord Horizons in Oncology Virtual Conference
Panel: Thursday, April 15, 2021, 1:00pm EDT

More information and the webcast for the presentation at Needham will be available on the Investors & Media section of the SQZ website. The webcast will be available for 90 days following the presentation.

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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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

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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.

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]).

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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

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"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.