On April 6, 2021 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that members of its senior management team are scheduled to participate in the 20th Annual Needham Virtual Healthcare Conference on Monday, April 12, 2021 at 9:30 a.m. ET (Press release, CRISPR Therapeutics, APR 6, 2021, View Source [SID1234577620]).

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A live webcast of the event will be available on the "Events & Presentations" page in the Investors section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 14 days following each presentation.

On April 6, 2021 Overland ADCT BioPharma, a joint venture created by Overland Pharmaceuticals and ADC Therapeutics SA (NYSE: ADCT), reported the appointment of Eric Koo, BSc, MBA, as Chief Executive Officer (Press release, ADC Therapeutics, APR 6, 2021, View Source [SID1234577619]). Mr. Koo brings more than 25 years of pharmaceutical industry and business management experience to Overland ADCT BioPharma with a proven track record of executing successful drug approvals and launches across Asia.

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"Overland ADCT BioPharma has a tremendous opportunity to bridge the clinical gap between the U.S., Europe and Asia through the expanded reach of innovative cancer medicines like antibody drug conjugates," said Eric Koo, BSc, MBA. "It is an honor to assume the role of Chief Executive Officer and I look forward to working closely with both teams at Overland Pharmaceuticals and ADC Therapeutics to develop and commercialize the pipeline in greater China and Singapore."

Mr. Koo most recently served as Vice President, Head of Oncology Business Unit at Takeda China focusing on multiple myeloma and lymphoma. Prior to Takeda China, Mr. Koo served as Director, Oncology Business Unit and Director, Market Access, External Affairs & Key Account Management at Merck, Sharp and Dome (MSD) Taiwan. Prior to MSD, he served as Regional Marketing Director for APAC & Specialty Care BU Head, Malaysia/Singapore at Bayer APAC. Mr. Koo started his pharmaceutical career at Pfizer, spending 16 years in various sales, product management and marketing positions at both Pfizer Taiwan and Pfizer Emerging Market Asia & China, including six years as the China/APAC Regional Marketing Director for Oncology.

Mr. Koo earned his BSc in Pharmacy from Taipei Medical University and his MBA from the University of North Carolina at Charlotte, Belk College of Business.

"Eric joins Overland ADCT BioPharma at an important time in the joint venture’s evolution as the U.S. PDUFA date for Lonca quickly approaches this May," said Chris Martin, Chief Executive Officer of ADC Therapeutics. "We are thrilled to welcome a highly qualified, respected and visionary leader like Eric to lead Overland ADCT BioPharma in its quest to develop and commercialize Lonca and other ADCs for difficult-to-treat hematologic and solid tumor indications in greater China and Singapore."

"Eric’s deep expertise and history of expanding access to life-changing cancer therapies in greater China and beyond gives me great confidence in Overland ADCT Biopharma’s ability to fulfill its mission of bringing innovative ADC medicines to patients in Asia and around the world," said Ed Zhang, MBA, Co-founder of Overland Pharmaceuticals. "Since its launch in December 2020, Overland

ADCT BioPharma has submitted two clinical trial applications to evaluate Lonca, underscoring the differentiated scale, speed and execution of this strategic business model. We look forward to supporting the advancement of Overland ADCT BioPharma’s pipeline under Eric’s leadership."

The lead program in the Overland ADCT BioPharma pipeline is Lonca, an ADC composed of a humanized monoclonal antibody directed against human CD19 and conjugated to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Lonca has been evaluated by ADC Therapeutics in a pivotal Phase 2 clinical trial in patients with relapsed or refractory DLBCL and is in two ongoing trials – a Phase 1/2 trial in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma and a Phase 3 confirmatory trial in combination with rituximab in patients with relapsed or refractory DLBCL. The Overland ADCT BioPharma portfolio also includes the clinical-stage candidates ADCT-602 targeting CD22, which is currently in a Phase 1/2 clinical trial in patients with relapsed or refractory acute lymphoblastic leukemia, and ADCT-601 targeting AXL, which is currently in a Phase 1 clinical trial in patients with selected advanced solid tumors. ADCT-901 targeting KAAG1 is in preclinical development for the treatment of advanced solid tumors with high unmet medical needs.

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 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 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that Organon Finance 1 LLC plans to offer, subject to market conditions, euro-denominated senior secured notes due 2028, U.S. dollar-denominated senior secured notes due 2028 and U.S. dollar-denominated senior unsecured notes due 2031 (collectively, the "notes"), in connection with the previously announced spinoff of Organon & Co. ("Organon") from Merck (Press release, Merck & Co, APR 6, 2021, View Source [SID1234577617]). As part of the spinoff, the notes will be assumed by Organon and a Dutch private limited company and wholly owned subsidiary of Organon which will act as co-issuer of the notes.

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Organon intends to use the net proceeds from the notes offering, together with available cash on its balance sheet and borrowings under senior secured credit facilities which Organon anticipates entering into, to repay one or more intercompany loans or notes owed by Organon to a Merck affiliate and to pay fees and expenses related to the spinoff. The proceeds of the notes offering will be held in escrow until satisfaction of the conditions precedent to the spinoff and certain other escrow release conditions.

The notes have not been and will not be registered under the U.S. Securities Act of 1933, as amended (the "Securities Act"), any state securities laws or the securities laws of any other jurisdiction, and may not be offered or sold in the United States absent registration or an applicable exemption from registration. Accordingly, the notes are being offered and sold only to persons reasonably believed to be qualified institutional buyers in accordance with Rule 144A under the Securities Act and to non-U.S. persons outside the United States in reliance on Regulation S under the Securities Act.

This announcement is an advertisement and is not a prospectus for the purposes of Regulation (EU) 2017/1129 (as amended, the "Prospectus Regulation") or Regulation (EU) 2017/1129 as it forms part of domestic law by virtue of the European Union (Withdrawal) Act 2018 (the "UK Prospectus Regulation").

In member states of the European Economic Area, this announcement is directed only at persons who are "qualified investors" within the meaning of the Prospectus Regulation. In the United Kingdom, this announcement is directed only at persons who are "qualified investors" within the meaning of the UK Prospectus Regulation.

Manufacturer target market (MiFID II product governance / UK MiFIR product governance) is eligible counterparties and professional clients only (all distribution channels). No PRIIPs key information document has been prepared as not available to retail in the EEA. No UK PRIIPs key information document has been prepared as not available to retail in the UK.

In the United Kingdom, this announcement is directed only at persons (i) that have professional experience in matters relating to investments falling within Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "Order"); (ii) falling within Article 49(2)(a) to (d) ("high net worth companies, unincorporated associations etc.") of the Order; or (iii) at whom this announcement may otherwise be directed without contravention of Section 21 of the Financial Services and Markets Act 2000, as amended (all such persons together being referred to as "relevant persons"). This announcement must not be acted on or relied on by persons who are not relevant persons. Any investment or investment activity to which this announcement relates is available only to relevant persons and will be engaged in only with relevant persons.

This press release does not constitute an offer to sell, or the solicitation of an offer to buy, any security and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful.