On November 9, 2020 Bristol-Myers Squibb Company (NYSE:BMY) reported that it has priced a public offering (the "Offering") of senior unsecured notes in a combined aggregate principal amount of $7 billion (collectively, the "Notes"). The Notes will be issued in six tranches: (i) $1,500,000,000 in aggregate principal amount of 0.537% notes due 2023, (ii) $1,000,000,000 in aggregate principal amount of 0.750% notes due 2025, (iii) $1,000,000,000 in aggregate principal amount of 1.125% notes due 2027, (iv) $1,250,000,000 in aggregate principal amount of 1.450% notes due 2030, (v) $750,000,000 in aggregate principal amount of 2.350% notes due 2040 and (vi) $1,500,000,000 in aggregate principal amount of 2.550% notes due 2050 (Press release, Bristol-Myers Squibb, NOV 9, 2020, View Source [SID1234570907]). Bristol Myers Squibb expects that the closing of the Offering will occur on November 13, 2020, subject to the satisfaction of customary closing conditions.

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 Offering is being conducted in connection with the previously announced proposed acquisition ("Acquisition") of MyoKardia, Inc. ("MyoKardia"), which is expected to close in the fourth quarter of 2020. Bristol Myers Squibb intends to use the net proceeds of the Offering to fund a portion of the aggregate cash consideration payable to MyoKardia shareholders in connection with the Acquisition and to pay related fees and expenses, with any remaining proceeds being used for general corporate purposes. The Offering is not conditioned upon the consummation of the Acquisition. However, if (i) the Acquisition has not been consummated on or prior to June 30, 2021 or (ii) prior to such date, Bristol Myers Squibb notifies the trustee in respect of the Notes that Bristol Myers Squibb will not pursue the consummation of the Acquisition, then Bristol Myers Squibb will be required to redeem all outstanding Notes at a special mandatory redemption price equal to 101% of the aggregate principal amount of the Notes, plus accrued and unpaid interest, if any, to, but not including, the applicable special mandatory redemption date.

Citigroup Global Markets Inc., J.P. Morgan Securities LLC, Barclays Capital Inc., and Deutsche Bank Securities Inc. are acting as joint book-running managers for the Offering.

The Offering of the Notes is being made pursuant to an effective shelf registration statement (including a prospectus and preliminary prospectus supplement) (File No. 333-236272) filed with the U.S. Securities and Exchange Commission (the "SEC"). You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, Bristol Myers Squibb, any underwriter or any dealer participating in the Offering will arrange to send you the prospectus and the preliminary prospectus supplement (or, if available, the prospectus supplement) if you request it by contacting Bristol Myers Squibb Investor Relations or Citigroup Global Markets Inc. at c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by telephone at 1-800-831-9146, J.P. Morgan Securities LLC at c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717 or by telephone at 1-866-803-9204, Barclays Capital Inc. at c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by email at [email protected] or by telephone at 1-888-603-5847, or Deutsche Bank Securities Inc. at Attn: Prospectus Department, 60 Wall Street, New York, New York 10005, by email at [email protected] or by telephone at 1-800-503-4611.

On November 9, 2020, Sierra Oncology, Inc. (the "Company") reported that it entered into an amendment (the "Amendment") to the License Agreement with CRT Pioneer Fund LP ("CPF"), dated September 27, 2016 (the "CRT License Agreement") (Filing, 8-K, Sierra Oncology, NOV 9, 2020, View Source [SID1234570762]).

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!

Pursuant to the CRT License Agreement, the Company made a one-time upfront payment of $7.0 million to CPF in October 2016 and paid $2.0 million to CPF in January 2017 for the successful transfer of two ongoing Phase 1 clinical trials. Pursuant to the terms of the original CRT License Agreement, additional milestone payments of up to an aggregate of $319.5 million was payable to CPF upon the achievement of certain developmental, regulatory and commercial milestones, including a milestone payment of $7.5 million upon the dosing of the first patient in the first Phase 1 trial of SRA737 in the United States, and a payment of $12.0 million upon the dosing of the first patient of a randomized Phase 2 trial of SRA737.

Pursuant to the terms of the Amendment, the Company has agreed to decreased additional milestone payments of up to an aggregate of $290.0 million that may be payable to CPF upon the achievement of certain developmental, regulatory and commercial milestones, including a milestone payment of $2.0 million upon the dosing of the first patient of the first trial of SRA737 following the effective date of the Amendment.

In the event that the milestone payment for Milestone Event, as defined in the CRT License Agreement, but no milestone payment for an earlier Milestone Event has been paid, then the milestone payment attached to the earlier Milestone Event will become due and payable contemporaneously with the payment for the later Milestone Event. These milestones will be accrued once they are considered probable of occurring.

In addition, the Company remains required to pay CPF, on a product-by-product and country-by-country basis, tiered high single-digit to low double-digit royalties on the net sales of any product successfully developed.

The foregoing summary of the Amendment is not complete and is qualified in its entirety by reference to the complete text of the Amendment, which the Company intends to file as an exhibit to its Annual Report on Form 10-K for the year ending December 31, 2020.

On November 9, 2020 Menarini Silicon Biosystems, the pioneer of liquid biopsy technology, reported the publication of a research study providing support for the reliability of using circulating tumor cell (CTC) count to guide frontline therapy choice for patients with estrogen receptor-positive (ER+), HER2-negative (HER2) metastatic breast cancer. Published in the November issue of JAMA Oncology, this is the first study to support clinical utility of CTC count in a ra (Press release, Menarini Silicon Biosystems, NOV 9, 2020, View Source [SID1234570666])ndomized clinical trial.

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!

"Based on our research, the use of the CTC count represents the first objective and reproducible decision tool to help physicians choose between hormone therapy or chemotherapy for this particular group of patients," said lead author Francois-Clement Bidard, MD, PhD, Professor of Medical Oncology at Institut Curie and University of Versailles. "Furthermore, our results indicate that the CTC count complements but does not duplicate the physician’s opinion on which treatment to choose and should be included in the decision algorithm. This CTC test may help customizing treatment decisions for all women suffering from ER+ HER2- metastatic breast cancer".

The randomized Phase III trial, known as the STIC CTC study, included 778 women with Stage 4 ER+, HER2- breast cancer and compared the outcomes of treatment decisions based on physician assessment vs. CTC count. Half of the patients were randomly assigned to the clinically driven treatment group, where treatment was selected by a physician based on clinical factors. The other half were assigned to a CTC-driven treatment group, in which patients with 5 or more CTCs in 7.5 mL of blood received chemotherapy, and those with less than 5 CTCs in 7.5 mL received hormone therapy. Menarini Silicon Biosystems’ CELLSEARCH CTC System was used to capture and isolate tumor cells circulating in the blood in all patients.

The results supported the reliability and clinical utility of using the CTC count to guide front line therapy choice. For most patients in the clinically driven arm, the CTC count correlated with the physician’s choice of treatment. In the CTC-driven group, escalation of treatment to frontline chemotherapy for patients with high CTC count significantly improved progression free survival (PFS), while de-escalation to hormone therapy for patients with low CTC count did not have a detrimental impact on PFS or overall survival (OS).

"The results of the STIC CTC study provide evidence that the CTC count can support physicians when making effective treatment decisions," said Fabio Piazzalunga, President and CEO of Menarini Silicon Biosystems. "As a company, we will continue to support research aimed at demonstrating the clinical utility of CTC and we maintain our commitment to improve patient management".

Since the trial began, the introduction of CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) in combination with endocrine therapy as a frontline option has changed the treatment algorithm for patients with ER+ HER2- metastatic breast cancer. As a result, Menarini Silicon Biosystems has now been asked to support the analysis of CTC count in an ongoing phase III study known as AMBRE, promoted by Unicancer, the only French hospital network entirely devoted to fighting cancer, and conducted within the French breast cancer intergroup (UCBG) network. The study (NCT04158362) compares chemotherapy and a combination of endocrine therapy with one of the new CDK4/6 inhibitors (abemaciclib) as the initial treatment for metastatic ER+/HER2- breast cancer with high tumor burdend.

About CELLSEARCH
CELLSEARCH is the first and only clinically validated blood test cleared by the U.S. Food & Drug Administration (FDA) for detecting and counting CTCs to aid physicians in managing patients with metastatic breast, prostate, and colorectal cancers when used in conjunction with other clinical methods of monitoring. The test is also approved by the China National Medical Products Administration (NMPA) for use in monitoring patients with Metastatic Breast Cancer. The CELLSEARCH System is the most extensively studied CTC technology, with research published in more than 650 peer-reviewed publications.

CELLSEARCH Circulating Tumor Cell Kit is not cleared or approved for use as a clinical utility test for guiding treatment decisions. For more information on the full intended use and limitations of CELLSEARCH system, please refer to the Instructions for Use at View Source

On November 9, 2020 DNAtrix, a biotech company advancing virus-driven immunotherapies for cancer, reported that four abstracts on the company’s platform technology have been accepted for presentation at the 25th Annual Scientific Meeting and Education Day of the Society for Neuro-oncology (SNO) to be held November 19-21, 2020 (Press release, DNAtrix, NOV 9, 2020, View Source [SID1234570665]). Updated data from the Phase 2 CAPTIVE study in recurrent glioblastoma (GBM) have been selected as a late-breaking abstract for oral presentation on Friday, November 20, 2020 at 11:45 a.m. ET.

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 Phase 2 multicenter CAPTIVE study is evaluating DNX-2401 (tasadenoturev), DNAtrix’s adenovirus-based immunotherapy, in combination with pembrolizumab for the treatment of GBM at first or second recurrence. Data from 49 patients will be presented.

Additionally, presentations will include data on DNX-2401 as a potential treatment for diffuse intrinsic pontine glioma (DIPG), a highly aggressive pediatric cancer of the brainstem.

The live and on-demand sessions can be found on the SNO event website at View Source

DNAtrix Late-Breaking Presentation:

Title:

Phase 2 multicenter study of the oncolytic adenovirus DNX-2401 (tasadenoturev) in combination with pembrolizumab for recurrent glioblastoma; CAPTIVE Study (KEYNOTE-192)

Abstract Number:

LTBK-04

Presenter:

Gelareh Zadeh, M.D., Ph.D., Princess Margaret Cancer Center

Date/Time:

November 20, 11:45 a.m. ET

Presentations:

Title:

Oncolytic virus for DIPG: The clinical experience with DNX-2401

Abstract Number:

CTIM-25

Presenter:

Marta M. Alonso, Ph.D., Clinica Universidad de Navarra

Date/Time:

On Demand – Pediatric (Clinical) Session I

Title:

Delta-24-RGDOX (DNX-2440) activation of the IDO-Kyn-AhR cascade in glioblastoma: old targets for a new therapy

Abstract Number:

EXTH-45

Presenter:

Teresa Nguyen, MD Anderson Cancer Center

Date/Time:

On Demand – Experimental and Translational Sciences Session IV

Title:

Characterization of the oncolytic adenovirus Delta-24-RGD (DNX-2401) as therapeutic agent for the treatment of the pediatric embryonal brain tumors AT/RT and CNS-PNET

Abstract Number:

EXTH-60

Presenter:

Marc Garcia-Moure, Ph.D., Clinica Universidad de Navarra

Date/Time:

On Demand – Pediatric (Basic Science) Session I

About DNX-2401 (Tasadenoturev)
DNX-2401 is an oncolytic adenovirus engineered specifically to infect, replicate in, and directly kill cancer cells, as well as elicit a broader anti-tumor immune response. DNX-2401 is currently being evaluated as a potential treatment for highly aggressive brain tumors, including recurrent glioblastoma in adults and newly-diagnosed diffuse intrinsic pontine glioma (DIPG) in children. Clinical studies have demonstrated that DNX-2401 was well tolerated and extended survival for patients with recurrent glioblastoma. DNX-2401 has been granted Fast Track and Orphan designation by the FDA and PRIME and Orphan designation by the EMA.

About DNX-2440
DNX-2440 is an oncolytic adenovirus expressing the immune modulator OX40 ligand, a powerful costimulatory molecule known to enhance T cell responses directed to tumors. DNX-2440 is in Phase 1 clinical testing following the demonstration of anti-cancer activity in preclinical studies, including tumor reductions, immune memory, and abscopal effect.

On November 9, 2020 Cygnal Therapeutics, the first company to build a platform to develop drugs in the new field of exoneural biology, reported that it will present a poster this week at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting (Press release, Cygnal Therapeutics, NOV 9, 2020, View Source [SID1234570664]). The conference will be held online as a virtual event . Cygnal’s poster will discuss research on the development and use of novel monoclonal antibodies to block tumor-promoting interactions with Neuropilin-1, leading to significant tumor growth inhibition in vivo.

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!

Title: A novel mechanism of Neuropilin-1 inhibition results in improved tumor growth inhibition in vivo
Number: 683
Presenters: Daniel Blom, Ph.D., Shalini Sethumadhavan, Ph.D., Eric Zhu, Ph.D.
Date and Time: Available virtually on Monday, November 9 from 8:00 a.m. ET onward

Registered event attendees can access the poster via their SITC (Free SITC Whitepaper) event login. Cygnal’s poster presenters will be available for questions online on Wednesday, November 11 from 5:15 to 5:45 p.m. ET and on Friday, November 13 from 4:40 to 5:10 p.m. ET.

To learn more about Cygnal and exoneural biology, please visit Cygnal’s website.