On July 7, 2020 Pacira BioSciences, Inc. (Nasdaq: PCRX) reported the pricing of $350.0 million aggregate principal amount of convertible senior notes due 2025 (the "notes") in a private placement to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Pacira Pharmaceuticals, JUL 7, 2020, View Source [SID1234561756]). The offering size was increased from the previously announced offering size of $300.0 million aggregate principal amount of notes. Pacira also granted the initial purchasers of the notes a 30-day option to purchase up to an additional $52.5 million aggregate principal amount of notes. The sale of the notes to the initial purchasers is expected to settle on July 10, 2020, subject to customary closing conditions.

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Pacira estimates that the net proceeds from the offering will be approximately $339.0 million (or approximately $389.9 million if the initial purchasers fully exercise their option to purchase additional notes), after deducting the initial purchasers’ discounts and commissions and estimated offering expenses. Pacira expects to use approximately $211.1 million of the net proceeds to repurchase $185.0 million aggregate principal amount of its outstanding 2.375% Convertible Senior Notes due 2022 (the "2022 Notes") concurrently with the note offering in privately negotiated transactions effected through one of the initial purchasers of the notes or its affiliate, as Pacira’s agent. Pacira intends to use the remainder of the net proceeds from the offering for general corporate purposes, including working capital, research and development expenditures and the license or acquisition of complementary products and/or technologies. Holders of the 2022 Notes that are repurchased in the concurrent repurchases described above may purchase shares of Pacira’s common stock in the open market to unwind any hedge positions they may have with respect to the 2022 Notes. These activities may affect the trading price of Pacira common stock and the initial conversion price of the notes.

The notes will be general unsecured senior obligations of Pacira and will mature on August 1, 2025, unless earlier repurchased, redeemed or converted in accordance with their terms. The notes will bear interest at a fixed rate of 0.750% per year, payable semi-annually in arrears on February 1 and August 1 of each year, beginning on February 1, 2021.

Prior to the close of business on the business day immediately preceding February 3, 2025, the notes are convertible at the option of the holders only under certain conditions. On or after February 3, 2025, until the close of business on the second scheduled trading day immediately preceding the maturity date, holders may convert their notes at their option, irrespective of these conditions. Pacira will settle conversions of the notes by paying or delivering, as the case may be, cash, shares of its common stock, or a combination of cash and shares of its common stock, at its election.

The conversion rate will initially be 13.9324 shares of common stock per $1,000 principal amount of notes, subject to adjustment in certain circumstances. This represents an initial conversion price of approximately $71.78 per share, representing a conversion premium of approximately 32.5% over the closing price of $54.17 per share of Pacira common stock on July 7, 2020.

On or after August 1, 2023, Pacira may redeem for cash all or part of the notes under certain circumstances at a redemption price equal to the principal amount of the notes to be redeemed, plus accrued and unpaid interest, if any. In addition, calling any note for redemption will constitute a make-whole fundamental change (as defined in the indenture governing the notes) with respect to that note, in which case the conversion rate applicable to the conversion of that note, if it is converted in connection with the redemption, will be increased in certain circumstances.

The offering of the notes is being made to qualified institutional buyers pursuant to Rule 144A under the Securities Act. The offer and sale of the notes and the shares of Pacira common stock, if any, issuable upon conversion of the notes have not been and will not be registered under the Securities Act or any state securities laws, and, unless so registered, the notes and such shares may not be offered or sold in the United States or to U.S. persons except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities laws.

On July 7, 2020 Biogen Inc. (Nasdaq:BIIB) reported it will report second quarter 2020 financial results Wednesday, July 22, 2020, before the financial markets open (Press release, Biogen, JUL 7, 2020, View Source [SID1234561755]).

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Following the release of the financials, the Company will host a live webcast with Biogen management at 8:00 a.m. ET. To access the live webcast, please go to the investors section of Biogen’s website at View Source Following the live webcast, an archived version of the call will be available on the website.

On July 7, 2020 Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, reported two recent publications validating the polygenic risk score (PRS) component of Myriad’s breast cancer risk stratification tool riskScore (Press release, Myriad Genetics, JUL 7, 2020, View Source [SID1234561739]). The publications clinically validate both the ability of the PRS component of riskScore to predict breast cancer risk in asymptomatic women and modify risk estimations for patients identified with pathogenic mutations.

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"Historically we’ve considered breast cancer risk most significant for women diagnosed with pathogenic mutations in hereditary cancer genes. These studies demonstrate clearly that other genetic factors evaluated through Myriad’s riskScore test can dramatically alter breast cancer risk both independent of, and in combination with, gene mutations," said Nicole Lambert, president of Myriad International, Oncology and Women’s Health. "This information can dramatically change patient clinical management and Myriad is currently working diligently to provide access to this important information for all women."

The first study published in JCO Precision Oncology described the PRS component of riskScore in over 150,000 women. It showed that independent of other hereditary breast cancer gene mutations (e.g., BRCA1), Myriad’s polygenic risk score can add great value and precision to breast cancer risk estimates. The PRS was highly associated with breast cancer risk with an odds ratio of 1.47 (95% confidence interval 1.45 to 1.49) per unit standard deviation in the PRS. This translated to women in the top PRS percentile having a three-fold higher risk of breast cancer than an average risk patient.

The second study published in the Journal of the American Medical Association Network Open demonstrates the ability of Myriad’s polygenic risk score to improve breast cancer risk stratification in women diagnosed with pathogenic mutations in common breast cancer genes. The study evaluated over 150,000 patients and approximately 10,000 patients who were carriers of pathogenic mutations in the BRCA1, BRCA2, CHEK2, ATM and PALB2 genes who were tested at Myriad. The study demonstrated that patients with high penetrant genes such as BRCA1 and BRCA2 did not warrant changes in clinical management; however, breast cancer risks in patients with moderate penetrant genes such as CHEK2, ATM, and PALB2 could vary significantly, warranting different clinical management considerations. For example, patients with a PALB2 mutation historically have been assessed to have an approximately 50 percent lifetime risk for breast cancer. However, after incorporating the data from Myriad’s 86 single nucleotide polymporphism (SNP) riskScore test, patient risks varied between 26 percent to 79 percent (see Graph 1 below).

"These are some of the largest polygenic risk score studies ever published. Patient medical management can vary dramatically depending on where patients with and without pathogenic mutations fall within the risk spectrum," said Thomas P. Slavin M.D., senior vice president for Medical Affairs in Oncology at Myriad Genetic Laboratories. "This information will help empower patients and clinicians to make more informed decisions based upon the most precise breast cancer risk estimates availiable."

About riskScore
riskScore is a new clinically validated personalized medicine tool that enhances Myriad’s myRisk Hereditary Cancer test. riskScore helps to further predict a women’s lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from more than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was prospectively validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

On July 7, 2020 Nucleai (www.Nucleaimd.com), an Israeli start-up providing an artificial intelligence-powered precision oncology platform for research and treatment decisions and Debiopharm (www.debiopharm.com), a Swiss-based biopharmaceutical company specializing in drug development, manufacturing and digital health investment, reported the Series-A initial closing of $6.5M (Press release, Nucleai, JUL 7, 2020, View Source [SID1234561733]).

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In recent years, cancer immunotherapies have revolutionized cancer treatment, providing long term benefits to certain patient populations. However, the efficacy of these treatments is often observed in only a small subset of patients. Without an adequate way to predict drug response, patients risk receiving ineffective treatment accompanied by unnecessary payor coverage. In light of the high percentage of clinical trial failure, this lack of predictive precision can also have a heavy impact on pharmaceutical companies conducting costly clinical research. Nucleai’s core technology analyzes large and unique datasets of tissue images using computer vision and machine learning methods to model the spatial characteristics of both the tumor and the patient’s immune system, creating unique signatures that are predictive of patient response. In a recent work performed in collaboration with leading researchers and published at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 conference, Nucleai has demonstrated the predictive power of tumor microenvironment AI-based spatial analysis for breast cancer.

Through this investment, Debiopharm and Nucleai will collaborate in order to leverage Debiopharm’s 40 years of pharmaceutical expertise towards an acceleration of predictive biomarker discovery for drug response and the improvement of data from clinical trials involving cancer patients. The company intends to use the funds to further progress the development of its advanced platform for use in Immuno-oncology and other diseases. The funds will be used also to further progress its commercial reach to pharmaceutical and biotech companies.

"We are excited to have Debiopharm’s corporate VC as our lead investor along with our longterm partner investors Vertex Ventures and Grove Ventures. Debiopharm is bringing decades of pharmaceutical expertise which will assist in accelerating our development and market reach," explained Avi Veidman, Nucleai’s CEO. "Nucleai has multiple revenue-generating, commercial partnerships, with leading Immunotherapies pharma companies and US-based payors. We plan to use these funds to expand our offering to additional indications and diseases as well as to increase our commercial footprint substantially."

Founded in Israel, a growing hotspot for computational biology innovation, Nucleai was founded by former members of an elite technological unit of Israeli intelligence corps specializing in artificial intelligence and big data: Avi Veidman (CEO), Eliron Amir (COO), and Lotan Chorev (VP R&D). This Tel Aviv hub positions the start-up to leverage a wealth of valuable resources including a centralized medical system, 25 years of EMR data, and top AI talents.

"Our team is thrilled to embark on this adventure to develop and further understand the extent to which AI can help pathologists and oncologists become more precise in both diagnosis and prediction," explained Tanja Dowe, CEO of Debiopharm Innovation Fund. "We recognize the huge impact that Nucleai’s AI-powered platform, could have on clinical research for pharmaceutical treatments."

Avi Veidman, Nucleai’s CEO added, "The battle between the tumor and the immune cells is clearly visible by inspecting the pathology slide, just like a satellite image of a battlefield. Our AI platform analyzes the hundreds of thousands of cells in a slide, examines the interplay between the tumor and the immune system and matches the right patient to the right drug based on these characteristics".

"Our solution is purely based on software which is embedded into the biomarker researcher workflow. This allows us to scale our solution rapidly, to provide service to a large number of pharmaceutical and biotech partners as well as to patients," expressed Eliron Amir, COO of Nucleai. "It is an elegant solution to a complex problem. There is no need for an expensive wet-lab biology operation. Our cloud-based solution allows us to gather huge amounts of immuno-oncology data from different sources, creating complex insights that a single pharma or institute cannot generate by itself."

On July 7, 2020 Quantum Leap Healthcare Collaborative (Quantum Leap) reorted the initiation of an investigational treatment arm with Byondis’ [vic-]trastuzumab duocarmazine (SYD985) in the ongoing I-SPY 2 TRIAL for neoadjuvant treatment of locally advanced breast cancer (Press release, QuantumLeap, JUL 7, 2020, View Source [SID1234561732]). This treatment arm will focus on treatment for HER2 low early-stage breast cancer.

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This study arm will evaluate if SYD985 will limit tumor growth in a population of patients whose tumors are not normally treated with HER2-targeted therapies. Specifically, these tumors have low expression of HER2, and require better HER2-targeted drugs in order to be as effectively treated as HER2+ patients.

SYD985 is being developed for the treatment of HER2 expressing or HER2 mutant tumors. In nonclinical and clinical studies, SYD985 has demonstrated potent antitumor activity. Based on the preliminary clinical observations in a Phase 1 study, SYD985 demonstrated antitumor activity in HER2-expressing cancers including breast cancer. Researchers and clinicians believe SYD985 inhibits tumor growth for the following reasons: SYD985 is a next generation ADC, comprised of the mAb (monoclonal antibody) trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of SYD895 binds to HER2 on the surface of the cancer cell and is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in death of dividing and non-dividing tumor cells. An earlier phase I study (SYD985.001) in patients with histologically-confirmed, locally advanced or metastatic tumors, concluded that SYD985 is effective in patients with high HER2 levels in their tumor, as well as in a subset of patients with lower levels of expression of the HER2 protein (HER2- low).

The SYD985 arm of the I-SPY 2 clinical trial will be open for randomization to the HER2-low subset of the HER2- I-SPY 2 population, further defined as HER2-low by HER2 immuno histo-chemical staining (i.e. IHC 1+ and 2+) and in-situ hybridization. Tumors will be further characterized by genetic testing employing MammaPrint (MP1 or MP2) and by hormone receptor status (HR+ or HR-). Within the HER2 negative population, patients will be excluded for HER2 IHC 0 and ISH negative.

"This I-SPY 2 TRIAL arm is designed to test a less toxic and a potentially highly effective approach where we need better options for patients." stated Dr. Laura Esserman, Lead PI for the I SPY 2 TRIALs. "Low levels of HER2 protein expression are not sufficient to generate a response to traditional HER 2 treatment currently on the market. This particular agent works differently and is a promising way to deliver a targeted toxin. We need to continue to push to find better therapies. The I-SPY investigators are excited to partner with Byondis to test this agent in I-SPY 2."

The I-SPY 2 TRIAL, sponsored by Quantum Leap, is a standing phase 2 randomized, controlled, multicenter study with an innovative Bayesian adaptive design aimed to rapidly screen and identify promising new treatments in specific subgroups of women with newly-diagnosed, high-risk (high likelihood of recurrence), locally-advanced breast cancer (Stage II/III).

Byondis will supply the investigational drug and provide financial and regulatory support. Quantum Leap, as sponsor, will provide the clinical sites and clinical expertise.