On July 25, 2019 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, reported an update on its oncology programmes (Press release, 4d Pharma, JUL 25, 2019, View Source [SID1234537775]). New preclinical data on the Company’s oncology candidates, MRx0518 and MRx1299, were presented at 1st Microbiome Movement Oncology Response Summit in Boston, USA by Research Director Imke Mulder. A clinical progress update on MRx0518 was also provided by 4D’s Chief Scientific Officer, Alex Stevenson.

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MRx1299

MRx1299 is a second-generation Live Biotherapeutic identified by 4D’s MicroRx discovery platform. One of the target host pathways identified for this Live Biotherapeutic is its potent histone deacetylase (HDAC) inhibition mediated by bacterial short-chain fatty acids (SCFAs). HDAC inhibition is thought to have multiple modes of anti-cancer activity, acting on both tumour and immune cells. Treatment with MRx1299 and its metabolites gives cytotoxic T lymphocytes the ability to reduce tumour growth in preclinical cancer models.

MRx0518

0MRx0518, the Company’s lead Live Biotherapeutic candidate in oncology, induces strong innate and adaptive immune responses in vitro and in vivo. New data presented demonstrates the ability of orally administered MRx0518 to modulate the frequency of immune cell populations with anti-tumour activity in the gastrointestinal tract, systemically and in the tumour microenvironment, acting through signalling pathways known to drive anti-cancer immunity.

The Company has previously published data on the mechanism of action of MRx0518 (Lauté-Caly et al. 2019), demonstrating that the bacterial flagellin protein, FliC, strongly activates immunostimulatory NF-κB signalling, via the TLR5 receptor. Research presented at the conference indicates a role for additional host receptors, including TLR9, in mediating the immuno-stimulatory effects of MRx0518.

Alex Stevenson, 4D’s Chief Scientific Officer, commented, "The identification of our new Live Biotherapeutic candidate, MRx1299, strengthens our leading oncology portfolio and expands the scope of oncology indications for our Live Biotherapeutics. MRx1299 has a different mechanism of action to MRx0518 and as such may be suitable for the treatment of different types of cancer. Studies of MRx1299’s efficacy in preclinical models of additional tumour types are ongoing, as is scale-up and process development."

He added, "The additional preclinical data on MRx0518 strengthens our knowledge of its mechanism of action and capacity to launch an immune response against cancer cells. In parallel, data generated from our ongoing clinical studies will assess the ability of MRx0518 to induce these anti-tumour immunological effects in patients. Our Phase I/II study of MRx0518 in combination with KEYTRUDA (pembrolizumab) in patients with solid tumours will provide us with specific biomarker data from both parts of the study. We anticipate the first of this data to be available by the end of 2019."

A copy of the presentations given can be found at View Source

On July 25, 2019 Wayshine Biopharm, a clinical-stage pharmaceutical company, reported that its First-in-Class CNS penetrable EGFR/EGFRvIII inhibitor, namely WSD0922, has received orphan drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of glioma (including Glioblastoma and Anaplastic Astrocytoma) (Press release, Wayshine Biopharm, JUL 25, 2019, View Source [SID1234537798]). Orphan drug designation was created to encourage the development of drugs which may provide significant benefit to patients suffering from rare diseases.

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WSD0922 has previously received IND approval from FDA for the treatment of Glioblastoma, Anaplastic Astrocytoma and cancers with CNS metastasis patients. Phase I/IIA to evaluate safety, tolerability, pharmacokinetics and anti-tumor activity of WSD0922 is ongoing at Minnesota, Arizona and Florida, the three campuses of Mayo Clinic.

"Orphan Drug Designation by the FDA for glioma is another significant milestone in the WSD0922 development program," commented Dr. Wei Zhong, Ph.D., CEO and Founder of Wayshine Biopharm. " We are very pleased that the FDA has granted broader indication than the indication proposed (GBM and AA). Fast grant for orphan drug designation by the FDA based on encouraging preclinical data truly reflects our innovation and commitments and the clinical potential of WSD0922 has been recognized and endorsed by the FDA, for this substantial unmet medical need and expansion to lower grade brain cancer."

Orphan drug designation by the FDA is granted to promote the development of drugs that target diseases affecting 200,000 or fewer U.S. patients annually and that are expected to provide significant therapeutic advantage over existing treatments. Orphan drug designation qualifies a company for benefits that apply across all stages of drug development, including an accelerated approval process, eligibility for orphan drug grants, seven years of market exclusivity following marketing approval, tax credits on U.S. clinical trials, and a waiver of certain administrative fees.

On July 25, 2019 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO – FR0010095596), ("Onxeo" or "the Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage response (DDR) in oncology, in particular against rare or resistant cancers, reported its consolidated half-year financials, as of June 30, 2019, and provided a business update (Press release, Onxeo, JUL 25, 2019, View Source [SID1234537742]).

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Judith Greciet, Chief Executive Officer of Onxeo, said: "During the first half of 2019, we have achieved major progress in our developments that continue to enhance the value of our first-in-class lead drug candidate AsiDNA and our other R&D assets.

With regards to AsiDNA, the well-executed DRIIV-1 phase I study of AsiDNA in solid tumors provided positive results by meeting each of its core objectives and notably confirming both the activity and the tolerance of AsiDNA. Based on these sound data, we have launched the first phase 1b study of AsiDNA in combination with a reference chemotherapy (carboplatin and paclitaxel) in patients suffering from eligible solid tumors. In parallel, we plan to initiate a second combination clinical study with a PARP inhibitor by year-end to assess the ability of AsiDNA to abrogate the acquired resistance to PARP inhibitors, a major limitation for their clinical use.

We also recently expanded our pipeline with our new optimized lead OX401 that entered a proof-of-concept preclinical phase. OX401 is based on the same decoy agonist mechanism as AsiDNA and was designed to be a next-generation PARP inhibitor that does not induce resistance but triggers a strong immune response through the activation of the STING pathway. This new candidate is at the crossroads of DNA Damage Response and immuno oncology, the two most attractive domains in cancer treatment.

By renewing our equity financing line with Nice & Green last June, we have secured the needed financial resources over at least the next 12 months to confidently move forward the developments of these two high potential candidates."

On July 25, 2019 Bristol-Myers Squibb Company (NYSE:BMY) reported results for the second quarter of 2019, which were highlighted by strong sales for Eliquis (apixaban) and Opdivo (nivolumab) and a robust operating performance across the portfolio (Press release, Bristol-Myers Squibb, JUL 25, 2019, View Source [SID1234537759]).

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"We had a very good second quarter where we delivered strong financial results while also advancing our integration planning for the acquisition of Celgene," said Giovanni Caforio, M.D., chairman and chief executive officer, Bristol-Myers Squibb. "Through strong commercial execution and financial discipline we are establishing a solid foundation from which we can build the leading biopharma company, well-positioned to address the unmet needs of our patients and create long-term shareholder value."

SECOND QUARTER FINANCIAL RESULTS

Bristol-Myers Squibb posted second quarter 2019 revenues of $6.3 billion, an increase of 10% compared to the same period a year ago. Revenues increased 13% when adjusted for foreign exchange impact.
U.S. revenues increased 14% to $3.7 billion in the quarter compared to the same period a year ago. International revenues increased 5%. When adjusted for foreign exchange impact, international revenues increased 12%.
Gross margin as a percentage of revenue decreased from 71.5% to 68.2% in the quarter primarily due to product mix and a $109 million impairment charge in connection with the expected sale of manufacturing and packaging operations in Anagni, Italy.
Marketing, selling and administrative expenses decreased 5% to $1.1 billion in the quarter.
Research and development expenses decreased 45% to $1.3 billion in the quarter primarily due to a $1.1 billion charge resulting from the Nektar collaboration in the second quarter last year.
The effective tax rate was 19.0% in the quarter, compared to 26.1% in the second quarter last year. The lower tax rate was due to a non-deductible equity investment loss in the second quarter last year.
The company reported net earnings attributable to Bristol-Myers Squibb of $1.4 billion, or $0.87 per share, in the second quarter, compared to net earnings of $373 million, or $0.23 per share, for the same period in 2018. The results for the second quarter of 2019 include $409 million of Celgene-related acquisition and integration expenses.
The company reported non-GAAP net earnings attributable to Bristol-Myers Squibb of $1.9 billion, or $1.18 per share, in the second quarter, compared to net earnings of $1.6 billion, or $1.01 per share, for the same period in 2018. An overview of specified items is discussed under the "Use of Non-GAAP Financial Information" section.
Cash, cash equivalents and marketable securities were $30.4 billion as of June 30, 2019, which includes $18.8 billion of net proceeds from the issuance of new notes in May 2019. The net cash position was $5.4 billion as of June 30, 2019.
ACQUISITION OF CELGENE CORPORATION

In June, the company announced plans to divest OTEZLA in light of concerns expressed by the U.S. Federal Trade Commission. The company expects to close the Celgene transaction by the end of 2019 or beginning of 2020. (link)
In June, the company announced the future leadership team of the combined company effective upon completion of the company’s pending acquisition of Celgene. (link)
OTEZLA is a trademark of Celgene Corporation.

SECOND QUARTER PRODUCT AND PIPELINE UPDATE

Product Sales/Business Highlights

Global revenues for the second quarter of 2019, compared to the second quarter of 2018, were driven by:

Eliquis, which grew by $392 million or 24% increase
Opdivo, which grew by $196 million or 12% increase
Orencia, which grew by 9%
Sprycel, which grew by 2%
Yervoy, which grew by 17%
Opdivo

Clinical

In July, the company announced Part 1a of the Phase 3 Checkmate -227 study evaluating Opdivo plus low dose Yervoy vs. chemotherapy met the co-primary endpoint of overall survival in first-line non-small cell lung cancer (NSCLC) patients whose tumors express PD-L1 ≥1%. (link)
In July, the company announced Part 2 of the Phase 3 Checkmate -227 study evaluating Opdivo plus chemotherapy versus chemotherapy did not meet its primary endpoint of overall survival in first-line non-squamous NSCLC patients regardless of PD-L1 status. (link)
In June, the company announced results of the Phase 3 Checkmate -459 study evaluating Opdivo versus sorafenib as a first-line treatment in patients with unresectable hepatocellular carcinoma (HCC). (link)
In June, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2019, the company announced important new data and analysis from three studies evaluating Opdivo as monotherapy and in combination with Yervoy (ipilimumab):
Checkmate -040: Results from the Phase 1/2 study evaluating Opdivo plus Yervoy in patients with advanced HCC previously treated with sorafenib. (link)
CA209-004: Results from the Phase 1 study evaluating Opdivo plus Yervoy in patients with previously treated or untreated advanced melanoma. (link)
Checkmate -067: Results from the Phase 3 study evaluating patient reported quality of life during extended therapy and following the discontinuation of therapy with Opdivo or Opdivo plus Yervoy in patients with previously untreated unresectable or metastatic melanoma. (link)
In May, the company announced results of the Phase 3 CheckMate -498 trial evaluating Opdivo plus radiation versus temozolomide plus radiation in patients with newly diagnosed O6-methylguanine-DNA methyltransferase-unmethylated glioblastoma multiforme. (link)
Orencia

Clinical

In June, at the Annual European Congress of Rheumatology, the company announced results from the Phase 4 mechanistic study exploring differences in the cellular and molecular mechanisms by which Orencia (abatacept) and adalimumab interfere with disease progression in moderate-to-severe early rheumatoid arthritis patients seropositive for certain autoantibodies. (link)
Empliciti

Clinical

In June, at the Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), the company announced results from the Phase 2 study evaluating Empliciti (elotuzumab) plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma. (link)
SECOND QUARTER BUSINESS DEVELOPMENT UPDATE

In July, the company, Bayer and Ono Pharmaceutical Co., Ltd. announced a clinical trial collaboration to evaluate Opdivo in combination with Bayer’s Stivarga in patients with micro-satellite stable metastatic colorectal cancer.
In July, the company announced the completion of its previously announced sale of its consumer health business, UPSA, to Taisho Pharmaceutical Co., Ltd.
In June, the company announced Catalent, Inc. has agreed to purchase its oral solid, biologics, and sterile product manufacturing and packaging facility in Anagni, Italy.
Stivarga is a trademark of Bayer.

2019 FINANCIAL GUIDANCE

Bristol-Myers Squibb is decreasing its 2019 GAAP EPS guidance range from $3.84 – $3.94 to $3.73- $3.83 and increasing its non-GAAP EPS guidance range from $4.10 – $4.20 to $4.20 – $4.30. Both GAAP and non-GAAP guidance assume current exchange rates. Key revised 2019 GAAP and non-GAAP line-item guidance assumptions are:

Research and development expenses decreasing in the low-double digits for GAAP and increasing in the mid-single digits for non-GAAP.
The financial guidance for 2019 excludes the impact of any potential future strategic acquisitions and divestitures, including any impact of the pending Celgene acquisition other than expenses incurred in 2019, and any specified items that have not yet been identified and quantified. The non-GAAP 2019 guidance also excludes other specified items as discussed under "Use of Non-GAAP Financial Information." Details reconciling adjusted non-GAAP amounts with the amounts reflecting specified items are provided in supplemental materials available on the company’s website.

Guidance inclusive of the Celgene acquisition will be provided after the close of the transaction.

Use of Non-GAAP Financial Information

This earnings release contains non-GAAP financial measures, including non-GAAP earnings and related EPS information that are adjusted to exclude certain costs, expenses, gains and losses and other specified items that are evaluated on an individual basis. These items are adjusted after considering their quantitative and qualitative aspects and typically have one or more of the following characteristics, such as being highly variable, difficult to project, unusual in nature, significant to the results of a particular period or not indicative of future operating results. Similar charges or gains were recognized in prior periods and will likely reoccur in future periods, including acquisition and integration expenses, restructuring costs, accelerated depreciation and impairment of property, plant and equipment and intangible assets, R&D charges or other income resulting from up-front or contingent milestone payments in connection with the acquisition or licensing of third-party intellectual property rights, divestiture gains or losses, pension, legal and other contractual settlement charges, interest expense on the new notes issued in May 2019 in connection with our pending acquisition of Celgene and interest income earned on the net proceeds of the notes and debt redemption gains or losses, among other items. Deferred and current income taxes attributed to these items are also adjusted for considering their individual impact to the overall tax expense, deductibility and jurisdictional tax rates. Non-GAAP information is intended to portray the results of the company’s baseline performance, supplement or enhance management, analysts and investors overall understanding of the company’s underlying financial performance and facilitate comparisons among current, past and future periods. For example, non-GAAP earnings and EPS information is an indication of the company’s baseline performance before items that are considered by us to not be reflective of the company’s ongoing results. In addition, this information is among the primary indicators that we use as a basis for evaluating performance, allocating resources, setting incentive compensation targets and planning and forecasting for future periods. This information is not intended to be considered in isolation or as a substitute for net earnings or diluted EPS prepared in accordance with GAAP and may not be the same as or comparable to similarly titled measures presented by other companies due to possible differences in method and in the items being adjusted.

Company and Conference Call Information

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook. For more information about Bristol-Myers Squibb’s pending acquisition of Celgene, please visit View Source

There will be a conference call on July 25, 2019 at 8:30 a.m. ET during which company executives will review financial information and address inquiries from investors and analysts. Investors and the general public are invited to listen to a live webcast of the call at View Source or by calling the U.S. toll free 888-254-3590 or international 323-994-2093, confirmation code: 9333832. Materials related to the call will be available at the same website prior to the conference call. A replay of the call will be available beginning at 11:45 a.m. ET on July 25, 2019 through 11:45 a.m. ET on August 8, 2019. The replay will also be available through View Source or by calling the U.S. toll free 888-203-1112 or international 719-457-0820, confirmation code: 9333832.

Website Information

We routinely post important information for investors on our website, BMS.com, in the "Investors" section. We may use this website as a means of disclosing material, non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investors section of our website, in addition to following our press releases, SEC filings, public conference calls, presentations and webcasts. We may also use social media channels to communicate with our investors and the public about our company, our products and other matters, and those communications could be deemed to be material information. The information contained on, or that may be accessed through, our website or social media channels are not incorporated by reference into, and are not a part of, this document.

On July 25, 2019 Snap Bio, Inc. and Torrey Pines Investment (TPI) reported that their joint early drug discovery program within the framework of the i2020 Accelerator has resulted in achieving the projected milestone in developing several small molecule lead candidates for treatment of Hepatocellular carcinoma (HCC) and Hepatoblastoma (Press release, Snap Bio, JUL 25, 2019, View Source [SID1234537776]). The milestone is marked with an outstanding selectivity profile and promising overall animal data in rodents for the lead candidates.

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This timeline-driven achievement was enabled­­ through the synergistic efforts of TPI’s i2020 Accelerator network, which includes ChemDiv, Inc. with its pertinent technical life-sciences expertise and its unique integrated drug discovery platform.

"The i2020 Accelerator was created to help take early stage research programs with differentiated biology and established development paradigms to the level of advanced leads and clinical candidates," comments Ronald Demuth, President of Torrey Pines Investment. "We were excited to start working with Snap Bio, their unique platform that integrates structure-based drug design and advanced synthetic biology allows for scaffold modification to be taken to a new level with improved optimization for all the key properties of highly effective and selective treatments. Snap Bio has been a great fit for our i2020 Accelerator portfolio, and we are glad to be seeing the first fruits of our collaboration thanks to the collective efforts of our global net of partners, including ChemDiv."

"With the help of TPI and the i2020 Accelerator, Snap Bio has discovered novel bispecific inhibitors, opening the door to a platform that offers small molecules with unique combinations of well-defined activities," comments Mark Burk, President and CEO at Snap Bio. "Bispecific small molecules can simultaneously and selectively inhibit two mechanistically distinct targets, which can provide important polypharmacological benefits, such as higher efficacy, fewer side effects, and reduced drug resistance. In addition, relative to drug combination therapies, bispecific inhibitors can target multiple disease pathways without pharmacokinetic disparity, leading to easier, faster, cheaper, and lower risk clinical trials."

About Torrey Pines Investment and i2020

Torrey Pines Investment (San Diego, CA) is a specialty life-science investment firm that invests in development stage molecules, diagnostics, and therapeutics in areas of high unmet medical need. [View Source By rapidly de-risking novel science and enriching partner pipelines with best-in-class molecules, i2020 platform helps accelerate early stage drug discovery platforms towards advanced lead and clinical candidate level within a two-year framework. i2020 Accelerator’s vast scientific and global resource network tailored specifically to the needs of early drug development programs allows it to take on projects in a wide array of therapeutic areas, from immunology to infectious diseases and beyond. By successfully leveraging agile development principles and flexible partnering business models, i2020 Accelerator plans to create and invest in multiple small-molecule early drug discovery programs. [www.i2020accelerator.com]