On February 4, 2021 Bristol Myers Squibb (NYSE:BMY) reported results for the fourth quarter and full year of 2020, which reflect robust sales, strong operating performance and advancement of the company’s product pipeline (Press release, Bristol-Myers Squibb, FEB 4, 2021, View Source [SID1234574618]).

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"In our first full year as a new company we delivered solid operational and financial results, and laid a strong foundation for the future," said Giovanni Caforio, M.D., board chair and chief executive officer, Bristol Myers Squibb. "I am grateful to our team whose resilience and continued focus enabled us to grow our inline business, launch promising new drugs and significantly advance our pipeline while keeping our colleagues safe and maintaining the supply of our medicines to patients. The growth opportunities from our in-line and launch portfolios combined with a robust product pipeline and disciplined business development strategy strongly position the company to accelerate the renewal of our portfolio and achieve long-term sustainable growth."

*The pro forma revenues assume the company’s acquisition of Celgene Corporation (Celgene Acquisition) and its divestiture of Otezla to Amgen Inc. (Otezla Divestiture) occurred on January 1, 2019 and exclude foreign currency hedge gains and losses. Management believes that measuring revenue rates on a comparable pro forma basis is an appropriate way for investors to best understand the underlying performance of the business. The pro forma revenue is presented for informational purposes only and does not purport to project the company’s revenue, results of operations or financial position for any future period or as of any future date. See "Worldwide Pro Forma Revenue" in Quarterly Package of Financial Information for this quarter and full year of 2020, which is available on bms.com/investors/financial-reporting/quarterly-results, for information on the revenue of the company and Celgene on a stand-alone basis for the prior-year period. Otezla is a trademark of Amgen Inc.

**In excess of +100%

FOURTH QUARTER FINANCIAL RESULTS

All comparisons are made versus the same period in 2019 unless otherwise stated.

Bristol Myers Squibb posted fourth quarter revenues of $11.1 billion, an increase of 39% on a reported basis and 10% on a pro forma basis. The increase was driven primarily by the impact of the Celgene Acquisition, which was completed on November 20, 2019.
U.S. revenues increased 43% to $6.8 billion in the quarter. International revenues increased 34% to $4.3 billion in the quarter. When adjusted for foreign exchange impact, international revenues increased 30%.
Gross margin increased from 68.6% to 73.7% in the quarter primarily due to product mix, lower unwinding of inventory purchase price accounting adjustments, partially offset by an impairment charge related to Inrebicmarketed product rights.
Marketing, selling and administrative expenses increased 57% to $2.7 billion in the quarter primarily due to $400 million of costs associated with the broader portfolio resulting from the Celgene Acquisition, as well as higher advertising and promotion expenses and cash settlement of MyoKardia unvested stock awards.
Research and development expenses increased 79% to $3.8 billion in the quarter primarily due to $500 million of costs associated with the broader portfolio resulting from the Celgene Acquisition, as well as license and acquisition charges related to Dragonfly, an in-process research and development (IPR&D) impairment charge related to the discontinuation of the orva-cel program development and cash settlement of MyoKardia unvested stock awards.
Amortization of acquired intangible assets increased to $2.5 billion in the quarter reflecting the full quarter amortization from the Celgene Acquisition.
IPR&D charge of $11.4 billion was included in the quarter due to the MyoKardia transaction being accounted for as an asset acquisition.
The effective tax benefit rate was 4.1% in the current quarter and includes the impact of the non-deductible MyoKardia IPR&D charge. Income taxes were $931 million despite pre-tax loss of $129 million in the same period a year ago primarily due to the Otezla divestiture, certain non-deductible expenses and purchase price adjustments.
The company reported net loss attributable to Bristol Myers Squibb of $10.0 billion, or $4.45 per share, in the fourth quarter, compared to net loss of $1.1 billion, or $0.55 per share, for the same period a year ago. The results in the current quarter include costs and expenses resulting from the IPRD charge related to the MyoKardia asset acquisition, purchase price accounting from the Celgene Acquisition, contingent value rights fair value adjustments, equity investment gains, intangible assets impairment charges and other acquisition and integration expenses.
The company reported non-GAAP net earnings attributable to Bristol Myers Squibb of $3.3 billion, or $1.46 per share, in the fourth quarter, compared to non-GAAP net earnings of $2.4 billion, or $1.22 per share, for the same period a year ago. A discussion of the non-GAAP financial measures is included under the "Use of Non-GAAP Financial Information" section.

*In excess of +100%. Product rights were acquired as part of the Celgene Acquisition.

**Pro forma product revenues assume the Celgene Acquisition and the Otezla Divestiture occurred on January 1, 2019 and exclude foreign currency hedge gains and losses. Management believes that measuring product revenue rates on a comparable pro forma basis is an appropriate way for investors to best understand the underlying performance of the business. The pro forma product revenue is presented for informational purposes only and does not purport to project product revenue for any future period or as of any future date. See "Worldwide Pro Forma Revenues" in the Quarterly Package of Financial Information for this quarter and full year of 2020, which is available on bms.com/investors/financial-reporting/quarterly-results, for information on the product revenue of the company and Celgene for the prior-year period. Otezla is a trademark of Amgen Inc.

*In excess of +100%. Product rights were acquired as part of the Celgene Acquisition.

**Pro forma product revenues assume the Celgene Acquisition and the Otezla Divestiture occurred on January 1, 2019 and exclude foreign currency hedge gains and losses. Management believes that measuring product revenue rates on a comparable pro forma basis is an appropriate way for investors to best understand the underlying performance of the business. The pro forma product revenue is presented for informational purposes only and does not purport to project product revenue for any future period or as of any future date. See "Worldwide Pro Forma Revenues" in the Quarterly Package of Financial Information for this quarter and full year of 2020, which is available on bms.com/investors/financial-reporting/quarterly-results, for information on the product revenue of the company and Celgene for the prior-year period. Otezla is a trademark of Amgen Inc.

FOURTH QUARTER PRODUCT AND PIPELINE UPDATE

Oncology

Opdivo

Regulatory

In January, the company announced that the U.S. Food & Drug Administration (FDA) approved OPDIVO(nivolumab) in combination with CABOMETYX(cabozantinib), for the first-line treatment of patients with advanced renal cell carcinoma. The approval is based on the Phase 3 Checkmate -9ER trial. (link)
In January, the company announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for Opdivo, in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer (GEJC) or esophageal adenocarcinoma (EAC), based on results from the CheckMate -649 trial. The U.S. FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of May 25, 2021.(link)
In January, the company announced that the U.S. FDA has accepted its supplemental sBLA for Opdivo for the treatment of patients with resected esophageal or gastroesophageal junction (GEJ) cancer in the adjuvant setting, after neoadjuvant chemoradiation therapy (CRT), based on results from the Phase 3 CheckMate -577 trial. The U.S. FDA granted the application Priority Review and assigned a PDUFA goal date of May 20, 2021.(link)
In January, the company announced that the European Medicines Agency (EMA) validated its Marketing Authorization Application (MAA) for Opdivo,based on results from the Phase 3 CheckMate -577 trial, as an adjuvant treatment for esophageal or GEJ cancer in adult patients with residual pathologic disease after neoadjuvant chemoradiotherapy (CRT) and resection. (link)
In January, the EMA validated the Type II Variation MAA for Opdivo in combination with fluoropyrimidine- and platinum-based combination chemotherapy for the first-line treatment of adult patients with advanced or metastatic gastric cancer (GC), GEJ cancer or esophageal adenocarcinoma (EAC). The filing was based on the Phase 3 CheckMate -649 trial. (link)
In November, the company announced that the European Commission (EC) has approved Opdivo for the treatment of adults with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based combination chemotherapy. (link)
In November, the company announced that the EC, based on results from the Phase 3 CheckMate -9LA trial, has approved Opdivo plus Yervoy (ipilimumab) with two cycles of platinum-based chemotherapy for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation. (link)
Clinical

In December, the company announced that CheckMate -548, a Phase 3 trial evaluating the addition of Opdivo to the current standard of care (temozolomide and radiation therapy) in patients with newly diagnosed glioblastoma multiforme (GBM) with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation following surgical resection of the tumor, did not meet its primary endpoint of overall survival (OS) in patients with no baseline corticosteroid use or in the overall randomized population. (link)
Hematology

Revlimid

Patent Update

In December, the company announced that its wholly owned subsidiary, Celgene, and Cipla Limited (Cipla) have settled their litigation related to patents for REVLIMID (lenalidomide). (link)
Inrebic

Regulatory

In December, the company announced the Committee for Medicinal Products for Human Use (CHMP) of the EMA has recommended approval of Inrebic(fedratinib) for the treatment of disease-related splenomegaly (enlarged spleen) or symptoms in adult patients with primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis, who are Janus Associated Kinase(JAK) inhibitor naïve or have been treated with ruxolitinib. The CHMP recommendation will now be reviewed by the EC, which has the authority to approve medicines for the EU. (link)
Medical Conferences

In December, at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the company announced important new data and analysis from its hematology portfolio:

QUAZAR AML-001: a study evaluating Onureg(azacitidine tablets; CC-486), an oral hypomethylating agent, as a treatment for adult patients with acute myeloid leukemia (AML) who achieved first complete remission (CR) or CR with incomplete blood count recovery following intensive induction chemotherapy. (link)
TRANSCEND CLL 004: longer-term follow-up from the Phase I study evaluating liso-cel in relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma with liso-cel as monotherapy and initial results from the combination cohort with ibrutinib. (link)
TRANSCEND NHL 001: safety and efficacy results in the cohort of patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) treated with liso-cel. (link)
OUTREACH: initial results evaluating outcomes of treatment with liso-cel for patients with relapsed or refractory large B-cell lymphoma (LBCL) across inpatient and outpatient settings. (link)
First efficacy and safety results from a triplet combination study including iberdomide, a cereblon E3 ligase modulator (CELMoD) agent, with daratumumab or bortezomib and dexamethasone in patients with heavily pretreated R/R multiple myeloma. (link)
The following data were also presented at the 2020 ASH (Free ASH Whitepaper) Annual Meeting by the company and bluebird bio, Inc. (Nasdaq: BLUE):

Phase 1 CRB-401: longer-term data from the original Phase 1 CRB-401 study evaluating the companies’ investigational B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR) T cell therapy, idecabtagene vicleucel (ide-cel) in relapsed and refractory multiple myeloma (RRMM). (link)
Phase 2 KarMMA: analyses from the Phase 2 KarMMA study of patients with triple-class exposed relapsed and refractory multiple myeloma (RMM). (link)
Immunology

Deucravacitinib (BMS-986165; TYK2 inhibitor)

Clinical

In February, the company announced results from POETYK PSO-2, the second Phase 3 trial evaluating deucravacitinib, a novel, oral, selective tyrosine kinase 2 (TYK2) inhibitor, for the treatment of patients with moderate to severe plaque psoriasis. POETYK PSO-2 met both co-primary endpoints evaluating deucravacitinib versus placebo, with significantly more patients achieving Psoriasis Area and Severity Index (PASI 75) and Physician’s Global Assessment (sPGA) scales and met multiple key secondary endpoints versus Otezla (apremilast). (link)
Zeposia

Clinical

In February, the company announced that U.S. FDA has accepted its supplemental New Drug Application (sNDA) for Zeposia for the treatment of adults with moderately to severely active ulcerative colitis (UC). The FDA granted Priority Review to the application and assigned a PDUFA goal date, or target action date, of May 30, 2021. (link)
In December, the company announced that the EMA has validated its MAA for Zeposia (ozanimod) for the treatment of adults with moderately to severely active ulcerative colitis (UC). (link)
Medical Conferences

In November, at the American College of Rheumatology (ACR) Convergence 2020, the company announced important new data and analysis across its Immunology portfolio:

deucravacitinib (BMS-986165): results from an ongoing Phase 2 study evaluating the safety and efficacy of deucravacitinib (BMS-986165) compared with placebo in adults with active psoriatic arthritis met the primary endpoint. (link)
Iberdomide: results from a Phase 2b trial in patients with active systemic lupus erythematosus (SLE) assessing iberdomide met its primary endpoint in patients with high Type 1 interferon or Aiolos gene expressions. (link)
Business Development

In November, the company announced that it has successfully completed its acquisition of MyoKardia (MyoKardia Acquisition) in an all cash transaction for approximately $13.1 billion. (link)
Capital Allocation

The company continues to maintain a consistent, balanced approach to capital allocation focused on prioritizing investment for growth through business development along with reducing debt, commitment to dividend growth and share repurchase.

Today, the company announced a debt tender offer for an aggregate purchase price of up to $4.0 billion. (link)
In January 2021, the company announced that its Board of Directors has authorized incremental share repurchases of up to an additional $2 billion of the company’s outstanding shares of common stock. With this increase, the remaining share repurchase capacity under the company’s share repurchase program was approximately $6.4 billion. During 2021, the company plans to repurchase $3.0-$4.0 billion of its shares. (link)
Commitment to Sustainability, Diversity and Inclusion

In December, the company announced it is strengthening its commitment to environmental sustainability on a global basis by setting new 2030 and 2040 goals. By 2030, the company will purchase 100% of the electricity it uses from renewable sources, and by 2040, it will be carbon neutral in its Scope 1 (direct) and Scope 2 (indirect) emissions and reach the targets of equitable water use, zero waste to landfill and 100% electric vehicles in its fleet. (link)
In November, the Bristol Myers Squibb Foundation and National Medical Fellowships announced that they will leverage $100 million of the previously announced commitment from Bristol Myers Squibb and the Bristol Myers Squibb Foundation to diversity and inclusion to develop a program to extend the reach of clinical trials into underserved patient populations in urban and rural U.S. communities. (link)
COVID-19 Pandemic Response

During the current world health crisis, the company continues to take all necessary actions to promote public health by carrying out its mission of providing life-saving medicines to the patients who depend on the company and supporting relief efforts across the globe. (link)

In February, the company and The Rockefeller University announced that they have entered into a definitive agreement under which Bristol Myers Squibb has been granted a global exclusive license to develop, manufacture, and commercialize Rockefeller’s novel monoclonal antibody ("mAb") duo treatment that neutralizes the SARS-CoV-2 virus for therapy or prevention of COVID-19. (link)
Financial Guidance

Bristol Myers Squibb is providing 2021 GAAP EPS guidance in the range of $3.12-$3.32 and is increasing its non-GAAP EPS guidance range from $7.15 – $7.45 to $7.35 – $7.55. Both GAAP and non-GAAP guidance assume current exchange rates. Key 2021 GAAP and non-GAAP line item guidance assumptions are:

Worldwide revenues increasing in the high-single digits.
Gross margin as a percentage of revenue to be approximately 80.5%.
Marketing, selling and administrative expenses to be in-line with 2020 levels for GAAP and increasing in the low-single digit range for non-GAAP.
Research and development expenses decreasing in the high-single digits for GAAP and increasing in the mid-single digits for non-GAAP.
An effective tax rate of approximately 22% for GAAP and approximately 16% for non-GAAP.
The 2021 financial guidance excludes the impact of any potential future strategic acquisitions and divestitures, and any specified items that have not yet been identified and quantified. The 2021 non-GAAP EPS guidance is explained and further excludes other specified items as discussed under "Use of Non-GAAP Financial Information." The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

Long-term Financial Targets

Bristol Myers Squibb is also affirming 2020-2025 long-term financial targets communicated in January 2021 (link):

Expects low to mid-single digit revenue CAGR and low double-digit revenue CAGR excluding Revlimid & Pomalyst at constant exchange rates
Expects to maintain low to mid-40s percent non-GAAP operating margin
Expects significant cash flow generation of $45-$50 billion dollars from 2021 -2023.
This financial guidance excludes the impact of any potential future strategic acquisitions and divestitures as well as any specified items as discussed under "Use of Non-GAAP Financial Information." There is no reliable or reasonably estimable comparable GAAP measures for this non-GAAP financial guidance. The financial guidance is subject to risks and uncertainties applicable to all forward-looking statements as described elsewhere in this press release.

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, Facebook, and Instagram.

There will be a conference call on February 4 at 10 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 dialing in the U.S. toll free 800-458-4121 or international +1 313-209-6672, confirmation code: 4441406, or using this link which becomes active 15 minutes prior to the scheduled start time and entering your information to be connected. 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 1:30 p.m. ET on February 4 through 1:30 p.m. ET on February 18, 2021. The replay will also be available through View Source or by dialing in the U.S. toll free 888-203-1112 or international 719-457-0820, confirmation code: 4441406.

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. Reconciliations of these non-GAAP financial measures to the most comparable GAAP measures are provided in the accompanying financial tables and also available on the company’s website at www.bms.com.

These non-GAAP 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 amortization of acquired intangible assets beginning in the fourth quarter of 2019, including product rights that generate a significant portion of our ongoing revenue, unwind of inventory fair value adjustments, 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 upfront or contingent milestone payments in connection with the acquisition or licensing of third-party intellectual property rights, costs of acquiring a priority review voucher, IPRD charge resulting from the MyoKardia acquisition, divestiture gains or losses, stock compensation resulting from accelerated vesting of Celgene awards, certain retention-related employee compensation charges related to the Celgene Acquisition, pension, legal and other contractual settlement charges, interest expense on the notes issued in May 2019 incurred prior to the Celgene Acquisition and interest income earned on the net proceeds of those notes, equity investment and contingent value rights fair value adjustments and amortization of fair value adjustments of debt acquired from Celgene in our 2019 exchange offer, 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. Certain other significant tax items are also excluded such as the impact resulting from internal transfer of intangible assets and the Otezla Divestiture. This earnings release also provides international revenues excluding the impact of foreign exchange.

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 are indications 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. We encourage investors to review our financial statements and publicly-filed reports in their entirety and not to rely on any single financial measure.

In connection with presenting our outlook, we are also providing revenue (ex-FX) and non-GAAP operating margin guidance for 2020-2025. There are no reliable or reasonably estimable comparable GAAP measures for this because we are not able to reliably predict the impact of specified items or currency exchange rates beyond the next twelve months. As a result, the reconciliation of these non-GAAP measures to the most directly comparable GAAP measures is not available without unreasonable effort. In addition, the company believes such a reconciliation would imply a degree of precision and certainty that could be confusing to investors. The variability of the specified items may have a significant and unpredictable impact on our future GAAP results.

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 February 4, 2021 Tyme Technologies, Inc. (NASDAQ: TYME), an emerging biotechnology company developing cancer metabolism-based therapies (CMBTs), reported financial and operating results for its third quarter ended December 31, 2020 (Press release, TYME, FEB 4, 2021, View Source [SID1234574635]). During the quarter, TYME continued to build its leadership team with the announcement of Richie Cunningham as the new CEO; the Company continued to grow its global patent portfolio; expanded its body of peer-reviewed data presentations on SM-88 (racemetyrosine) at ASCO (Free ASCO Whitepaper) GI; continued enrolling patients in multiple studies including, second and third-line pancreatic cancer trials and the HopES Sarcoma Phase II trial; proceeded with next steps for initiation of the proof-of-concept trial (RESPOnD) evaluating TYME-19 as a potential new approach against COVID-19; advanced opportunities for clinical trials in metastatic breast cancer and hematological cancers.

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"TYME is at an exciting juncture in its history. As I am getting acquainted with the many facets of the Company, I am deeply impressed with the spirit of innovation and dedication towards the development of products that improve the lives of people," said Richie Cunningham, Chief Executive Officer of TYME. "I am currently fully engaged in an ongoing strategic business review with a focus on setting forth our operational priorities to determine the best path forward to maximize stakeholder value and look forward to sharing our corporate vision at the next business update."

Third Quarter Fiscal 2021 Financial Results

As of the third quarter ended December 31, 2020, the Company had approximately $13.5 million in cash and cash equivalents compared to $19.4 million as of the second quarter ended September 30, 2020. TYME’s operational cash burn rate for the third quarter of fiscal year 2021 was $5.9 million compared to $6.6 million for the second quarter of fiscal year 2021 and $4.5 million for the third quarter of fiscal year 2020. The burn rate was below current estimates and predominantly reflected expenses associated with the ongoing clinical trials in pancreatic and sarcoma cancers.

Based on active clinical trials in pancreatic and sarcoma cancers and other business developments, TYME continues to anticipate that its quarterly cash usage, or "cash burn rate", will average approximately $6.0 to $6.5 million per quarter during fiscal year 2021.

Anticipated Upcoming Key Events

At present, TYME currently expects the following key events in calendar year 2021:

Continue to advance enrollment in the HopES Sarcoma Phase II Trial; expect data readout in calendar year 2021
Present clinical data on SM-88 at a major medical meeting
Continue to advance enrollment in TYME-88-Panc pivotal study; full enrollment and data readout are not expected before calendar year 2022
Continue to advance enrollment in PanCAN’s Precision Promise℠ adaptive randomized Phase II/III registration-intent trial in patients with pancreatic cancer using oral SM-88 in second-line monotherapy
Initiate the proof-of-concept trial (RESPOnD) to evaluate TYME-19 as a potential new approach against COVID-19
Corporate Developments

On November 30, 2020, TYME announced that Richie Cunningham, former Icagen CEO and Boehringer Ingelheim executive was appointed as TYME’s Chief Executive Officer. The Company also announced that Steve Hoffman remains in the role of Chairman of the board of directors and continues as the Company’s Chief Science Officer, after his successful tenure as Chief Executive Officer since 2015.

Summary of Recent Developments

TYME Presented Data From TYME-88-Panc Study at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Gastrointestinal Cancers Symposium

On January 17, 2021, TYME presented preliminary supporting data from the TYME-88-Panc pivotal study, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual 2021 Gastrointestinal Cancers Symposium. The new data demonstrate the potential role of SM-88 (racemetyrosine) in advanced pancreatic cancer through the analysis of circulating tumor cells (CTCs) and passively acquired biometrics data from a wearable device. TYME is presently enrolling patients in a multicenter randomized controlled pivotal trial evaluating SM-88 in patients with third-line pancreatic cancer. Learn more at View Source

CTCs correlate with poor prognosis at baseline and throughout treatment may be a clinically relevant biomarker for patients with metastatic pancreatic cancer. These results demonstrated that CTC collection and enumeration were feasible for correlation with traditional trial outcomes. Furthermore, passively acquired biometrics from a wearable device can be collected for correlation with other clinically meaningful outcomes. Also, given that the longest lesion diameter was correlated with CTCs at baseline, additional radiologic feature analysis may prove to validate the importance of CTCs as a predictive biomarker for patients with pancreatic ductal adenocarcinoma.

As of September 15, 2020, the study reported that SM-88 was well tolerated with no treatment-related Grade 4 or 5 adverse advents (AEs). There was one Grade 3 AE that was deemed possibly related to SM-88. The poster presentation is available on our website at (www.tymeinc.com/data-publications).

The select data from the TYME-88-Panc trial are from an investigational study. SM-88 is not approved for the treatment of patients with any disease condition. Patients and physicians can access www.TYMETRIALS.com for more information about ongoing SM-88 clinical trials.

TYME Granted U.S. Patent Claims Covering Use of TYME-19 to Treat COVID-19 Infections

On February 3, 2021, TYME announced that it received notification that the United States Patent and Trademark Office had granted additional patent claims related to the Company’s metabolomic technology platform. U.S. Patent No. 10,905,698 is directed to methods for treating COVID-19 with TYME-19. This patent expands TYME’s patent portfolio to nearly 200 global granted and/or pending patents, broadly covering compositions, methods, manufacturing and use of the Company’s pipeline to 2032, and beyond.

TYME-19 is an investigational compound that is not approved in the U.S. for any disease indication. TYME intends to initiate the appropriate clinical trials to substantiate the safety and efficacy of TYME-19.

About SM-88

SM-88 is an oral investigational modified proprietary tyrosine derivative that is believed to interrupt the metabolic processes of cancer cells by breaking down the cells’ key defenses and leading to cell death through oxidative stress and exposure to the body’s natural immune system. Clinical trial data have shown that SM-88 has demonstrated encouraging tumor responses across 15 different cancers, including pancreatic, lung, breast, prostate and sarcoma cancers with minimal serious grade 3 or higher adverse events. SM-88 is an investigational therapy that is not approved for any indication in any disease. Learn more.

About TYME-18

TYME-18 is a CMBT compound under development that is delivered intratumorally. TYME-18 leverages a member of the bile acid family to create a potential treatment for inoperable tumors. Preliminary observations of the local administration of TYME-18, a combination of a proprietary surfactant system and natural sulfonic acid, suggested its potential as an important regulator of energy metabolism that may impede the ability of tumors to increase in size, which, in addition to its lytic functionality, could prove useful in difficult-to-treat cancers. In initial preclinical xenograft mouse studies, TYME-18 was able to completely resolve over 90 percent (11/12 mice) of established colorectal tumors within 12 days versus an average of over 600 percent growth in the control animals. Learn more.

About TYME-19

TYME-19 is an oral synthetic member of the bile acid family that the Company also uses in its anticancer compound, TYME-18. Because of its expertise in metabolic therapies, the Company was able to identify TYME-19 as a potent, well characterized antiviral bile acid and has performed preclinical experiments establishing effectiveness against COVID-19. Bile acids have primarily been used for liver disease; however, like all steroids, they are messenger molecules that modulate a number of diverse critical cellular regulators. Bile acids modulate lipid and glucose metabolism and can remediate dysregulated protein folding, with potentially therapeutic effects on cardiovascular, neurologic, immune, and other metabolic systems. Some agents in this class also have antiviral properties. In preclinical testing, TYME-19 repeatedly prevented COVID-19 viral replication without attributable cytotoxicity to the treated cells. Previous preclinical research has also shown select bile acids like TYME-19 have had broad antiviral activity.

About TYME-88-Panc Pivotal Trial

The TYME-88-Panc pivotal trial applies the latest advances in the field of cancer metabolism by evaluating the efficacy and safety of an oral investigational compound that targets the metabolic mechanisms of the disease at its source. A prospective, open label pivotal trial in metastatic pancreatic cancer for patients who have failed two lines of any prior systemic therapy. The trial is designed to evaluate the safety and efficacy of SM-88 used with MPS (methoxsalen, phenytoin and sirolimus) in advanced pancreatic cancer and will measure multiple endpoints, including overall survival, progression free survival, relevant biomarkers, quality of life, safety, and overall response rate. Learn more.

On February 4, 2021 I-Mab (the "Company") (NASDAQ: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, reported that the first patient has been dosed in a phase 2 clinical trial (NCT04600817) of TJ107 (efineptakin alpha), a novel long-acting recombinant human interleukin-7 (rhIL-7), in patients with glioblastoma multiforme (GBM) in China (Press release, I-Mab Biopharma, FEB 4, 2021, View Source [SID1234574653]).

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The phase 2 trial is a randomized, single-blind, placebo-controlled study to evaluate the efficacy and safety of TJ107 in lymphopenic patients with newly diagnosed GBM who have been treated with standard concurrent chemoradiotherapy. The study’s goal is to determine the proportion of patients with an increase in the absolute lymphocyte counts and associated clinical response after the administration of the first TJ107 dose.

There is increasing evidence that lymphopenia induced by radiotherapy and chemotherapy is associated with poor survival in cancer patients. In case of GBM, standard treatments induce long-lasting lymphopenia in most patients, and currently there are no definitive therapies for it. A phase 1b study conducted by Genexine Inc. (KOSDAQ: 095700) demonstrated that TJ107 rapidly increased absolute lymphocyte counts and restored T cell counts especially in the naïve and memory subsets but not the regulatory T cells in terminally ill patients with solid tumors. TJ107 was well tolerated with no dose-limiting toxicity or cytokine release syndrome observed.

"Despite advances in standard therapy, GBM is associated with poor clinical outcomes and survival rates," said Professor Wenbin Li, Director of Department of Neuro-Oncology at Beijing Tiantan Hospital of Capital Medical University and the leading principal investigator of the clinical trial. "Based on its preclinical and clinical data, TJ107 promises to improve tolerance to the standard therapy, quality of life and prognosis in patients with GBM, and we look forward to making this drug accessible to our patients."

"TJ107 is the first and only long-acting rhIL-7 in the clinical stage globally and early studies have shown its potential to treat patients with GBM whose prognosis is still poor," said Dr. Joan Shen, Chief Executive Officer of I-Mab. "The initiation of the phase 2 trial brings us one step closer to delivering a highly innovative therapy to treat patients with one of the most life-threatening forms of cancer."

GBM is the most aggressive type of glial cancer which can arise in the brain de novo or evolve from existing tumors. GBM accounts for 17% of new brain and nervous system cancers in China, according to data from the World Health Organization in 2018.[1]

[1] Ostrom Q T, Gittleman H, Liao P, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014[J]. Neuro-oncology, 2017, 19(suppl_5): v1-v88.

About TJ107/GX-I7

TJ107/GX-I7 (efineptakin alpha) is the world’s first and only long-acting recombinant human interleukin-7 (rhIL-7), known to boost T lymphocytes by increasing their number and functions. It emerged from Genexine’s proprietary hyFc platform for discovering of long-acting biologics. I-Mab has acquired exclusive rights from Genexine to develop and commercialize TJ107/GX-I7 in Greater China. TJ107/GX-I7 may have utility in cancer treatment-related lymphopenia (low blood lymphocyte levels), a common condition that occurs in cancer patients who have received chemotherapy or radiation therapy, for which there is no approved treatment. TJ107/ GX-I7 has also been shown to synergize with a PD-1 antibody in various tumor animal models potentially through increased T-lymphocyte activation and proliferation.

On February 4, 2021 argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases and cancer, reported that the underwriters of its previously announced global offering of ordinary shares (including ordinary shares represented by American Depositary Shares (ADSs)) have exercised their option to purchase 468,750 additional ADSs in full on the same terms and conditions as the global offering (Press release, argenx, FEB 4, 2021, View Source,ordinary%20shares%20(including%20ordinary%20shares [SID1234574619]). This option exercise brings the anticipated total gross proceeds from the global offering to approximately $1.15 billion (approximately €954.8 million) from the sale of an aggregate of 3,593,750 ordinary shares (including ordinary shares represented by ADSs).

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J.P. Morgan, Morgan Stanley, BofA Securities and Cowen acted as joint bookrunning managers for the offering.

The closing of the global offering, including with respect to the ADSs subject to the option, is expected to occur on February 5, 2021, subject to customary closing conditions.

The securities were offered in the United States pursuant to an automatically effective shelf registration statement that was previously filed with the Securities and Exchange Commission (SEC). A preliminary prospectus supplement relating to the securities was filed with the SEC on February 1, 2021. The final prospectus supplement relating to the securities will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, copies of the final prospectus supplement and the accompanying prospectus relating to the U.S. offering may be obtained for free from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; from Morgan Stanley & Co. LLC, 180 Varick Street, 2nd Floor, New York, NY 10014, Attn: Prospectus Department, by email at [email protected], or by telephone at (866) 718-1649; from BofA Securities, NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, North Carolina 28255-0001, Attn: Prospectus Department, or by email at [email protected]; or from Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by email at [email protected], or by telephone at (833) 297-2926.

This press release is for information purposes only and does not constitute, and should not be construed as, an offer to sell or the solicitation of an offer to buy or subscribe to any securities, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale is not permitted or to any person or entity to whom it is unlawful to make such offer, solicitation or sale. Reference is also made to the restrictions set out in "Important information" below. This press release is not for publication or distribution, directly or indirectly, in or into any state or jurisdiction into which doing so would be unlawful or where a prior registration or approval is required for such purpose.

On February 4, 2021 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that two abstracts featuring data from clinical studies evaluating Rubraca (rucaparib) in metastatic castration-resistant prostate cancer (mCRPC) and one abstract describing adverse events associated with mCRPC treatment based on real world evidence have been accepted for poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Genitourinary Cancers Symposium to be held virtually, February 11-13, 2021 (Press release, Clovis Oncology, FEB 4, 2021, View Source [SID1234574636]).

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"These data underscore our continued commitment to fully understanding the clinical role of Rubraca and to accelerating the delivery of transformative therapies to the advanced prostate cancer community," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "The data that will be shared add to growing scientific knowledge about the science of mCRPC and broaden our understanding of Rubraca as a treatment option for patients diagnosed with mCRPC."

The following Clovis-sponsored abstracts will be available on February 8 at 5:00 pm ET and will also be available as posters for viewing starting February 11 at 8:00 am ET on ASCO (Free ASCO Whitepaper)’s Meeting Library. The posters can also be viewed at View Source starting February 11 at 8:00 am ET.

Abstract Number 80: Association of co-occurring gene alterations and clinical activity of rucaparib in patients with BRCA1 or BRCA2 mutated (BRCA+) metastatic castration-resistant prostate cancer (mCRPC)

Poster Session: Prostate Cancer – Advanced Disease
Date/Time: Thursday, February 11 at 8:00 am ET
Lead Author: Wassim Abida, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York
Abstract Number 79: Rucaparib plus enzalutamide in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Pharmacokinetics (PK) and safety data from the phase 1b RAMP study

Poster Session: Prostate Cancer – Advanced Disease
Date/Time: Thursday, February 11 at 8:00 am ET
Lead Author: Arpit Rao, MBBS, University of Minnesota Medical School, Minneapolis, Minnesota
Abstract Number 61: Clinically significant events associated with metastatic castration-resistant prostate cancer (mCRPC) treatments

Poster Session: Prostate Cancer – Advanced Disease
Date/Time: Thursday, February 11 at 8:00 am ET
Lead Author: Kelvin A. Moses, MD, PhD, FACS, Vanderbilt University Medical Center, Nashville, Tennessee
About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed multiple tumor types, including ovarian and prostate cancers, as monotherapy and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for Rubraca.

Rubraca U.S. FDA Approved mCRPC Indication

Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca.

This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) has occurred in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1146 treated patients, MDS/AML occurred in 20 patients (1.7%), including those in long term follow-up. Of these, 8 occurred during treatment or during the 28 day safety follow-up (0.7%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 53 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents. In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation.

Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective methods of contraception during treatment and for 3 months following last dose of Rubraca. Advise male patients not to donate sperm during therapy and for 3 months following the last dose of Rubraca.

Most common adverse reactions in TRITON2 (≥ 20%; Grade 1-4) were fatigue/asthenia (62%), nausea (52%), anemia (43%), AST/ALT elevation (33%), decreased appetite (28%), rash (27%), constipation (27%), thrombocytopenia (25%), vomiting (22%), and diarrhea (20%).

Co-administration of rucaparib can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring.