On November 30, 2017 Portola Pharmaceuticals, Inc. (Nasdaq:PTLA) reported that new data on the Company’s first FDA-approved anticoagulant, betrixaban, and its two investigational hematologic compounds – the anticoagulant reversal agent andexanet alfa and the oral, dual Syk/JAK kinase inhibitor cerdulatinib – will be presented at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 9-12 in Atlanta, Georgia (Press release, Portola Pharmaceuticals, NOV 30, 2017, View Source;p=RssLanding&cat=news&id=2319373 [SID1234522319]). The Company also will present outcomes-based research on prophylaxis of venous thromboembolism in two real-world settings.

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Oral Presentation Details:

• Presentation Title: Effect of Andexanet-TFPI Interaction on in Vitro Thrombin Formation and Coagulation Markers in the TF-Pathway

Session: 332 (Antithrombotic Therapy: Anticoagulation in Cancer and Beyond)
Presenter: Genmin Lu, Ph.D., Portola Pharmaceuticals
Presentation Date and Time: Monday, Dec. 11, 2017 at 11:30 a.m. ET
Location: Building B, Level 2, B207-B208 (Georgia World Congress Center)
Poster Presentation Details:

• Poster Title: Physiologically-Based Pharmacokinetic (PBPK) Modeling for Betrixaban and the Impact of P-glycoprotein Inhibition on Betrixaban Pharmacokinetics

Poster Session: 321 (Blood Coagulation and Fibrinolytic Factors: Poster III)
Presenter: Janet M. Leeds, Ph.D., Portola Pharmaceuticals
Presentation Date and Time: Monday, Dec. 11, 2017 from 6:00 p.m. – 8:00 p.m. ET
Location: Building A, Level 1, Hall A2 (Georgia World Congress Center)
• Poster Title: Impact of D-Dimer Assays Performed at Local Labs vs. Central Laboratory in the Evaluation of APEX Trial Outcomes

Poster Session: 332 (Antithrombotic Therapy: Poster II)
Presenter: Lisa Jennings, Ph.D., CirQuest Labs, Memphis, Tennessee
Presentation Date and Time: Sunday, Dec. 10, 2017 from 6:00 p.m. – 8:00 p.m. ET
Location: Building A, Level 1, Hall A2 (Georgia World Congress Center)
• Poster Title: Did Patients with Renal Disease Receive Sufficient Prophylaxis for Venous Thromboembolism in the Real-World Settings?: A Study Among Hospitalized Acutely Medically Ill Patients

Poster Session: 903 (Outcomes Research—Non-Malignant Conditions: Poster II)
Presenter: Donna Hesari, R.N., Portola Pharmaceuticals
Presentation Date and Time: Sunday, Dec. 10, 2017 from 6:00 p.m. – 8:00 p.m. ET
Location: Building A, Level 1, Hall A2 (Georgia World Congress Center)
• Poster Title: The Frequency of Venous Thromboembolism (VTE) Prophylaxis Among Patients Hospitalized for Cancer in the US

Poster Session: 903 (Outcomes Research—Non-Malignant Conditions: Poster III)
Presenter: Andrea Hafeman, Ph.D., Portola Pharmaceuticals
Presentation Date and Time: Monday, Dec. 11, 2017 from 6:00 p.m. – 8:00 p.m. ET
Location: Building A, Level 1, Hall A2 (Georgia World Congress Center)
• Poster Title: Cerdulatinib Pharmacodynamics and Relationships to Tumor Response Following Oral Dosing in Patients with Relapsed/Refractory B Cell Malignancies: Results from a Phase I Dose Escalation Study

Poster Session: 623 (Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster II)
Presenter: Greg Coffey, Ph.D., Portola Pharmaceuticals
Presentation Date and Time: Sunday, Dec. 10, 2017 from 6:00 p.m. – 8:00 p.m. ET
Location: Building A, Level 1, Hall A2 (Georgia World Congress Center)

Important U.S. Safety Information for Bevyxxa (betrixaban) capsules

INDICATION
Bevyxxa is indicated for the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for VTE.

LIMITATIONS OF USE
The safety and effectiveness of Bevyxxa have not been established in patients with prosthetic heart valves because this population has not been studied.

SELECT IMPORTANT SAFETY INFORMATION

___________________________________________________________________________________________________________________________________________________

WARNING: SPINAL/EPIDURAL HEMATOMA
EPIDURAL OR SPINAL HEMATOMAS MAY OCCUR IN PATIENTS TREATED WITH BEVYXXA WHO ARE RECEIVING NEURAXIAL ANESTHESIA OR UNDERGOING SPINAL PUNCTURE. THE RISK OF THESE EVENTS MAY BE INCREASED BY THE USE OF IN‑DWELLING EPIDURAL CATHETERS OR THE CONCOMITANT USE OF MEDICAL PRODUCTS AFFECTING HEMOSTASIS. THESE HEMATOMAS MAY RESULT IN LONG-TERM OR PERMANENT PARALYSIS. CONSIDER THESE RISKS WHEN SCHEDULING PATIENTS FOR SPINAL PROCEDURES.
___________________________________________________________________________________________________________________________________________________

CONTRAINDICATIONS

Active pathological bleeding
Severe hypersensitivity reaction to Bevyxxa

WARNINGS AND PRECAUTIONS
Risk of Bleeding

Bevyxxa increases the risk of bleeding and can cause serious and potentially fatal bleeding
Concomitant use of drugs affecting hemostasis increases the risk of bleeding. These include aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs)
Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room
Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement
Discontinue Bevyxxa in patients with active pathological bleeding
There is no established way to reverse the anticoagulant effect of Bevyxxa, which can be expected to persist for at least 72hours after the last dose
It is unknown whether hemodialysis removes Bevyxxa
Protamine sulfate, vitamin K, and tranexamic acid are not expected to reverse the anticoagulant activity of Bevyxxa

Spinal/Epidural Anesthesia or Puncture

When neuraxial anesthesia (spinal/epidural anesthesia) or spinal/epidural puncture is employed, patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis
Do not remove an epidural catheter earlier than 72hours after the last administration of Bevyxxa. The next Bevyxxa dose is not to be administered earlier than 5hours after the removal of the catheter. If traumatic puncture occurs, delay the administration of Bevyxxa for 72hours
Monitor patients frequently for signs and symptoms of neurological impairment (e.g., numbness or weakness of the legs, bowel or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is necessary
Prior to neuraxial intervention, consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis

Use in Patients with Severe Renal Impairment

Patients with severe renal impairment (CrCl ≥ 15 to < 30 mL/min computed by Cockcroft-Gault) taking Bevyxxa may have anincreased risk of bleeding events
Reduce dose of Bevyxxa, monitor patients closely, and promptly evaluate any signs or symptoms of blood loss in these patients

Use in Patients on Concomitant P-glycoprotein (P-gp) Inhibitors

Patients on concomitant P-gp inhibitors with Bevyxxa may have an increased risk of bleeding
Reduce dose of Bevyxxa in patients receiving or starting concomitant P-gp inhibitors, monitor patients closely, and promptly evaluate any signs or symptoms of blood loss in these patients
Avoid use of Bevyxxa in patients with severe renal impairment receiving concomitant P‑gp inhibitors

ADVERSE REACTIONS

The most common adverse reactions with Bevyxxa were related to bleeding (> 5%)

USE IN SPECIFIC POPULATIONS
Hepatic Impairment

Bevyxxa has not been evaluated in patients with hepatic impairment, because these patients may have intrinsic coagulation abnormalities
Bevyxxa is not recommended in patients with hepatic impairment

On November 30, 2017 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported that enrollment has opened in its open-label, Phase 1 study of CDX-1140 in patients with advanced solid tumors. CDX-1140 is a fully human antibody targeted to CD40, a key activator of immune response that is found on dendritic cells, macrophages and B cells and is also expressed on many cancer cells (Press release, Celldex Therapeutics, NOV 30, 2017, View Source [SID1234522315]).

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"CD40 has long been an important target for immunotherapy, as it plays a critical role in the activation of innate and adaptive immune responses; however, balancing systemic dosing and safety has proven elusive to date for CD40 targeted activating therapeutics. CDX-1140 is a unique, potent CD40 agonist that we believe has the potential to successfully balance systemic doses for good tissue and tumor penetration with an acceptable safety profile," said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. "We look forward to characterizing CDX-1140 in this Phase 1 study and rapidly moving into combination studies with other anti-tumor agents."

Study Overview
This study, which is expected to enroll up to approximately 105 patients with recurrent, locally advanced or metastatic cancers, is designed to determine the maximum tolerated dose during a dose-escalation phase and to recommend dose(s) for further study in a subsequent expansion phase. During the dose-escalation phase, patients will receive CDX-1140 at dose levels ranging from 0.01 mg/kg to 3.0 mg/kg once every four weeks until disease progression or intolerance. The expansion phase is designed to further evaluate the tolerability and biologic effects of selected dose(s) of CDX-1140 in specific tumor types. Secondary objectives of the study include analyses of safety and tolerability, pharmacodynamics, pharmacokinetics, immunogenicity and assessment of anti-tumor activity across a broad range of endpoints, such as objective response rate, clinical benefit rate, duration of response, progression-free survival and overall survival. More information about this study is available on www.clinicaltrials.gov (Identifier: NCT03329950).

About CDX-1140
CDX-1140 is a fully human antibody targeted to CD40, a key activator of immune response that is found on dendritic cells, macrophages and B cells and is also expressed on many cancer cells. Potent CD40 agonist antibodies have shown encouraging results in early clinical studies; however, systemic toxicity associated with broad CD40 activation has limited their dosing. CDX-1140 has unique properties relative to other CD40 agonist antibodies: potent agonist activity is independent of Fc receptor interaction, contributing to more consistent, controlled immune activation; CD40L binding is not blocked, leading to potential synergistic effects of agonist activity near activated T cells in lymph nodes and tumors; and the antibody does not promote cytokine production in whole blood assays. CDX-1140 has shown direct anti-tumor activity in preclinical models of lymphoma. The Company believes that the potential for CDX-1140 will be best defined in combination studies with other immunotherapies or conventional cancer treatments.

ABX196, a first-in-class iNKT agonist boosting the immune response in cancer

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ABIVAX is currently developing ABX196, a state of the art immune enhancer candidate based on iNKT activation. This product is largely derived from the technology and exclusive patent rights transferred to ABIVAX by the Scripps Research Institute (La Jolla, CA), the University of Chicago (Chicago, IL) and the Brigham Young University (Salt Lake City, UT)

A phase I clinical trial in healthy volunteers has been completed and showed activation of iNKT cells. Based on these data, new immuno-oncology pre-clinical studies were conducted that demonstrated the potential of the product in oncology, in particular in turning tumors not responsive to anti-PD-1 (cold) to tumors responsive to anti-PD-1 (hot). As ABIVAX is focusing on the antiviral and anti-inflammatory therapeutic spaces and does not intend to play a role in the immune-oncology field, ABIVAX is seeking to out-license this interesting product candidate.

The characteristics of ABX196 are as follows:

ABX196 has been developed from a platform technology proprietary to ABIVAX that identifies "iNKT Agonists" that demonstrate immune enhancing effects in cancer models
ABX196 is a synthetic agonist (glycolipid) of iNKT (invariant Natural Killer T) cells, in a liposomal formulation
ABX196 is well characterized, with stability studies and full toxicity package (including non-human primate studies) conducted prior to the phase I clinical trial in healthy volunteers
Phase I showed ABX196 is well tolerated and triggered both humoral as well as iNKT immune responses in human volunteers
Pre-clinical data show that ABX196 enhances anti-tumoral activity when used alone and in combination with anti-PD-1 antibody, doxorubicin or sorafenib
ABX196 turns a cold (i.e. non-responding to anti-PD-1 antibody) tumor into a hot, responsive tumor in the mouse melanoma model, corresponding to an increase in survival time
ABX196 potentiates the anti-tumoral response to chemotherapy (doxorubicin) in the mouse melanoma model, corresponding to an increase in survival time
ABX196 controls tumor progression in an orthotopic hepatocellular cancer model in mice, again showing a prolongation of survival
In total, POC of anti-tumoral activities has been established in four preclinical cancer models
Easy-to-use liposome formulation, with scaled-up and controlled manufacturing
Strong IP protection and FTO: 5 patent families

On November 29, 2017 Daiichi Sankyo Company, Limited (Headquarters: Chuo-ku, Tokyo; hereafter, Daiichi Sankyo) reported that at a Board of Directors Meeting held today a resolution was passed for an absorption-type merger (hereafter, the merger) with its research subsidiary Asubio Pharma Co., Ltd. (Office location: Kobe-shi, Hyogo Prefecture; hereafter, Asubio), effective April 1, 2018, and an absorption-type merger agreement dated today was concluded (Press release, Daiichi Sankyo, NOV 29, 2017, View Source [SID1234522308]).

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As the merger is a simplified absorption-type merger with a wholly owned subsidiary company, some items and details are omitted in its disclosure.

1. Purpose of merger
Asubio mainly focuses on psychiatric and neurological diseases, immune and inflammatory diseases and regenerative medicine, conducting research based on its position as a drug discovery venture within the Daiichi Sankyo Group.
Daiichi Sankyo expects the integration of the venture spirit of Asubio into other research activities of Daiichi Sankyo to contribute to improving R&D productivity.

2. Summary of merger
(1) Merger schedule
Date of Board of Directors resolution (Asubio) November 29, 2017
Date of Board of Directors resolution (Daiichi Sankyo) November 30, 2017
Date of conclusion of merger agreement November 30, 2017
Date of merger (effective date) April 1, 2018
Note: For Daiichi Sankyo the merger is a simplified merger as stipulated in Article 796, Paragraph 2 of the Companies Act and for Asubio it is a short form merger as stipulated in Article 784, Paragraph 1 of the Companies Act. Therefore, neither company will hold a general shareholders meeting to approve the merger agreement.

(2) Form of merger
The form of the merger is an absorption-type merger with Daiichi Sankyo as the surviving company; Asubio will be dissolved.

(3) Allocations with merger
Since Asubio is a wholly owned consolidated subsidiary of Daiichi Sankyo, there will be no issuance of new shares or cash allocation with the merger.

(4) Handling of subscription rights to shares and bonds with subscription rights to shares of extinct company
Asubio has not issued any subscription rights to shares or bonds with subscription rights to shares.

3. Outline of merging companies
[Surviving company]
(1) Company name
Daiichi Sankyo Company, Limited
(2) Headquarters location
3-5-1, Nihonbashi Honcho, Chuo-ku, Tokyo, Japan
(3) Representative
Sunao Manabe, Representative Director, President and COO
(4) Type of business
Research & development, manufacture, sales, and marketing of pharmaceutical products, etc.
(5) Paid-in capital
50 billion yen
(6) Foundation date
September 28, 2005
(7) Number of ordinary shares issued
709,011,343
(8) Settlement of accounts
March 31
(9) Primary shareholders and percent of shares held (As of September, 2017)
・ The Master Trust Bank of Japan, Ltd. (trust account): 7.95%
・ Japan Trustee Services Bank, Ltd. (trust account): 6.80%
・ Nippon Life Insurance Company: 5.05%
・ JP MORGAN CHASE BANK 380055: 2.26%
・ Trust & Custody Services Bank, Ltd. as trustee for Mizuho Bank, Ltd. Retirement Benefit Trust Account re-entrusted by Mizuho Trust & Banking Co., Ltd.: 2.03%
(10) Financial position and operating results for immediately preceding business year (ending March, 2017) Japanese accounting standards
Net assets
888,519
million yen
Total assets
1,463,461
million yen
Net assets per share
1,336.57
yen
Revenue
629,151
million yen
Operating income
18,483
million yen
Ordinary income
40,976
million yen
Net income
10,479
million yen
Net income per share
15.61
yen

[Extinct company]
(1) Company name
Asubio Pharma Co., Ltd.
(2) Office location
6-4-3 Minatojima-minamimachi, Chuo-ku, Kobe-shi, Hyogo Prefecture, Japan
(3) Representative
Yoshiharu Minamitake, President & CEO
(4) Type of business
Entrusted research & development of pharmaceuticals, etc.
(5) Paid-in capital
50 million yen
(6) Foundation date
October 16, 2009
(7) Number of ordinary shares issued
1,000
(8) Settlement of accounts
March 31
(9) Principal shareholders, percent of shares held
Daiichi Sankyo Company, Ltd.; 100%
(10)Financial position and operating results for immediately preceding business year (ending March 2017) Japanese accounting standards
Net assets
417
million yen
Total assets
5,753
million yen
Net assets per share
417,792.94
yen
Revenue
8,153
million yen
Operating income
2,870
million yen
Ordinary income
2,870
million yen
Net loss
32
million yen
Net loss per share
32,248.23
yen

4. Situation after merger
Asubio’s office and base of operations in Kobe will be closed and Daiichi Sankyo will take over its business and functions. There will be no change to Daiichi Sankyo’s company name, headquarters location, name and title of representative, type of business, paid-in capital or accounts settlement date with the merger.

5. Expected effect of merger on results
As the merger is with a wholly owned subsidiary, it will have a marginal effect on Daiichi Sankyo’s consolidated results.

On November 29, 2017 Protalix BioTherapeutics, Inc. (NYSE American:PLX) (TASE:PLX), reported the completion of enrollment in the Company’s phase II clinical trial evaluating OPRX-106, the Company’s oral antiTNF product candidate, in patients with ulcerative colitis (UC) (Press release, Protalix, NOV 29, 2017, View Source;p=RssLanding&cat=news&id=2319080 [SID1234522311]). OPRX-106 is the Company’s proprietary plant cell-expressed recombinant human tumor necrosis factor receptor II fused to an IgG1 Fc domain (TNFRII-Fc). When administered orally and while passing through the digestive tract, the plant cells function as a natural delivery capsule, having the unique attribute of a cellulose cell wall, which makes them resistant to degradation compared to proteins produced via mammalian cell expression systems. The Company expects to report top-line results from this study in the first quarter of 2018.

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"Despite a number of approved treatments for ulcerative colitis, there remains a large unmet medical need in this patient population," said Mr. Moshe Manor, Protalix’s President and Chief Executive Officer. "We look forward to reporting initial results from our phase II study, which may provide proof of concept data not only for OPRX-106 in the treatment of UC, but also for our oral-delivery protein technology. If successful, OPRX-106 will be the first ever oral protein treatment, as currently there are no other oral recombinant protein treatments available."

The phase II clinical trial is a randomized, open label, 2-arm study of OPRX-106 in 19 patients with active mild to moderate ulcerative colitis. Patients have been randomized to receive 2 mg or 8 mg of OPRX-106 protein administered orally, once daily, for 8 weeks. Key efficacy endpoints of the study, in addition to safety, include relevant disease parameters of the drug, including Mayo score and rectal bleeding.