On December 1, 2017 Carrick Therapeutics, a biopharmaceutical company focusing on the innovative research and development of transformative oncology medicines, reported that the first patient has been dosed in the phase 1 clinical programme of CT7001 – an orally bio-available Cyclin-dependent Kinase 7 (CDK7) selective inhibitor, that has shown striking efficacy in multiple pre-clinical cancer models (Press release, Evotec, DEC 1, 2017, View Source [SID1234522324]).

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Elaine Sullivan, chief executive of Carrick Therapeutics, said:

"We are excited by the potential of CT7001 to make a major difference in cancer treatment, and intend to rapidly progress CT7001 through clinical development and bring this promising new medicine to patients as quickly as possible. This is a significant achievement for Carrick to take a pre-clinical candidate to first patient dosed in less than two years."

CDK7 inhibition has emerged as a promising strategy in a range of cancer indications. CDK7 acts as a master regulator of transcription, as well as a regulator of the cell cycle through phosphorylation of members of the CDK family. Inhibition of CDK7 suppresses the expression of key oncogenes such as c-Myc.

CT7001 was found to be effective in pre-clinical models of breast cancer, both hormone receptor positive and triple-negative, and transcriptionally driven cancers such as acute myeloid leukemia and small-cell lung cancer (SCLC). All these cancers continue to have major unmet medical need, for example, very little progress has been made for decades in the treatment of SCLC and triple-negative breast cancer (TNBC). Due to its differentiated mechanism, CT7001 is also predicted to be efficacious where resistance has developed to current therapies.

CT7001 originated from Cancer Research UK funded scientists at Imperial College London and was licensed to Carrick by the charity’s Commercial Partnerships Team. Rapid subsequent preclinical development by the company’s experienced research and development team has led to approval for the first-in-human Phase I study. Efficacy studies are planned to start in 2018.

Carrick Therapeutics was established with an initial funding round that saw it raise $95 million, and continues to build its portfolio through partnering. Significantly, whilst other companies bank on a single molecule or biological mechanism, Carrick will build a portfolio that targets multiple mechanisms that drive cancer. In close partnership with a network of clinicians and scientists in internationally leading research institutes and hospitals, the business will drive its portfolio of ground-breaking cancer therapies from laboratories to the clinic.

The funding of Carrick Therapeutics was co-led by ARCH Venture Partners and Woodford Investment Management, with participation from Cambridge Enterprise, Cambridge Innovation Capital, Evotec, GV (formerly Google Ventures), and Lightstone Ventures.

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.

On November 30, 2017 GT Biopharma, Inc. (OTCQB: GTBP and Euronext Paris GTBP.PA) ("GT Biopharma" or the "Company") reported that Dr. Jeffrey Miller, Deputy Director of the Masonic Cancer Center, University of Minnesota, will be presenting data on its second-generation anti-CD16-IL-15-anti-CD33 TriKE (OXS-C3550); another first of its kind, single-chain, tri-specific NK cell engager (TriKE) (Press release, GT Biopharma , NOV 30, 2017, View Source [SID1234539536]).

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The TriKE platform technology, developed by Dr. Miller and his colleagues at the University of Minnesota, is designed to enhance the activity of Natural Killer (NK) cells. NK cells are a type of white blood cell which are an important component of the innate immune system and play a major role in the rejection of tumor and virally infected cells.

The original anti-CD16-IL-15-anti-CD33 TriKE (OXS-3550) utilizes the inclusion of a modified Interleukin-15 (IL-15), a peptide that activates NK cells, while the "engager" further increases NK cancer-cell killing capabilities and improves their function in the tumor microenvironment (Vallera et al, 2016). OXS-3550 is expected to enter human clinical trials in 2018. OXS-C3550, the second-generation anti-CD16-IL-15-anti-CD33 TriKE, utilizes a modified anti-CD16 component while incorporating the wild-type IL-15.

The OXS-C3550 TriKE was developed following continued research with the TriKE platform at the University of Minnesota Masonic Cancer Center. As demonstrated in non-clinical models, this targeted immunotherapy directs immune cells to kill cancer cells while diminishing drug-related toxicity.

The TriKE platform technology can be viewed as a protein version of CAR-T; but unlike traditional CAR-T platforms, it is anticipated that TriKEs could service a much larger part of the cancer population at a fraction of the cost. TriKEs are an antibody platform that could be tailored to treat any form of cancer, liquid or solid tumors.

OXS-C3550 will focus on acute myeloid leukemia (AML), the most common form of adult leukemia with 43,000 new cases each year. These patients will require frontline therapy, usually chemotherapy including cytarabine and an anthracycline, a therapy that has not changed in over 40 years. Also, about half of these patients are likely to have relapses and require alternative therapies. In addition, OXS-C3550 could be used to treat myelodysplastic syndrome (MDS), which has about 20,000 new cases diagnosed each year with minimal current treatment options (Siegel et al, 2014). At a minimum, OXS-3550 is expected to serve as a relatively safe, inexpensive, and easy to use therapy for resistant or relapsing AML. From a biologic standpoint, it could also be combined with chemotherapy as frontline therapy.

GT Biopharma Chief Medical officer (CMO) Dr. Raymond Urbanski said, "The data on our second-generation TriKE, which will be presented at the upcoming ASH (Free ASH Whitepaper) meeting, will be noticed by investigators in the field and will set the tone for all future discussions on the use of NK cells in the treatment of cancer. We believe the distinctions and potential benefits relative to other immunotherapies, including CAR-T, will become apparent."

GT Biopharma Chief Executive Officer (CEO) Dr. Kathleen Clarence-Smith said, "In collaboration with the experts from the University of Minnesota Masonic Cancer Center, GT Biopharma continues to advance the search for next generation anti-cancer treatments, especially on novel ways to enhance the cancer-killing capabilities of NK cells. In my view, the potential for the success of this immunotherapy approach is substantial and the possibility of extending it to solid tumors gives us even added hope."

GT Biopharma Executive Chairman Anthony J. Cataldo said, "This is another milestone achievement for the company as we continue to close out a very productive 2017."

On November 30, 2017 MorphoSys Increases Financial Guidance for 2017 Following Signature of Regional License Agreement for Antibody MOR202 with I-Mab (Press release, MorphoSys, NOV 30, 2017, View Source [SID1234556341])

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MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) and I-Mab announced today that they have entered into an exclusive regional licensing agreement to develop and commercialize MOR202 in China, Taiwan, Hong Kong and Macao. MOR202 is MorphoSys’s proprietary investigational antibody against CD38, for which recruitment of a European Phase 1/2a clinical study in relapsed/refractory multiple myeloma has been concluded.

Under the terms of the agreement, I-Mab Biopharma (a fully owned affiliate of I-Mab) will assume exclusive responsibility for all subsequent development and commercialization of MOR202 in the agreed territory. MorphoSys receives an immediate upfront payment of USD 20 million. MorphoSys will be entitled to receive additional success-based clinical and commercial milestone payments from I-Mab of up to approximately USD 100 million, as well as tiered, double-digit royalties on net sales of MOR202 in the territory.

In connection with the license agreement with I-Mab, MorphoSys has increased its financial guidance. For the year 2017, MorphoSys now expects revenues in the range from EUR 63 to 66 million (up from previously EUR 46 to 51 million) and earnings before interest and taxes (EBIT) of EUR -66 to -71 million (up from previously EUR -75 to -85 million). Guidance for revenues and EBIT includes royalty income on Tremfya(R) sales in Q3 2017, but does not include any royalty income on Tremfya(R) sales in Q4 2017. Following the partnering of MOR202, proprietary R&D expenses will be in the range from EUR 96 to 100 million (previously EUR 85 to 95 million).