On February 23, 2018 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, today reported financial results for the fourth quarter and year ended December 31, 2017 (Press release, Leap Therapeutics, FEB 23, 2018, View Source;p=RssLanding&cat=news&id=2334290 [SID1234524139]). Leap additionally announced that its Annual Meeting of Stockholders will be held on Thursday, May 3, 2018, at 11:00 a.m., Eastern Time, at the offices of Morgan, Lewis & Bockius LLP, One Federal Street, Boston, Massachusetts 02110.

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"We had a very successful 2017 at Leap, our first year as a public company. We have advanced clinical development of both of our innovative cancer programs to explore novel combinations with immunotherapies and chemotherapies and have laid the foundation for a data-rich 2018," said Christopher K. Mirabelli, Ph.D., Chief Executive Officer of Leap. "We additionally strengthened our balance sheet to continue to grow the company and further advance our pipeline."

2017 Accomplishments

DKN-01

Announced parallel development strategy to evaluate DKN-01 in patients with documented alterations of the Wnt signaling pathway and to evaluate DKN-01 as a combination immunotherapy.
Wnt Signaling Studies
Initiated a Phase 2 clinical trial evaluating DKN-01 as a monotherapy and in combination with paclitaxel in patients with advanced endometrioid gynecologic malignancies. The study will enroll approximately 50% of patients with Wnt signaling abnormalities.
Announced an investigator-sponsored clinical trial, DIAL-1, in patients with advanced hepatocellular carcinoma (HCC) with activated Wnt signaling at the University Medical Center of the Johannes Gutenberg-University Mainz in Germany.
Immunotherapy Studies:
Enrolled first patient in combination study evaluating DKN-01 with anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with esophagogastric cancer.
Announced an immunotherapy collaboration, DINAMIC, with the European Organisation for Research and Treatment of Cancer (EORTC). The cooperative group sponsored clinical trial will evaluate DKN-01 in combination with atezolizumab (TECENTRIQ) +/- paclitaxel in advanced esophagogastric malignancies and DKN-01 + atezolizumab in advanced biliary tract cancers at EORTC centers across Europe.
Presented proof of concept clinical data of DKN-01 in combination with chemotherapy in patients with advanced biliary tract or esophagogastric cancers at major medical conferences including the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancer Symposium. The data included encouraging overall response and disease control rates, progression-free survival data, and biomarker data.
TRX518:

Fully enrolled the monotherapy cohorts of the 003 repeat-dose clinical trial evaluating TRX518 in patients with advanced solid tumors.
Presented interim data from the repeat-dose monotherapy study, including robust disease control and signs of pharmacodynamic activity including CD8+ T cell activation.
Initiated combination cohorts of study 003 evaluating TRX518 in combination with gemcitabine chemotherapy or in combination with KEYTRUDA (pembrolizumab) or Opdivo (nivolumab), anti-PD-1 therapies marketed by Merck (known as MSD outside the United States and Canada) or Bristol-Myers Squibb, respectively.
Business:

Completed $18M private-placement financing with participation from Eli Lilly and Company and other existing and new investors.
Completed a clinical collaboration agreement with Merck for the study of the combination of DKN-01 and KEYTRUDA (pembrolizumab).
2018 Objectives

DKN-01 Program Objectives

Present interim data from clinical trial evaluating DKN-01 and KEYTRUDA (pembrolizumab) in patients with advanced esophagogastric cancer.
Present interim data from the Phase 2 clinical trial evaluating DKN-01 ± paclitaxel in patients with advanced gynecologic cancers enriched for patients with Wnt pathway alterations.
Present final data from the combination study of DKN-01 with gemcitabine and cisplatin in advanced biliary tract cancers.
Enroll first patient in the DIAL-1 clinical trial.
Enroll first patient in the DINAMIC clinical trial.
TRX518 Program Objectives

Present interim data from study of TRX518 in combination with gemcitabine chemotherapy, KEYTRUDA (pembrolizumab), or Opdivo (nivolumab).
Present TRX518 clinical biomarker data from monotherapy studies.
Selected Year-End and Fourth Quarter 2017 Financial Results

Net loss was $29.7 million for the year ended December 31, 2017, compared to $25.6 million for the year ended December 31, 2016. Net loss was $6.6 million for the fourth quarter of 2017, compared to $5.7 million for the same period in 2016.

Research and development expenses were $22.5 million for the full year 2017, compared to $23.3 million for the same period in 2016. This decrease was primarily due to reduced manufacturing expenses of our clinical product candidates. Research and development expenses were $4.4 million for the fourth quarter of 2017, compared to $7.4 million for the same period in 2016.

General and administrative expenses were $9.8 million for the full year 2017, compared to $4.0 million for the same period in 2016. This increase was primarily due to increased personnel, stock-based compensation, and expenses related to operating as a public company. General and administrative expenses were $2.1 million for the fourth quarter of 2017, compared to $0.5 million for the same period in 2016.

Cash, cash equivalents and marketable securities totaled $25.7 million at December 31, 2017. Research and development incentive receivables totaled $1.7 million.

Annual Meeting of Stockholders

The Annual Meeting of Stockholders will be held on Thursday, May 3, 2018, at 11:00 a.m., Eastern Time, at the offices of Morgan, Lewis & Bockius LLP, One Federal Street, Boston, Massachusetts 02110. The record date for the Annual Meeting of Stockholders is March 28, 2018. Leap expects to mail its definitive proxy statement to all stockholders of record in the first week of April.

Rule 14a-8 Stockholder Proposal Deadline

The 2018 Annual Meeting date represents Leap’s first Annual Meeting of Stockholders. As a result, pursuant to Rule 14a-8 under the Securities Exchange Act of 1934, as amended, the deadline for the receipt of any stockholder proposals submitted pursuant to Rule 14a-8 for inclusion in Leap’s proxy materials for the 2018 Annual Meeting, is required to be a reasonable time before the Company begins to print and mail the proxy materials. Taking into consideration the time and process for addressing any deficiencies in proposals that may be submitted, the Company has determined that close of business on March 9, 2018 should be the deadline for receipt of proposals pursuant to Rule 14a-8. Such proposals should be delivered to: Leap Therapeutics, 47 Thorndike Street, Suite B1-1, Cambridge, Massachusetts 02141, Attention: Corporate Secretary. Leap recommends that such proposals be sent by certified mail, return receipt requested. Such proposals also will need to comply with the rules of the Securities and Exchange Commission regarding the inclusion of stockholder proposals in Leap’s proxy materials and may be omitted if not in compliance with applicable requirements.

Bylaws Advance Notice Deadline for Stockholder Proposals and Nominations

For stockholder proposals not submitted pursuant to Rule 14a-8 and stockholder nominations of directors, the stockholder must give timely notice thereof in writing and in accordance with the requirements set forth in the Company’s bylaws to the Company’s Secretary no later than 5:00 p.m., Eastern Time on March 9, 2018 at the address noted above.

On February 23, 2018 AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US (known as MSD outside the US and Canada) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion, recommending a marketing authorisation of Lynparza (olaparib) tablets (300mg twice daily) for use as a maintenance therapy for patients with platinum-sensitive relapsed high grade, epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete response or partial response to platinum-based chemotherapy (Press release, AstraZeneca, FEB 23, 2018, View Source [SID1234524132]). Lynparza is recommended for treatment in this setting regardless of patients’ BRCA mutation status.

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Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The data show that Lynparza provides long-term disease control, delaying the need for further chemotherapy for this broader group of women with platinum-sensitive relapsed ovarian cancer, irrespective of their BRCA status. It also offers a well-characterised safety and tolerability profile, which is critical to help enable patients to stay on treatment."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "We welcome this positive opinion based upon data which indicate the potential impact for Lynparza as maintenance therapy for women with platinum-sensitive relapsed ovarian cancer. We look forward to our continued work with AstraZeneca to bring Lynparza to patients in the EU."

The CHMP recommendation is based on two randomised trials, SOLO-2 and Study 19, which showed Lynparza reduced the risk of disease progression or death for platinum-sensitive relapsed patients compared to placebo.

Summary of key efficacy results from randomised trials:

Analysis

SOLO-2

[germline BRCA-mutated]

n=295

Study 19

[platinum-sensitive relapsed]

n=265

Lynparza

Placebo

Lynparza

Placebo

Reduction in the risk of disease progression or death (PFS)

70%

(HR 0.30 [95% CI, 0.22-0.41], P<0.0001; median 19.1 vs 5.5 months)*

65%

(HR 0.35 [95% CI, 0.25-0.49], P<0.0001; median 8.4 vs 4.8 months)*

Reduction in the risk of death (OS)

Data not yet mature

27%

(HR 0.73 [95% CI, 0.55-0.95], P=0.02138**;

median 29.8 vs 27.8 months)***

PFS = progression-free survival; OS = overall survival

* By investigator-assessed analysis
** P-value considered nominal as criterion for statistical significance (P<0.0095) not met
*** Not adjusted for treatment crossover

The most frequently observed adverse reactions across clinical trials in patients receiving Lynparza monotherapy (≥ 10%) were nausea, vomiting, diarrhoea, dyspepsia, fatigue, headache, dysgeusia, decreased appetite, dizziness and anaemia.

Lynparza, the first poly ADP-ribose polymerase (PARP) inhibitor approved, was initially licensed as a capsule formulation. The new tablet formulation will reduce dosing from 8 capsules twice daily to 2 tablets twice daily.

Lynparza is available in nearly 60 countries and has treated more than 20,000 patients globally. It has the broadest clinical development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to bring Lynparza to more patients across multiple cancers. In January 2018, Lynparza was approved by the US FDA for use in metastatic breast cancer, becoming the first PARP inhibitor licensed beyond ovarian cancer.

NOTES TO EDITORS
About Ovarian Cancer in Europe

Among women in Europe, ovarian cancer is the fifth most common cancer and the sixth leading cause of cancer death. The five-year survival rate for ovarian cancer in Europe is 38%. In 2012, there were nearly 65,000 new cases diagnosed and around 42,700 deaths. As there is no cure for relapsed ovarian cancer, the primary aim of treatment is to slow progression of the disease for as long as possible and improve or maintain the patient’s quality of life.

About SOLO-2

SOLO-2 was a Phase III, randomised, double-blinded, multicentre trial designed to determine the efficacy of Lynparza tablets compared to placebo as maintenance monotherapy in patients with platinum-sensitive relapsed or recurrent germline BRCA-mutated ovarian, fallopian tube and primary peritoneal cancer. The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), randomised 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least two prior lines of platinum-based chemotherapy and were in complete or partial response. Eligible patients were randomised to receive 300mg Lynparza tablets twice daily or placebo tablets twice daily.

About Study 19

Study 19 was a Phase II, randomised, double-blinded, placebo-controlled, multicentre trial, which evaluated the efficacy and safety of Lynparza capsules compared with placebo in relapsed, high-grade serous ovarian cancer patients. The trial randomised 265 patients regardless of BRCA mutation status and who had completed at least two courses of platinum-based chemotherapy and their most recent treatment regimen. Eligible patients were randomised to receive Lynparza maintenance monotherapy at a dose of 400mg per day or matching placebo.

About Lynparza (olaparib)

Lynparza is a first-in-class poly ADP-ribose polymerase (PARP) inhibitor and the first targeted treatment to potentially exploit tumour DNA damage response (DDR)-pathway deficiencies to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death.

Lynparza is being investigated in a range of DDR-deficient tumour types and is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DDR mechanisms in cancer cells.

About the AstraZeneca and MSD Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. The collaboration is based on increasing evidence that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of tumour types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as a monotherapy. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody-Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On February 23, 2018 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported that it has received notification from the U.S. Food and Drug Administration (FDA) outlining the criteria required for lifting the clinical hold on U.S. studies of BPX-501 (Press release, Bellicum Pharmaceuticals, FEB 23, 2018, View Source [SID1234524133]). To address the FDA requirements, the Company plans to implement revisions to the U.S. study protocols, including the addition of more comprehensive monitoring and management of neurotoxicity. In addition, the Company will revise the Investigator Brochure and Informed Consent Documents to inform healthcare providers, patients and caregivers of the changes. The Company expects to provide a full response to the FDA within a few weeks.

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The clinical hold does not affect the Company’s BP-004 registration trial in Europe.

About BPX-501
BPX-501 is an adjunct T cell therapy administered after allogeneic hematopoietic stem cell transplant (HSCT) to improve outcomes in patients who lack a matched donor. It is comprised of genetically modified donor T cells incorporating Bellicum’s CaspaCIDe safety switch. BPX-501 is designed to provide a safety net to eliminate alloreactive BPX-501 T cells (via administration of activator agent rimiducid) should uncontrollable GvHD occur. This enables physicians to more safely perform stem cell transplants by administering BPX-501 engineered T cells to speed immune reconstitution, provide control over viral infections and enhance Graft-versus-leukemic effect without unacceptable GvHD risk.

Emergent BioSolutions has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Emergent BioSolutions, 2018, FEB 23, 2018, View Source [SID1234524129]).

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On February 23, 2018 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the first patient has been enrolled in a Phase 2 clinical trial evaluating the efficacy and safety of defibrotide for the prevention of acute Graft-versus-Host-Disease (aGvHD) in adult and pediatric patients after allogeneic hematopoietic stem cell transplant (HSCT) (Press release, Jazz Pharmaceuticals, FEB 23, 2018, View Source;p=RssLanding&cat=news&id=2334320 [SID1234524137]). The defibrotide clinical trial will be conducted across approximately 60 medical centers in the United States (U.S.), Canada and European Union.

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"Potential complications of hematopoietic stem cell transplant such as acute Graft-versus-Host Disease can be life threatening and even fatal," said Karen Smith, M.D., Ph.D., executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals. "Despite the use of current immunoprophylaxis strategies, Graft-versus-Host Disease remains a leading cause of non-relapse mortality after allogeneic stem cell transplant. Jazz is committed to advancing our understanding of how defibrotide may address this unmet need."

The Phase 2 clinical trial is a prospective, randomized, open-label study of the efficacy and safety of defibrotide added to standard of care immunoprophylaxis for the prevention of aGvHD, compared to the standard of care alone. Jazz expects to enroll approximately 150 adult and pediatric patients who have undergone allogeneic HSCT from an unrelated donor. The primary endpoint is cumulative incidence of Grade B-D aGvHD by day +100 post-allogeneic HSCT. Additional information about the trial, including eligibility criteria and a list of clinical trial sites can be found at: View Source (ClinicalTrials.gov Identifier: NCT03339297).

This Phase 2 trial complements the company’s ongoing Phase 3 clinical trial evaluating defibrotide for prevention of hepatic veno-occlusive disease (VOD) in high-risk adult and pediatric patients undergoing hematopoietic stem cell transplant.

About GvHD
Graft-versus-Host-Disease (GvHD) is a life-threatening complication of HSCT, a potentially curative option for several malignant and non-malignant disorders, and occurs when immune cells from a non-identical donor (graft) recognize the transplant recipient (host) as foreign. GvHD is the most frequent cause of morbidity and non-relapse mortality following allogeneic HSCT.1 One in five patients receiving a transplant from an unrelated donor dies from GvHD. Approximately 24,000 allogeneic patients in the United States and Europe are at risk for acute GvHD (aGvHD), which usually occurs within the first 100 days following HSCT and typically involves damage to the skin, gastrointestinal tract and/or liver.1,2,3,4 The International Bone Marrow Transplant Registry (IBMTR) Severity Index grades aGvHD as follows: Grade A includes patients with stage 1 skin aGvHD only; B includes those with stage 2 skin and no visceral aGvHD or stage 0-2 skin with stage 1 or 2 visceral aGvHD; C includes patients with stage 3 skin, liver and/or gut aGvHD; D includes those with stage 4 skin, liver and/or gut aGvHD.5

About Defitelio (defibrotide sodium)
In the U.S., Defitelio (defibrotide sodium) injection 80mg/mL received U.S. FDA marketing approval on March 30, 2016 for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT) and is the first and only FDA-approved therapy for patients with this rare, potentially fatal complication. Defitelio is not approved for the treatment of prevention of GvHD or prevention of VOD.

Defitelio is contraindicated in patients currently taking anticoagulants or fibrinolytics and in patients who are allergic to Defitelio or any of its ingredients. Defitelio may increase the risk of bleeding and should be withheld or stopped if significant bleeding occurs. Patients should be monitored for allergic reactions, especially if there is a history of previous exposure to Defitelio. The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds.

Please see full Prescribing Information for Defitelio.

In Europe, defibrotide is marketed under the name Defitelio▼(defibrotide). In October 2013, the European Commission granted marketing authorization to Defitelio under exceptional circumstances for the treatment of severe VOD in patients undergoing HSCT therapy. It is the first and only approved treatment in Europe for severe VOD. In Europe, Defitelio is indicated in patients over one month of age. It is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy.

▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system found under section 4.8 of the SmPC. (View Source)

About VOD
HSCT is an aggressive, potentially curative procedure to treat patients with malignant and non-cancerous hematologic disorders such as leukemia, lymphoma and aplastic anemia, and congenital immunodeficiency and autoimmune disorders.6 VOD is a rare complication of HSCT that occurs in approximately 9-14% of HSCT patients.7,8 Hepatic VOD, also known as SOS, is an early and life-threatening complication affecting the sinusoidal endothelial cells of the liver, which can typically occur within the first 21 days following HSCT.8,9 Hepatic VOD progresses to become life-threatening in approximately 30-50% of cases.9 VOD with multi-organ dysfunction (MOD), when left untreated, can be associated with an overall mortality (death) rate of 84%.7 MOD is characterized by the presence of renal or pulmonary dysfunction.10,11 VOD is often characterized by sudden weight gain, hepatomegaly (abnormally enlarged liver), and elevated bilirubin.10,11