Lixte Biotechnology 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, Lixte Biotechnology, 2018, MAR 23, 2018, View Source [SID1234524959]).

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TapImmune 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, TapImmune, 2018, MAR 23, 2018, View Source [SID1234524960]).

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On March 23, 2018 Aradigm Corporation (NASDAQ: ARDM) (the "Company") reported financial results for the fourth quarter and full year ended December 31, 2017 (Press release, Aradigm, MAR 23, 2018, View Source [SID1234524961]).

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Fourth Quarter 2017 Results

The Company recorded $2.4 million in revenue in the fourth quarter of 2017 compared with $125,000 in revenue in the fourth quarter of 2016. The Company recognized $2.3 million in contract revenue – related party, $27,000 in government contract revenue and $71,000 in government grant revenue for the fourth quarter of 2017, as compared to $116,000 in government contract revenue and $9,000 in government grant revenue for the fourth quarter of 2016. The increase in revenue was from the Company’s adoption of ASC Topic 606, Revenue from Contracts with Customers and primarily resulted from regulatory submission services provided for the New Drug Application (NDA) filing.

Total operating expenses for the fourth quarter of 2017 were $5.6 million, compared with total operating expenses of $7.2 million for the fourth quarter of 2016. The decrease in operating expenses was primarily due to lower research and development expenses because the Linhaliq Phase 3 clinical trials in non-cystic fibrosis bronchiectasis (NCFBE) are complete. This decrease was offset by higher consulting expenses in support of the regulatory approval process and higher costs in general and administrative expenses related to stock compensation expense, bonus expense and corporate insurance expense.

The Company’s net loss for the fourth quarter of 2017 was $4.2 million, or $0.28 per share, compared with a net loss of $7.9 million, or $0.54 per share, for the same period in 2016. For the quarter ended December 31, 2017, the decrease in net loss resulted primarily from an increase in revenue of $2.2 million and a decrease in operating expenses of $1.6 million, partially offset by an increase in interest expense of $0.1 million.

Full Year Results

Revenues for the year ended December 31, 2017 were $14.5 million, compared with revenues of $195,000 thousand in 2016. The Company recognized $14.1 million in contract revenue – related party, $268,000 in government contract revenue and $122,000 in government grant revenue for the year ended December 31, 2017, as compared to $40,000 in contract revenue – related party, $116,000 in government contract revenue and $39,000 in government grant revenue for the year ended December 31, 2016. The increase in revenue was primarily from the Company’s adoption of ASC Topic 606, Revenue from Contracts with Customers, which resulted in the recognition of $9.5 million in contract revenue – related party associated with regulatory submission and approval of services provided for the NDA filing combined with $4.5 million in contract revenue – related party from a change in estimated variable consideration associated with the $5 million regulatory milestone for the NDA filing allocated to performance obligations satisfied in the current or prior periods.

Total operating expenses for 2017 were $21.4 million, compared with total operating expenses of $30.2 million in 2016. Research and development expenses decreased by $10.6 million and general and administrative expenses increased by $1.8 million. The decrease in research and development expenses was due to lower contract manufacturing, contract testing and clinical trial costs because the Linhaliq Phase 3 clinical trials in non-cystic fibrosis bronchiectasis (NCFBE) are complete. The decrease was offset by higher employee-related expenses, higher consulting, meeting and travel expenses in support of the Linhaliq regulatory process towards U.S. and European Union approvals for market authorization. The increase in general and administrative expenses of $1.8 million was primarily related to higher performance bonus expense, higher legal expense, higher corporate insurance expense, higher non-cash stock compensation expense and higher consulting expense.

The net loss for the year ended December 31, 2017 was $10.7 million, or $0.72 per share, compared with a net loss of $32.9 million, or $2.23 per share, in 2016. Net loss decreased primarily from an increase in revenue of $14.3 million, a decrease in operating spend of $8.8 million related to the completion of the Phase 3 clinical trials for Linhaliq in non-CF BE in the fourth quarter of 2016, a decrease in other expense of $0.6 million in 2017, offset by an increase in interest expense of $1.5 million related to the Note Financing.

Liquidity and Capital Resources and Related Matters

As of December 31, 2017, the Company’s cash and cash equivalents totaled $7.1 million.

Aradigm received a Complete Response Letter (CRL) from the FDA regarding the New Drug Application (NDA) for Linhaliq as a treatment for non-cystic fibrosis bronchiectasis (NCFBE) patients with chronic lung infections with Pseudomonas aeruginosa (P. aeruginosa).

The CRL states that the FDA has determined that it cannot approve the NDA in its present form and provides specific reasons for this action along with recommendations needed for resubmission; the areas of concern include clinical data, human factor validation study and product quality.

The Aradigm Board of Directors approved temporary measures on February 9, 2018 intended to preserve the Company’s cash resources. The cash preservation measures include the termination of the Amended and Restated Aradigm Corporation Executive Officer Severance Benefit Plan, the reduction of the annual base salary by 50% of certain executive officers and the reduction of the cash compensation paid to members of the Board for service on the Board and committees by 50%. Effective February 11, 2018 the three Senior Executive Officers resigned all offices and positions; the Board appointed Dr. John Siebert as the Principal Executive Officer and the Principal Financial Officer.

"We are pursuing potential alternatives to resolve our cash position in the short term as well as developing strategic options that would provide for our long term viability. We feel it is important to bring Linhaliq to commercialization in as many geographies as possible to allow patients suffering from NCFBE to get the benefits of Linhaliq. Patients, patient advocacy groups and key opinion leaders have expressed support as we work towards this goal. The MAA was filed in early March which is the first step in achieving regulatory approval in Europe," said John M. Siebert, PhD

About Non-Cystic Fibrosis Bronchiectasis

Non-CF BE is a severe, chronic and rare disease characterized by abnormal dilatation of the bronchi and bronchioles, frequently associated with chronic lung infections. It is often a consequence of a vicious cycle of inflammation, recurrent lung infections, and bronchial wall damage. Non-CF BE represents an unmet medical need with high morbidity and mortality that affects more than 150,000 people in the U.S. and over 200,000 people in Europe. There is currently no drug approved for the treatment of this condition.

On March 23, 2018 Euronext Paris: FR0010331421 – IPH) reported that its partner MedImmune, AstraZeneca’s global biologics research and development arm, has amended the clinical trial protocol of the ongoing Phase I trial investigating the safety and efficacy of monalizumab, Innate’s investigational first-in-class anti-NKG2A monoclonal antibody, in combination with AstraZeneca’s approved anti-PD-L1 immune checkpoint inhibitor, durvalumab, in patients with advanced solid tumors (Press release, Innate Pharma, MAR 23, 2018, http://www.innate-pharma.com/en/news-events/press-releases/partner-medimmune-expands-colorectal-cancer-patient-cohort-ongoing-phase-i-trial-evaluating-monalizumab-combination-imfinzir-durvalumab [SID1234525390]). The trial protocol has been expanded to add new expansion cohorts aiming at testing monalizumab in combination with durvalumab and standard of care in patients with 1st- and 2nd-line, metastatic colorectal cancer (CRC).

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The dose-escalating part of the study has been completed, while the expansion cohorts in selected advanced solid tumors are ongoing.
The primary objective of the new study arms will be safety, with Overall Response Rate (ORR) and Duration of Response (DOR), amongst others, as secondary outcome measures.
Pierre Dodion, Chief Medical Officer of Innate Pharma, commented: "We are delighted that our partner MedImmune has decided to further expand the colorectal patient population to evaluate the safety and efficacy of monalizumab in combination with durvalumab and the current standard of care in 1st- and 2nd-line therapy. In addition, we look forward to the first clinical data read-outs from the Phase I study and initial expansion cohort program during 2018."
An update to study D419NC00001 including the new additional study arms has been published on clinicaltrials.gov.

On March 23, 2018 Eisai Co., Ltd. and Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the multiple receptor tyrosine kinase inhibitor LENVIMA (lenvatinib mesylate) has been approved in Japan for unresectable hepatocellular carcinoma (HCC) (Press release, Merck & Co, MAR 23, 2018, View Source [SID1234525467]). This is the first approval worldwide for LENVIMA for the indication of unresectable HCC and the first new systemic therapy to be approved in Japan for the front line treatment of HCC in approximately 10 years. Additionally, this is the first regulatory approval for LENVIMA under the global strategic collaboration agreement executed in March 2018 between Eisai and Merck for the co-development and co-commercialization of LENVIMA.

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This approval was based on a phase 3 clinical study (Study 304/REFLECT study) conducted by Eisai investigating LENVIMA as a first-line treatment in patients with unresectable HCC. In this study, LENVIMA demonstrated statistically significant non-inferiority of overall survival (OS) (13.6 months) compared to sorafenib (12.3 months) (hazard ratio [HR] 0.92, 95% confidence interval [CI]=0.79-1.06). Additionally, LENVIMA showed highly statistically significant and clinically meaningful improvements as compared to sorafenib in the secondary endpoints of progression-free survival (PFS) (HR 0.66, 95% CI=0.57-0.77, p<0.00001), time to progression (TTP) (HR 0.63, 95% CI=0.53-0.73, p<0.00001), and objective response rate (ORR) (LENVIMA 24% versus sorafenib 9%, p<0.00001). Furthermore, LENVIMA helped to delay deterioration in several quality of life (QOL) and symptom domains (pre-specified secondary endpoint), including in areas such as pain and diarrhea, compared to sorafenib (nominal p-value<0.05).

In this study, the five most common adverse events observed in the LENVIMA arm were hypertension (42%), diarrhea (39%), decreased appetite (34%), weight loss (31%) and fatigue (30%), which is consistent with the known safety profile of LENVIMA.

Liver cancer is the second leading cause of cancer-related deaths, with approximately 750,000 deaths per year estimated globally. Additionally, approximately 780,000 cases are newly diagnosed each year, about 80 percent of which occur in Asia, including Japan and China. HCC accounts as the primary reason for 85 percent to 90 percent of liver cancer cases. It is estimated that there are approximately 42,000 HCC patients in Japan, with approximately 26,000 deaths every year. To date, treatment options for unresectable HCC have been limited, and the prognosis is very poor, emphasizing that this is an area of high unmet medical need.

"With the approval of this additional indication of unresectable HCC for LENVIMA, we are proud to be able to deliver the first new front-line systemic therapy treatment option for HCC in Japan in approximately 10 years, and expect this will contribute to HCC treatment," said Dr. Takashi Owa, Eisai Oncology Business Group Chief Medicine Creation Officer. "Eisai will continue with its efforts in oncology research and development in order to deliver hopes for a potential cure for cancer to patients and their families."

"Today’s approval is an important first for LENVIMA and a significant first regulatory event under our collaboration with Eisai," said Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories. "We congratulate Eisai on the approval of this new indication and look forward to working together to bring this important treatment option to patients."

Having received approval of this indication, Eisai will receive a development milestone payment from Merck. There are no changes to Eisai’s consolidated financial results forecasts for the fiscal year ending March 31, 2018 based on the receipt of this milestone payment.

LENVIMA Product Details in Japan (underlined parts have been added)

1) Product name

LENVIMA Capsule 4 mg

2) Generic name

Lenvatinib mesylate

3) Indication

Unresectable thyroid cancer, unresectable hepatocellular carcinoma

4) Dosage and Administration

Unresectable thyroid cancer

The usual adult dose is 24 mg as lenvatinib administered orally once a day. The dose may be reduced depending on the condition of the individual patient.

Unresectable hepatocellular carcinoma

The usual adult dose is an amount of lenvatinib in accordance with body weight administered orally once a day. For adults weighing 60 kg and over, the dose should be 12 mg. For adults weighing less than 60 kg, the dose should be 8 mg. The dose may be reduced depending on the condition of the individual patient.

About LENVIMA (lenvatinib mesylate) capsules, 10 mg and 4 mg

Discovered by Eisai, LENVIMA is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor angiogenesis, tumor progression and modification of tumor immunity.

Currently, LENVIMA is approved as a treatment for refractory thyroid cancer in over 50 countries, including the United States, Japan, in Europe and Asia. Additionally, Eisai has obtained approval for the agent in combination with everolimus as a treatment for renal cell carcinoma (second-line) in over 40 countries, including the United States and in Europe. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma.

Outside of Japan, Eisai has submitted applications for an indication covering hepatocellular carcinoma in the United States and Europe (July 2017), China (October 2017), Taiwan (December 2017) and other countries