On August 7, 2017 BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) reported financial results for the second quarter ended June 30, 2017 (Press release, BioCryst Pharmaceuticalsa, AUG 7, 2017, View Source [SID1234520059]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited by the positive results previously reported in Parts 1 and 2 of the APeX-1 clinical trial that indicate we have an active oral drug, and look forward to completing the trial and reporting complete trial results in the third quarter of this year," said Jon P. Stonehouse, President & Chief Executive Officer. "These trial results should give us additional information to determine what doses we propose to regulatory authorities later this year for the Phase 3 program, with the goal of starting a pivotal trial early next year."

Second Quarter Financial Results

For the three months ended June 30, 2017, revenues decreased to $3.1 million from $4.8 million in the second quarter of 2016. The decrease in revenue was primarily due to a decrease in collaboration revenue under U.S. Government development contracts.

Research and Development (R&D) expenses for the second quarter of 2017 increased to $15.8 million from $14.2 million in the second quarter of 2016, primarily due to increased spending on the Company’s hereditary angioedema (HAE) portfolio.

General and administrative (G&A) expenses for the second quarter of 2017 of $2.8 million were in line with $2.7 million of G&A expense in the second quarter of 2016.

Interest expense was $2.1 million in the second quarter of 2017 as compared to $1.4 million in the second quarter of 2016, an increase related primarily to the September 2016 closing of a $23 million senior credit facility. Also, a $400,000 mark-to-market loss on the Company’s foreign currency hedge was recognized in the second quarter of 2017, as compared to a $3.7 million mark-to-market loss in the second quarter of 2016. These losses result from periodic changes in the U.S. dollar/Japanese yen exchange rate. During the second quarters of 2017 and 2016, we also realized currency gains of $921,000 and $811,000, respectively, from the exercise of a U.S. Dollar/Japanese yen currency option within our foreign currency hedge.

The net loss for the second quarter of 2017 was $16.9 million, or $0.21 per share, compared to a net loss of $16.3 million, or $0.22 per share, for the second quarter 2016.

Cash, cash equivalents and investments totaled $95.6 million at June 30, 2017, and reflect an increase from $65.1 million at December 31, 2016. Net operating cash use for the second quarter of 2017 was $12.2 million, and the first six months of 2017 was $21.0 million, which excludes the impact of $47.8 million of net proceeds from our March 2017 public offering.

Year to Date Financial Results

For the six months ended June 30, 2017, revenues increased to $12.5 million from $9.6 million in the first half of 2016. The increase in revenue was primarily due to a $4.3 million increase in royalty revenue from Shionogi & Co. Ltd., Green Cross Corporation and Seqirus, and a $2.0 million milestone payment from Seqirus associated with the Canadian regulatory approval of RAPIVAB. The increase in royalty revenue was largely the result of continued Japanese Government stockpiling of RAPIACTA. Future government stockpiling orders are difficult to predict, as they are subject to the relevant appropriation and stockpiling processes. These revenue increases were partially offset by a decrease in collaboration revenue under U.S. Government development contracts.

R&D expenses decreased to $32.5 million from $34.7 million in the first half of 2016, primarily due to lower development costs for the HAE portfolio of product candidates and, to a lesser extent, a decrease in galidesivir expenses under U.S. Government development contracts.

G&A expenses for the first half of 2017 of $5.9 million were in line with $5.9 million of G&A expense in the first half of 2016.

Interest expense was $4.2 million in the first half of 2017 as compared to $2.9 million in the first half of 2016, an increase related primarily to the September 2016 closing of a $23 million senior credit facility. A $1.9 million mark-to-market loss on the Company’s foreign currency hedge was recognized in the first half of 2017, as compared to a $6.4 million mark-to-market loss in the first half of 2016. These losses result from periodic changes in the U.S. dollar/Japanese yen exchange rate. During 2017 and 2016, we also realized currency gains of $921,000 and $811,000, respectively, from the exercise of a U.S. Dollar/Japanese yen currency option within our foreign currency hedge.

The net loss for the first half of 2017 was $31.1 million, or $0.40 per share, compared to a net loss of $39.1 million, or $0.53 per share, for the first half 2016.

Clinical Development Update & Outlook

On May 25, BioCryst announced positive results from a second interim analysis of its Phase 2 APeX-1 clinical trial in HAE. This second interim analysis of pooled data from Parts 1 and 2 evaluated doses of BCX7353 125 mg (n=7), 250 mg (n=6) and 350 mg (n=18) QD versus placebo (n=20) for 28 days. The pre-specified per-protocol (PP) interim analysis included data on a total of 44 subjects with confirmed Type 1 or Type 2 HAE completing 28 days of treatment. The percentage reductions by treatment group in the mean rate of independently-adjudicated angioedema attacks for the pre-defined effective dosing period (weeks 2 through 4) in BCX7353 treated subjects were: 125 mg QD, 73% (p=0.002); 250 mg QD, 37% (p=0.128) and 350 mg QD, 58% (p=0.001) compared to placebo. In the intent-to-treat (ITT) population, corresponding reductions by treatment group were: 125 mg QD, 73% (p=0.004); 250 mg QD, 44% (p=0.090) and 350 mg QD, 45% (p=0.014) compared to placebo.

Oral BCX7353 once-daily for 28 days was generally safe and well tolerated in subjects with HAE. There were no serious AEs and no severe AEs. Three subjects in the BCX7353 350 mg treatment arm discontinued study drug before day 28. The most common treatment-emergent adverse events were the common cold and diarrhea. The gastrointestinal AEs previously observed in the 350 mg arm were not seen at the 125 mg dose. Additionally, no significant laboratory abnormalities were observed in the two lower dose groups.

On August 2, BioCryst announced the dosing of the first subject into ZENITH-1, a clinical trial studying up to three dosage strengths of a liquid formulation of BCX7353 given as a single oral dose for the acute treatment of angioedema attacks in patients with HAE.

On June 5, BioCryst announced that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental New Drug Application (sNDA) for a pediatric indication of RAPIVAB (peramivir injection), which was submitted in March 2017. The sNDA has been classified by the FDA as a priority review and has a Prescription Drug User Fee Act (PDUFA) goal date for a decision by the end of September 2017.

After discussions with the FDA, NIAID and BARDA, we have delayed the initiation of the galidesivir IV Phase 1 clinical trial. Based upon ongoing conversations, we expect the next step in galidesivir’s development will be to conduct an additional nonclinical efficacy study in a delayed treatment setting in Ebola disease before finalizing the Phase 1 clinical trial protocol design.

On May 30, BioCryst announced the appointment of Robert A. Ingram as Chairman of its Board of Directors.
Financial Outlook for 2017

Based upon development plans and our awarded government contracts, BioCryst continues to expect its 2017 net operating cash use to be in the range of $30 to $50 million, and its 2017 operating expenses to be in the range of $53 to $73 million. Our operating expense range excludes equity-based compensation expense due to the difficulty in reliably projecting this expense, as it is impacted by the volatility and price of the Company’s stock, as well as by the vesting of the Company’s outstanding performance-based stock options.

Conference Call and Webcast

BioCryst’s leadership team will host a conference call and webcast Monday, August 7, 2017 at 11:00 a.m. Eastern Time to discuss these financial results and recent corporate developments. To participate in the conference call, please dial 1-877-303-8027 (United States) or 1-760-536-5165 (International). No passcode is needed for the call. The webcast can be accessed by logging onto www.BioCryst.com. Please connect to the website at least 15 minutes prior to the start of the conference call to ensure adequate time for any software download that may be necessary.

About BCX7353

Discovered by BioCryst, BCX7353 is a novel, oral, once-daily, selective inhibitor of plasma kallikrein currently in development for the prevention and treatment of angioedema attacks in patients diagnosed with HAE. BCX7353 has been generally safe and well tolerated in the ongoing Phase 2 APeX-1 clinical trial for prophylaxis and in clinical pharmacology studies in healthy volunteers.

On August 7, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, reported that the independent Data Monitoring Committee (DMC) for the Company’s 550 patient, multinational, double-blind, placebo-controlled, pivotal Phase III clinical study of ThermoDox in combination with radiofrequency ablation (RFA) for primary liver cancer (the OPTIMA study), has completed a planned interim analysis of the first 50% of patients randomized in the trial as of April 2017 for safety and efficacy and unanimously recommended that the study continue according to protocol to its final data readout based on the risk to benefit analysis by the Committee (Press release, Celsion, AUG 7, 2017, View Source [SID1234520058]). The OPTIMA study to date has accumulated data within acceptable safety parameters.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The DMC is comprised of an independent group of medical and scientific experts and is responsible for reviewing and evaluating patient safety and efficacy data for the Company’s Phase III OPTIMA Study. The DMC reviews study data at regular intervals in order to ensure the safety of all patients enrolled in the trial and to monitor the quality and overall conduct of the trial including each site’s compliance with the minimum RFA heating time of 45 minutes specified in the study protocol. The Company also announced that enrollment in the OPTIMA Study is now over 60% of the 550 patients necessary to ensure that its primary end point, overall survival, can be achieved with statistical significance.
"Following independent confirmation of our hypothesis by the National Institutes of Health (NIH) in November 2016 that ThermoDox in combination with optimized RFA can be a treatment with curative intent for primary liver cancer, we are very pleased that the DMC has recommended continuation of the OPTIMA Study without modification. Based on their review of all the available study data from 275 patients enrolled as of April 2017, the DMC has concluded that ThermoDox is safe for newly diagnosed, intermediate stage patients and that the study is being conducted according to the highest of clinical research standards," said Nicholas Borys, MD, Celsion’s senior vice president and chief medical officer. "A key component of the OPTIMA Study protocol is the investigators’ adherence to the recommended RFA heating time for tumors greater than 3 cm. We are pleased to report that there has been a greater than 99% compliance rate with the study protocol."
On November 29, 2016, the Company announced results from an independent retrospective analysis conducted by the NIH on the intent-to-treat population of the 701 patient HEAT Study of ThermoDox plus optimized RFA for the treatment of primary liver cancer. The NIH analysis, which sought to evaluate the correlation between RFA burn time per tumor volume (min/ml) and clinical outcome, concluded that increased RFA "burn time" per tumor volume significantly improved overall survival (OS) in patients with solitary lesions treated with RFA + ThermoDox compared to patients treated with RFA alone. The NIH analysis included 437 patients with a single lesion from the Company’s HEAT Study, the same patient population being treated in the Company’s ongoing Phase III OPTIMA study.
The NIH findings are consistent with Celsion’s own analysis of the HEAT Study data, which demonstrated that over a 3.5 year period, there was a statistically significant survival benefit of approximately 2 years for patients treated with ThermoDox plus optimized RFA over the optimized RFA only group.
"We are very pleased that the DMC has unanimously recommended continuation of the OPTIMA study based on their review of all available clinical data, both safety and efficacy, in over 275 patients," stated Mr. Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "The DMC’s affirmative review is further evidence of ThermoDox’s potential to provide a new and important first line therapeutic option for patients with primary liver cancer."
Regulatory Strategy for ThermoDox. ThermoDox has received FDA Fast Track Designation and in the prior HEAT Study had been designated as a Priority Trial for primary liver cancer by the National Institutes of Health. ThermoDox has been granted orphan drug designation for primary liver cancer in both the U.S. and Europe. Based on prior discussions and subject to a successful trial, Celsion fully expects that the U.S. FDA and European EMA enrollment objectives will be met, and that the OPTIMA Study will also enrolled a sufficient number of patients to support registrational filings in China, South Korea, Taiwan and Vietnam, four other large and important markets for ThermoDox.
In December 2016, the Company met with the China Food and Drug Administration (CFDA) to discuss the ongoing Phase III OPTIMA program and regulatory pathway for ThermoDox in China. During the meeting, Celsion presented the final overall survival data from the Chinese patient cohort from the prior HEAT study, which demonstrated a survival benefit in patients treated with ThermoDox plus optimized RFA versus optimized RFA alone. The CFDA informed Celsion that if the ongoing Phase III OPTIMA trial is successful, the trial could serve as the basis for a direct regulatory filing in China without the need to file for prior approval in the U.S. or European Union which is currently required for foreign company application. This would allow the Company to accelerate its plans for a regulatory filing in China and, if approved, provide for a significantly earlier launch date in China than originally expected.
The OPTIMA study’s design and statistical plan incorporates two pre-planned interim efficacy analysis by the DMC (after patient enrollment is complete) with the intent of evaluating safety, efficacy and futility to determine if there is overwhelming evidence of clinical benefit or a low probability of treatment success to continue, modify or terminate the study. The results from the first interim efficacy analysis are expected to be made public following DMC review in Q1 of 2019.
About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 70 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus optimized RFA alone. The primary endpoint for the trial is Overall Survival, which is supported by post-hoc analysis of data from the Company’s 701 patient HEAT Study, where optimized RFA has demonstrated the potential to significantly improve survival when combined with ThermoDox. The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee.

On August 7, 2017 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical-stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported the initiation of a randomized Phase 2 trial of CB-839, the company’s glutaminase inhibitor, combined with AFINITOR (everolimus)‎ in patients with clear cell renal cell carcinoma (Press release, Calithera Biosciences, AUG 7, 2017, View Source [SID1234520057]).

“Despite the advances in the treatment of renal cell carcinoma, there remains significant unmet need for patients who have progressed following treatment with an anti-PD1 and/or tyrosine kinase inhibitors,” said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. “The initiation of this study marks an important milestone for our company, as it is the first randomized trial of CB-839 that we believe has the potential for U.S Food and Drug Administration (FDA) registration and approval. In recognition of the lack of treatment options available to patients with renal cell carcinoma, the FDA has granted Fast Track Designation to CB-839 in this setting.”

The randomized, double-blind, placebo controlled trial is designed to evaluate the safety and efficacy of CB-839 in combination with everolimus versus placebo with everolimus in approximately 250 patients with metastatic, clear cell renal cell carcinoma (RCC) patients who have been treated with at least two prior lines of systemic therapy including a VEGFR-targeting tyrosine kinase inhibitor and at least one of either CABOMETYX (cabozantinib) or an active PD-1/PD-L1 inhibitor. Patients will be randomized in a 2:1 ratio. The primary endpoint is progression free survival assessed by an independent review committee; overall survival will be assessed as a secondary endpoint. The multicenter, international study will be conducted at multiple sites in the United States, Europe and Canada. Clinical trial sites have been activated and the study is open for enrollment. For a listing of clinical sites and additional details about the clinical trial, please see www.clinicaltrials.gov (NCT03163667).

CB-839 takes advantage of the pronounced dependency many cancers have on the nutrient glutamine for growth and survival. CB-839 inhibits glutaminase, an enzyme required by cancer cells to utilize glutamine effectively, resulting in inhibition of tumor growth. In 2017, RCC is estimated to be diagnosed in approximately 63,990 people in the United States, according to the National Cancer Institute. Clear cell is the most common form of kidney cancer, comprising 70-75% of cases. Most patients with clear cell RCC lack the tumor suppressor gene VHL, making them more dependent on glutamine due to a loss of ability to make fatty acids from glucose1,2,3. Since the mTOR inhibitor everolimus impairs the use of glucose by cancer cells, the combination of CB-839 with everolimus induces dual metabolic inhibition.

On August 7, 2017 Bayer reported the European Commission (EC) has granted marketing authorization for Stivarga (regorafenib) for the treatment of adult patients with HCC who have been previously treated with Nexavar (sorafenib) (Press release, Bayer, AUG 7, 2017, View Source [SID1234520056]). Stivarga is the first and only treatment that has demonstrated a significant improvement in overall survival (OS) in second-line HCC. This marks the third major approval in five months for Stivarga, with the product also gaining approval in the U.S. and Japan for second-line treatment of HCC in April and June, respectively.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Until now, there was no effective second-line systemic treatment option for liver cancer patients and their treating physicians in Europe. With the EU approval of Stivarga in HCC, the outlook could significantly improve for patients with HCC, as they have now for the first time, a treatment plan with two approved therapies involving the use of Stivarga directly after Nexavar," said Dr. Jordi Bruix, lead investigator for the RESORCE trial, BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBEREHD, Spain.

The approval is based on data from the international, multicenter, placebo-controlled Phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma; NCT 01774344] trial, which investigated patients with HCC whose disease had progressed during treatment with Nexavar. In the trial, regorafenib plus best supportive care (BSC) was shown to provide a statistically significant and clinically meaningful improvement in OS versus placebo plus BSC (10.6 vs. 7.8 months, respectively, (HR 0.63; 95% CI 0.50-0.79; p<0.0001)), which translates to a 37% reduction in the risk of death over the trial period. Adverse events observed in the RESORCE trial were generally consistent with the known safety profile of regorafenib. The most common treatment-emergent adverse events were hand-foot skin reaction, diarrhea, fatigue and hypertension.

"Liver cancer is often diagnosed late and difficult to treat, but the EU approval of Stivarga for HCC marks the first treatment advance for patients in nearly a decade. Bayer continues to support the liver cancer community and is committed to ongoing research in the field, as well as continuing to pursue additional regulatory filings for Stivarga across the world," said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer.

Liver cancer is often more difficult to treat than other cancers with an annual mortality rate of 48,000 in the EU. Globally, it is the second leading cause of cancer-related deaths.

Additional regulatory filings for Stivarga in HCC are under review in other countries around the world, including China. The product was approved in the U.S. and Japan for second-line treatment of HCC in April and June, respectively. Stivarga is already approved in more than 90 countries worldwide, including the U.S., Japan, China and countries in the EU, for the treatment of metastatic colorectal cancer. Stivarga is also approved in more than 80 countries globally, including the U.S., Japan, China and countries in the EU, for the treatment of metastatic gastrointestinal stromal tumors.

About Hepatocellular Carcinoma
Hepatocellular carcinoma, or HCC, is the most common form of liver cancer representing approximately 70-85 percent of liver cancer worldwide. Liver cancer is the sixth most common cancer in the world and the second leading cause of cancer-related deaths globally. More than 780,000 cases of liver cancer are diagnosed worldwide each year (52,000 in the European Union, 501,000 in the Western Pacific region and 30,000 in the United States) and the incidence rate is increasing. In 2012, approximately 746,000 people died of liver cancer including approximately 48,000 in the European Union, 477,000 in the Western Pacific region and 24,000 in the United States.
 
About Regorafenib (Stivarga)
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

In the EU, Stivarga is indicated as monotherapy for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy, as well as for the treatment of adult patients with unresectable or metastatic GIST who progressed on or are intolerant to prior treatment with imatinib and sunitinib, and for the treatment of adult patients with HCC who have been previously treated with sorafenib.

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative cancer treatments. The oncology franchise at Bayer currently includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways, with the potential to impact the way that cancer is treated.