On March 19, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted an exemption to the Import Alert placed on the Centre for Probe Development and Commercialization (CPDC) for the use of CLR 131 in connection with the company’s pediatric IND (Press release, Cellectar Biosciences, MAR 19, 2019, View Source [SID1234534493]). This exemption will allow Cellectar to immediately begin enrolling patients in its Phase 1 pediatric study for the treatment of select relapsed or refractory solid tumors including neuroblastoma, lymphomas and malignant brain tumors.

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Cellectar is already enrolling patients in its Phase 1 and Phase 2 multiple myeloma and select B-cell lymphoma studies of CLR 131 after having received FDA exemption to the CPDC Import Alert in November 2018 for its hematology IND.

"We are grateful that the FDA has granted this additional exemption for CLR 131, which allows us to immediately initiate our pediatric clinical study in children battling life-threatening cancers," said James Caruso, president and CEO of Cellectar. "These patients have a very poor prognosis and low rates of survival as a result of limited effective treatment options. Based on our preclinical and ongoing clinical studies, we are optimistic that CLR 131 has the potential to provide a meaningful treatment option for children suffering from cancers with high unmet medical needs."

About the Phase 1 Pediatric Study of CLR 131

The Phase 1 pediatric study will be an open-label, sequential-group, dose-escalation study to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers, including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors. Secondary objectives of the study are to identify the recommended Phase 2 dose of CLR 131 and to determine preliminary antitumor activity (treatment response) of CLR 131 in children and adolescents. We plan to initiate this Phase 1 study at 5-7 pediatric cancer centers, within and possibly outside the US.

About CLR 131

CLR 131 is a small-molecule, cancer-targeting radiotherapeutic PDC designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. CLR 131 is our lead therapeutic PDC product candidate and is currently being evaluated in both Phase 2 and Phase 1 clinical studies. In December 2014, the FDA granted orphan drug designation for CLR 131 for the treatment of multiple myeloma. In 2018, the FDA granted orphan drug and rare pediatric disease designations for CLR 131 for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. The FDA previously accepted our IND application for a Phase 1 open-label, dose-escalating study to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors

On March 18, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that updated results from the cervical cancer cohort of SUMMIT, an ongoing Phase II basket trial examining the efficacy of neratinib in HER2-mutated cancers, were reported at the Society of Gynecologic Oncology (SGO) 2019 Annual Meeting in Honolulu, Hawaii (Press release, Puma Biotechnology, MAR 18, 2019, View Source [SID1234534416]). "Neratinib in patients with HER2-mutant, metastatic cervical cancer: findings from the phase II SUMMIT ‘basket’ trial," was presented during the Scientific Plenary Session by Anishka D’Souza, M.D., Assistant Professor of Clinical Medicine, Keck School of Medicine of University of Southern California (USC). SGO selected this abstract as the recipient of the 2019 SGO Presidential Award. Slides from the presentation are available on the Puma Biotechnology website.

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The Phase II SUMMIT ‘basket’ trial is an open-label, multicenter, multinational study to evaluate the safety and efficacy of neratinib administered daily to patients who have solid tumors with activating, somatic HER2 mutations. The cervical cancer cohort was comprised of 11 patients with advanced and/or metastatic disease treated with neratinib monotherapy. Patients received a median of 2 (range 1–4) prior regimens in the recurrent or metastatic setting before entering this trial. Six patients (54.5%) had been previously treated with bevacizumab prior to entering the study; 7 patients (63.6%) had received prior surgery; and 9 patients (81.8%) received prior radiation therapy. The objective response rate was 27.3% (95% CI: 6.0%–61.0%). The clinical benefit rate was 54.5% (95% CI: 23.4%–83.3%) and included 3 patients with confirmed partial responses and 3 patients with stable disease that lasted greater than 16 weeks. The median progression free survival was 7.0 months (95% CI: 0.7–20.1 months).

The safety profile observed in neratinib-treated cervical cancer patients in SUMMIT was consistent with that reported for HER2-amplified metastatic breast cancer. The most frequently observed adverse event was diarrhea, any grade (n=9, 81.8%) including 1 (9%) grade 3 diarrhea event. The duration of grade 3 diarrhea was 1 day. None of the diarrhea events resulted in dose reduction, dose discontinuation or hospitalization.

"Somatic HER2 mutations represent a distinct class of oncogenic driver mutations that appear to be clinically actionable for metastatic cervical cancers. Treatment with neratinib led to durable responses and disease control in metastatic patients with HER2-mutant cervical cancer," said Dr. D’Souza, who practices oncology at the USC Norris Comprehensive Cancer Center.

Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are very pleased with the activity seen with neratinib in this cohort of patients with HER2-mutated cervical cancer. We look forward to the further development of neratinib in this patient population."

On March 18, 2019 Novavax, Inc. (Nasdaq: NVAX) reported its financial results and operational highlights for the fourth quarter and twelve months ended December 31, 2018 (Press release, Novavax, MAR 18, 2019, View Source [SID1234534467]).

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"In 2018, we committed to focus on our two lead programs, ResVax and Nanoflu, and reflecting on last year’s activities, I am proud to say we have achieved significant results for both," said Stanley C. Erck, President and CEO of Novavax, Inc. "Although we were disappointed to miss the primary endpoint of our Prepare trial, ResVax is the first RSV vaccine to demonstrate efficacy for the prevention of RSV disease in a Phase 3 clinical trial. In addition, the successful Phase 2 results for our NanoFlu vaccine provide an opportunity to now confirm with the FDA the use of accelerated approval for licensure. We are now prepared to make meaningful advances on these programs during 2019."

Fourth Quarter 2018 and Subsequent Operational Highlights

ResVax Program

In February 2019, Novavax announced top-line data from the Prepare trial, which was initiated in December 2015 to determine the efficacy of ResVax against medically significant RSV-positive lower respiratory tract infection (LRTI) in infants. Although the Prepare trial results did not meet the pre-specified primary efficacy endpoint, they demonstrate efficacy against a secondary objective (RSV LRTI hospitalizations). In addition, other pre-specified exploratory endpoints and post-hoc analyses highlight ResVax’ potential to improve global health against serious RSV disease.
NanoFlu Program

In January 2019, Novavax announced positive top-line results of its Phase 2 clinical trial of NanoFlu comparing various quadrivalent formulations, with or without Novavax’ Matrix-M adjuvant, with two U.S.-licensed influenza vaccines in older adults. These results show that NanoFlu with Matrix-M generated enhanced immune responses compared to the unadjuvanted formulation, and importantly, showed superior hemagglutination inhibition antibody (HAI) responses against wild-type A(H3N2) viruses, including drifted strains, when compared to Fluzone High-Dose, the leading flu vaccine in older adults.
Key Upcoming Events

Continue ongoing discussions with the FDA, European regulatory agencies, and potentially other national regulatory agencies, to assess opportunities for submission of marketing license applications for ResVax.
Reach agreement with the FDA during the second quarter of 2019 on a proposed Phase 3 study design for NanoFlu utilizing accelerated approval criteria.
Present ResVax Phase 3 trial data at the 37th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID) on May 7, 2019.
Financial Results for the Three and Twelve Months Ended December 31, 2018

Novavax reported a net loss of $49.3 million, or $0.13 per share, for the fourth quarter of 2018, compared to a net loss of $50.8 million, or $0.16 per share, for the fourth quarter of 2017. For the twelve months ended December 31, 2018, the net loss was $184.7 million, or $0.50 per share, compared to a net loss of $183.8 million, or $0.63 per share, for the same period in 2017.

Novavax revenue in the fourth quarter of 2018 was $6.1 million, compared to $10.4 million in the same period in 2017. This 41% decrease was driven by the completion of enrollment of participants in the Prepare trial in the second quarter of 2018.

Research and development expenses decreased 13% to $43.4 million in the fourth quarter of 2018, compared to $49.7 million for the same period in 2017. This decrease was primarily due to decreased development activities of ResVax and lower employee-related costs, partially offset by increased development activities of NanoFlu.

General and administrative expenses increased 8% to $9.2 million in the fourth quarter of 2018, compared to $8.5 million for the same period in 2017. The increase was primarily due to higher professional fees.

Interest income (expense), net for the fourth quarter of 2018 was ($2.8) million, compared to ($3.1) million for the same period of 2017.

As of December 31, 2018, Novavax had $103.9 million in cash, cash equivalents, marketable securities and restricted cash, compared to $186.4 million as of December 31, 2017. Net cash used in operating activities for the fourth quarter of 2018 was $45.3 million, compared to $43.4 million for same period in 2017.

Conference Call

Novavax will host its quarterly conference call today at 4:30 p.m. ET. The dial-in numbers for the conference call are (877) 212-6076 (Domestic) or (707) 287-9331 (International), passcode 9559037. A replay of the conference call will be available starting at 7:30 p.m. ET on March 18, 2019 until 7:30 p.m. ET on March 25, 2019. To access the replay by telephone, dial (855) 859-2056 (Domestic) or (404) 537-3406 (International) and use passcode 9559037.

A webcast of the conference call can also be accessed via a link on the home page of the Novavax website (novavax.com) or through the "Investor Info"/"Events" tab on the Novavax website. A replay of the webcast will be available on the Novavax website until June 18, 2019.

About RSV in Infants

Globally, RSV (respiratory syncytial virus) is the leading viral cause of severe lower respiratory tract disease in infants and young children.1 It is the second leading cause of death in children under one year of age.2 Estimated annual hospitalizations of 1.4 million and an estimated 27,300 in-hospital deaths were due to RSV acute lower respiratory infection in children under six months of age.3 RSV results in a total global economic burden of $6.2 billion annually.

In the U.S., RSV is the leading cause of hospitalization of infants.4 Estimated annual hospitalizations are up to 76,000.5,6 While RSV can impact all infants, babies under six months of age are among those at highest risk, as approximately 77% of all first-year RSV infections occur before six months. In the U.S., the total economic burden is $2.7 billion annually.

About ResVax

ResVax is an RSV fusion (F) protein recombinant nanoparticle vaccine with aluminum phosphate as an adjuvant. It is being developed to protect infants from RSV disease via maternal immunization, which may offer the best method of protection from RSV disease in infants through the first months of life. In February 2019, Novavax announced top-line data from Prepare, a global Phase 3 clinical trial in 4,636 pregnant women, at least 3,000 of whom have received the vaccine, and their infants. Prepare is supported by an $89.1 million grant from the Bill & Melinda Gates Foundation (BMGF).

About Influenza

Influenza is a world-wide infectious disease that causes illness in humans with symptoms ranging from mild to life-threatening or even death. Serious illness occurs not only in susceptible populations such as infants, young children and older adults, but also in the general population largely because of infection by continuously evolving strains of influenza which can evade the existing protective antibodies in humans. An estimated one million deaths globally each year are attributed to influenza.7 Current estimates for seasonal influenza vaccine growth in the top seven markets (U.S., Japan, France, Germany, Italy, Spain and UK), show a potential increase from approximately $3.2 billion in 2012-13 season to $5.3 billion by the 2021-22 season.8

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1 Nair, H., et al. (2010) Lancet. 375:1545-1555
2 Losano R., et al. (2012/Dec15) Lancet. 380: 2095
3 Ting S/Nair H. Lancet. 2017/Sep2;390:946
4 Leader S., et al. (2003) J Pediatr. 143: S127
5 Hall CB. N Engl J Med 2009;360:588
6 CDC-Stockman LJ. Pediatr Infect Dis J 2012;31:5
7 Resolution of the World Health Assembly. (2003) WHA56.19.28
8 Influenza Vaccines Forecasts. Datamonitor (2013)

About NanoFluand Matrix M

NanoFlu is a recombinant hemagglutinin (HA) protein nanoparticle influenza vaccine produced by Novavax in its SF9 insect cell baculovirus system. NanoFlu uses HA protein amino acid sequences that are the same as the recommended wild-type circulating virus HA sequences. NanoFlu contains Novavax’ patented saponin-based Matrix-M adjuvant, which is potent and well- stimulates both high quality and durable antibody responses as well as multifunctional CD4 and CD8 T-cell responses. In January 2019, Novavax announced positive top-line data from its Phase 2 clinical trial in older adults of quadrivalent formulations of NanoFlu in 1,375 healthy older adults across clinical sites in the U.S.

About Accelerated Approval

Accelerated approval may be granted for certain biological products that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments. Such an approval will be based on adequate and well-controlled clinical trials establishing that the biological product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. For seasonal influenza vaccines, the hemagglutination inhibition (HAI) antibody response may be an acceptable surrogate marker of activity that is reasonably likely to predict clinical benefit. To be considered for accelerated approval, a biologics license application for a new seasonal influenza vaccine should include results from one or more well-controlled studies designed to meet immunogenicity endpoints and a commitment to conduct confirmatory post-marketing studies of clinical effectiveness in preventing influenza.

On March 18, 2019 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of drugs to treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of the stress hormone cortisol, reported the appointment of Andreas Grauer, M.D., as Chief Medical Officer (Press release, Corcept Therapeutics, MAR 18, 2019, https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-appoints-former-amgen-development-executive [SID1234534417]). Dr. Grauer most recently served as Vice President of Global Development at Amgen.

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"We are delighted Andreas will be joining us," said Joseph K. Belanoff, M.D., Corcept’s Chief Executive Officer. "His extensive experience advancing novel compounds through every stage of development and regulatory approval will be invaluable as Corcept’s pipeline progresses."

"There is much to do," said Dr. Belanoff. "Relacorilant is in the midst of its Phase 3 trial as a treatment for patients with hypercortisolism and in Phase 2 as a treatment for patients with advanced ovarian cancer. More indications for relacorilant, including metastatic pancreatic cancer, are under consideration. We expect to select a dose this year of CORT125281 as a treatment for patients with castration-resistant prostate cancer. And CORT118335 will enter the clinic soon as a treatment for antipsychotic induced weight gain and, later this year, non-alcoholic steatohepatitis."

"I am excited to join Corcept at this key moment," said Dr. Grauer. "Cortisol modulation has the potential to improve the lives of many seriously ill patients. I look forward to bringing my experience and expertise to bear to develop truly novel, beneficial medications."

Prior to joining Corcept, Dr. Grauer spent more than ten years at Amgen in a variety of leadership roles, most recently as Vice President of Global Development, where he led or oversaw programs in therapeutic areas including bone, nephrology, and inflammation throughout all phases of development. Dr. Grauer also brings significant experience in regulatory filings across the world that culminated in multiple new drug application and biologic license application approvals. Before Amgen, he held senior executive positions at Procter & Gamble Pharmaceuticals. Dr. Grauer holds an M.D. from the University of Heidelberg Medical School, where he graduated magna cum laude. He is Board Certified in both internal medicine and endocrinology in Germany.

On March 18, 2019 Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs, reported financial results for the fourth quarter and year ended December 31, 2018 and provided a corporate update (Press release, Regulus, MAR 18, 2019, View Source [SID1234534442]).

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"2018 was a challenging year for Regulus, but I am encouraged by our program advancements and recent corporate and cost-saving efforts. Importantly, we have nearly completed the transition of the RG-012 program to Sanofi, have positioned the Company to advance our prioritized pipeline, and significantly reduced our operating cash burn. In January, we submitted a comprehensive data package to FDA for RGLS4326 for the treatment of Autosomal Dominant Polycystic Kidney Disease, or ADPKD, and look forward to their feedback, which we hope will define the path forward to resume clinical development," said Jay Hagan, President and Chief Executive Officer of Regulus.

Corporate Updates

Restructuring of Sanofi Collaboration and Transition of RG-012 to Sanofi: In November 2018, Regulus announced that it amended and restructured its Collaboration and License Agreement with Sanofi (the "Amendment"). Under the Amendment, Regulus granted Sanofi a worldwide exclusive license to develop and commercialize its investigational drug targeting miR-21 for all indications, including Alport syndrome. Under the terms of the Amendment, Regulus is eligible to receive approximately $7 million in upfront and material transfer payments. Regulus is also eligible to receive up to $40 million in development milestone payments. In addition, Sanofi will reimburse Regulus for certain out-of-pocket transition activities and assume Regulus’ upstream license royalty obligations. The transition activities for the RG-012 program to Sanofi are nearly complete and upon completion will trigger the remainder of the upfront payment due to Regulus of $2.5 million.

Term Loan Amendments: In January 2019 and March 2019, the Company amended its Term Loan with Oxford Finance to provide for additional periods of interest only for the months of February 2019 and March 2019, respectively. The maturity date of the Term Loan remains unchanged.

Lease Agreement: In February 2019, the Company entered into an amendment of its current lease (the "Lease Amendment") for approximately 59,248 square feet located at 10614 Science Center Drive, San Diego, California 92121. Under the terms of the Lease Amendment, the expiration of the current lease will be accelerated from April 30, 2024 to April 1, 2019. Concurrently with the Lease Amendment, the Company entered into a new lease agreement (the "Lease") for approximately 24,562 square feet at 10628 Science Center Drive, Suite 100, San Diego, California, 92121 which it expects to use as its new principal offices and laboratory for research and development. The commencement date of the Lease is expected to be April 1, 2019. This relocation will reduce the Company’s facility size by approximately 60% and reduce its future contractual lease obligations by approximately 70%.

Financial Results

Cash Position: As of December 31, 2018, Regulus had cash and cash equivalents of $13.9 million.

Research and Development (R&D) Expenses: R&D expenses were $5.3 million and $34.0 million for the quarter and year ended December 31, 2018, respectively, compared to $10.5 million and $53.2 million for the same periods in 2017. The decreases in R&D expenses were primarily attributable to a reduction in external development expenses associated with RG-012 during the negotiation and transfer of the program to Sanofi in the second half of 2018 and a reduction in personnel-related costs subsequent our corporate restructurings.

General and Administrative (G&A) Expenses: G&A expenses were $2.7 million and $12.9 million for the quarter and year ended December 31, 2018, respectively, compared to $3.3 million and $17.0 million for the same periods in 2017. The decreases in G&A expenses were primarily driven by non-recurring severance charges and non-recurring, non-cash stock-based compensation charges recorded during the year ended December 31, 2017 in connection with our May 2017 corporate restructuring.

Revenue: Revenue was less than $0.1 million for the quarters ended December 31, 2018 and 2017, and $0.1 million for the years ended December 31, 2018 and 2017.

Net Loss: Net loss was $8.6 million and $48.7 million for the quarter and year ended December 31, 2018, respectively, compared to a net loss of $14.4 million and $71.9 million for the same periods in 2017. Basic and diluted net loss per share was $0.98 and $5.59 for the quarter and year ended December 31, 2018, respectively, compared to $1.67 and $11.47 for the same periods in 2017.

About Autosomal Dominant Polycystic Kidney Disease (ADPKD)

ADPKD, caused by the mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading genetic cause of end-stage renal disease. The clinical hallmark of this disease is the development of multiple fluid filled cysts primarily in the kidneys and to a lesser extent in the liver and other organs. Excessive kidney tubule derived cyst cell proliferation, a central pathological feature, fuels the expansion of cysts, ultimately causing end-stage renal disease in approximately 50% of ADPKD patients by age 60. Approximately 1 in 1,000 people bear a mutation in either PKD1 or PKD2 genes worldwide.

About RGLS4326

RGLS4326 is a novel oligonucleotide designed to inhibit miR-17 and designed to preferentially target the kidney. Preclinical studies with RGLS4326 have demonstrated direct regulation of PKD1 and PKD2 in human ADPKD cyst cells, a reduction in kidney cyst formation, improved kidney weight/body weight ratio, decreased cyst cell proliferation, and preserved kidney function in mouse models of ADPKD.