On March 7, 2019 Cytori Therapeutics, Inc. (NASDAQ: CYTX) reported that it officially filed a formal new drug application pre-submission request to the European Medicine Agency (EMA) for Doxorubicin Hydrochloride Cytori (Press release, Cytori Therapeutics, MAR 7, 2019, View Source [SID1234534097]). This submission is the precursor to filing an Article 58 Application for a Marketing Authorization Application (MAA) via EMA’s centralized approval procedure. In June 2017, the EMA Committee for Medicinal Products for Human Use (CHMP) confirmed that Doxorubicin Hydrochloride Cytori was eligible for submission of a MAA via the centralized procedure.

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In addition, in late 2018, the EMA CHMP Name Review Group validated Doxorubicin Hydrochloride Cytori as the official invented name to replace ATI-0918. Doxorubicin Hydrochloride Cytori is a liposomal nanoparticle medicinal product being developed for cancer patients that contains the active substance doxorubicin, a widely used chemotherapy drug. Doxorubicin Hydrochloride Cytori is intended for the treatment of breast cancer, ovarian cancer, multiple myeloma, and Kaposi’s sarcoma.

"Liposomal doxorubicin is a commonly prescribed chemotherapeutic drug for patients with advanced breast and ovarian cancer as well as other indications," said Dr. Marc Hedrick MD, President/CEO of Cytori Therapeutics. "Bringing Doxorubicin Hydrochloride Cytori to market in Europe as an alternative to the branded drug is an important near-term corporate goal."

As a ‘hybrid medicine’, Doxorubicin Hydrochloride Cytori is intended to be similar to a ‘reference medicine’, Adriamycin, already authorized in the EU. Doxorubicin Hydrochloride Cytori is different than Adriamycin in that the active substance is encapsulated in tiny lipid nanospheres called liposomes that are coated in polyethylene glycol or PEG. Cytori believes that it has successfully completed all clinical development work for Doxorubicin Hydrochloride Cytori and is currently manufacturing the drug in its dedicated plant in San Antonio, Texas.

Cytori expects to receive assignment of a rapporteur and co-rapporteur, who will work with the company through the MAA submission and review process, by the end of April 2019. The MAA submission is planned for later in 2019 or early 2020.

Cytori’s MAA will present data from the scientific literature and from non-clinical studies, including comparisons with Janssen’s Caelyx, an authorized medicine containing doxorubicin in pegylated liposomal form. The company will also present the results of a completed clinical study intended to investigate whether Doxorubicin Hydrochloride Cytori is ‘bioequivalent’ to Caelyx, meaning that they both produce the same levels of the active substance in the body.

Janssen’s Caelyx first received a marketing authorization for the EU in 1996, is currently approved for the treatment of breast cancer, ovarian cancer, multiple myeloma, and Kaposi’s sarcoma, and generated over €110M in sales across Europe in 2017. No generic versions of Caelyx are currently approved and available in Europe.

On March 7, 2019 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months and year ended December 31, 2018 and provided a corporate update (Press release, DURECT, MAR 7, 2019, http://investors.durect.com/phoenix.zhtml?c=121590&p=irol-newsArticle&ID=2390574 [SID1234534138]).

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Total revenues were $3.6 million and net loss was $7.3 million for the three months ended December 31, 2018 as compared to total revenues of $19.5 million and net profit of $8.2 million for the three months ended December 31, 2017. Revenues for the three months ended December 31, 2017 included the recognition of $15.4 million in deferred revenue from the $20 million upfront fee associated with our terminated agreement with Sandoz AG.
Total revenues were $18.6 million and net loss was $25.3 million for the year ended December 31, 2018, compared to total revenues of $49.2 million and net loss of $3.7 million for the year ended December 31, 2017. Revenues for the year ended December 31, 2018 included a $5 million milestone payment from Indivior related to the NDA approval of PERSERIS (risperidone); revenues for the year ended December 31, 2017 included a $20 million upfront fee from Sandoz AG and a $12.5 million upfront payment from Indivior.
At December 31, 2018, cash and investments were $34.5 million, compared to cash and investments of $36.9 million at December 31, 2017. Debt at December 31, 2018, including partial accrual for the final payment of our term loan, was $20.5 million.
"Based on encouraging data from both of the completed moderate and severe alcoholic hepatitis (AH) 30 mg cohorts, the relatively rapid enrollment of severe AH patients, and strong encouragement from several of our key expert advisors and clinical trial investigators, we have decided to continue our AH trial by conducting the next cohort of severe AH patients at the 90 mg dose. In parallel, we are continuing to recruit patients in the moderate AH 90 mg cohort and work with Dr. McClain at the University of Louisville on enabling initiation of his NIH-funded DUR-928 AH trial. We also look forward to generating and reporting data this year from the NASH and psoriasis trials in which patients will receive daily doses of DUR-928 for 28 days," stated James E. Brown, D.V.M., President and CEO of DURECT. "In addition, we will be requesting approval of POSIMIR when we submit to the FDA a full response to the Complete Response Letter. If successful, this could lead to FDA approval this year. Also, Indivior announced that the commercial launch of PERSERIS in the U.S. took place in February 2019. We receive quarterly earn-out payments on U.S. net sales of PERSERIS."

Potential milestones in 2019:

Reporting initial data from a DUR-928 multi-dose trial in NASH patients
Reporting top-line data from a DUR-928 Phase 2a proof-of-concept trial in mild to moderate plaque psoriasis patients
Completing the 90 mg cohort in severe AH patients
Submission to and acceptance by the FDA of a full response to the CRL for POSIMIR and potential NDA approval following an expected six-month review period
Commercial launch of PERSERIS by Indivior in the U.S.
Commercial launch of Methydur by Orient Pharma in Taiwan
New license and collaboration agreements
Update on Selected Programs and Transactions:

Epigenetic Regulator Program. DUR-928, the lead product candidate in the Company’s Epigenetic Regulator Program, is an endogenous, first-in-class small molecule, which may have broad applicability in several hepatic and renal diseases such as NASH, in acute organ injuries such as AH and acute kidney injury (AKI), and in inflammatory skin disorders such as psoriasis and atopic dermatitis.

Clinical Trials

Non-Alcoholic Steatohepatitis (NASH)

This will be an open-label, Phase 1b study conducted in the U.S. to evaluate safety, pharmacokinetics and signals of biological activity of DUR-928 in patients with NASH. Three doses of oral DUR-928 (low, middle and high) will be administered daily for 28 consecutive days. We plan to enroll approximately 20 patients per dose group for a total of approximately 60 patients in the trial. We expect to begin enrolling patients during the first quarter of 2019 and announce initial data from this study in the second half of 2019.
In the Company’s previous Phase 1b NASH study, reported at the European Association for the Study of the Liver (EASL) in April 2017, exploratory biomarker analysis demonstrated that a single oral dose of DUR-928 in NASH patients, at both dose levels tested (50 mg and 200 mg), resulted in statistically significant reductions from baseline of both full-length and cleaved cytokeratin-18 (CK-18), bilirubin, hsCRP and IL-18.
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in both children and adults. It is estimated that NAFLD affects about 20% to 30% of adults and 10% of children in the United States. NASH, a more severe and progressive form of NAFLD, is one of the most common chronic liver diseases worldwide, with an estimated prevalence of more than 10% of adults in the United States, Europe, Japan and other developed countries. No drug is currently approved for NAFLD or NASH.
Alcoholic Hepatitis (AH)

DURECT is conducting a Phase 2a clinical trial with intravenously administered DUR-928 in patients with alcoholic hepatitis (AH). This is an open label, dose escalation, multi-center U.S. study, originally designed to be conducted in two sequential parts. Part A includes patients with moderate AH (as determined by the Model of End-Stage Liver Disease (MELD) scores, a common scoring system to assess the severity and prognosis of AH patients), and Part B includes patients with severe AH. Three dose levels (30, 90 and 150 mg) were planned for testing in Part A. Dose escalation may occur following review of safety and pharmacokinetic (PK) results of the prior dose level by a Dose Escalation Committee (DEC). The target number of patients for the study is 4 per dose group. The objectives of this study include assessment of safety, PK and pharmacodynamic (PD) signals, including liver biochemistry and biomarkers.
After completing dosing for the low-dose 30 mg cohort (n=4) of Part A (moderate AH patients), the DEC approved commencement of the 90 mg cohort in Part A while simultaneously commencing recruitment for Part B (severe AH patients) with the 30 mg dose.
We have now completed dosing of the 30 mg cohort (n=4) of Part B, the enrollment of which was much more rapid than Part A. After reviewing the safety and PK data, the DEC has approved commencement of the 90 mg cohort in Part B. Based on the encouraging data from both the moderate and severe 30 mg cohorts, the relatively rapid enrollment of severe AH patients, and strong encouragement from several of our key expert advisors and clinical trial investigators, we have decided to continue our trial by conducting the next cohort of severe AH patients at the 90 mg dose.
In parallel with our recruitment of patient for both of the 90 mg cohorts in our trial, we are supporting Dr. Craig McClain’s efforts to initiate his NIH-funded study at the University of Louisville.
AH is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of alcohol, and encompasses a spectrum that ranges from mild injury to severe, life threatening liver damage. The prevalence of AH is estimated to occur in 10-35% of heavy drinkers. According to an article in the Journal of Clinical Gastroenterology (2015 July; 49(6): 506-511), there were over 320,000 hospitalizations related to alcoholic hepatitis in 2010, resulting in hospitalization costs of nearly $50,000 per patient.
Psoriasis

In this Phase 2a, randomized, double-blind, vehicle-controlled proof-of-concept clinical trial, DUR-928 will be applied topically once-daily for four weeks in patients with mild to moderate plaque psoriasis. The trial will be conducted at multiple clinical sites in the U.S. Twenty patients are planned to be enrolled to obtain approximately 15 evaluable patients. Patients will serve as their own controls, applying DUR-928 to the plaque on one arm and the vehicle to a similar plaque on the other arm. After the treatment period, patients will be followed for an additional four weeks. The primary efficacy endpoint will be the change in local psoriasis scores from baseline in the DUR-928-treated plaques compared to that in the vehicle-treated plaques. We expect to begin enrolling patients during the first quarter of 2019 and announce top line data from this study in the second half of 2019. Additional information on the trial design, including eligibility criteria and site locations, can be found at www.clinicaltrials.gov using the NCT Identifier 03837743.
The Company previously conducted an exploratory Phase 1b trial in psoriasis patients (9 evaluable patients) in Australia. The trial was randomized, double-blinded, placebo and self-controlled, using a micro-plaque assay with intralesional injections of DUR-928. The results were encouraging and warranted advancing into the current proof-of-concept trial with topically applied DUR-928. In support of the Phase 2a study, the Company has completed multiple non-clinical safety studies for topically applied DUR-928.
Psoriasis is an inflammatory skin disease and an immune-mediated condition that causes the body to make new skin cells in days rather than weeks. In the United States, there are about 150,000 new cases of psoriasis every year and it affects an estimated 7.5 million Americans. According to the International Federation of Psoriasis Associations (IFPA), nearly 3% of the world’s population has some form of psoriasis or about 125 million people. Psoriasis causes itchiness and irritation and may be painful. There’s no cure for psoriasis yet, but treatment can ease symptoms. Approximately 80% of patients with psoriasis have localized disease, which can be treated with topical therapies. As such, topical agents remain the mainstay of psoriasis treatment.
POSIMIR (bupivacaine extended-release solution) Post-Operative Pain Relief Depot. POSIMIR is the Company’s investigational post-operative pain relief depot that utilizes the Company’s patented SABER technology and is designed to deliver bupivacaine to provide up to 3 days of pain relief after surgery.

After a comprehensive review of the POSIMIR program in light of the issues raised by the FDA in our communications with them, including the Complete Response Letter (CRL), we are planning to submit a full response to the CRL in the first half of 2019. As the submission will be a response to a CRL, we expect a 6-month FDA review period.
The effort to evaluate the program, develop a strategy for filing the response, and the actual writing of key sections of the response, has been under the direction of Dr. Lee Simon, who was formerly FDA’s Division Director of Analgesic, Anti-inflammatory and Ophthalmologic Drug Products.
We believe that the completed inguinal hernia and subacromial decompression (shoulder) clinical trials support the efficacy of POSIMIR in post-operative pain and meet the requirements to be considered as adequate and well-controlled pivotal clinical trials. Both trials demonstrated a significant decrease in pain and opioid use over the 0-72 hour period following surgery as compared to placebo.
We have completed 16 clinical trials in the POSIMIR program, involving over 1,400 patients, over 850 of whom received POSIMIR with the remainder in control groups. We believe this is a sufficiently sized safety database. We believe that, with the PERSIST safety data included, we now have sufficient data to address FDA’s issues raised in the CRL and that the data package meets the requirements for FDA approval.
POSIMIR has not been approved by the FDA for marketing in the U.S. for any indication and there can be no assurance that FDA will approve the planned submission described above.
Indivior Agreement and PERSERIS. In September 2017, the Company entered into a patent purchase agreement with an affiliate of Indivior PLC, whereby the Company assigned certain of its U.S. patent rights to Indivior. This assignment may provide further intellectual property protection for PERSERIS (risperidone) extended-release injectable suspension for the treatment of schizophrenia in adults.

Under the terms of the agreement, Indivior has paid the Company $12.5 million upfront and a $5 million milestone based on NDA approval of PERSERIS. The Company also receives quarterly earn-out payments based on a single digit percentage of U.S. net sales for certain products covered by the patent rights, including PERSERIS. The patent rights include granted patents extending into at least 2026.
Through press releases on December 18, 2018, and February 14 and 27, 2019, Indivior has stated that:
PERSERIS was made available in the U.S. in late November 2018.
The PERSERIS commercial launch took place in February 2019 with a field force of 50 representatives.
As of February 14, 2019, payor access was at 38% and Indivior is targeting quality of access comparable with peers.
Indivior is targeting appropriate health care providers (HCPs) with high volume Long Acting Injectables (LAI) practices.
Indivior plans to focus on key differentiating product specific attributes, including the first and only once-monthly risperidone LAI, supplemental oral risperidone or loading dose not recommended, initial peak plasma concentrations achieved in 4 to 6 hours, and just one subcutaneous injection monthly
Indivior remained confident in its peak year net revenue goal for PERSERIS of $200 to $300 million.
U.S. sales of long acting injectables to treat schizophrenia were in excess of $3 billion in 2017.
Full prescribing information for PERSERIS, including BOXED WARNING, and Medication Guide can be found at www.perseris.com.
Methydur Sustained Release Capsules (ORADUR-methylphenidate ER Capsules). In September 2018, our licensee, Orient Pharma, informed DURECT that it had obtained marketing authorization from the Ministry of Health and Welfare in Taiwan for Methydur Sustained Release Capsules. This product is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) and Orient Pharma has stated that it expects to make Methydur Sustained Release Capsules commercially available in Taiwan in 2019, while seeking a partner in China and pursuing regulatory approvals in selected other countries where it has commercialization rights and a commercial presence. DURECT retains rights to North America, Europe, Japan and all other countries not specifically licensed to Orient Pharma. DURECT is entitled to receive a royalty on sales of Methydur Sustained Release Capsules by Orient Pharma. Orient Pharma has also committed to supply a portion of the commercial requirements in territories other than the United States for Methydur Sustained Release Capsules.

Debt Amendment. In November 2018, the Company amended its existing $20 million term loan with Oxford Finance such that principal payments now commence 18 months later than previously scheduled (i.e., commencing June 1, 2020 rather than December 1, 2018) and the final maturity date is moved back by 30 months (i.e., from August 1, 2020 to November 1, 2022). The interest rate and final payment remain unchanged, and the Company paid Oxford Finance an amendment fee of $900,000.

Earnings Conference Call
A live audio webcast of a conference call to discuss fourth quarter 2018 and year ended December 31, 2018 results and provide a corporate update will be broadcast live over the internet at 4:30 p.m. Eastern Time on March 7 and is available by accessing DURECT’s homepage at www.durect.com and clicking "Investor Relations." A replay of the call will be archived on DURECT’s website under Audio Archive in the "Investor Relations" section.

On March 7, 2019 BioXcel Therapeutics, Inc. ("BTI" or "Company") (Nasdaq: BTAI), reported quarterly results for the fourth quarter and full year ended December 31, 2018 and provided an update on key strategic and operational initiatives (Press release, BioXcel Therapeutics, MAR 7, 2019, View Source [SID1234534061]). BTI is a clinical-stage biopharmaceutical development company utilizing novel artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology.

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Fourth Quarter 2018 and Recent Highlights:

(BXCL501)-Neuroscience Program-

·Dosed multiple patient cohorts in the first-in-human pharmacokinetic (bioavailability) and safety study of BXCL501, a novel sublingual thin film formulation of dexmedetomedine (Dex)

·Received FDA Fast Track Designation for BXCL501 for acute treatment of mild to moderate agitation associated with schizophrenia, bipolar disorder, or dementia

·Reported positive proof-of-concept data from two independent Phase 1 studies of intravenously administered Dex with high response rates in Schizophrenia and Alzheimer’s Disease / Dementia, supporting BXCL501 as a potential therapy for acute treatment of agitation in these indications

·Expanded indication for BXCL501 to treat symptoms associated with opioid withdrawal based on positive data from a third Phase 1b study of IV Dex

(BXCL701)-Immuno-Oncology Program-

·Received FDA acceptance of IND for BXCL701, an orally-available systemic innate-immune activator that inhibits dipeptidyl peptidase (DPP) 8/9 and fibroblast activation protein (FAP), for treatment emergent neuroendocrine prostate cancer (tNEPC); patient recruitment ongoing

·Received FDA IND acceptance for clinical trial of BXCL701 in pancreatic cancer to advance understanding of its mechanism of action (MoA); clinical site being activated

·Established clinical partnership with Pfizer and Merck KGaA, Darmstadt, Germany, to evaluate BXCL701 combination therapy in pancreatic cancer, along with Nektar Therapeutics

·Received positive feedback from FDA pre-IND meeting on proposed clinical trial of BXCL701, NKTR-214 and avelumab for treatment of metastatic pancreatic cancer

·Continued to explore additional combination therapy approaches to expand BXCL701’s target indications beyond tNEPC and pancreatic cancer

Emerging Programs-

·Continued to leverage the artificial intelligence platform owned by BioXcel Corporation, BTI’s parent, to select and prioritize additional development opportunities to expand the current portfolio and broaden the addressable market for its lead programs through identification of new indications

Dr. Vimal Mehta, Chief Executive Officer of BTI said, "Following our successful Initial Public Offering we achieved significant clinical, regulatory and operational milestones throughout 2018. Over the last 12 months, we have initiated multiple human clinical trials for BXCL501 and BXCL701, reported positive human proof-of-concept data from several trials, signed new clinical partnerships, significantly advanced Chemistry, Manufacturing and Controls (CMC) work on our lead programs and expanded the addressable markets for these programs. In addition, we are in discussions with a number of highly qualified Board candidates and anticipate appointing a new board member in the near future. As we evolve to a late-clinical-stage organization, we remain confident in the potential of our pipeline assets to generate meaningful clinical benefit for patients in need."

"We dosed multiple patient cohorts in our first-in-human pharmacokinetic (bioavailability) and safety study of BXCL501, and we are on track to report data from this study in the first half of 2019. This data will help establish a foundation to launch registration studies later this year. Additionally, we received FDA Fast Track designation for BXCL501 for the acute treatment of mild to moderate agitation associated with schizophrenia, bipolar disorder, or dementia. This regulatory designation would potentially facilitate the development of BXCL501, allow more frequent meetings and more frequent written communication with the FDA, and expedite its regulatory review.

"In the fourth quarter of 2018, we reported positive data from the Phase 1 studies of Dex for acute treatment of agitation in Schizophrenia and Senile Dementia of the Alzheimer’s Type (SDAT) patients. The positive data from these trials support the continued clinical development of BXCL501 for the acute treatment of agitation in schizophrenia and dementia. We also recently announced positive data from a Phase 1b trial that established the potential application of BXCL501 for the treatment of opioid withdrawal symptoms.

"In our BXCL701 program, we received IND acceptances from the FDA to commence trials in both tNEPC and pancreatic cancer. The Phase 1b trial, which was initiated in late 2018 for tNEPC, will be conducted in combination with pembrolizumab (Keytruda) and will examine safety, pharmacokinetics and anti-tumor activity of the combination therapy. Data from this trial is expected throughout 2019. We also plan to initiate a clinical study to understand the underlying role of BXCL 701 and its mechanism of action in treatment of pancreatic cancer. Pfizer and Merck KGaA recently joined our clinical collaboration with Nektar to advance the triple combination of BXCL701, NKTR-214 and avelumab in this indication. This collaboration reinforces the industry’s enthusiasm around the potential of BXCL701 to treat pancreatic cancer. We believe that our triple combination therapy has the ability to target multiple facets of the disease etiology as well as activate the immune system to produce a clinical benefit in pancreatic cancer patients. We are highly encouraged by this collaboration and look forward to leveraging the regulatory and clinical expertise of our partners as we move forward with our development plans."

Dr. Mehta concluded, "In an effort to further expand the addressable indications for BXCL701, we continue to explore additional combination therapy approaches beyond tNEPC and pancreatic cancer. We are pleased to announce that a recent preclinical study of BXCL701 in combination with an OX40-Agonist was accepted as a late-breaking abstract at the upcoming AACR (Free AACR Whitepaper) Annual Meeting, which we believe demonstrates the broader potential of our lead immuno-oncology candidate beyond tNEPC and pancreatic cancer.

"We are extremely pleased with the substantial progress we have made in advancing both BXCL501 and BXCL701, and believe that our recent achievements have positioned us well for continued growth in 2019 and beyond."

Fourth Quarter & Full Year 2018 Financial Results

BTI reported a net loss of $7.1 million for the fourth quarter of 2018, compared to a net loss of $2.5 million for the same period in 2017.

Research and development expenses were $6.0 million for the fourth quarter of 2018, as compared to $1.4 million for the same period in 2017. The increase was primarily due to an expansion of research and development activities, including increased personnel costs, professional fees, clinical trials, and manufacturing costs associated with BTI’s two lead drug candidates.

General and administrative expenses were $1.3 million for the fourth quarter of 2018, as compared to $1.1 million for the same period in 2017. The increase was primarily due to additional payroll and payroll-related expenses, professional fees and costs associated with operating as a public company.

BTI reported a net loss of $19.3 million for the full year 2018, compared to a net loss of $4.5 million for the same period in 2017.

Research and development expenses were $14.5 million for full year 2018, as compared to $2.7 million for the same period in 2017. The increase was primarily due to an expansion of research and development activities, including increased personnel costs, professional fees, clinical trials, and manufacturing costs associated with BTI’s two lead drug candidates.

General and administrative expenses were $5.4 million for full year 2018, as compared to $1.8 million for the same period in 2017. The increase was primarily due to additional payroll and payroll-related expenses, professional fees and costs associated with operating as a public company.

As of December 31, 2018, cash and cash equivalents totaled $42.6 million.

Upcoming investor conferences:

· 39th Annual Cowen Healthcare Conference — March 11-13, 2019, Boston

· Barclays Global Healthcare Conference — March 12-14, 2019, Miami

· Oppenheimer & Co. 29th Annual Healthcare Conference — March 19-20, 2019, New York City

· H.C. Wainwright Global Life Sciences Conference — April 7-9, 2019, London

· ThinkEquity Conference — May 2, 2019, New York City

· UBS Conference — May 20-22, 2019, New York City

· BMO Capital Markets Prescription for Success Healthcare Conference — May 25, 2019, New York City

About BXCL501:

BXCL501 is a first in class, sublingual film of dexmedetomidine, a selective alpha 2a receptor agonist for the treatment of acute agitation. BTI believes that BXCL501 directly targets a causal agitation mechanism and has demonstrated anti-agitation effects in preclinical and clinical studies. It has a well-established regulatory and reimbursement path in schizophrenia and bipolar disorder, as demonstrated by a previously-approved drug, Adasuve.

About BXCL701:

BXCL701 is a first in class oral immunotherapy with dual mechanisms of action, with an established safety profile from 700 healthy subjects and cancer patients. Designed to stimulate both the innate and acquired immune systems, BXCL701 works by inhibiting dipeptidyl peptidase (DPP) 8/9 and blocking immune evasion by targeting fibroblast activation protein (FAP). Preclinical combination data evaluating BXCL701, a checkpoint inhibitor and other IO agents has demonstrated encouraging anti-tumor activity in multiple tumor types and formation of functional immunological memory. It is under development for tNEPC and pancreatic cancer.

On March 7, 2019 ArQule, Inc. (Nasdaq: ARQL) reported its financial results for the fourth quarter and full year of 2018 (Press release, ArQule, MAR 7, 2019, View Source [SID1234534077]).

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For the quarter ended December 31, 2018, the Company reported a net loss of $8,487,000 or $0.08 per share, compared with net loss of $7,760,000 or $0.09 per share, for the quarter ended December 31, 2017. The Company reported a net loss of $15,482,000 or $0.16 per share, for the year ended December 31, 2018, compared with a net loss of $29,203,000 or $0.39 per share, for the year ended December 31, 2017.

As of December 31, 2018, the Company had a total of approximately $99,558,000 in cash, equivalents, and marketable securities.

Key Highlights from 2018

ARQ 531, our potent and reversible dual inhibitor of both wild-type and C481S-mutant BTK. Successfully progressedrecruitment in our ongoing phase 1 dose escalation trial in 2018, enrolling over 20 patients at 7 dose cohorts ranging from 5mg to 65mg QD. Data from this trial was presented at 3 major conferences (AACR, EHA (Free EHA Whitepaper), ASH (Free ASH Whitepaper)) in 2018 and demonstrated a good safety profile, profound target engagement and encouraging signs of dose-dependent clinical activity in both lymphomas and C481S-mutant CLL
Miransertib, our potent and selective first-generation AKT inhibitor. Presented first-of-its kind clinical data in Proteus syndrome and PROS at the American Society of Human Genetics (ASHG), received FDA Fast Track Designation in PROS, and worked with regulators to define registrational trial designs for both indications
ARQ 751, our highly potent and selective next-generation AKT inhibitor. Progressed the phase 1 basket trial in R/R or metastatic cancer patients harboring an AKT, PI3K or PTEN mutation, identified a recommended phase 2 dose of 75mg QD and presented data at the EORTC/AACR/NCI congress in November
Derazantinib, our FGFR inhibitor, partnered with Basilea and Sinovant, in a registrational trial for intrahepatic cholangiocarcinoma. Continued the timely recruitment and transfer of clinical and other responsibilities to Sinovant and Basilea following the outlicensing to both companies in February and April of last year, respectively
Capital Structure. Strengthened our capital structure through business development activities, which included funding from our collaborators and a successful offering of our common stock which raised gross proceeds of about $70 million
Stock Index Inclusions. Added to the family of Russell 2000 Index companies in June and the NASDAQ Biotechnology Index in December
Key Catalysts & Goals for 2019

ARQ 531: Dual BTK Inhibitor in B-Cell Malignancies

Complete the dose escalation portion of phase 1 trial
Determine a recommended phase 2 dose and initiate expansion cohort(s)
Present results of dose escalation phase 1 trial at major industry conference(s)
Miransertib: AKT Inhibitor in Proteus syndrome and PROS

Finalize regulatory interactions with the FDA
Initiate registrational trial cohorts in both Proteus syndrome and PROS
ARQ 751 (and Miransertib): AKT Inhibitors in Oncology

Complete recruitment in ongoing clinical trials
Present data sets at major medical conferences this year
Derazantinib: FGFR Inhibitor in iCCA

Complete the orderly and timely transfer of all clinical, manufacturing and regulatory responsibilities to our partners, Basilea and Sinovant
"2018 was a watershed year for ArQule," remarked Paolo Pucci, Chief Executive Officer. "The clinical progress we made across the entire portfolio positions us well for an even more transformational 2019. Specifically in rare disease, we now have the ability to expand the scope of the miransertib registrational trial beyond Proteus syndrome to the PROS family of overgrowth spectrum disorders which represents a particularly exciting opportunity because of their significantly larger prevalence."

Dr. Brian Schwartz, Chief Medical Officer, added "We made tremendous progress in 2018, enrolling over 20 patients across 7 cohorts in our dose escalation study with ARQ 531 which is now positioned as the first and best in class drug candidate to address the emerging medical need in BTK mutated malignancies. We are looking forward to advance ARQ 531, miransertib and ARQ 751 respectively into the next phase of development. I want to thank our collaborators such as the Ohio State University, the National Institute of Health and Bambino Gesu’, and others for their continued support in advancing these programs."

Revenues and Expenses

Revenues for the quarter ended December 31, 2018, were $2,941,000 compared with revenues of zero for the quarter ended December 31, 2017. Revenues for the year ended December 31, 2018 were $25,764,000 compared with revenues of zero for the year ended December 31, 2017. Research and development revenue increased in 2018 due to revenue of $5.9 million from our February 2018 Sinovant licensing agreement, $18.5 million from our April 2018 Basilea licensing agreement and $1.3 million from a non-exclusive license agreement for certain of our library compounds.

Research and development expenses in the fourth quarter of 2018 were $8,850,000 compared with $4,721,000 for the fourth quarter 2017. Fiscal 2018 research and development expenses were $28,710,000 compared with $19,468,000 for fiscal 2017. The $4.1 million increase in research and development expense in the fourth quarter of 2018 compared with the fourth quarter of 2017 was primarily due to higher outsourced preclinical, clinical and product development costs of $3.5 million and $0.6 million from labor and related costs.

The $9.2 million increase in research and development expense in 2018 was primarily due to higher outsourced preclinical, clinical and product development costs of $8.5 million and $0.7 million from labor and related costs.

General and administrative expenses in the fourth quarter of 2018 were $2,739,000, compared with $1,849,000 for the fourth quarter of 2017. General and administrative expenses for fiscal 2018 were $10,753,000, compared to $7,551,000 for fiscal 2017. The $0.9 million increase in general and administrative expense in the fourth quarter of 2018 compared with the fourth quarter of 2017 was principally due to higher consulting and professional fees of $0.4 million and labor and related costs of $0.5 million. The $3.2 million increase in general and administrative expense in 2018 was principally due to higher consulting and professional fees of $2.1 million and labor and related costs of $1.1 million.

2019 Financial Guidance

For 2019, ArQule expects revenue to range between $3 and $5 million. Net loss is expected to range between $40 and $43 million, and net loss per share to range between $(0.37) and $(0.39) for the year. ArQule expects to end 2019 with between $60 and $63 million in cash and marketable securities.

Conference Call and Webcast

ArQule will hold its fourth quarter and full year financial results call today, March 7, 2019 at 9:00 a.m. ET. The live webcast can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations." You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. A replay will be available two hours after the completion of the call and can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations."

On March 7, 20019 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported its financial results for the fourth quarter and full year of 2018 (Press release, Navidea Biopharmaceuticals, MAR 7, 2019, View Source [SID1234534123]). Navidea reported total revenues for the quarter of $119,000. Net loss attributable to common stockholders was $3.2 million.

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"Navidea had a productive quarter as we advanced the business and our novel imaging pipeline," said Mr. Jed A. Latkin, Chief Executive Officer of Navidea. "While we had many successes this past quarter, we will continue to work hard to advance the science and seek the go ahead from the FDA to commence our pivotal RA diagnostic trials. Our newly reconstituted board and the addition of our new Chief Medical Officer have reinvigorated our efforts to make this company a success."

Fourth Quarter 2018 Highlights and Subsequent Events

Filed a comprehensive three-part clinical trial proposal for imaging of rheumatoid arthritis with the U.S. Food and Drug Administration ("FDA"), following end-of-Phase 2 discussions

Presented corporate overviews at the 2018 BIO Investor Forum and the 2018 LD Micro Annual Event

Presented data on the Manocept platform at the 2018 ACR Annual Meeting and at the 2018 Radiological Society of North American Scientific Assembly and Annual Meeting

Received notification of acceptance by the NYSE American of the Company’s plan to regain compliance with continued listing standards; also received an extension of the deadline to remedy the low stock price to March 31, 2019

Won dismissal of Platinum litigation

Announced release of a letter by the FDA to the U.S. Patent and Trademark Office ("USPTO") indicating that the USPTO is allowed to extend the patent for Lymphoseek through May 2025

Appointed Adam D. Cutler and S. Kathryn Rouan, Ph.D. to the Navidea Board of Directors

Hired Michael S. Rosol, Ph.D. as Navidea’s Chief Medical Officer

Financial Results

Our consolidated balance sheets and statements of operations have been reclassified, as required by current accounting standards, for all periods presented to reflect the line of business sold to Cardinal Health 414, LLC in March 2017 as a discontinued operation. Accordingly, this discussion focuses on describing results of our operations as if we had not operated the discontinued operation during the periods being disclosed.

Total revenues for the fourth quarter of 2018 were $119,000, compared to $395,000 in the same period of 2017. The decrease was primarily due to a reduction in grant revenue related to SBIR grants from the NIH supporting Manocept development. Total revenues for the full year of 2018 were $1.2 million, compared to $1.8 million in 2017. The decrease was primarily due to a reduction in grant revenue, offset by increased license revenue related to the sublicense of NAV4694 to Meilleur. Revenue in both years included other revenue from our marketing partners in Europe and China related to development work performed at their request.

Research and development ("R&D") expenses for the fourth quarter of 2018 were $854,000, compared to $1.7 million in the same period of 2017. R&D expenses for the full year of 2018 were $4.2 million, compared to $4.5 million in 2017. The decrease in both periods was primarily due to net decreases in Manocept development costs for clinical trials, coupled with decreased compensation costs resulting from headcount reduction.

Selling, general and administrative ("SG&A") expenses for the fourth quarter of 2018 were $1.4 million, compared to $2.2 million in the same period of 2017. SG&A expenses for the full year of 2018 were $7.7 million, compared to $11.2 million during 2017. The net decrease in both periods was primarily due to decreased legal and professional services, as well as decreased general office, insurance, depreciation, rent, and travel expenses, offset by termination costs associated with the resignation of our former CEO in 2018.

Navidea’s net loss attributable to common stockholders for the fourth quarter of 2018 was $3.2 million, or $0.02 per share (basic), compared to a net loss attributable to common stockholders of $4.1 million, or $0.03 per share, for the same period in 2017. Navidea’s net loss attributable to common stockholders for the full year of 2018 was $16.1 million, or $0.09 per share (basic), compared to net income attributable to common stockholders of $74.9 million, or $0.47 per share, in 2017.

Navidea ended the fourth quarter of 2018 with $4.3 million in cash and investments.

Conference Call Details

Investors and the public are invited to dial into the earnings call through the information listed below, or participate via the audio webcast on the company website. Participants who would like to ask questions during the question and answer session will be prompted by the moderator, who will provide instructions.

Event:

Fourth Quarter 2018 Earnings and Business Update Conference Call

Date:

Thursday, March 7, 2019

Time:

5:00 pm (Eastern Time)

U.S. & Canada Dial-in:

877-407-0312

Conference ID:

13687788

Webcast Link:

View Source

The recorded conference call can be replayed and will be available for 90 days following the call, available on the investor relations page of Navidea’s corporate website at www.navidea.com.