On February 25, 2019 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic diseases, and cancer, reported financial results for the fourth quarter and full year ended December 31, 2018 and provided a review of recent business and clinical highlights (Press release, Xencor, FEB 25, 2019, View Source [SID1234533628]).

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"In 2018, we rapidly expanded our bispecific antibody oncology pipeline to position ourselves at the forefront of this growing field, starting two Phase 1 programs and submitting INDs for an additional two for which we will soon begin dosing patients. We also reported encouraging initial data from the Phase 1 study of XmAb14045 in patients with acute myeloid leukemia, and we are now working with the FDA to resolve the partial clinical hold on the study. To end the year, our partner Alexion announced the early U.S. marketing approval of Ultomiris for adult patients with PNH, making it the first approved antibody with XmAb technology," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Earlier this month we entered into a co-development partnership and profit share with Genentech for our first bispecific Fc engineered cytokine, XmAb24306, and our IL-15 program, and we are planning an extensive clinical program to explore combination agents. We will support Genentech’s efforts to submit an IND for XmAb24306 in the second half of 2019 and plan to continue the expansion of our oncology pipeline this year."

Dr. Dahiyat added, "Given our focus on the growing opportunities provided by our bispecific Fc technology, we do not plan to start late-stage clinical development for obexelimab, which has demonstrated disease modifying activity in lupus and IgG4-related disease, prior to securing a partner. This approach will allow us to maximize the drug candidate’s potential for the broadest set of patients."

Recent Business Highlights and Upcoming Clinical Plans

XmAb14045: XmAb14045 is a CD123 x CD3 bispecific antibody being evaluated through a Phase 1 study in patients with relapsed or refractory acute myeloid leukemia and other CD123-expressing hematologic malignancies.

Partial Clinical Hold: On February 20, 2019, Xencor announced that the U.S. Food and Drug Administration (FDA) had placed a partial clinical hold on the Phase 1 study pending review of additional details regarding two patient deaths, safety and efficacy information across the study, and satisfactory review of amendments to the study protocol and related documents. One patient experienced cytokine release syndrome (CRS) after their first dose, the treatment of which was complicated by the patient’s decision to withdraw care. Another patient developed acute pulmonary edema following several doses of XmAb14045. Xencor is coordinating a response to the partial hold by the FDA and plans to continue development of XmAb14045 pending resolution of the partial hold.
Multiple Complete Remissions Achieved: In December 2018, initial data from the Phase 1 study, presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, indicated multiple complete remissions had been achieved with weekly dosing of XmAb14045 in this heavily-pretreated patient population. Cytokine release syndrome (CRS) was the most common toxicity occurring in 55% of patients. 6% of patients experienced Grade 3 or 4 CRS. CRS was more severe on the initial dose and was generally manageable with premedication. Additional adverse events consistent with CRS but not reported as such, including chills, fever, tachycardia, hypotension and hypertension within 24 hours of infusion, were reported in an additional 29% of patients. 28% of evaluable patients (n=5/18) achieved either complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the two highest initial dose levels studied (1.3 and 2.3 mcg/kg weekly).
Collaboration for XmAb24306 and Novel IL-15 Cytokines with Genentech: In February 2019, Xencor entered into a research and license agreement with Genentech, a member of the Roche Group, to develop and commercialize novel IL-15 cytokine therapeutics, including XmAb24306, an IL-15/IL-15Rα cytokine complex engineered with Xencor’s bispecific Fc domain and Xtend Fc technology and Xencor’s most advanced preclinical cytokine program. Xencor will pay 45% of development costs and receive 45% of profits and losses. Genentech will commercialize medicines worldwide, and Xencor has the option to co-promote in the United States. Additionally, the companies will engage in a two-year research program to discover new IL-15 drug candidates, including ones targeted to specific immune cell populations. Xencor will receive $120 million upfront and will be eligible to receive up to $160 million in development milestones for the XmAb24306 program and up to $180 million in development milestones for each new IL-15 drug candidate. The agreement is subject to customary closing conditions, including Hart-Scott-Rodino clearance, and closing is expected to occur in the first quarter of 2019.

Oncology Pipeline: Xencor’s bispecific Fc domains are being used to develop several classes of novel drug candidates in oncology, including: CD3 bispecific antibodies, tumor microenvironment (TME) activator bispecific antibodies and cytokines. Xencor’s XmAb Fc domains confer long circulating half-lives, stability and ease of manufacture.

CD3 Bispecific Antibodies: Xencor’s initial bispecific antibody programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3). These bispecific antibodies activate T cells for highly potent and targeted killing of malignant cells. In January 2019, Xencor announced that as part of a strategic pipeline reprioritization, its partner Novartis decided to return its rights to develop and commercialize XmAb13676 (CD20 x CD3) and that the Company intends to continue development of XmAb13676 as planned. In addition to working toward resolution of the partial clinical hold on the Phase 1 study of XmAb14045, initial data from the Phase 1 studies of XmAb13676 in patients with B-cell malignancies and XmAb18087 (SSTR2 x CD3) in patients with neuroendocrine tumors or gastrointestinal stromal tumors, are expected in the second half of 2019.
TME Activator Bispecific Antibodies: Xencor’s bispecific pipeline includes a suite of TME activators that engage multiple, different targets, such as T-cell checkpoint or agonist receptors. Initial data from DUET-2, a Phase 1 study of XmAb20717 (PD-1 x CTLA-4) in patients with advanced solid tumors, are expected in the second half of 2019. Initiation of a Phase 1 study of XmAb23104 (PD-1 x ICOS) in patients with select advanced solid tumors and initiation of a Phase 1 study of XmAb22841 (CTLA-4 x LAG-3) in patients with select advanced solid tumors as a monotherapy and in combination with pembrolizumab are expected in the first half of 2019.
Cytokines: Xencor uses its bispecific Fc domain and Xtend technology to engineer cytokines that have potency tuned to improve therapeutic index and have longer half-life. The Company’s first cytokine candidate is XmAb24306, which is being co-developed with Genentech. IL-15 cytokines, like XmAb24306, may be promising candidates for oncology combination therapies, and under the Genentech Agreement, Xencor retained the right to perform clinical studies of collaboration products in combination with other therapeutic agents, subject to certain requirements. XmAb24306 is currently in IND-enabling studies, and the Company will support Genentech’s efforts to submit an IND application for this candidate in the second half of 2019.
Obexelimab (XmAb5871): Obexelimab is a first-in-class monoclonal antibody that targets CD19 with its variable domain and uses Xencor’s XmAb immune inhibitor Fc domain to target FcγRIIb, a receptor that inhibits B-cell function. Obexelimab has the potential to address a key unmet need in autoimmune diseases due to its combination of potent reversible B-cell inhibition without B-cell depletion, enabling the immune system to resume natural function once treatment is no longer needed. Phase 2 clinical studies have demonstrated the potential disease modifying ability of obexelimab in autoimmune indications such as systemic lupus erythematosus (SLE) and IgG4-related disease (IgG4-RD). Data from these studies demonstrate the potential of obexelimab in these and other B-cell mediated autoimmune indications. The Company is seeking to partner obexelimab with a partner that has the infrastructure and resources to continue late-stage development of obexelimab and maximize the potential of this drug candidate for a broad set of patient populations.

Partnered XmAb Programs: Eight pharmaceutical companies and the National Institutes of Health are advancing novel drug candidates either discovered at Xencor or that rely on Xencor’s proprietary XmAb technology. Several such programs are currently undergoing clinical testing, including MOR208, which is in Phase 3 development as a combination agent for the treatment of relapsed or refractory diffuse large B-cell lymphoma, and AMG 424, a CD38 x CD3 bispecific antibody, which Amgen announced had entered into a Phase 1 study for the treatment of patients with multiple myeloma in the third quarter of 2018. In the fourth quarter of 2018, Amgen announced that AMG 509, a bispecific antibody that is being developed for prostate cancer, is currently in preclinical development.

In December 2018, Ultomiris, the first antibody that incorporates an XmAb technology was approved by the FDA for commercial marketing. Ultomiris is a complement inhibitor indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) that was developed by Alexion, and it incorporates Xtend Fc technology which allows for a longer duration of action and less frequent dosing regimens compared to Soliris. Marketing authorizations that Alexion submitted to regulatory authorities in the EU and Japan are under review.

Fourth Quarter and Full Year Ended December 31, 2018 Financial Results

Effective January 1, 2018, Xencor adopted the new revenue recognition standard, Accounting Standard Codification 606 (ASC 606). In addition to adopting the standard for 2018, revenue reported for the prior period ending December 31, 2017 has been revised to reflect the new standard.

Cash, cash equivalents and marketable securities totaled $530.5 million as of December 31, 2018, compared to $363.3 million at December 31, 2017. The increase reflects net proceeds of $245.5 million from Xencor’s sale of additional stock in March 2018, partially offset by cash used to fund operating activities in the twelve months ended December 31, 2018.

Total revenue for the three- and twelve-month periods ended December 31, 2018 was $11.6 and $40.6 million, respectively, compared to $30.2 and $46.2 million of revenue reported for the same periods in 2017. Revenues in the three months ended December 31, 2018 were primarily milestone payments received from the Company’s Alexion collaboration, and revenues for the twelve months ended December 31, 2018 included milestone payments received from the Alexion collaboration and revenue recognized under the Company’s Novartis collaboration.

Research and development expenditures for the fourth quarter ended December 31, 2018 were $27.1 million, compared to $20.4 million for the same period in 2017. Total research and development expenditures for the year ended December 31, 2018 were $97.5 million, compared to $71.8 million for the same period in 2017. The increased research and development spending for the three and twelve months ended December 31, 2018 reflects additional spending on Xencor’s bispecific Fc technologies and its expanding pipeline of bispecific oncology candidates.

General and administrative expenses for the fourth quarter ended December 31, 2018 were $5.5 million, compared to $4.4 million in the same period in 2017. Total general and administrative expenditures for the year ended December 31, 2018 were $22.5 million, compared to $17.5 million for the same period in 2017. The increased spending on general and administrative expenses for the three and twelve months ended December 31, 2018 reflects increased compensation costs including increased stock-based compensation charges.

Non-cash, stock-based compensation expense for the year ended December 31, 2018 was $20.5 million, compared to $13.7 million for same period in 2017.

Net loss for the fourth quarter ended December 31, 2018 was $18.2 million, or $(0.32) on a fully diluted per share basis, compared to net income of $7.4 million, or $0.15 on a fully diluted per share basis, for the same period in 2017. The net loss reported for three months ended December 31, 2018 over the income for the same period in 2017 is primarily due to revenue recognized from Xencor’sNovartis and Amgen collaborations in 2017 compared to revenue recognized from Xencor’s Alexion collaboration in 2018. For the year ended December 31, 2018, net loss was $70.4 million, or $(1.31) on a fully diluted per share basis, compared to a net loss of $38.5 million, or $(0.82) on a fully diluted per share basis, for the same period in 2017. The increased loss for the year ended December 31, 2018 over amounts for the same period in 2017 is primarily due to increased spending in research and development and general and administrative in 2018.

The total shares outstanding were 56,279,542 as of December 31, 2018, compared to 47,002,488 as of December 31, 2017. The additional shares outstanding at December 31, 2018 reflect the 8,395,000 shares sold in Xencor’sMarch 2018 financing.

Financial Guidance
Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations into 2023. Xencor expects to end 2019 with approximately $575 to $600 million in cash, cash equivalents and marketable securities.

Conference Call and Webcast
Xencor will host a conference call today at 4:30 p.m. ET (1:30 p.m. PT) to discuss these fourth quarter and full year 2018 financial results and provide a corporate update.

The live call may be accessed by dialing (877) 359-9508 for domestic callers or (224) 357-2393 for international callers and referencing conference ID number 6482077. A live webcast of the conference call will be available online from the Investors section of the Company’s website at www.xencor.com. The webcast will be archived on the company’s website for 90 days.

On February 25, 2019 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), reported that it has submitted an Investigational New Drug (IND) application for CG-806 to the U.S. Food and Drug Administration (FDA) requesting approval to initiate its Phase 1 clinical trial program (Press release, Aptose Biosciences, FEB 25, 2019, View Source [SID1234533629]). CG-806 is an oral, first-in-class small molecule inhibitor of all known forms of FLT3 and BTK kinases being developed for the treatment of patients with select hematologic malignancies, including chronic lymphocytic leukemia (CLL/SLL) and non-Hodgkin’s lymphomas, as well as for patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

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Pending regulatory allowance, Aptose plans to conduct a Phase 1 trial with orally administered CG-806 in patients with relapsed or refractory B cell malignancies, including CLL/SLL and non-Hodgkin lymphomas (NHL) who failed or are intolerant to standard therapies. Pending the collection of predictive pharmacokinetic data in humans, Aptose would seek allowance from the FDA to move into the AML/MDS patient population in a separate Phase1 trial. The initial goal of both trials is to evaluate safety, tolerability and pharmacokinetics of CG-806 in these patient populations.

"In preclinical studies, Aptose and collaborators demonstrated that CG-806 potently inhibits all known forms of FLT3 and BTK and suppresses multiple oncogenic pathways to cripple the malignant cells and avoid rapid emergence of drug resistance, but is not a "dirty" drug that inadvertently inhibits numerous targets associated with toxicity. CG-806 delivers safety and durability of cures in animal models of cancer and readily differentiates from competitor FLT3 and BTK inhibitors," said William Rice, Ph.D., Chairman, President & CEO. "Principle investigators from across the country have voiced their eagerness to enroll patients in both clinical trials, and we hope CG-806 can serve as a new tool for clinicians to treat patients critically ill with hematologic cancers, particularly those who discontinued other BTK or FLT3 inhibitors."

About CG-806

CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor. This small molecule, in-licensed from CrystalGenomics Inc. in Seoul S. Korea, demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B cell cancers and AML.

On February 25, 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 its financial results for the quarter- and year-ended December 31, 2018 (Press release, Corcept Therapeutics, FEB 25, 2019, https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-announces-fourth-quarter-and-full-year-1 [SID1234533647]).

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Financial Highlights

2018 revenue of $251.2 million, an increase of 58 percent from 2017
Fourth quarter revenue of $66.8 million, an increase of 25 percent from fourth quarter 2017
2018 GAAP net income of $0.60 per share, compared to $1.04 per share in 2017 (2017 includes one-time, non-cash tax benefit of $0.61 per share)
Fourth quarter GAAP net income of $0.18 per share, compared to $0.77 per share in fourth quarter 2017 (including $0.60 per share tax benefit)
Fourth quarter repurchases of 1.1 million shares of common stock; 2018 repurchases
totalling 1.8 million shares
Cash and investments at December 31, 2018 of $206.8 million, compared to $104.0 million
at December 31, 2017
Reiterated 2019 revenue guidance of $285 – 315 million
Relacorilant Phase 2 Trial Positive Top-Line Results

Relacorilant’s Phase 2 trial enrolled 35 patients, each of whom received a daily dose of relacorilant that was increased in 50 mg increments, as tolerable, every four weeks. The first 17 patients to enroll (the "low-dose cohort") started at 100 mg per day. The next 18 patients (the "high dose cohort") started at 250 mg per day.

Applying the endpoints for clinical benefit from relacorilant’s Phase 3 trial ("GRACE") to the high-dose cohort produces the following results:

Fifty percent of patients with hyperglycemia achieved improved glucose control, as shown by (i) a 0.5 percent or greater reduction in HbA1c or (ii) normalization of 2-hour oGTT glucose or decreased by at least 50 mg/dL or (iii) a 25 percent or greater decrease in antidiabetic medications
Sixty-four percent of patients with uncontrolled hypertension achieved a five millimeter or greater drop in either systolic or diastolic blood pressure, as measured by 24-hour ambulatory monitoring
No evidence of progesterone receptor affinity or hypokalemia
Plan to present data at the American Association of Clinical Endocrinologist ("AACE") Annual Scientific and Clinical Conference in Los Angeles, California, April 24-28th
Oncologic & Metabolic Disorders

Placebo-controlled, Phase 2 trial of relacorilant plus Abraxane in metastatic ovarian cancer underway, with planned enrollment of 180 patients in the United States and Europe
Data from dose-finding trial of relacorilant plus Abraxane to treat patients with metastatic, pancreatic cancer expected in second quarter
Dosing continues in Phase 1/2 trial of CORT125281 plus Xtandi to treat patients with metastatic castration-resistant prostate cancer
Placebo-controlled trial of CORT118335 for prevention of antipsychotic-induced weight gain to start second quarter; two trials in the reversal of antipsychotic-induced weight gain to start in second half of the year
Placebo-controlled, Phase 2 trial of CORT118335 to treat non-alcoholic steatohepatitis ("NASH") to start in second half of the year
Financial Results

Corcept’s 2018 revenue was $251.2 million, compared to $159.2 million in 2017. Fourth quarter revenue was $66.8 million, compared to $53.3 million in the fourth quarter of 2017. The company reiterated its 2019 revenue guidance of $285 – 315 million.

GAAP net income was $75.4 million for the year and $22.0 million in the fourth quarter of 2018, compared to $129.1 million for the year and $98.3 million in the fourth quarter of 2017. Fourth quarter 2017 net income included a one-time, non-cash gain of $76.4 million from the recognition of deferred tax assets.

Excluding non-cash tax benefits, non-cash expenses related to stock-based compensation, accreted interest on the company’s now-retired royalty financing obligation and related tax effects, non-GAAP net income was $30.4 in the fourth quarter, compared to $24.7 million in the fourth quarter of 2017. For the full-year, non-GAAP net income was $108.2 million, compared to $63.3 million in 2017. A reconciliation of GAAP to non-GAAP net income is included below.

Cash and investments increased by $10.1 million in the fourth quarter, to $206.8 million. This increase was after the expenditure of $14.8 million to acquire 1.1 million shares of the company’s common stock pursuant to its stock repurchase program. Under the program’s current terms, $76.3 million remains available for the repurchase of shares.

"2018 saw increased use of Korlym by patients with Cushing’s syndrome in every region of the country," said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. "In the fourth quarter, 583 physicians were treating patients with the medication – a number that we expect to grow. Increased Korlym uptake fueled our strong financial results: revenue increased by $92.0 million, non-GAAP net income increased by $45.0 million. Cash and investments nearly doubled to $206.8 million. In addition, we repurchased 1.8 million shares of our common stock.

"We continue to protect and extend our Cushing’s syndrome franchise. On February 5th, for example, we were issued a patent (U.S. Pat. No. 10,195,214) covering the co-administration of Korlym and strong CYP3A4 inhibitors – a class of drugs that includes powerful antiviral, antibiotic, antifungal and antidepressant medications. The scientific discoveries that gave rise to this patent constituted an important advance in the safe treatment of patients taking Korlym, which is why corresponding instructions to prescribers are included in Korlym’s label.

"In 2018, we also made important clinical advances in our Cushing’s syndrome program. Data from the Phase 2 trial of our candidate to succeed Korlym – the proprietary, selective cortisol modulator, relacorilant – were strongly positive, with many patients exhibiting meaningful clinical benefit. Just as important, there were no instances of the two off-target effects – progesterone receptor affinity and increased cortisol levels – that cause Korlym’s most common and serious adverse events – termination of pregnancy, endometrial thickening, vaginal bleeding and low potassium (hypokalemia). We immediately began relacorilant’s Phase 3 trial."

Relacorilant Phase 2 Data

Applying the endpoints for clinical benefit from relacorilant’s Phase 3 trial, 50 percent of patients with hyperglycemia in the high-dose cohort achieved improved glucose control (see Figure 1). The response rate in patients with hypertension was 64 percent (see Figure 2). These response rates are comparable to those exhibited by patients at 16 weeks and a dose of 1200 mg in Korlym’s pivotal trial ("SEISMIC").

Patients in the high-dose group also met a wide range of secondary endpoints, including statistically significant improvements in hypercoagulopathy, liver function, insulin resistance, cognition and mood.

Figure 1 Figure 2.
Figure 1. Patients achieving clinically meaningful reductions in HbA1c, 2-hour oGTT or use of antidiabetic medications. Figure 2. Patients achieving clinically meaningful improvements in hypertension.
Relacorilant was well-tolerated. The most commonly reported adverse events were backpain, peripheral edema, headache and nausea – adverse events that are frequently seen when excess cortisol activity is reduced and that tend to be transitory.

Relacorilant’s Phase 3 GRACE trial is underway. It is expected to enroll 130 patients at 60 sites in the United States, Canada, Europe and Israel.

Oncology & Metabolic Disease

"We expect our oncology and metabolic disease programs to take important steps forward in 2019," said Dr. Belanoff. "Following encouraging data from our Phase 1/2 dose-finding study, we have begun a 180 patient, controlled Phase 2 trial of relacorilant plus Abraxane to treat patients with metastatic ovarian cancer, a disease with few good treatment options. We continue to gather data in metastatic pancreatic cancer and plan to release our results and clinical development plan at the time of the ASCO (Free ASCO Whitepaper) meeting this June. We expect to select the optimal dose of CORT125281 plus Xtandi to treat patients with metastatic castration-resistant prostate cancer this year."

"We are excited to advance CORT118335 as a potential treatment for antipsychotic-induced weight gain and NASH," added Dr. Belanoff. "We plan three placebo-controlled trials in antipsychotic-induced weight gain: the first will investigate CORT118335’s ability to prevent weight gain in healthy subjects given olanzapine (Eli Lily’s Zyprexa). We plan to start this trial in the second quarter. The second two trials will be in patients taking antipsychotic medications – one to study the reversal of recently-established weight gain and the other to study the reversal of long-standing weight gain. They are planned to start in the second half of the year. Our placebo-controlled, Phase 2 trial of CORT118335 as a treatment for NASH is also planned for the second half of 2019."

Conference Call

We will hold a conference call on February 25, 2019, at 5:00 p.m. Eastern Time (2:00 p.m. Pacific Time). To participate, dial 1-888-220-8451 from the United States or 1-323-794-2588 internationally approximately 10 minutes before the start of the call. The passcode is 6598298. A replay will be available through March 11, 2019 at 1-888-203-1112 from the United States and 1-719-457-0820 internationally. The passcode will be 6598298.

Hypercortisolism

Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the stress hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients being diagnosed each year. Symptoms vary, but most people experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing’s syndrome can affect every organ system in the body and can be lethal if not treated effectively.

On February 25, 2019 Abbott (NYSE: ABT) reported that it will present at the Barclays Global Healthcare Conference on Wednesday, March 13, 2019 (Press release, Abbott, FEB 25, 2019, View Source [SID1234533630]). Brian Yoor, executive vice president of finance and chief financial officer, will present at 1:05 p.m. Central time.

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A live audio webcast will be accessible through Abbott’s Investor Relations website at www.abbottinvestor.com.

On February 25, 2019 Alder BioPharmaceuticals, Inc. (NASDAQ:ALDR), a biopharmaceutical company focused on developing novel therapeutic antibodies for the treatment of migraine, reported its financial results for the fourth quarter and full year ended December 31, 2018 (Press release, Alder Biopharmaceuticals, FEB 25, 2019, View Source [SID1234533649]). Alder also noted that it announced the completion of its Biologics License Application (BLA) submission for eptinezumab, the company’s investigational monoclonal antibody (mAb) for migraine prevention targeting the calcitonin gene-related peptide and lead commercial candidate, with the Food and Drug Administration (FDA) on February 22, 2019.

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r Alder, capped by the completion of eptinezumab’s BLA submission to the FDA last week," said Bob Azelby, president and chief executive officer of Alder. "We achieved all of the significant milestones we targeted for the year including positive top-line data from our PROMISE 2 Phase 3 clinical trial and positive PROMISE 1 and PROMISE 2 Phase 3 data demonstrating sustained or increased migraine prevention following subsequent infusions, as well as positive results from a pharmacokinetic study, to name a few. The achievement of these milestones further demonstrates eptinezumab’s differentiated profile, which we believe will allow Alder to compete in the highly impacted migraine patient segment."

Mr. Azelby added, "As we look ahead to 2019, we continue to make substantial progress advancing our supply chain, building commercial inventory, expanding our commercial and operational infrastructure, and executing on key pre-launch initiatives to enable a successful commercial launch of eptinezumab in the first quarter of 2020, if approved. Additionally, consistent with our commitment to forever change migraine treatment and give patients their lives back, we are focused on advancing our pre-clinical candidate, ALD1910. The totality of our pre-clinical data to date gives us confidence that we will be positioned to initiate a first in-human clinical trial by the end of 2019."

2019 Highlights and Upcoming Milestones

On February 22, Alder announced it completed its BLA submission for eptinezumab with the FDA. The BLA submission was supported by positive results from Alder’s two positive Phase 3 trials of eptinezumab, positive results from an open-label safety study and a pharmacokinetic (PK) comparability study, and chemistry, manufacturing, and controls (CMC) data packages.

Alder remains on track for the potential commercial launch of eptinezumab in the first quarter of 2020, and continues to advance its manufacturing and commercial readiness activities in anticipation of launch. Currently, Alder is advancing its supply chain, building commercial inventory, continuing to build out its commercial and operational infrastructure, and executing against other key pre-launch initiatives.

Alder continues to advance its pre-clinical candidate, ALD1910, a monoclonal antibody targeting PACAP-38 (pituitary adenylate cyclase-activating peptide-38). ALD1910 is currently undergoing Investigational New Drug (IND)-enabling preclinical studies and Alder expects to initiate its first in-human clinical study by the end of 2019.

In January, Alder announced the appointment of Dr. Paul Streck as Chief Medical Officer. He brings more than 25 years of experience in drug development, regulatory and medical affairs leadership across both large and small publicly traded biopharmaceutical companies. Dr. Streck previously served as Chief Medical Officer at Insmed Incorporated, where he played an instrumental role as a member of the executive leadership team and successfully led the Arikayce regulatory filing, approval and launch.

2018 Company Milestones

In December, Alder announced the appointment of Carlos Campoy as Chief Financial Officer. He brings nearly 30 years of financial leadership and expertise across global publicly-traded companies, including more than 20 years in the biopharmaceutical and healthcare sectors. Mr. Campoy previously served as Vice President of Finance, International at Allergan plc, where he had financial responsibility for $3B in sales and drove significant growth across all product divisions, including Neurosciences and BOTOXÒ.

In October, Alder announced positive results from a comparative PK study that supported the comparability evaluation of the clinical supply for eptinezumab and its planned commercial supply. Both the primary and key secondary PK results met the standard pre-specified acceptance criteria for drug product comparability.

In June, new data from Alder’s PROMISE 1 and PROMISE 2 Phase 3 clinical trials for eptinezumab in episodic and chronic migraine patients, respectively, were presented at the American Headache Society Meeting. The new data highlighted the strength of eptinezumab’s efficacy data by showing sustained or increased efficacy following subsequent quarterly administrations of eptinezumab.

In April, new data from Alder’s PROMISE 1 Phase 3 clinical trial for eptinezumab in episodic migraine patients were presented at the 70th Annual AAN Meeting. The new data demonstrated long-term and sustained or further increased efficacy in episodic migraine following the third and fourth quarterly infusion, as well as increased migraine-free intervals and improved quality of life outcomes.

Also in the second quarter of 2018, Alder completed a one-year safety study of eptinezumab, which generated favorable safety and tolerability data and demonstrated a favorable safety profile consistent with previous eptinezumab studies.

In January, Alder announced eptinezumab significantly reduced migraine risk and met the primary and all key secondary endpoints in its pivotal PROMISE 2 Phase 3 clinical trial for chronic migraine prevention.

Also in January 2018, Alder entered into a settlement and global license agreement with Teva Pharmaceuticals International GmbH, which provided clarity regarding Alder’s freedom to develop, manufacture and commercialize eptinezumab in the U.S. and globally.

Fourth Quarter and Year-End 2018 Financial Results

As of December 31, 2018, Alder had $412.4 million in cash and cash equivalents, short-term investments and restricted cash, compared to $484.7 million as of Sept. 30, 2018 and compared to $286.2 million as of December 31, 2017.

Research and development expenses for the fourth quarter ended December 31, 2018 totaled $64.4 million, compared to $44.7 million for the same period in 2017. For the full year 2018, research and development expenses totaled $239.1 million, compared to $252.9 million for the full year 2017. The year-over-year decrease was primarily due to lower clinical trial costs in 2018 as a result of the completion of several clinical trials.

General and administrative expenses for the fourth quarter ended December 31, 2018 totaled $13.0 million, compared to $10.3 million for the same period in 2017. For the full year 2018, general and administrative expenses totaled $47.5 million, compared to $38.1 million for the full year 2017. The year-over-year increases reflect Alder’s continued commitment to advance the eptinezumab program and position Alder for commercialization.

Net loss applicable to common stockholders for the fourth quarter ended December 31, 2018 totaled $81.5 million, or $1.19 per share, compared to net loss of $54.4 million, or $0.80 per share on a fully-diluted basis, for the same period in 2017. For the full year 2018, net loss applicable to common stockholders totaled $331.9 million, or $4.87 per share on a fully-diluted basis, compared to net loss of $288.9 million, or $4.95 per share, for the full year 2017.

Financial Outlook

Alder expects full-year 2019 net cash used in operating activities and purchases of property and equipment will be in the range of $285 to $315 million dollars. The majority of the spend is focused on ensuring that Alder is prepared for the potential launch of eptinezumab in the first quarter of 2020, including advancing eptinezumab’s supply chain, building commercial inventory, continuing to build out Alder’s commercial footprint and other pre-launch market readiness activities.

Alder believes its available cash, cash equivalents, short-term investments and restricted cash will be sufficient to meet the company’s projected operating requirements into 2020 and the anticipated launch of eptinezumab.

Conference Call and Webcast

Alder will host a conference call today at 5:00 p.m. ET to discuss these financial results and recent corporate highlights. The live call may be accessed by dialing (877) 430-4657 for domestic callers or (484) 756-4339 for international callers and providing conference ID number 7655239. The webcast will be broadcast live and can be accessed from the Events & Presentations page in the Investors section of Alder’s website at www.alderbio.com. The webcast will be available for replay following the call for at least 30 days.