Operational Update

On May 1, 2019 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported an update for the ongoing development of its product candidates (Press release, Immutep, MAY 1, 2019, View Source [SID1234535559]).

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Efti Clinical Update

AIPAC – Phase IIb Clinical Trial

To date, there have been 211 patients enrolled in the Company’s Phase IIb AIPAC clinical trial, which is evaluating eftilagimod alpha ("efti" or "IMP321") in combination with paclitaxel, a chemotherapy, in metastatic breast cancer. Full recruitment of the trial, 226 patients, is expected to occur in the second quarter of this year. The trial is being conducted at 33 clinical trial sites across Germany, the UK, France, Hungary, Belgium, Poland and the Netherlands.

The first read out of Progression Free Survival (PFS) data is expected within the next 11 months, but not before Q4 2019, depending on the number of predefined progression events. Other endpoints include Overall Response Rate (ORR) and Overall Survival (OS).

TACTI-002 – Phase II Clinical Trial

15 patients have been enrolled in Immutep’s Phase II TACTI-002 clinical trial across seven clinical sites in the U.S., Europe and Australia. This figure includes 11 patients in the first line non-small cell lung cancer (NSCLC) cohort, which requires 17 patients to complete recruitment of this initial cohort.

The TACTI-002 study is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada) and is evaluating the combination of efti with MSD’s KEYTRUDA (or pembrolizumab, an anti-PD-1 therapy) in up to 109 patients with second line head and neck squamous cell carcinoma or NSCLC in first and second line.

Patient recruitment is ongoing and Immutep expects to report first data from the study in mid-2019.

LOGO

TACTI-mel – Phase I Clinical Trial

Immutep reported positive, more mature data from its ongoing and fully recruited TACTI-mel Phase I clinical study in melanoma in March. The trial is evaluating the combination of efti with anti-PD-1 therapy KEYTRUDA (pembrolizumab) in 24 patients with unresectable or metastatic melanoma.

Key findings from the ongoing trial were as follows:


Part A (starting cycle 5 of

pembrolizumab therapy) N=18


Part B (starting day 1 cycle 1 of

pembrolizumab therapy) N=6

Overall Response Rate (ORR)

33% (61%*) 50%
Disease Control Rate (DCR)

66% 66%
*Exploratory ORR when tumour size is measured according to irRC from day 1 of cycle 1 of pembrolizumab and following combination therapy (which starts at cycle 5 of prembrolizumab treatment).

In addition, efti continues to have a very favorable safety profile in doses up to 30 mg administered s.c. every 2 weeks. The data was presented at the World Immunotherapy Congress 2019.

INSIGHT & INSIGHT-004 – Phase I Clinical Trials

INSIGHT-004 is a Phase I clinical trial in collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc. and the Institute of Clinical Cancer Research, Krankenhaus Nordwest GmbH (IKF) which is evaluating the combination of efti with avelumab, a human anti-PD-L1 antibody, in patients with advanced solid malignancies. The trial protocol has now been approved by the competent authority and ethics committee and Immutep expects the first patient to be recruited in Q2 2019.

This study is taking place as an extension to the INSIGHT trial, an investigator sponsored explorative trial which is already underway and being run by our partner, IKF.

13 patients are now enrolled in the INSIGHT clinical trial, which is evaluating the potential of efti in different settings in terms of route of administration and indications.

IMP761 Update

IMP761—Preclinical Results

Immutep reported positive results from its preclinical study of IMP761, a novel LAG-3 agonist antibody being developed for the treatment of autoimmune diseases, in March. The preclinical results showed that IMP761 decreases inflammation at the tissue site, demonstrating its potential as a new therapy that could treat the cause of autoimmune disease, rather than just the symptoms.

Specifically, in vitro results showed that IMP761 caused the down-regulation of human T cell proliferation and activation. In addition, the in vivo studies showed that IMP761 causes down-modulation of T cell infiltration in a non-human-primate animal model. These results were presented at the 14th Congress of European Crohn’s and Colitis Organisation (ECCO) Conference.

The Company is continuing cell line development and GMP manufacturing preparations for IMP761 to progress the antibody towards clinical development.

Update on programs fully funded by Immutep’s licensing partners

GlaxoSmithKline – GSK2831781 / IMP731

GlaxoSmithKline (GSK) has announced that it will be pursuing a proof-of-concept study in ulcerative colitis for GSK2831781, which is derived from Immutep’s IMP731 antibody. This Phase II clinical study is expected to commence shortly.

Novartis—LAG525 / IMP701

Novartis is continuing its clinical development program for LAG525, or IMP701, in oncology. Currently, there are five ongoing Phase I/II clinical trials evaluating this product candidate.

CYTLIMIC—efti

Immutep is working with CYTLIMIC to prepare for CYTLIMIC’s clinical trials to evaluate efti as part of a therapeutic cancer vaccine, called CYT001. The vaccine contains cancer antigens to boost a patient’s own immune cells to recognise and kill cancer cells related to the antigens.

Eddingpharm (EOC Pharma)—efti

Immutep’s partner and Chinese licensee, EOC Pharma, is continuing the recruitment of patients for its Phase I clinical study of efti for the treatment of metastatic breast cancer. Immutep expects further progress from EOC Pharma later in 2019.

MacroGenics Provides Update on Corporate Progress and First Quarter 2019 Financial Results

On May 1, 2019 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, provided an update on its corporate progress and reported financial results for the quarter ended March 31, 2019 (Press release, MacroGenics, MAY 1, 2019, View Source [SID1234535558]).

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"In February, we reported topline results from SOPHIA showing that in the Phase 3 trial, progression-free survival was prolonged following treatment with margetuximab and chemotherapy compared to trastuzumab with chemotherapy. We look forward to presenting detailed results at ASCO (Free ASCO Whitepaper). In addition, we anticipate submitting a BLA for this program to the FDA in the second half of 2019. If approved by regulators, margetuximab could offer the potential of a new treatment option for patients living with HER2-positive metastatic breast cancer in a third line and beyond setting where there are currently no FDA-approved therapies. In seeking to address unmet needs of patients with HER2-postive cancers beyond breast cancer, we plan to initiate in the second half of 2019 a registration-directed trial to evaluate margetuximab for treating gastric cancer patients in the frontline setting," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics.

"Mechanistically, we believe the results achieved in the SOPHIA study have validated our Fc-optimization technology, also used in enoblituzumab, our investigational monoclonal antibody targeting B7-H3," continued Dr. Koenig. "To date, we have made tremendous progress with our immuno-oncology pipeline of nine clinical product candidates with multiple molecules demonstrating clinical proof of concept to support ongoing and/or planned registration studies."

Key Pipeline Updates
Margetuximab. Recent updates related to the Company’s investigational Fc-optimized monoclonal antibody (mAb) that targets human epidermal growth factor receptor 2 (HER2) include:

•Oral Presentation of SOPHIA Data at ASCO (Free ASCO Whitepaper); Plans to Submit BLA in 2H2019: In February 2019, MacroGenics announced that SOPHIA, the Phase 3 clinical trial of margetuximab in patients with HER2-positive metastatic breast cancer, met the trial’s first sequential primary endpoint of prolongation of progression-free survival (PFS) in patients treated with the combination of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy. An abstract containing data from SOPHIA was selected for presentation in an oral session to be held on Tuesday, June 4, 2019 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. MacroGenics anticipates submitting a Biologics License Application (BLA) to the U.S. FDA for margetuximab, based on the PFS results, in the second half of 2019.
•Additional Validating Mechanistic Data in Posters at AACR (Free AACR Whitepaper) and ASCO (Free ASCO Whitepaper): Data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2019 showed improved Fc-dependent activity of margetuximab compared to trastuzumab in vitro. These preclinical data validate the molecule’s underlying mechanism of action and the Company’s Fc-optimization platform. In addition, an abstract containing data describing HER2-specific immunity observed in patients with HER2-positive cancers treated with margetuximab in the Phase 1 trial was selected for presentation in a poster session at ASCO (Free ASCO Whitepaper) on Sunday, June 2, 2019.

Exhibit 99.1
•Plans to Initiate Front-line Gastric Cancer Trial in 2H2019: At the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2019, data were presented demonstrating encouraging anti-tumor activity and acceptable safety and tolerability of margetuximab in combination with an anti-PD-1 mAb in a Phase 2 clinical trial in patients with HER2-positive gastric or gastroesophageal junction cancer. MacroGenics and its partner in Greater China, Zai Lab, expect to initiate a Phase 2/3 registration-directed clinical trial of margetuximab in combination with checkpoint inhibitor molecules, including MGA012 (anti-PD-1 mAb) and MGD013 (bispecific PD-1 x LAG-3 DART molecule) in the second half of 2019.

B7-H3 Franchise. MacroGenics is developing a portfolio of investigational antibody-based therapeutics that target B7-H3 through complementary mechanisms of action taking advantage of this antigen’s broad expression across multiple solid tumor types. Recent program highlights include:

•Plans to Advance Enoblituzumab in Head and Neck Cancer Study: Enoblituzumab is an Fc-optimized mAb that targets B7-H3. Encouraging data from the Phase 1 clinical study of enoblituzumab in combination with an anti-PD-1 mAb were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2018. Based on these data, MacroGenics is planning to initiate a Phase 2 study of enoblituzumab in combination with MGA012 in patients with squamous cell carcinoma of the head and neck (SCCHN) in the second half of 2019.
•MGD009 Phase 1 Studies Ongoing: MGD009 is a bispecific DART molecule designed to target B7-H3 expressed on tumor cells and CD3 expressed on normal T cells. MacroGenics is enrolling patients in two Phase 1 clinical trials of MGD009, one as monotherapy and another in combination with MGA012.
•MGC018 Dose Escalation Ongoing: MGC018 is an antibody-drug conjugate (ADC) designed to target solid tumors expressing B7-H3. MacroGenics is evaluating MGC018 in a Phase 1 dose escalation study.

PD-1 Franchise. MacroGenics is advancing multiple investigational PD-1-directed programs to provide differentiation from existing PD-1-based treatment options and enable a broad set of combination opportunities across the Company’s portfolio. Recent program highlights include:

•MGA012 Registration-directed Studies Ongoing: MGA012 (INCMGA0012) is an anti-PD-1 mAb exclusively licensed to Incyte Corporation on a worldwide basis. Incyte is initially pursuing development of MGA012 monotherapy through three potentially registration-directed trials in MSI-high endometrial cancer, Merkel cell carcinoma and anal cancer and Incyte and MacroGenics are each conducting multiple studies of MGA012 in combination with other agents. MacroGenics retains the right to develop its pipeline of product candidates in combination with MGA012.
•MGD013 Dose Expansion Ongoing: MGD013 is a first-in-class bispecific DART molecule designed to provide co-blockade of PD-1 and LAG-3, two immune checkpoint molecules expressed on T cells. MacroGenics is evaluating MGD013 in a Phase 1 dose expansion study in up to nine tumor types and expects to present data from this trial in the second half of 2019.
•MGD019 Dose Escalation Ongoing: MGD019 is a bispecific DART molecule designed to provide co-blockade of PD-1 and CTLA-4, two immune checkpoint inhibitors expressed on T cells. MacroGenics is currently evaluating MGD019 in a Phase 1 dose escalation study.

Flotetuzumab. A recent update related to the Company’s investigational, bispecific DART molecule that recognizes both CD123 and CD3, includes:

•Data from Ongoing Study Expected 2H2019: Based on data presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018 showing anti-leukemic activity and acceptable tolerability of flotetuzumab in patients with relapsed/refractory AML, MacroGenics is enrolling additional patients in a dose expansion cohort enriched for primary refractory patients and expects to announce updated data from the trial in the second half of 2019. The Company’s collaborator, Servier, has development and commercialization rights outside North America, Japan, Korea and India for flotetuzumab, also known as S80880.

First Quarter 2019 Financial Results

Exhibit 99.1
•Cash Position: Cash, cash equivalents and marketable securities as of March 31, 2019, were $320.4 million, compared to $232.9 million as of December 31, 2018.
•Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $9.7 million for the quarter ended March 31, 2019, compared to $4.7 million for the quarter ended March 31, 2018. Revenue from collaborative agreements included revenue received under a clinical supply agreement with Incyte, as well as the recognition of deferred revenue from payments received in previous periods and payments received during the quarter.
•R&D Expenses: Research and development expenses were $47.1 million for the quarter ended March 31, 2019, compared to $45.7 million for the quarter ended March 31, 2018. This increase was due to increased clinical trial costs for MGD013, MGC018 and flotetuzumab, as well as increased development/manufacturing costs related to MGA012 (largely offset by revenue from Incyte). These increases were partially offset by decreased expenses related to the SOPHIA and enoblituzumab clinical studies.
•G&A Expenses: General and administrative expenses were $10.2 million for the quarter ended March 31, 2019, compared to $9.2 million for the quarter ended March 31, 2018.
•Net Loss: Net loss was $45.0 million for the quarter ended March 31, 2019, compared to net loss of $49.5 million for the quarter ended March 31, 2018.
•Shares Outstanding: Shares outstanding as of March 31, 2019 were 48,805,008.

Conference Call Information

MacroGenics will host a conference call today at 4:30 p.m. ET to discuss financial results for the quarter ended March 31, 2019 and provide a corporate update. To participate in the conference call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) five minutes prior to the start of the call and provide the Conference ID: 8788605.

The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

Sangamo Therapeutics Announces First Quarter 2019 Conference Call And Webcast

On May 1, 2019 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported that the Company will release its first quarter 2019 financial results after the market closes on Wednesday, May 8, 2019 (Press release, Sangamo Therapeutics, MAY 1, 2019, View Source [SID1234535517]). The press release will be followed by a conference call at 5:00 p.m. ET, which will be open to the public via telephone and webcast. During the conference call, the Company will review its financial results and provide a business update.

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The conference call dial-in numbers are (877) 377-7553 for domestic callers and (678) 894-3968 for international callers. The conference ID number for the call is 7577586. Participants may access the live webcast via a link on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. A conference call replay will be available for one week following the conference call. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 7577586.

Vanda Pharmaceuticals Reports First Quarter 2019 Financial Results

On May 1, 2019 Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) reported financial and operational results for the first quarter ended March 31, 2019 (Press release, Vanda Pharmaceuticals, MAY 1, 2019, View Source [SID1234535516]).

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"During the first quarter, Vanda made significant advances towards its commercial and research goals. Patients on treatment with Hetlioz continue to increase steadily, driven by broader awareness and recognition of Non-24. We are preparing for a possible launch later this year in jet lag disorder, an indication that has the potential to drive significant growth for our Hetlioz franchise. Tradipitant clinical development is advancing for three indications, atopic dermatitis, gastroparesis and motion sickness," said Mihael H. Polymeropoulos, M.D., Vanda’s President and CEO. "We believe that Vanda is well positioned for significant growth in the coming quarters and years given its strong commercial and clinical development pipeline and its exceptional people."

Key Financial Highlights:

Total net product sales from HETLIOZ and Fanapt were $47.7 million in the first quarter of 2019, a 10% decrease compared to $53.0 million in the fourth quarter of 2018 and a 9% increase compared to $43.6 million in the first quarter of 2018.
HETLIOZ net product sales were $29.0 million in the first quarter of 2019, an 11% decrease compared to $32.4 million in the fourth quarter of 2018 and a 14% increase compared to $25.4 million in the first quarter of 2018. In the first quarter of 2019, HETLIOZ units sold to patients declined by 2% compared to the fourth quarter of 2018.
Fanapt net product sales were $18.8 million in the first quarter of 2019, a 9% decrease compared to $20.6 million in the fourth quarter of 2018 and a 3% increase compared to $18.2 million in the first quarter of 2018. In the first quarter of 2019, Fanapt prescriptions, as reported by IQVIA, declined by 5% compared to the fourth quarter of 2018.
Cash, cash equivalents and marketable securities (Cash) were $267.8 million as of March 31, 2019, representing an increase to Cash of $10.5 million and $19.0 million as compared to December 31, 2018 and March 31, 2018, respectively.
Key Research and Development Highlights:

Tradipitant – Clinical Development

Vanda plans to meet with the U.S. Food and Drug Administration (the FDA) in the second quarter of 2019 to further define and confirm the path towards approval of tradipitant in the treatment of patients with gastroparesis.
Vanda plans to initiate a Phase III clinical study of tradipitant in gastroparesis in the second quarter of 2019.
Enrollment in the Phase III clinical study (EPIONE) of tradipitant in atopic dermatitis is ongoing. Results are expected in the first half of 2020. A second Phase III clinical study is expected to begin in the first quarter of 2020.
In January 2019, Vanda initiated a Phase II clinical study of tradipitant in motion sickness. Study results are expected in the third quarter of 2019.
HETLIOZ (tasimelteon)

The HETLIOZ supplemental New Drug Application (sNDA) for the treatment of jet lag disorder is under review by the FDA with a Prescription Drug User Fee Act target action date of August 16, 2019.
Vanda expects to meet with the FDA in the third quarter of 2019 to confirm the regulatory path forward for HETLIOZ in the treatment of patients with SMS and expects to file an sNDA in the third quarter of 2019.
Vanda plans in the third quarter of 2019 to initiate a Phase II clinical study of HETLIOZ in delayed sleep phase disorder (DSPD) in patients who have a mutation in the CRY1 gene, which is believed to be causative in a subset of patients with DSPD.
Fanapt (iloperidone)

Enrollment is ongoing in a pharmacokinetic study for the once-a-month long acting injectable (LAI) formulation of Fanapt.
A randomized study of Fanapt in bipolar disorder is planned to begin in 2019.
VTR-297 (histone deactetylase (HDAC) inhibitor)

Enrollment is ongoing in a Phase I clinical study (1101) of VTR-297 in hematologic malignancies.
Tradipitant – Partial Clinical Hold and FDA Dispute

In April 2018, Vanda submitted a protocol amendment to the FDA, proposing a 52-week open-label extension (OLE) period for patients who had completed the tradipitant Phase II clinical study (2301) in gastroparesis. In May 2018, based on feedback from the FDA, Vanda amended the protocol limiting the duration of treatment in the 2301 study to a total of three months, while continuing to seek further dialogue with the FDA on extending the study duration to 52-weeks. As a part of this negotiation process, in September 2018, Vanda submitted a new follow-on 52-week OLE protocol to the FDA (2302) for patients who had completed the 2301 study. While waiting for further feedback, no patients were ever enrolled in any study beyond 12 weeks. In December 2018, the FDA imposed a partial clinical hold (PCH) on two of Vanda’s proposed clinical studies of tradipitant, stating that Vanda is required first to conduct additional chronic toxicity studies in canines, monkeys or minipigs before allowing patients access in any clinical protocol beyond 12 weeks. The original PCH was not based on any safety or efficacy data related to tradipitant. Rather, the FDA informed Vanda that these additional toxicity studies are required by a guidance document.

In February 2019, Vanda filed a lawsuit against the FDA in the United States District Court for the District of Columbia (DC District Court), challenging the FDA’s legal authority to issue the PCH, and seeking an order to set it aside. On February 14, 2019, the FDA filed a Motion for Voluntary Remand to the Agency and for a Stay of the Case. On March 14, 2019, the DC District Court granted the FDA’s request for voluntary remand and returned the matter to the FDA for further consideration. On April 26, 2019, the FDA provided its remand response, in which it indicated that, after re-evaluation, it believes a partial clinical hold continues to be appropriate. After reviewing the FDA’s remand response, Vanda continues to believe that additional chronic toxicity studies are unjustified, and that Vanda has provided the FDA with sufficient information regarding the safety of tradipitant to justify the continued study of tradipitant in patients beyond 12 weeks, in accordance with applicable law and FDA regulations. On April 29, 2019, Vanda and the FDA filed a Joint Motion for Extension of Time to Propose a Scheduling Order for this matter. On April 30, 2019, the DC District Court granted the motion, thereby extending the deadline until May 3, 2019 for the FDA and Vanda to file proposals regarding a scheduling order. Vanda intends to continue vigorously pursuing its interests in the matter.

Vanda does not expect the PCH to have any impact on its ongoing clinical studies in atopic dermatitis and motion sickness, each of which is under 12 weeks in duration, or its planned 12-week Phase III study in gastroparesis, none of which are subject to the PCH. Nor does Vanda expect the PCH to impact the potential timing of a New Drug Application (NDA) filing. If the matter has not been fully resolved prior to the date on which Vanda is ready to file the first NDA for tradipitant, then Vanda may choose to file with the safety data it has available at that time. Vanda may pursue additional studies of durations in excess of 12 weeks in countries where the conduct of such studies may be permitted (or it may choose to file for approval of a limited indication). If the FDA determines that Vanda’s NDA does not contain safety data sufficient for approval, it may not accept the NDA for filing. Vanda will continue to reassess the situation as events unfold.

Non-GAAP Financial Results

Non-GAAP net income was $3.0 million for the first quarter of 2019, or $0.06 per share, compared to a Non-GAAP net income of $6.6 million, or $0.14 per share, for the first quarter of 2018.

Vanda provides Non-GAAP financial information, which it believes can enhance an overall understanding of its financial performance when considered together with GAAP figures. Refer to the sections of this press release entitled "Non-GAAP Financial Information" and "Reconciliation of GAAP to Non-GAAP Financial Information" for more detailed information regarding Non-GAAP financial information.

2019 Financial Guidance

Vanda reiterates its prior 2019 financial guidance and expects to achieve the following financial objectives in 2019:

Full Year 2019

Financial Objectives

Full Year 2019

Guidance

Combined net product sales
from both HETLIOZ and
Fanapt

$215 to $225 million

HETLIOZ net product sales

$137 to $143 million

Fanapt net product sales

$78 to $82 million

Year-end 2019 Cash

Greater than $260 million

Conference Call

Vanda has scheduled a conference call for today, Wednesday, May 1, 2019, at 4:30 PM ET. During the call, Vanda’s management will discuss the first quarter 2019 financial results and other corporate activities. Investors can call 1-866-688-9426 (domestic) or 1-409-216-0816 (international) and use passcode 6195579. A replay of the call will be available on Wednesday, May 1, 2019, beginning at 7:00 PM ET and will be accessible until Wednesday, May 8, 2019, at 11:59 PM ET. The replay call-in number is 1-855-859-2056 for domestic callers and 1-404-537-3406 for international callers. The passcode number is 6195579.

The conference call will be broadcast simultaneously on Vanda’s website, www.vandapharma.com. Investors should click on the Investor Relations tab and are advised to go to the website at least 15 minutes early to register, download, and install any necessary software or presentations. The call will also be archived on Vanda’s website for a period of 30 days.

Non-GAAP Financial Information

Vanda believes that the Non-GAAP financial information provided in this press release can assist investors in understanding and assessing the ongoing economics of Vanda’s business and reflect how it manages the business internally and sets operational goals. Vanda’s "Non-GAAP Selling, general and administrative expenses" and "Non-GAAP Research and development expenses" exclude stock-based compensation. Vanda’s "Non-GAAP Net income (loss)," "Non-GAAP Net income (loss) per share" and "Non-GAAP Operating expenses excluding Cost of goods sold" exclude stock-based compensation and intangible asset amortization.

Vanda believes that excluding the impact of these items better reflects the recurring economic characteristics of its business, as well as Vanda’s use of financial resources and its long-term performance.

These Non-GAAP financial measures, as presented, may not be comparable to similarly titled measures reported by other companies since not all companies may calculate these measures in an identical manner and, therefore, they are not necessarily an accurate measure of comparison between companies.

The presentation of these Non-GAAP financial measures is not intended to be considered in isolation or as a substitute for guidance prepared in accordance with GAAP. The principal limitation of these Non-GAAP financial measures is that they exclude significant elements that are required by GAAP to be recorded in Vanda’s financial statements. In addition, they are subject to inherent limitations as they reflect the exercise of judgments by management in determining these Non-GAAP financial measures. In order to compensate for these limitations, Vanda presents its Non-GAAP financial guidance in connection with its GAAP guidance. Investors are encouraged to review the reconciliation of our Non-GAAP financial measures to their most directly comparable GAAP financial measure.

NuVasive Announces First Quarter 2019 Financial Results

On May 1, 2019 NuVasive, Inc. (NASDAQ: NUVA), the leader in spine technology innovation, focused on transforming spine surgery with minimally disruptive, procedurally integrated solutions, reported financial results for the quarter ended March 31, 2019 (Press release, NuVasive, MAY 1, 2019, View Source [SID1234535515]).

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First Quarter 2019 Highlights

Revenue increased 5.5% to $274.8 million, or 6.4% on a constant currency basis;
GAAP operating profit margin of 7.3%; Non-GAAP operating profit margin of 14.9%; and
GAAP diluted earnings per share of $0.18; Non-GAAP diluted earnings per share of $0.53.
"In the first quarter 2019, NuVasive delivered a solid start to the year with focused execution across our U.S. Spinal Hardware, U.S. Surgical Support and International businesses," said Chris Barry, chief executive officer of NuVasive. "Coupled with these financial results, we continued to operate the business with rigor and discipline to drive profitability while strategically investing in key growth areas. This includes the recently launched X360 System for lateral single-position surgery integrated with Surgical Intelligence, further differentiation of our Advanced Materials Science portfolio and upcoming launch of the Pulse platform—all which enable our surgeon partners to provide better, more reproducible clinical outcomes for their patients through minimally invasive surgery."

A full reconciliation of GAAP to non-GAAP financial measures can be found in the tables of this news release.

First Quarter 2019 Results
NuVasive reported first quarter 2019 total revenue of $274.8 million, a 5.5% increase compared to $260.5 million for the first quarter 2018. On a constant currency basis, first quarter 2019 total revenue increased 6.4% compared to the same period last year.

For the first quarter 2019, both GAAP and non-GAAP gross profit was $200.3 million and GAAP and non-GAAP gross margin was 72.9%. These results compared to GAAP and non-GAAP gross profit of $186.7 million and $187.1 million, respectively, and GAAP and non-GAAP gross margin of 71.7% and 71.8%, respectively, for the first quarter 2018.

The Company reported GAAP net income of $9.4 million, or diluted earnings per share of $0.18, for the first quarter 2019 compared to a GAAP net loss of $(27.1) million, or diluted loss per share of $(0.53), for the first quarter 2018. On a non-GAAP basis, the Company reported net income of $27.6 million, or diluted earnings per share of $0.53 per share, for the first quarter 2019 compared to net income of $20.6 million, or diluted earnings per share of $0.40 per share, for the first quarter 2018.

Annual Financial Guidance for 2019
The Company reiterated its full-year 2019 guidance:

Prior guidance reflects the range provided February 20, 2019. Current guidance reflects the range provided May 1, 2019.

Constant currency is a measure that adjusts US GAAP revenue for the impact of currency over the same period in the prior year.

The Company estimates revenue for full year 2019 to be in the range of $1.14 billion to $1.16 billion, reflecting reported growth in the range of 3.5% to 5.5%;
Non-GAAP earnings per share in a range of $2.20 to $2.30;
Non-GAAP operating profit margin of 15.0% to 15.5%;
EBITDA margin of 25.2% to 25.7%; and
Non-GAAP effective tax expense rate of approximately 23%.
Supplementary Financial Information
For additional financial detail, please visit the Investor Relations section of the Company’s website at www.nuvasive.com to access Supplementary Financial Information.

Reconciliation of Full Year EPS Guidance

Items may not foot due to rounding.

Prior guidance reflects the range provided February 20, 2019. Current guidance reflects the range provided May 1, 2019.

Effective tax expense rate of ~24% applied to GAAP earnings and ~23% applied to Non-GAAP earnings.

Effective tax expense rate of ~22% applied to GAAP earnings and ~23% applied to Non-GAAP earnings.

Costs related to acquisition, integration and business transition activities which include severance, relocation, consulting, leasehold exit costs, third party merger and acquisitions costs, contingent consideration fair value adjustments, and other costs directly associated with such activities.

Represents costs associated with non-cash purchase accounting adjustments, such as acquired inventory fair market value adjustments, which are amortized over the period in which underlying products are sold.

Represents the loss recorded in connection with the settlement of the Madsen Medical, Inc. litigation matter, as well as expenses associated with ongoing litigation with a former Board member and his current employer related to various matters, including infringement of the Company’s intellectual property.

Non-recurring consulting fees associated with the implementation of our state tax-planning strategy.

Purchase of an in-process research and development asset which had no future alternative use.

Represents costs specific to updating our quality system, product labeling, asset write-offs and product remanufacturing to comply with European medical device regulation.

The impact on results from taxes include tax effecting the adjustments above at the statutory rate as well as taking into account discrete items and including those discrete items in the annual effective tax rate calculation. The Company also includes those adjustments that would have benefited the tax rate in lieu of the above adjustments as part of the Company’s tax filings. The impact of the changes to the tax rate results in an annual rate of ~43% benefit on a GAAP basis and ~18% on a non-GAAP basis in 2018.

Adjusted non-GAAP diluted WASO excludes the impact of dilutive convertible notes and warrants for which the Company is economically hedged through its anti-dilutive bond hedge arrangements.

Reconciliation of Non-GAAP Operating Margin %

Items may not foot due to rounding.

Prior guidance reflects the range provided February 20, 2019. Current guidance reflects the range provided May 1, 2019.

Represents costs associated with non-cash purchase accounting adjustments, such as acquired inventory fair market value adjustments, which are amortized over the period in which underlying products are sold.

Non-recurring consulting fees associated with the implementation of our state tax-planning strategy.

Expenses associated with ongoing litigation with a former Board member and his current employer related to various matters, including infringement of the Company’s intellectual property.

Represents the loss recorded in connection with the settlement of the Madsen Medical, Inc. litigation matter.

Purchase of an in-process research and development asset which had no future alternative use.

Represents costs specific to updating our quality system, product labeling, asset write-offs and product remanufacturing to comply with European medical device regulation.

Costs related to acquisition, integration and business transition activities which include severance, relocation, consulting, leasehold exit costs, third party merger and acquisitions costs, contingent consideration fair value adjustments, and other costs directly associated with such activities.

Reconciliation of EBITDA Margin %

Items may not foot due to rounding.

Effective tax expense rate of ~43% benefit applied to GAAP earnings and ~18% applied to Non-GAAP earnings.

Effective tax expense rate of ~24% applied to GAAP earnings and ~23% applied to Non-GAAP earnings.

Effective tax expense rate of ~22% applied to GAAP earnings and ~23% applied to Non-GAAP earnings.

Prior guidance reflects the range provided February 20, 2019. Current guidance reflects the range provided May 1, 2019.

Costs related to acquisition, integration and business transition activities which include severance, relocation, consulting, leasehold exit costs, third party merger and acquisitions costs, contingent consideration fair value adjustments, and other costs directly associated with such activities.

Represents costs associated with non-cash purchase accounting adjustments, such as acquired inventory fair market value adjustments, which are amortized over the period in which underlying products are sold.

Represents the loss recorded in connection with the settlement of the Madsen Medical, Inc. litigation matter, as well as expenses associated with ongoing litigation with a former Board member and his current employer related to various matters, including infringement of the Company’s intellectual property.

Non-recurring consulting fees associated with the implementation of our state tax-planning strategy.

Purchase of an in-process research and development asset which had no future alternative use.

Represents costs specific to updating our quality system, product labeling, asset write-offs and product remanufacturing to comply with European medical device regulation.

Reconciliation of Non-GAAP Information
Management uses certain non-GAAP financial measures such as non-GAAP earnings per share, non-GAAP net income, non-GAAP operating expenses and non-GAAP operating profit margin, which exclude amortization of intangible assets, business transition costs, purchased in-process research and development, one-time restructuring and related items in connection with acquisitions, investments and divestitures, non-recurring consulting fees, certain litigation expenses and settlements, certain European medical device regulation costs, gains and losses from strategic investments, and non-cash interest expense (excluding debt issuance cost). Management also uses certain non-GAAP measures which are intended to exclude the impact of foreign exchange currency fluctuations. The measure constant currency utilizes an exchange rate that eliminates fluctuations when calculating financial performance numbers. The Company also uses measures such as free cash flow, which represents cash flow from operations less cash used in the acquisition and disposition of capital. Additionally, the Company uses an adjusted EBITDA measure which represents earnings before interest, taxes, depreciation and amortization and excludes the impact of stock-based compensation, business transition costs, purchased in-process research and development, one-time restructuring and related items in connection with acquisitions, investments and divestitures, non-recurring consulting fees, certain litigation expenses and settlements, certain European medical device regulation costs, gains and losses on strategic investments, and other significant one-time items.

Management calculates the non-GAAP financial measures provided in this earnings release excluding these costs and uses these non-GAAP financial measures to enable it to further and more consistently analyze the period-to-period financial performance of its core business operations. Management believes that providing investors with these non-GAAP measures gives them additional information to enable them to assess, in the same way management assesses, the Company’s current and future continuing operations. These non-GAAP measures are not in accordance with, or an alternative for, GAAP, and may be different from non-GAAP measures used by other companies. Set forth below are reconciliations of the non-GAAP financial measures to the comparable GAAP financial measure.

During the quarter ended June 30, 2018, the Company began excluding from its non-GAAP financial results certain litigation related expenses associated with ongoing litigation with a former Board member and his current employer related to various matters, including infringement of the Company’s intellectual property. For consistency and comparability, the Company has re-casted non-GAAP financial results for each of the quarters ended Dec. 31, 2017 and March 31, 2018 to exclude these litigation expenses in such periods, which were $0.4 million and $0.6 million, respectively.

For the Three Months Ended March 31, 2019

Reconciliation of GAAP to Non-GAAP Financial Measures

Represents expenses associated with ongoing litigation with a former Board member and his current employer related to various matters, including infringement of the Company’s intellectual property.

Costs related to acquisition, integration and business transition activities which include severance, relocation, consulting, leasehold exit costs, third party merger and acquisitions costs, contingent consideration fair value adjustments, and other costs directly associated with such activities.

Represents costs specific to updating our quality system, product labeling, asset write-offs and product remanufacturing to comply with European medical device regulation.

Represents the impact from tax affecting the adjustments above at their statutory tax rate. As of May 1, 2019, the Company estimated an annual tax rate of ~22% on a GAAP basis and ~23% on a non-GAAP basis.

Adjusted non-GAAP diluted WASO excludes the impact of dilutive convertible notes and warrants for which the Company is economically hedged through its anti-dilutive bond hedge arrangements.

For the Three Months Ended March 31, 2018

Reconciliation of GAAP to Non-GAAP Financial Measures

(Unaudited – in thousands, except per share data)

Represents costs associated with non-cash purchase accounting adjustments, such as acquired inventory fair market value adjustments, which are amortized over the period in which underlying products are sold.

Non-recurring consulting fees associated with the implementation of our state tax-planning strategy.

Represents the loss recorded in connection with the settlement of the Madsen Medical, Inc. litigation matter, as well as expenses associated with ongoing litigation with a former Board member and his current employer related to various matters, including infringement of the Company’s intellectual property.

Costs related to acquisition, integration and business transition activities which include severance, relocation, consulting, leasehold exit costs, third party merger and acquisitions costs, contingent consideration fair value adjustments, and other costs directly associated with such activities.

Represents the impact from tax affecting the adjustments above at their statutory tax rate. As of May 1, 2018, the Company estimated an annual tax rate of ~31% on a GAAP basis and ~23% on a non-GAAP basis.

Adjusted non-GAAP diluted WASO excludes the impact of dilutive convertible notes and warrants for which the Company is economically hedged through its anti-dilutive bond hedge arrangements.

Investor Conference Call
NuVasive will hold a conference call today at 4:30 p.m. ET / 1:30 p.m. PT to discuss the results of its financial performance for the first quarter 2019. The dial-in numbers are 1-877-407-9039 for domestic callers and 1-201-689-8470 for international callers. A live webcast of the conference call will be available online from the Investor Relations page of the Company’s website at www.nuvasive.com. After the live webcast, the call will remain available on NuVasive’s website through May 31, 2019. In addition, a telephone replay of the call will be available until May 8, 2019. The replay dial-in numbers are 1-844-512-2921 for domestic callers and 1-412-317-6671 for international callers. Please use pin number: 13689332.