On April 29, 2016 NewLink Genetics Corporation (NASDAQ:NLNK), a biopharmaceutical company at the forefront of discovering, developing and commercializing novel immuno-oncology product candidates, including both cellular immunotherapy and checkpoint inhibitor programs, to improve the lives of patients with cancer, reported consolidated financial results for the first quarter of 2016 (Press release, NewLink Genetics, APR 29, 2016, View Source [SID:1234511634]).

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

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

                  Schedule Your 30 min Free Demo!

"We had a productive quarter and made solid progress in achieving our mission of bringing patients with cancer better treatment options," said Charles J. Link, Jr., M.D., Chairman, Chief Executive Officer and Chief Scientific Officer. "The pivotal IMPRESS trial for patients with resected pancreatic cancer is moving rapidly toward final analysis. And, we are preparing for multiple updates from both our proprietary and partnered IDO pathway inhibitor clinical programs at key scientific meetings in 2016."

Nicholas Vahanian M.D., President and Chief Medical Officer, added, "With the upcoming clinical trial read outs, we anticipate that these data will bring us closer to clinical validation of our IDO pathway inhibitor program. The team at NewLink Genetics continues with confidence and excitement as our partner, Genentech begins to report on the clinical development of GDC-0919 alone and in combination studies. We look forward to Genentech reporting on the results from these studies this year. "

Program Updates:

HyperAcute Cellular Immunotherapy Program

Algenpantucel-L/IMPRESS Trial

Today, the company reported that it expects to report top-line results from the IMPRESS trial during the second quarter of 2016. Algenpantucel-L is the most advanced clinical program utilizing NewLink Genetics’ HyperAcute Cellular Immunotherapy platform technology. IMPRESS is a randomized, controlled, two-arm Phase 3 trial (n=722) for patients with resected pancreatic cancer designed to test algenpantucel-L in combination with the standard of care versus the standard of care alone.

IDO Pathway Inhibitor Programs

Indoximod

At the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 3 to 7, 2016 in Chicago, NewLink Genetics expects to report on clinical updates on its proprietary IDO pathway inhibitor programs. Abstracts that have been selected include:

Interim data update from a Phase 2 trial with a target enrollment of 80 patients evaluating the addition of indoximod to gemcitabine/nab-paclitaxel for patients with metastatic pancreatic cancer.
Mid-trial and safety data update from a Phase 2 trial with a target enrollment of 96 patients of indoximod and ipilimumab or PD-1 inhibitors for patients with stage 3 or 4 advanced or metastatic melanoma.
Additional data updates expected in the second half of 2016 include:

Mid-trial update from a Phase 2 trial with a target enrollment of 132 patients of indoximod for patients with refractory malignant brain tumors.
Guidance on timing of preliminary results in a randomized Phase 2 trial with a target enrollment of 154 patients of indoximod for patients with metastatic breast cancer.
GDC-0919 Small Molecule Program

The company is anticipating a clinical update from the combination study of GDC-0191. Genentech recently reported that it will update the Phase 1b study with a target enrollment of 224 patients in solid tumors at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) from October 7-11, 2016 in Denmark. The dose-escalation and expansion study combines GDC-0919 and atezolizumab (PD-L1 Mab).

In 2014, NewLink Genetics entered into an exclusive worldwide license agreement with Genentech, a member of the Roche Group, for the development of NLG919, NewLink Genetics’ IDO pathway inhibitor. The parties also entered into a research collaboration for the discovery of next generation IDO/TDO compounds.

Financial Results for the Three-Month Period Ended March 31, 2016

Cash Position: NewLink Genetics ended the quarter on March 31, 2016, with cash, cash equivalents, and certificates of deposit totaling $178 million compared to $197.8 million for the year ending December 31, 2015. The decrease was attributable primarily due to the increased operating expenses for R&D and pre-commercialization development, offset by amounts received under government contracts.

R&D Expenses: Research and development expenses in the first quarter of 2016 were $21.9 million compared to $18 million during the comparable period in 2015. The increase was primarily due to increases in clinical trial and manufacturing expenses related to NewLink Genetics’ broad pipeline of product candidates.

G&A Expenses: General and administrative expenses in the first quarter of 2016 were $9.2 million compared to $8.4 million during the comparable periods in 2015. The increase was primarily due to an increase in share-based compensation expense, as well as increases in travel expenses and medical affairs and marketing.

Net Income/Loss: NewLink Genetics reported a net loss of $23.7 million or a $0.82 loss per diluted share for the first quarter of 2016 compared to net income of $11.2 million or earnings of $0.35 per diluted share for the comparable period in 2015.

NewLink Genetics ended the quarter with 28,860,925 shares outstanding.

Financial Guidance and Upcoming Investor Meetings

NewLink Genetics has reiterated their goal and expectation is to finish 2016 with two years of cash on hand.

We have presented at five investor meetings since the beginning of the year and expect to present at Bank of America Healthcare Conference on May 12 and Cantor Fitzgerald Healthcare Conference on July 12 and 13.

HyperAcute Cellular Immunotherapy Program

HyperAcute Cellular Immunotherapies are unique, tumor-specific product candidates that take advantage of a pre-existing human immune response to initiate a powerful cascade, potentially educating the body’s natural defenses to identify and destroy cancer cells. Unlike certain immuno-oncology products, HyperAcute Cellular Immunotherapies do not require patient tissue or cancer cells and are designed to be easy to administer. HyperAcute Cellular Immunotherapies use allogeneic (disease-specific, not patient-specific), tumor-specific human cell lines that have been modified to express alpha-gal. Intact, whole cells are used rather than cell fragments or purified proteins, which we believe result in the stimulation of a more powerful immune response. Our most advanced clinical program utilizing this technology is for patients with pancreatic cancer. Additionally, there are ongoing clinical development programs and data on induced immune responses targeting non-small-cell lung cancer, melanoma, prostate cancer and kidney cancer.

Indoleamine 2,3-Dioxygenase (IDO) Checkpoint Inhibitor Programs

The indoleamine 2,3-dioxygenase (IDO) pathway regulates immune response by suppressing T cell function and enabling local tumor immune escape. NewLink Genetics is researching two IDO pathway inhibitors, GDC-0919 (in partnership with Genentech) and indoximod, small-molecule product candidates that have the potential to disrupt mechanisms by which tumors evade the immune system.

NewLink Genetics’ indoximod and GDC-0919 each have a distinct mechanism of action within the IDO pathway and are in Phase 1 or 2 clinical trials for a range of cancers, including breast cancer, melanoma, and other solid tumors.

On April 29, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion in favor of the use of IMBRUVICA (ibrutinib) for the treatment of adult patients with previously-untreated chronic lymphocytic leukemia (CLL) in the European Union (EU) (Press release, AbbVie, APR 29, 2016, View Source [SID:1234511707]). The positive CHMP recommendation follows the March 4, 2016 U.S. Food and Drug Administration (FDA) approval of IMBRUVICA for the first-line treatment of patients with CLL.1 If approved by the European Commission (EC), this would be the fifth treatment indication for IMBRUVICA in the EU to date.

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

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

                  Schedule Your 30 min Free Demo!

CLL is a chronic disease, and the prevalence rate in Europe among men and women is approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively.2 An expansion of the CLL indication in Europe would mean a larger number of CLL patients, in addition to those with the genetic mutations del 17p or TP53, could initiate their treatment with a safe and effective oral alternative option to chemotherapy, rather than having to wait until they have become relapsed or refractory on another treatment option.

IMBRUVICA is jointly developed and commercialized in the U.S. by Pharmacyclics LLC, an AbbVie company and Janssen Biotech, Inc. In Europe, Janssen-Cilag International NV (Janssen) holds the marketing authorization and its affiliates market IMBRUVICA in EMEA (Europe, Middle East, Africa), as well as the rest of the world. IMBRUVICA is already approved in Europe to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL), adult patients with CLL who have received at least one prior therapy or who have del 17p or TP53 mutations, and adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy, or as a first-line treatment for WM patients unsuitable for chemo-immunotherapy.3 The EC will review the CHMP opinion and is expected to render a final decision on the use of IMBRUVICA for previously untreated patients with CLL later this year.

"If approved by the European Commission, IMBRUVICA will be available as a treatment option for all CLL patients, including those who are treatment-naïve. The ability to offer a safe and effective, oral, single-agent alternative to chemotherapy in the first-line setting is a landmark few therapies are able to reach," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "The fact that IMBRUVICA has been granted this initial recommendation in the first-line setting is a testament to the dedication of those working on the compound to improve the lives of patients around the world who are suffering from CLL."

The positive CHMP opinion was based on data from the Phase 3, randomized, open-label RESONATE-2 (PCYC-1115) trial, which were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2015 and simultaneously published in The New England Journal of Medicine (NEJM). After a median of 18 months of follow-up, IMBRUVICA was associated with a significant improvement in all efficacy endpoints versus chlorambucil in patients aged 65 or older with newly diagnosed CLL. Specifically, IMBRUVICA was associated with a 90% progression-free survival (PFS; the primary endpoint) rate versus 52% for chlorambucil. Moreover, IMBRUVICA significantly prolonged overall survival (OS; a key secondary endpoint), with a 24-month survival rate of 98% versus 85% for chlorambucil (HR: 0.16; 95% CI, 0.05, 0.56). The safety of IMBRUVICA in the treatment-naïve CLL patient population was consistent with previously reported studies.

About the RESONATE-2 Study
RESONATE-2 is a Pharmacyclics-sponsored study which enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older in the U.S., EU and other regions. Patients were randomized to receive either IMBRUVICA 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg. The primary endpoint of the study was PFS as assessed by an Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis. Key secondary endpoints included overall response rate (ORR; based on the same iWCLL criteria), OS and safety.

About IMBRUVICA
IMBRUVICA is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK).1 BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.1,4 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.1

IMBRUVICA is approved in the U.S. to treat patients with chronic lymphocytic leukemia (CLL), patients with mantle cell lymphoma (MCL) who have received at least one prior therapy and patients with Waldenström’s macroglobulinemia (WM). Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.1

IMBRUVICA is approved in the EU to treat adult patients with relapsed or refractory MCL, adult patients with CLL who have received at least one prior therapy or who have the genetic mutations del 17p or TP53, and adult patients with WM who have received at least one prior therapy, or as a first-line treatment for WM patients unsuitable for chemo?immunotherapy. 3

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers. More than 6,000 patients have been treated with IMBRUVICA in clinical trials. Currently, 14 Phase 3 trials have been initiated with IMBRUVICA and more than 90 trials are registered on www.clinicaltrials.gov.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) occurred in patients treated with IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and dose modification.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.5 months (range, 0.03 to 18.40 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS
The most common adverse reactions (?20%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia* (57%, 53%, 43%), diarrhea (51%, 48%, 37%), anemia* (41%, 37%, 13%), neutropenia* (47%, 46%, 44%), musculoskeletal pain (37%, 32%†, NA‡), fatigue (41%, 29%, 21%), bruising (30%, 25%†, 16%†), nausea (31%, 24%, 21%), rash (25%, 23%†, 22%†), and upper respiratory tract infection (34%, 19%, 19%).

*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).
†Includes multiple ADR terms.
‡Not applicable; no associated ADRs.

The most common Grade 3 or 4 non-hematologic adverse reactions (?5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 4% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.

Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, subdural hematomas, and atrial fibrillation (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

Please see Full Prescribing Information: View Source

On April 28, 2016 Seattle Genetics, Inc. (NASDAQ: SGEN) reported financial results for the first quarter ended March 31, 2016 (Press release, Seattle Genetics, APR 28, 2016, View Source;p=RssLanding&cat=news&id=2162985 [SID:1234511558]). The company also highlighted ADCETRIS (brentuximab vedotin) commercialization, regulatory and clinical development accomplishments, vadastuximab talirine (SGN-CD33A; 33A) activities and progress with other proprietary pipeline programs and technologies.

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

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

                  Schedule Your 30 min Free Demo!

"In the first quarter, ADCETRIS net sales increased 20 percent compared to the first quarter of 2015, and we are completing three ongoing phase 3 trials designed to support additional label expansions. We expect top-line data from the first of these trials, ALCANZA, in the third quarter of this year, followed by ECHELON-1 in the 2017 to mid-2018 timeframe and ECHELON-2 in the 2017 to 2018 timeframe," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "With our pipeline, we remain on track to advance 33A into a phase 3 trial in acute myeloid leukemia (AML) by the third quarter, and we expect to report data from multiple programs over the course of 2016. Our strong financial position of more than $690 million in cash and investments at the end of March, and no debt, enables us to continue investing in our substantial opportunities to help people with cancer."

Recent ADCETRIS, Pipeline and Other Corporate Highlights

Achieved a $20 million one-time milestone payment from Takeda Pharmaceutical Company Limited (Takeda) triggered by Takeda surpassing ADCETRIS annual net sales of $200 million in its territory during 2015. The milestone was recognized as royalty revenue in the first quarter of 2016.
Takeda continues to receive additional marketing approvals for ADCETRIS, which is now commercially available in 64 countries worldwide following recent approvals in Russia and Egypt.
Initiated a phase 1/2 clinical trial of 33A in combination with azacitidine for patients with previously untreated myelodysplastic syndrome (MDS). MDS is often a precursor to AML, and both diseases broadly express CD33.
Reported research and preclinical data in multiple sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting highlighting antibody-drug conjugate (ADC) and other innovative targeted therapies, including:
Preclinical data supporting development activities with SGN-LIV1A and SEA-CD40;
Two novel preclinical programs, including an ADC for the treatment of multiple myeloma (SGN-CD352A) and a small molecule that enhances T-cell-mediated antitumor activity (2-fluorofucose; 2FF);
Data showing the ability of auristatin-based ADCs, including ADCETRIS, to initiate immunogenic cell death, supporting evaluation of ADCs in combination with checkpoint inhibitors; and,
A new auristatin-based drug-linker as well as several novel linkers that expand Seattle Genetics’ proprietary ADC technology platform and may enable conjugation with previously inaccessible cytotoxic payloads.
Initiated a phase 1 clinical trial of SGN-CD19B for relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL) and grade 3 follicular lymphoma. SGN-CD19B is an anti-CD19 ADC utilizing the same ADC technology as 33A, which includes a highly potent cytotoxic DNA-crosslinking agent called a pyrrolobenzodiazepine (PBD) dimer linked via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb).
Generated fees from ongoing ADC collaboration with Genentech upon its extension of the research term and renewal of exclusive licenses to specific ADC targets.
Added to and promoted several members of the senior management team, including:
Promoting Darren Cline to Executive Vice President, Commercial. Mr. Cline has been with Seattle Genetics since November 2010. During his tenure, he has been an integral member of the commercial leadership team, including significant contributions in the successful launch and ongoing commercialization of ADCETRIS in the United States and Canada.
Hiring Brandi Robinson as Senior Vice President, Corporate Communications. Ms. Robinson previously spent four years as Vice President and Head of Communications, North America for Sanofi. Before that, she was at Novartis for more than a decade.
Hiring Christopher Thomson, Ph.D., as Vice President, Commercial Planning. Dr. Thomson will oversee the company’s new European operations. He previously spent eight years at Astellas Pharma Europe, most recently as Vice President, Head of Oncology Business Unit. Prior to that, he spent three years with IMS Health and eight years with Bayer.
Promoting Kristin Rand to Vice President and Compliance Officer. Since joining Seattle Genetics in October 2012, Ms. Rand has grown the company’s compliance program to ensure its integrity, ethics and compliance with applicable laws and regulations.
Anticipated Upcoming Activities

ADCETRIS

Report data in the third quarter of 2016 from the phase 3 ALCANZA trial in patients with relapsed CD30-expressing cutaneous T-cell lymphoma (CTCL).
Report data in the 2017 through mid-2018 timeframe from the phase 3 ECHELON-1 trial in frontline classical Hodgkin lymphoma.
Complete enrollment in the phase 3 ECHELON-2 trial in frontline mature T-cell lymphoma (MTCL) during 2016 and report data in the 2017 to 2018 timeframe.
ADCETRIS is not currently approved for use in CTCL, frontline MTCL or frontline Hodgkin lymphoma.

Vadastuximab Talirine (SGN-CD33A)

Initiate a phase 3 trial to evaluate 33A in combination with hypomethylating agents, or HMAs, in older patients with AML by the third quarter of 2016.
Report additional data from a phase 1 trial of 33A in combination with HMAs at the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting being held June 9 to 12, 2016 in Copenhagen, Denmark.
Report data in 2016 from a phase 1b trial of 33A in combination with cytarabine and daunorubicin for frontline, younger AML patients.
More information about 33A and ongoing clinical trials can be found at www.ADC-CD33.com.

Additional Pipeline Programs

Initiate a randomized phase 2 trial of denintuzumab mafodotin (SGN-CD19A; 19A) in frontline DLBCL in the first half of 2016.
Report phase 1 clinical data from ASG-15ME and ASG-22ME at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting being held June 3 to 7, 2016 in Chicago, Illinois. These programs are in development for solid tumors, notably bladder cancer, under a 50:50 co-development collaboration with Astellas.
Initiate a phase 1 trial of SGN-CD123A in AML during 2016.
Advance SGN-CD352A, a novel ADC for multiple myeloma, into a phase 1 clinical trial. Preclinical data were reported at AACR (Free AACR Whitepaper) on this novel ADC, which is composed of an anti-CD352 antibody utilizing the company’s PBD and EC-mAb technology.
First Quarter 2016 Financial Results

Total revenues in the first quarter of 2016 were a record $111.2 million, an increase of 35 percent over first quarter 2015 revenues of $82.2 million. Revenues in the first quarter of 2016 included:

ADCETRIS net product sales of $58.6 million, a 20 percent increase from net product sales of $48.9 million for the first quarter of 2015.
Royalty revenues of $32.3 million on international sales of ADCETRIS by Takeda, compared to $11.1 million for the same period in 2015. First quarter 2016 royalty revenues included a $20 million one-time milestone payment triggered by Takeda surpassing ADCETRIS annual net sales of $200 million in its territory during 2015.
Amounts earned under the company’s ADCETRIS and ADC collaborations totaling $20.2 million in the first quarter of 2016, compared to $22.2 million in the first quarter of 2015.
Total costs and expenses for the first quarter of 2016 were $132.2 million, compared to $103.9 million for the first quarter of 2015. The planned increase in 2016 costs and expenses was primarily related to progress with ADCETRIS and investment in the company’s pipeline programs, including expanded 33A clinical development and manufacturing activities.

Non-cash, share-based compensation cost for the first quarter of 2016 was $12.2 million, compared to $7.7 million for the first quarter of 2015.

Net loss for the first quarter of 2016 was $20.5 million, or $0.15 per share, compared to a net loss of $21.7 million, or $0.17 per share, for the first quarter of 2015.

As of March 31, 2016, Seattle Genetics had $691.7 million in cash, cash equivalents and investments, compared to $712.7 million as of December 31, 2015.

On April 28, 2016 Agenus Inc. (NASDAQ:AGEN), an immuno-oncology company developing checkpoint antibodies and cancer vaccines, reported a corporate update and reported financial results for the first quarter ended March 31, 2016 (Press release, Agenus, APR 28, 2016, View Source [SID:1234511561]).

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

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

                  Schedule Your 30 min Free Demo!

"In the first quarter we advanced our checkpoint antibodies by gaining FDA clearance for the Investigational New Drug applications for our CTLA-4 antagonist antibody AGEN1884, and for our GITR agonist antibody partnered with Incyte, INCAGN1876," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "Earlier this week, we commenced a Phase 1 trial of AGEN1884 in solid tumors with the first patient in the trial having been dosed. During the remainder of 2016, we expect to begin clinical trials for additional checkpoint antibody candidates. Our plans this year and into next include initiating one or more randomized trials with Prophage, including combination trials with approved and/or experimental immunotherapeutic agents. Within the next 12 months we also plan to initiate a Phase 1 trial of our AutoSynVax or ASV vaccine, a synthetic autologous vaccine candidate that targets cancer neoantigens. Finally, we expect to consummate non-dilutive funding strategies and evaluate additional strategic alliances and partnerships to strengthen our immuno-oncology capabilities."

First Quarter 2016 and Recent Corporate Highlights

April: Initiated Phase 1 trial of AGEN1884, a CTLA-4 antagonist antibody, in solid tumors. AGEN1884 is the first of a series of checkpoint antibodies the Company is developing. AGEN1884 was developed using Agenus’ powerful in-house antibody technology platform.
April: Presented preclinical data for three checkpoint antibody programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference: INCAGN1949 (an OX40 agonist antibody, partnered on a 50/50 financial basis with Incyte), INCAGN1876 (an agonist antibody for the glucocorticoid-induced TNFR-related protein, or GITR, also partnered on a 50/50 basis with Incyte), and our anti-CTLA-4 program (AGEN1884 and AGEN2041, partnered with Recepta for certain South American territories). The poster presentations covered preclinical pharmacology for each antibody, including detailed studies to support potential in vivo mechanism(s) of action. Data from the INCAGN1949 and INCAGN1876 programs will also be presented at the upcoming Protein and Antibody Engineering Summit (PEGS) in Boston tomorrow, April 29.
January: Investigational New Drug applications received clearance from the U.S. Food and Drug Administration for two checkpoint antibodies: AGEN1884 (CTLA-4 antagonist) and INCAGN1876 (GITR agonist partnered with Incyte).
January: Began integration efforts for our antibody manufacturing facility acquired from Xoma in December 2015. The facility will enable the Company to manufacture checkpoint antibodies for its own programs and those of its collaborators. The facility is expected to provide Agenus’ antibody supply requirements for most programs through clinical proof-of-concept studies.
First Quarter 2016 Financial Results

For the first quarter ended March 31 2016, Agenus reported a net loss attributable to common stockholders of $31.8 million, or $0.37 per share, basic and diluted, including $9.6 million in non-cash expenses. This compares to a net loss attributable to common stockholders for the first quarter of 2015 of $18.8 million, or $0.28 per share, basic and diluted. The increase in net loss attributable to common stockholders for the three months ended March 31, 2016, compared to the net loss attributable to common stockholders for the same period in 2015, was primarily due to the advancement of our checkpoint programs.

Cash, cash equivalents and short-term investments were $148.2 million as of March 31, 2016.

On April 28, 2016 BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) reported financial results for the first quarter ended March 31, 2016 (Press release, BioMarin, APR 28, 2016, View Source [SID:1234511564]). Non-GAAP net loss was $27.2 million for the quarter ended March 31, 2016, compared to non-GAAP net loss of $25.4 million for the first quarter of 2015. GAAP net loss was $85.1 million, or $0.53 per basic and diluted share for the first quarter of 2016, compared to GAAP net loss of $67.5 million, or $0.43 per basic and diluted share, for the first quarter of 2015.

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

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

                  Schedule Your 30 min Free Demo!

Total BioMarin Revenue was $236.7 million for the first quarter of 2016, an increase of 16.7% compared to the same period in 2015. This strong result was driven by year over year growth of 43.5% and 53.2% of Vimizim and Kuvan, respectively. Kuvan revenue from ex-North America territories since BioMarin acquired worldwide rights in January 2016 contributed $16.9 million and revenues in North America contributed $60.0 million in the quarter. Naglazyme patient growth was 8.5% compared to a year ago, the 40th straight quarter since the product was launched in 2005. Naglazyme revenue in the first quarter 2016 was lower than revenue in the first quarter 2015 primarily due to the timing of central government orders from Latin America.

As of March 31, 2016, BioMarin had cash, cash equivalents and investments totaling $771.3 million, as compared to $1,018.3 million on December 31, 2015.

Commenting on the quarter, Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin said, "Our commercial base business is robust and is expected to generate over one billion dollars in revenues this year. Prospects for new product launches in 2017 increased during the quarter due to positive data readouts for cerliponase alfa and pegvaliase that we expect will lead to two new product filings later this year. In addition, at our recent Research and Development Day for analysts and investors, we highlighted very encouraging preliminary data from our gene therapy product BMN 270 for hemophilia A and robust 12 month data with vosoritide for achondroplasia. If the data from these programs continue to mature as we hope, we believe that these products could each ultimately drive a billion dollars in revenue when commercialized. Finally, we continue to expect to manage this growing business with the goal of achieving non-GAAP break-even or better in 2017 regardless of the regulatory outcome of Kyndrisa in Europe."

Net Product Revenue (in millions of U.S. dollars, unaudited)

Total Revenue

Three Months Ended March 31,
2016 2015 $ Change % Change

Vimizim (1) $ 72.6 $ 50.6 $ 22.0 43.5 %
Naglazyme (1) 65.4 78.2 (12.8 ) (16.4 )%
Kuvan (2) 76.9 50.2 26.7 53.2 %
Aldurazyme 16.4 18.2 (1.8 ) (9.9 )%
Firdapse 4.1 4.1 - 0.0 %
Net product revenues 235.4 201.3 34.1 16.9 %

Collaborative agreement revenues 0.2 0.4 (0.2 )
Royalty, license and other revenues 1.1 1.2 (0.1 )
Total BioMarin revenues $ 236.7 $ 202.9 $ 33.8 16.7 %

(1) Vimizim and Naglazyme revenues experience quarterly fluctuations primarily due to the timing of government ordering patterns in certain countries. The Company does not believe these fluctuations reflect a change in underlying demand.
(2) Growth in North America contributed $60.0 million in the first quarter with an additional $16.9 million coming from newly acquired ex-North American territories.

Reconciliation of Aldurazyme Revenues

Three Months Ended March 31,
2016 2015 $ Change % Change
Aldurazyme revenue reported by Genzyme $ 52.8 $ 53.4 $ (0.6 ) (1.1 )%

Three Months Ended March 31,
2016 2015 $ Change
Royalties earned from Genzyme $ 21.5 $ 22.3 $ (0.8 )
Net product transfer revenues (3) (5.1 ) (4.1 ) (1.0 )
Total Aldurazyme net product revenues $ 16.4 $ 18.2 $ (1.8 )

(3) To the extent units shipped to third party customers by Genzyme exceed BioMarin inventory transfers to Genzyme, BioMarin will record a decrease in net product revenue from the royalty payable to BioMarin for the amount of previously recognized product transfer revenue. If BioMarin inventory transfers exceed units shipped to third party customers by Genzyme, BioMarin will record incremental net product transfer revenue for the period. Positive net product transfer revenues result in the period if BioMarin transferred more units to Genzyme than Genzyme sold to third-party customers.

2016 Financial Guidance

Revenue Guidance ($ in millions)

Item
Provided
February 25, 2016 Updated April 28, 2016
Total BioMarin Revenues $1,050 to $1,100 Unchanged
Vimizim Net Product Revenue $300 to $330 $315 to $340
Naglazyme Net Product Revenue $290 to $320 Unchanged
Kuvan Net Product Revenue $320 to $350 Unchanged

Select Income Statement Guidance ($ in millions, except percentages)

Item
Provided
February 25, 2016 Updated April 28, 2016
Cost of Sales (% of Total Revenue) 18.0% to 19.0% Unchanged
Selling, General and Admin. Expense $470 to $490 Unchanged
Research and Development Expense $680 to $720 Unchanged
Non – GAAP Net Loss $(75) to $(100) Unchanged
GAAP Net Loss $(400) to $(430) $(355) to $(385)*

*GAAP Net Loss guidance updated April 28, 2016 based on impact of final purchase accounting treatment for the PKU franchise acquisition from Merck that closed in the first quarter 2016.

Key Program Updates at R&D Day April 20, 2016

BMN 270 gene therapy product for hemophilia A: The Company provided encouraging preliminary data from an ongoing Phase 1/2 clinical trial with BMN 270, an investigational gene therapy treatment for hemophilia A. A total of eight patients with severe hemophilia A received a single dose of BMN 270, six of whom have been treated at the highest dose of 6 x 1013 vector genomes (VG)/kilogram (kg), and to date, post-treatment follow-up ranges from five to 16 weeks. As stated at R&D Day, patients at the highest dose experienced increasing Factor VIII activity levels ranging between 4% and 60% (as a percentage of normal calculated based on the numbers of International Units (IU) per milliliter of whole blood), with five of six patients treated at the high dose now over 5% and two of six at over 50%. All high dose patients improved from severe to either moderate, mild or normal range in terms of factor levels based on World Federation of Hemophilia criteria. (See BioMarin press release from April 20, 2016 for further details.)

Vosoritide for achondroplasia: The Company provided an update on its Phase 2 study of vosoritide, an analog of C-type Natriuretic Peptide (CNP), in children with achondroplasia, the most common form of dwarfism. After 12 months of daily dosing at 15 µg/kg/day, the cohort 3 patients (n=10) experienced a 46% or 1.9 cm/year increase in mean annualized growth velocity from baseline (p-value = 0.02). These findings provide evidence of durability of effect consistent with previously presented 6-month data for these patients, which demonstrated an annualized increase of 50% or 2.0 cm/year in mean annualized growth velocity. In addition, 6-month data for 12 patients who were initiated on a lower dose and switched to 15 µg/kg/day showed an increase of 65% or 2.3 cm/year in mean annualized growth velocity from baseline (p-value = 0.002). (See BioMarin press release from April 20, 2016 for further details.)

Cerliponase alfa for CLN2, late-infantile form of Batten disease: Complete results from the Phase 1/2 study of cerliponase alfa, a recombinant human tripeptidyl peptidase 1 (rhTPP1), for the treatment of patients with late-infantile neuronal ceroid lipofuscinosis type 2 (NCL-2), a form of Batten disease were announced at the WORLD LSD Symposium on March 2, 2016. Based on the robust data results announced at that meeting, the Company shared plans to submit in the U.S. and E.U. for regulatory approval mid-year 2016. (See BioMarin press release from March 2, 2016 for further details.)

Pegvaliase for phenylketonuria (PKU): Pivotal results for the Phase 3 PRISM-2 study (formerly referred to as 165-302) that pegvaliase met the primary endpoint of change in blood Phe compared with placebo (p<0.0001) were announced March 21, 2016. The pegvaliase treated group maintained mean blood Phe levels at 527.2 umol/L compared to their RDT baseline of 503.9 umol/L, whereas the placebo treated group mean blood Phe levels increased to 1385.7 umol/L compared to their RDT baseline of 536.0 umol/L. The treatment effect demonstrated in this study represents an approximately 62% improvement in blood Phe compared to placebo. Based on the supportive data results, the Company plans to submit a Biologics License Application (BLA) to U.S. FDA in the second half of 2016. (See BioMarin press release from March 21, 2016 for further details.)