On November 1, 2016 NewLink Genetics Corporation (NASDAQ:NLNK), a biopharmaceutical company focused on bringing novel immuno-oncology therapies to patients with cancer, reported consolidated financial results for the third quarter of 2016 and progress in its clinical and pipeline development programs (Press release, NewLink Genetics, NOV 1, 2016, View Source [SID1234516135]).

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"We continue to focus our clinical developmental efforts targeting the IDO pathway. We have two distinct IDO pathway inhibitors advancing in the clinic, GDC-0919 with our partner Genentech and indoximod, our proprietary IDO pathway inhibitor," said Charles J. Link, Jr. MD, Chairman, Chief Executive Officer and Chief Scientific Officer. "We are also encouraged by recent clinical data that increasingly validate the IDO pathway as an important target in immuno-oncology."

The Company hosted an investor day on October 25, outlining its vision and execution plans for the future. A webcast of the Company’s presentations can be found at View Source

"As described at our investor day, we believe 2017 will be an important year in the development of both GDC-0919 and indoximod and we look forward to providing further updates and results," added Nicholas N. Vahanian, MD, President and Chief Medical Officer.

The program featured leaders in the field of immuno-oncology and pioneers in the science of IDO: George C. Prendergast, PhD, President & CEO, Lankenau Institute for Medical Research (LIMR) and Editor in Chief, Cancer Research; David H. Munn, MD, Professor of Pediatric Hematology-Oncology, Medical College of Georgia, Augusta University; Montaser Shaheen MD, Associate Professor, University of New Mexico Cancer Center; and Ashkan Emadi, MD, PhD, Associate Professor, University of Maryland.

Key takeaways from the Investor Day included:

1. Validation of IDO as a Target. The IDO pathway can allow cancer to escape the immune system. Many cancers have developed the ability to employ IDO to evade immune attack. We believe clinical results are increasingly validating the IDO pathway as a target for cancer therapies. Just as scientists discovered the role of PD-1/PD-L1 expression and the usefulness of PD-1/PD-L1 blockade, there is an increasing body of research into the role of the IDO pathway in cancer.

2. NewLink’s Two IDO Pathway Inhibitor Clinical Candidates. NewLink Genetics is engaged in clinical trials for two IDO pathway inhibitor product candidates, each with its own distinct mechanism of action.

GDC-0919, a direct IDO enzymatic inhibitor, is being developed in partnership with Genentech. GDC-0919 is currently in a Phase 1b trial, in combination with atezolizumab in solid tumors. In October, 2014, NewLink and Genentech entered in to a license and collaboration agreement with an upfront payment of $150 million, more than $1 billion in potential milestones, and substantial royalties.
Indoximod, an IDO pathway inhibitor, is proprietary to NewLink Genetics. Indoximod is being tested in the clinic in multiple indications including melanoma, pancreatic cancer, malignant brain tumors, breast cancer, acute myeloid leukemia, and non-small cell lung cancer.
3. Indoximod Clinical Development. The Company reported that it will evaluate the data and report on several clinical trials underway in 2017. Furthermore, our clinical development strategy for indoximod includes formulation optimization intended to improve the candidate’s clinical and commercial potential.

4. Future R&D. NewLink also discussed its program targeting the PTEN pathway in regulatory T cells (Treg cells) as a central driver of tumor immunosuppression. NewLink Genetics is an early leader in the field of PTEN research, just as it was in developing IDO as a potential pathway for immune suppression in cancer.

Financial Results for the Three-Month Period Ended September 30, 2016

Cash Position: NewLink Genetics ended the quarter on September 30, 2016, with cash and equivalents totaling $148.3 million, compared to $197.8 million for the year ending December 31, 2015.

R&D Expenses: Research and development expenses in the third quarter of 2016 were $24.5 million, compared to $22.5 million during the comparable period in 2015. The increase was primarily due to a $3.2 million increase in contract manufacturing costs, a $340,000 increase in stock compensation expense, and a $400,000 increase in clinical trial expenses, offset by a decrease in equipment and supplies of $1.3 million, wages of $490,000 and a $160,000 decrease in consulting.

G&A Expenses: General and administrative expenses in the third quarter of 2016 were $7.7 million compared to $7.4 million during the comparable period in 2015. The increase was due primarily to an increase of $300,000 in consulting and personnel-related expenses.

Net Income/Loss: NewLink Genetics reported a net loss of $15.5 million, or a loss of $0.54 per diluted share, for the third quarter of 2016, compared to a net loss of $15.9 million, or a loss of $0.55 per diluted share, for the comparable period in 2015.

NewLink Genetics ended the quarter with 29,091,652 shares outstanding.

Financial Guidance and Upcoming Investor Meetings

NewLink Genetics expects to have approximately $132 million in cash and equivalents on December 31, 2016.

We have presented at seven investor meetings and conferences since the beginning of the year, including our own investor day held last week. We expect to present at three upcoming conferences in New York City, including the Global Mizuho Investor Conference on November 14, the Stifel 2016 Healthcare Conference on November 15, and the Piper Jaffray 28th Annual Healthcare Conference on November 29.

On November 1, 2016 Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), reported financial results for the third quarter ended September 30, 2016 and provided an overview of key milestones for the company’s lead drug candidates (Filing, Q3, Lexicon Pharmaceuticals, 2016, NOV 1, 2016, View Source [SID1234516134]).

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"We achieved a key milestone in the third quarter with the release of positive top-line results from our first pivotal Phase 3 clinical trial of sotagliflozin in patients with type 1 diabetes, followed by favorable results in October from a Phase 2 study that supported our Phase 3 dose selection and demonstrated results on several important measures beyond A1C," said Lonnel Coats, Lexicon’s president and chief executive officer. "We are enthusiastic about the clinical results demonstrated by sotagliflozin to date, and we are looking forward to announcing the results from two additional clinical trials, including our second pivotal Phase 3 study, by the end of the year."

Pipeline Progress

Telotristat ethyl is the first investigational drug in clinical studies to target tryptophan hydroxylase (TPH), the rate-limiting enzyme involved in serotonin production. Excess production of serotonin within metastatic neuroendocrine tumor cells can lead to carcinoid syndrome, a condition characterized by serious consequences including frequent and debilitating diarrhea, facial flushing, abdominal pain, and heart valve damage.

In July, the European Medicines Agency accepted a marketing authorization application filed for telotristat ethyl by Ipsen, Lexicon’s collaborator for the commercialization of telotristat ethyl in Europe and other countries outside the U.S. and Japan. The current Prescription Drug User Fee Act ("PDUFA") target action date for Lexicon’s new drug application with the U.S. Food and Drug Administration for telotristat ethyl is February 28, 2017.

Sotagliflozin, which is being developed as a potential treatment for type 1 and type 2 diabetes, is a dual inhibitor of sodium-glucose transporters 1 and 2 (SGLT1 and SGLT2), each of which modulates glucose levels, and is the first investigational medicine developed to target both of these two proteins.

In September, Lexicon announced positive top-line results of its first pivotal Phase 3 clinical trial of sotagliflozin in patients with type 1 diabetes, on a background of optimized insulin (inTandem1). Lexicon is conducting a second pivotal Phase 3 clinical trial (inTandem2) from which top-line results are expected in December 2016. Lexicon is also completing a Phase 2 clinical trial in collaboration with JDRF in young adults with type 1 diabetes, from which results are expected prior to the end of the year. A third type 1 diabetes Phase 3 clinical trial, inTandem3, is underway globally and is studying approximately 1,400 patients treated with sotagliflozin 400mg once daily or placebo on a background of any insulin therapy, but without insulin optimization prior to randomization.

Lexicon entered into a collaboration and license agreement with Sanofi in November 2015 under which Lexicon granted Sanofi an exclusive, worldwide, royalty-bearing right and license to develop, manufacture and commercialize sotagliflozin. Lexicon is responsible for all clinical development activities relating to type 1 diabetes and retains an exclusive option to co-promote and have a significant role, in collaboration with Sanofi, in the commercialization of sotagliflozin for the treatment of type 1 diabetes in the United States. Sanofi is responsible for all clinical development and commercialization of sotagliflozin for the treatment of type 2 diabetes worldwide and is solely responsible for the commercialization of sotagliflozin for the treatment of type 1 diabetes outside the United States. Sanofi is expected to commence Phase 3 clinical trials for sotagliflozin in patients with type 2 diabetes this year.

Financial Highlights

Revenues: Lexicon’s revenues for the three months ended September 30, 2016 increased to $27.7 million from $0.6 million for the corresponding period in 2015, primarily due to revenues recognized from the collaboration and license agreement with Sanofi. For the nine months ended September 30, 2016, revenues increased to $60.3 million from $2.7 million for the corresponding period in 2015.

Research and Development Expenses: Research and development expenses for the three months ended September 30, 2016 increased 127 percent to $52.5 million from $23.1 million for the corresponding period in 2015, primarily due to increases in external clinical and nonclinical research and development costs. For the nine months ended September 30, 2016, research and development expenses increased 113 percent to $137.8 million from $64.7 million for the corresponding period in 2015.

Change in Fair Value of Symphony Icon Purchase Liability: In connection with the acquisition of Symphony Icon, Lexicon made an initial estimate of the fair value of the liability for the associated base and contingent payments. Changes in this liability, based on the development of the programs and the time until such payments are expected to be made, are recorded in Lexicon’s consolidated statements of operations. The change in fair value of the Symphony Icon purchase liability was $(2.1) million and $3.4 million for the three months ended September 30, 2016 and 2015, respectively, and was $(0.7) million and $5.1 million for the nine months ended September 30, 2016 and 2015, respectively.

General and Administrative Expenses: General and administrative expenses for the three months ended September 30, 2016 increased 128 percent to $12.3 million from $5.4 million for the corresponding period in 2015, primarily due to increased costs in preparation for commercialization of telotristat ethyl. For the nine months ended September 30, 2016, general and administrative expenses increased 67 percent to $29.1 million from $17.4 million for the corresponding period in 2015.

Impairment Loss on Buildings: In 2014, Lexicon began to market its buildings and land in The Woodlands, Texas for sale. Lexicon recognized non-cash impairment losses on its buildings of $2.3 million for the three and nine months ended September 30, 2015 as a result of writing down the buildings to the estimated net selling price.

Consolidated Net Loss: Net loss for the three months ended September 30, 2016 was $36.0 million, or $0.35 per share, compared to a net loss of $35.3 million, or $0.34 per share, in the corresponding period in 2015. Net loss for the nine months ended September 30, 2016 was $109.0 million, or $1.05 per share, compared to a net loss of $91.4 million, or $0.88 per share, in the corresponding period in 2015. For the three and nine months ended September 30, 2016, net loss included non-cash, stock-based compensation expense of $1.9 million and $5.7 million, respectively. For the three and nine months ended September 30, 2015, net loss included non-cash, stock-based compensation expense of $1.7 million and $5.4 million, respectively.

Cash and Investments: As of September 30, 2016, Lexicon had $395.6 million in cash and investments, as compared to $429.4 million as of June 30, 2016 and $521.4 million as of December 31, 2015.

On November 1, 2016 Array BioPharma Inc. (Nasdaq: ARRY), a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule cancer therapies, reported results for its first quarter of fiscal 2017 and provided an update on the progress of its key clinical development programs (Press release, Array BioPharma, NOV 1, 2016, View Source;p=RssLanding&cat=news&id=2217854 [SID1234516133]).

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Array BioPharma. (PRNewsFoto/Array BioPharma Inc.) (PRNewsFoto/)
"We were pleased to report that COLUMBUS met its primary endpoint and demonstrated a robust PFS benefit associated with the combination of binimetinib plus encorafenib versus vemurafenib in patients with BRAF-mutant melanoma," said Ron Squarer, Chief Executive Officer of Array BioPharma. "We look forward to sharing results at SMR, partnering with global regulatory authorities on planned 2017 submissions for COLUMBUS and preparing for potential commercialization."

KEY COMPANY AND PIPELINE UPDATES
Binimetinib (MEK162) and encorafenib (LGX818)
Novartis continues to substantially fund all ongoing trials with binimetinib and encorafenib that were active or planned as of the close of the Novartis Agreements in 2015, including the NEMO and COLUMBUS Phase 3 trials. Reimbursement revenue from Novartis was approximately $129.0 million for the previous 12 months, of which $31.3 million was recorded over the past quarter.

COLUMBUS: Global Phase 3 trial of binimetinib plus encorafenib versus vemurafenib in BRAF-mutant melanoma patients
In September 2016, Array announced top-line results from Part 1 of the Phase 3 COLUMBUS study evaluating LGX818 (encorafenib), a BRAF inhibitor, and MEK162 (binimetinib), a MEK inhibitor, in patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The study met its primary endpoint, with the combination of encorafenib and binimetinib ("combination") significantly improving progression free survival (PFS) compared with vemurafenib, a BRAF inhibitor, alone. In the analysis of the primary endpoint, the median PFS for patients treated with the combination was 14.9 months versus 7.3 months for patients treated with vemurafenib; Hazard ratio (HR) 0.54, (95% CI 0.41-0.71, p<0.001). The combination was generally well-tolerated and reported adverse events were overall consistent with previous clinical trial results of the combination in BRAF-mutant melanoma patients. Analysis of a secondary endpoint comparing the median PFS of patients treated with the combination to patients treated with encorafenib alone showed 14.9 months versus 9.6 months, respectively; HR 0.75, (95% CI 0.56-1.00, p=0.051), which did not reach statistical significance. A complete analysis of these results will be provided to global regulatory authorities as part of planned submissions in 2017. In addition, data from Part 2 of the COLUMBUS trial are anticipated in mid-2017 and will also be provided to global health authorities as part of planned regulatory submissions seeking approval of these product candidates.

Further results from Part 1 of the COLUMBUS trial will be presented at the Society for Melanoma Research Congress on November 9, 2016. Analysis of the secondary endpoint of overall survival (OS) was not planned as part of these initial results. Binimetinib and encorafenib are investigational medicines and are not currently approved in any country.

Melanoma is the fifth most common cancer among men and the seventh most common cancer among women in the United States, with more than 76,000 new cases and over 10,000 deaths from the disease expected in 2016. Novel therapies that target the RAS/RAF/MEK/ERK pathway have a strong scientific rationale for activity in this disease, as up to 50 percent of patients with metastatic melanoma have activating BRAF mutations, the most common gene mutation in this patient population. Current marketed MEK/BRAF combination agents have a run rate forecasted to approach $1 billion in annual worldwide sales.

NEMO: Global Phase 3 trial of binimetinib versus dacarbazine in NRAS-mutant melanoma patients
In September 2016, Array announced that the FDA has accepted its NDA for binimetinib in NRAS-mutant melanoma with a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2017. Also, the binimetinib Marketing Authorization Application (MAA) submitted by Pierre Fabre was validated and is currently under evaluation by the Committee for Medicinal Products for Human Use (CHMP). The FDA indicated that it plans to hold an advisory committee meeting (ODAC) in the first half of 2017 as part of the review process.

Activating NRAS mutations are present in up to 20 percent of patients with metastatic melanoma, and are a poor prognostic indicator for these patients. Treatment options for this population remain limited beyond immunotherapy, and these patients face poor clinical outcomes and high mortality.

BEACON CRC: Global Phase 3 trial of binimetinib, encorafenib and Erbitux (cetuximab) versus Erbitux in BRAF-mutant colorectal cancer (CRC) patients
Array is advancing BEACON CRC, a global Phase 3 trial of encorafenib and Erbitux (cetuximab), with or without binimetinib, versus standard of care in patients with BRAF-mutant CRC who have previously received first-or second-line systemic therapy. In September 2016, Array announced that it has reached agreement with the FDA regarding a Special Protocol Assessment (SPA) related to BEACON CRC. The SPA acknowledges that the design and planned analysis of BEACON CRC adequately address the objectives necessary to support a regulatory submission for the approval of the doublet regimen of encorafenib and Erbitux. The FDA also communicated that sharing evidence from the study that the triplet regimen (encorafenib, Erbitux and binimetinib) both met its primary endpoint (Overall Survival) as compared to the control arm, and demonstrated a clinically meaningful benefit as compared to the doublet regimen, would provide support for approval of the triplet regimen and that determination regarding approval of the triplet regimen will consider the totality of the data. Array expects to have data from the safety lead-in portion of the study in 2017.

BEACON CRC was initiated based on results from a Phase 2 study of the combination of encorafenib and cetuximab, with or without alpelisib, a selective PI3K alpha inhibitor, in patients with advanced BRAF-mutant CRC, which were presented at the 2016 ASCO (Free ASCO Whitepaper) meeting. Data from this study suggest that mOS for these patients may exceed one year, which is more than double several historical published benchmarks for this population.

Colorectal cancer is the third most common cancer among men and women in the United States, with more than 134,000 new cases and nearly 50,000 deaths from the disease projected in 2016. In the United States, BRAF mutations occur in 8 to 15 percent of patients with colorectal cancer and represent a poor prognosis for these patients.

ARRY-382
Phase 1/2 dose escalation study advancing with ARRY-382, a colony-stimulating factor-1 receptor (CSF-1R) inhibitor, in combination with pembrolizumab, a PD-1 antibody, for the treatment of patients with advanced solid tumors

Array is advancing a Phase 1/2 dose escalation immuno-oncology trial of ARRY-382 in combination with pembrolizumab (Keytruda), a Programmed Cell Death Receptor 1 (PD-1) antibody, in patients with advanced solid tumors. ARRY-382 is a wholly-owned, highly selective and potent, small molecule inhibitor of CSF-1R kinase activity.

The study will enroll up to 18 patients with selected advanced solid tumors to determine the maximum tolerated dose and/or recommended Phase 2 dose of the combination. In addition, the safety profile, pharmacodynamic effects, and preliminary assessment of activity of the combination will be assessed. With appropriate results, Array has the option to advance the combination into expansion cohorts of patients with metastatic melanoma or advanced non-small cell lung cancer (NSCLC). Array expects to have data from the dose-escalation portion of the study in 2017.

Results from a prior Phase 1 study designed to assess the safety, pharmacokinetics and pharmacodynamics of ARRY-382 for treating patients with cancer have been presented and a dose and schedule that demonstrates target engagement based on multiple pharmacodynamic biomarkers was identified for further study. ARRY-382 is an investigational new drug and is not currently approved for any use in any country.

ARRY-797 (ARRY-371797)
Phase 2 trial in patients with LMNA A/C-related dilated cardiomyopathy (LMNA-related DCM)
In August 2016, Array announced results from a Phase 2 study of ARRY-797, an oral, selective p38 mitogen-activated protein kinase inhibitor, in patients with LMNA-related DCM, a rare, degenerative cardiovascular disease caused by mutations in the LMNA gene and characterized by poor prognosis. The trial results were presented at the European Society of Cardiology Congress 2016. The results demonstrated an absolute mean change from baseline of 69 meters on the six-minute walk test (6MWT) at week 12, the study’s primary endpoint (baseline 6MWT ranged from 246 to 412 meters). This magnitude of improvement exceeded historical benchmarks for 6MWT that have served as the basis for recent approvals of other drugs in other rare diseases. ARRY-797 administration also resulted in sustained improvements in N-terminal pro-brain natriuretic peptide (NT-proBNP), functional capacity and cardiac function through 48 weeks in LMNA-related DCM patients. Patients who rolled over to a continuing treatment protocol maintained improvements in the 6MWT and NT-proBNP levels through 72 weeks of treatment. Other secondary endpoints measured including echocardiographic measures of left and right ventricular function and patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ), and both mirrored the improvements seen with the 6MWT. ARRY-797 was well tolerated with most patients experiencing mild to moderate adverse events, including stomatitis, acne and upper respiratory tract infection.

Taken together, the data to date suggest a path forward for this program, and Array has met with regulators to discuss the design of a study that could be the basis for marketing approval. Array is evaluating different options to advance the ARRY-797 program, including advancing it on its own, partnering the program for further development and commercialization or creating a separate company based on this asset.

LMNA-related DCM is estimated to occur in about 6,000 – 10,000 patients in the US. The number of patients currently identified with a molecular diagnosis is likely to be less than this estimate because of underutilization of genetic testing. Patients with LMNA-related DCM typically begin experiencing symptoms in their twenties or thirties and by age 45, nearly 70 percent of patients have had a heart transplant, have experienced a major cardiac event or have died. By comparison, only 25 percent of DCM patients who do not have LMNA mutations experience similar events by age 45. Currently, there are no disease-specific treatments approved for LMNA-related DCM. ARRY-797 is an investigational new drug and is not currently approved for any use in any country.

FINANCIAL HIGHLIGHTS
Raised $132.25 million in public offering
Array completed an underwritten public offering of 21,160,000 shares of its common stock at a price of $6.25 per share on October 3, 2016. The total gross proceeds from the offering are $132.25 million, before underwriting discounts and commissions and offering expenses.

First Quarter of Fiscal 2017 Compared to Fourth Quarter of Fiscal 2016 (Sequential Quarters Comparison)

Revenue for the first quarter of fiscal 2017 was $39.3 million, compared to $43.2 million for the prior sequential quarter, mainly driven by reduced Novartis reimbursed activity.
Cost of partnered programs for the first quarter of fiscal 2017 was $8.8 million, compared to $5.4 million for the prior quarter. The increase in cost of partnered programs was primarily due to the initiation of the BEACON CRC trial.
Research and development expense was $46.6 million, compared to $49.5 million in the prior quarter. The slight decrease in research and development expense is primarily related to the ongoing transition of binimetinib and encorafenib trials from Novartis to Array.
Net loss for the first quarter was $28.6 million, or ($0.20) per share, and was $25.0 million, or ($0.17) per share in the prior quarter.
First Quarter of Fiscal 2017 Compared to First Quarter of Fiscal 2016 (Prior Year Comparison)

Revenue for the first quarter of fiscal 2017 increased $23.1 million compared to the same quarter of fiscal 2016. The increase was primarily due to reimbursement revenue from Novartis.
Cost of partnered programs increased $2.6 million compared to the first quarter of fiscal 2016. The increase was primarily due to the BEACON CRC trial.
Research and development expense increased $25.6 million, compared to the first quarter of fiscal 2016. The increase was due to binimetinib and encorafenib expenses as we transitioned activity from the "Novartis Agreements."
Net loss for the first quarter of fiscal 2017 was $28.6 million, or ($0.20) per share, and was $21.0 million, or ($0.15) per share, for the same quarter in fiscal 2016.