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Innovation Pharmaceuticals Further Engages Locust Walk to Lead Out-Licensing Negotiations for Rights to Phase 3-Ready Oral Mucositis Drug Candidate

On January 29, 2020 Innovation Pharmaceuticals Inc. (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, has further engaged Locust Walk, a leading global life sciences transaction firm serving as its strategic advisor, to lead the Company’s out-licensing negotiations for rights to oral rinse Brilacidin for the treatment of Oral Mucositis (OM) (Press release, Innovation Pharmaceuticals, JAN 29, 2020, View Source [SID1234553652]).

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The Company had previously engaged Locust Walk to assess the value of its clinical assets, which included recently an in-depth assessment of the commercial opportunity of oral rinse Brilacidin-OM—a Phase 3-ready, FDA Fast Track-designated clinical asset in late-stage development targeting a substantial untapped market in supportive cancer care.

This renewed engagement is a continuation of Innovation Pharmaceutical’s business relationship with Locust Walk toward realizing the market potential of the Company’s pipeline.

Illumina Reports Financial Results for Fourth Quarter and Fiscal Year 2019

On January 29, 2020 Illumina, Inc. (NASDAQ: ILMN) reported its financial results for the fourth quarter and fiscal year 2019 (Press release, Illumina, JAN 29, 2020, View Source [SID1234553651]).

Fourth quarter 2019 results:

•Revenue of $953 million, a 10% increase compared to $867 million in the fourth quarter of 2018
•GAAP net income attributable to Illumina stockholders for the quarter of $239 million, or $1.61 per diluted share, compared to $210 million, or $1.41 per diluted share, for the fourth quarter of 2018
•Non-GAAP net income attributable to Illumina stockholders for the quarter of $252 million, or $1.70 per diluted share, compared to $197 million, or $1.32 per diluted share, for the fourth quarter of 2018 (see the "Reconciliation Between GAAP and Non-GAAP Net Income Attributable to Illumina Stockholders" table for a reconciliation of these GAAP and non-GAAP financial measures)
•Cash flow from operations of $443 million compared to $300 million in the fourth quarter of 2018
•Free cash flow (cash flow from operations less capital expenditures) of $386 million for the quarter compared to $235 million in the fourth quarter of 2018

Gross margin in the fourth quarter of 2019 was 69.5% compared to 68.1% in the prior year period. Excluding amortization of acquired intangible assets, non-GAAP gross margin was 70.2% for the fourth quarter of 2019 compared to 69.1% in the prior year period.

Research and development (R&D) expenses for the fourth quarter of 2019 were $161 million compared to $176 million in the prior year period. Excluding restructuring charges, non-GAAP R&D expenses as a percentage of revenue were 16.8% compared to 20.3% in the prior year period.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2019 were $233 million compared to $217 million in the prior year period. Excluding amortization of acquired intangible assets, acquisition-related expenses, and restructuring charges, non-GAAP SG&A expenses as a percentage of revenue were 22.2% compared to 24.5% in the prior year period.

Depreciation and amortization expenses were $46 million and capital expenditures for free cash flow purposes were $57 million during the fourth quarter of 2019. At the close of the quarter, the company held $3.4 billion in cash, cash equivalents and short-term investments, compared to $3.5 billion as of December 30, 2018.

Fiscal year 2019 results:

•Revenue of $3,543 million, a 6% increase compared to $3,333 million in fiscal 2018
•GAAP net income attributable to Illumina stockholders of $1,002 million, or $6.74 per diluted share, compared to $826 million, or $5.56 per diluted share, in fiscal 2018
•Non-GAAP net income attributable to Illumina stockholders of $976 million, or $6.57 per diluted share, compared to $850 million, or $5.72 per diluted share, in fiscal 2018. Non-GAAP net income excludes unrealized net gains of $66 million from mark-to-market adjustments on our strategic investments, primarily from our marketable equity securities (see the "Itemized Reconciliation Between GAAP and Non-GAAP Net Income Attributable to Illumina Stockholders" table for a reconciliation of these GAAP and non-GAAP financial measures)
•Cash flow from operations of $1,051 million compared to $1,142 million in fiscal 2018

•Free cash flow (cash flow from operations less capital expenditures) of $842 million, compared to $846 million in fiscal 2018

Gross margin for fiscal 2019 was 69.6% compared to 69.0% in the prior year. Excluding amortization of acquired intangible assets, non-GAAP gross margin was 70.6% for fiscal 2019 compared to 70.1% in the prior year period.

R&D expenses for fiscal 2019 were $647 million compared to $623 million in the prior year. Excluding restructuring charges, non-GAAP R&D expenses as a percentage of revenue were 18.2% compared to 18.7% in the prior year period.

SG&A expenses for fiscal 2019 were $835 million compared to $794 million in the prior year period. Excluding amortization of acquired intangible assets, acquisition-related expenses, and restructuring charges, non-GAAP SG&A expenses as a percentage of revenue were 22.0% compared to 23.6% in the prior year period.

"Illumina shipped a record 2,400 sequencing systems in 2019, including a record number of our high-throughput NovaSeq systems and mid-throughput NextSeq systems, reflecting strong demand for research and clinical sequencing," said Francis deSouza, President and CEO. "With the launch of our most innovative system to date in the NextSeq 2000, and a growing pipeline of clinical IVD and software solutions, Illumina continues to improve the accessibility of sequencing. Almost 17 years after the first human genome was sequenced, we believe that this is the decade that genomics becomes available to cancer and genetic disease patients on a mass scale and integrates into standard of care."

Updates since our last earnings release:

•Announced the NextSeq 1000 and NextSeq 2000 Sequencing Systems offering breakthrough system design, chemistry innovations and on-instrument integrated informatics for rapid secondary analysis
•Shared plans for additional product launches including TruSight Software Suite to enable sample-to-report for genetic disease and NovaSeq Dx to fulfill the growing interest in a Dx platform for deeper sequencing at higher throughput, and TruSight NIPT
•Partnered with Roche to broaden the adoption of distributable next-generation sequencing-based (NGS) testing in oncology
•Partnered with Genomics England to provide sequencing services to the United Kingdom’s National Health Service to sequence 300,000 to 500,000 whole genomes by 2025
•Mutually terminated the merger agreement with Pacific Biosciences
•Filed patent infringement suits against BGI in Sweden and the United Kingdom
•Repurchased $63 million of outstanding common stock in the fourth quarter of 2019 under the previously announced share repurchase program, which had a remaining balance of approximately $226 million as of December 29, 2019

Financial outlook and guidance

The non-GAAP financial guidance discussed below reflects certain pro forma adjustments to assist in analyzing and assessing our core operational performance. Please see our Reconciliation of Non-GAAP Financial Guidance included in this release for a reconciliation of the GAAP and non-GAAP financial measures.

For fiscal 2020, the company expects year over year revenue growth in the range of 9% to 11%, and expects GAAP earnings per diluted share of $6.45 to $6.65 and non-GAAP earnings per diluted share of $6.80 to $7.00. GAAP guidance does not include any potential impact resulting from the termination of our merger agreement with Pacific Biosciences on January 2, 2020.

Quarterly conference call information

The conference call will begin at 2:00 pm Pacific Time (5:00 pm Eastern Time) on Wednesday, January 29, 2020. Interested parties may access the live teleconference through the Investor Info section of Illumina’s website under the "Company" tab at www.illumina.com. Alternatively, individuals can access the call by dialing 1 (866) 211-4597 or 1 (647) 689-6853 outside North America, both with conference ID 2966099.

A replay of the conference call will be posted on Illumina’s website after the event and will be available for at least 30 days following.

Independent Researchers Find Genprex’s TUSC2 May Be a Novel Target and Biomarker for Thyroid Cancer Therapy

On January 29, 2020 Genprex, Inc.("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company utilizing a unique, non-viral proprietary platform designed to deliver tumor suppressor genes to cancer cells, reported that independent researchers reported in a recent study that TUSC2, a tumor suppressor gene and the active agent in Genprex’s Oncoprex immunogene therapy, is a potential target and biomarker for thyroid carcinoma (Press release, Genprex, JAN 29, 2020, View Source [SID1234553649]). Genprex has no affiliation with these researchers.

Published in the International Journal of Molecular Sciences, the study reports that TUSC2 overexpression decreased thyroid cancer proliferation, migration and invasion. Cell proliferation, migration and invasion ability are essential steps in tumor metastasis. TUSC2 forced expression reduced thyroid cancer cell proliferation and could represent an important tool to arrest cancer cell proliferation, while TUSC2 restoration decreased the migration and invasion of thyroid cancer cell lines.

The study also found that TUSC2 increased sensitivity to apoptosis by increasing the SMAC/DIABLO and Cytochrome C proteins, which play major roles in apoptosis. TUSC2 forced expression increased these protein levels, and, inversely, the silencing of TUSC2 induced resistance to apoptosis.

Based on the results of the study, researchers concluded that TUSC2 is negatively associated with thyroid cancer aggressiveness and, thus could be a novel target and biomarker for thyroid cancer therapy.

"We continue to be encouraged by data resulting from studies conducted at multiple research institutions suggesting that TUSC2 may be an effective treatment for many types of cancer, now including thyroid cancer," said Rodney Varner, Genprex’s Chairman and Chief Executive Officer.

The authors further state that thyroid carcinoma is the most common endocrine cancer and includes many different forms. Anaplastic thyroid carcinoma (ATC) is the rarest but most lethal subtype. ATC patients usually present a rapidly enlarging neck mass, a high rate of distant metastases and approximately 95 percent mortality at six months. Conversely, papillary thyroid carcinoma (PTC), the most common type of thyroid cancer, is generally characterized by good outcomes, as it is highly curable by surgery and radioiodine therapy. However, some PTC patients have an aggressive disease and can develop distant metastasis.

The same researchers have previously reported that TUSC2 is downregulated in almost all ATC samples and in the vast majority of PTC samples, suggesting TUSC2’s important role in thyroid cancer progression. In 2019, an estimated 50,000 patients in the U.S. were diagnosed with thyroid cancer.Genprex is conducting clinical and pre-clinical research to evaluate the effectiveness of TUSC2 when combined with targeted therapies and immunotherapies for non-small cell lung cancer. Existing pre-clinical data also suggest that TUSC2 may be effective against breast cancer, small cell lung cancer, glioblastoma, head and neck cancer, kidney cancer, and bone and soft tissue sarcomas. This new independent study raises the possibility that TUSC2 may also be used to treat thyroid cancer.

New inhibitor shows promise against metastatic prostate cancer

On January 29, 2020 Stony Brook University reported When prostate cancer spreads it is often a deadly disease, but now a Stony Brook University-led research team believes a new approach that inhibits a specific fatty acid binding protein (FABP) may be the key to halting disease progression (Press release, Stony Brook University, JAN 29, 2020, View Source [SID1234553648]). Their research results on FABP5 inhibitors as promising therapeutic agents against metastatic prostate cancer led to a new five-year grant from the National Cancer Institute (NCI) totaling $4.2 million to advance the research to 2025.

Lead investigator Iwao Ojima, PhD, Distinguished Professor of Chemistry and Director of the Institute of Chemical Biology and Drug Discovery (ICB&DD), along with colleagues at Stony Brook and Cold Spring Harbor Laboratory, in collaboration with Artelo Biosciences, are investigating FABPs in the treatment of inflammation, pain and against certain cancers, as drug targets themselves or in combination with current chemotherapy treatments.

Dr. Ojima and Martin Kaczocha, PhD, (ICB&DD) received a seed grant called a "Fusion Award" from the Renaissance School of Medicine at Stony Brook University to conduct a preliminary study of FABP5 and its inhibitors as potential prostate cancer therapeutic target and agents. Their original work and collaboration with Lloyd Trotman, PhD, a Professor at Cold Spring Harbor Laboratory, led to a paper in The Prostate that showed novel FABP5 inhibitors developed by the ICB&DD team exhibited significant cytotoxicity against highly drug-resistant metastatic prostate cancer cells. FABP5 also enhanced the antitumor effects of taxene drugs in animal models. These promising findings led to the acquisition of the NCI grant.

"This grant is a tremendous example of how collaborative research involving Stony Brook University, Cold Spring Harbor Laboratory and industry have pushed forward a bioscience concept initially supported by seed money from our school to a level where the National Cancer Institute sees its potential as a new and better treatment for metastatic prostate cancer," said Kenneth Kaushansky, MD, Vice President for Health Sciences and Dean of the Renaissance School of Medicine at Stony Brook University.

Under the grant, the team will leverage structure-based drug design and chemical synthesis approaches to identify best FABP5 inhibitors for potency and selectivity, employ a robust in vitro inhibitor testing platform, and access the efficacy of candidate inhibitors in mouse models. They will also investigate FABP5 inhibitors when used as monotherapies, as well as in combination with FDA approved drugs.

"This award highlights the outstanding research capabilities and innovative drug designs that have been created at the ICB & DD under Professor Ojima’s leadership," said Richard J. Reeder, PhD, Vice President for Research at Stony Brook University. "The collaborative work also demonstrates how such partnerships benefit Stony Brook’s growing focus on cancer research."

"We expect to continue the momentum of breakthroughs with our cancer research enterprise," said Yusuf Hannun, MD, Director of the Stony Brook University Cancer Center. "This work is at the frontier of driving novel cancer therapeutics, a major goal for the Stony Brook Cancer Center. This expansion of the research by Dr. Ojima and his colleagues with new federal funding is the type of progressive work we hope sets the bar toward our NCI cancer center designation and impacts patient care in the near future."

Taxanes are used to treat metastatic prostate cancer. While they can be effective, tumors often build up resistance to these drugs. Patients also often experience adverse effects to these drugs, which results in termination of treatment. The emergence of FABP5 inhibitors could be a potential solution to treating advanced disease more effectively and minimize adverse effects.

"In our research, neither docetaxel or cabazitaxel alone was able to eradicate prostate cancer cells in vitro, while combinations of taxanes with FABP5 inhibitors resulted in complete prostate cell death with synergism at very low concentrations of taxanes," said Dr. Ojima.

"While the FABP5 inhibitors produced limited or no cell cytotoxicity in noncancerous cells, they achieved near-complete cell death in the prostate cancer cell lines used in our study, which suggests the FABP5 inhibitors would have much fewer side-effects compared with the current taxane/steroid-based therapy," added Martin Kaczocha, PhD, Assistant Professor, Department of Anesthesiology and co-leader of the collaborative team.

To develop the FABP5 inhibitors for testing against prostate cancer, Dr. Ojima and Dr. Kaczocha are collaborating with Robert Rizzo, PhD, Professor, Department of Applied Mathematics and Statistics, and Trotman, who has developed a unique and highly promising mouse model for metastatic prostate cancer.

They will also collaborate with scientists at Artelo to develop leading FABP inhibitors against prostate cancer.

In 2018, Artelo entered into an exclusive license with the Research Foundation for the State University of New York to the intellectual property of FABP inhibitors for the modulation of the endocannabinoid system for the treatment of pain, inflammation and cancer.

Lilly Receives FDA Priority Review for the Selpercatinib New Drug Application

On January 29, 2020 Eli Lilly and Company (NYSE: LLY) reported that the U.S. Food and Drug Administration (FDA) has granted priority review for the New Drug Application (NDA) for selpercatinib (LOXO-292), for the treatment of patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC), RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer (Press release, Eli Lilly, JAN 29, 2020, View Source [SID1234553646]). The NDA is based on data from the LIBRETTO-001 Phase 1/2 trial in RET-altered lung and thyroid cancers. The FDA has filed the NDA and set a Prescription Drug User Fee Act (PDUFA) date in the third quarter of this year.

"We are pleased the FDA granted priority review status for the NDA for selpercatinib. This represents an important step toward providing a new precision therapy for people living with certain RET-driven cancers," said Anne White, president of Lilly Oncology. "Combined with the recent opening of our two Phase 3 selpercatinib clinical trials, we are thrilled with the positive momentum of this program and hope to deliver a practice-changing treatment to patients with RET-driven cancers as soon as possible."

In previous regulatory actions, based on early data from the Phase 1/2 LIBRETTO-001 trial, the FDA granted selpercatinib Breakthrough Therapy Designation for treatment in people with:

Metastatic RET-fusion-positive NSCLC who require systemic therapy and have progressed following platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy;
RET-mutant MTC who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment option; and
Advanced RET-fusion-positive thyroid cancer who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment options.
In 2019, selpercatinib received orphan drug designation for the treatment of RET fusion-positive NSCLC and for the treatment of RET fusion-positive and RET-mutant thyroid cancers including poorly differentiated thyroid cancer, undifferentiated or anaplastic thyroid cancer, MTC and locally advanced or metastatic follicular or papillary thyroid cancer.

In December of 2019, Lilly opened two selpercatinib Phase 3 trials: LIBRETTO-431 for patients with treatment-naïve RET fusion-positive NSCLC, and LIBRETTO-531 for patients with treatment-naïve RET-mutant MTC. Each trial will enroll 400 patients.

About RET-Driven Cancers
Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2 percent of NSCLC, 10-20 percent of papillary and other thyroid cancers and a subset of other cancers. Activating RET point mutations account for approximately 60 percent of MTC. RET fusion cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET.

About LIBRETTO-001
The LIBRETTO-001 Phase 1/2 trial was the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor. The trial included a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). The Phase 2 portion of the trial had a primary endpoint of objective response rate (ORR) and secondary endpoints of duration of response (DoR), progression free survival (PFS) and safety. Results from the NSCLC population were presented at the 2019 IASLC World Congress on Lung Cancer (WCLC), while results from the thyroid populations were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress.

About LIBRETTO-431
LIBRETTO-431 is a randomized Phase 3 clinical trial of patients with treatment-naïve RET fusion-positive NSCLC. The trial will enroll 400 patients with advanced or metastatic RET fusion-positive NSCLC who have received no prior systemic therapy for metastatic disease. Enrolled trial participants will be randomized 1:1 to receive either selpercatinib or platinum-based (carboplatin or cisplatin) and pemetrexed therapy with or without pembrolizumab as initial treatment of their advanced or metastatic RET fusion-positive NSCLC. RET fusions may be identified using local testing. This trial’s efficacy endpoints are PFS, overall survival (OS), ORR, DoR, and intracranial ORR. For patients randomized to the control arm, crossover is allowed at progression.

About LIBRETTO-531
LIBRETTO-531 is a randomized Phase 3 clinical trial of patients with treatment-naïve RET-mutant MTC. The trial will enroll 400 patients with advanced or metastatic RET-mutant MTC who have received no prior systemic therapy for metastatic disease. Enrolled trial participants will be randomized 2:1 to receive either selpercatinib or physician’s choice of cabozantinib or vandetanib as initial treatment of their advanced or metastatic RET-mutant MTC. RET mutations may be identified using local testing. This trial’s efficacy endpoints are PFS, treatment failure-free survival (TFFS), OS, ORR, and DoR. For patients randomized to the control arm, crossover is allowed at progression.

About Selpercatinib (LOXO-292)
Selpercatinib (LOXO-292) is a highly selective and potent, oral investigational new medicine in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions and mutations occur across multiple tumor types with varying frequency. Selpercatinib was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms.