On October 1, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis) for the treatment of various cancers including prostate, colorectal and leukemia, reported the presentation of its Phase 1b/2 trial evaluating onvansertib in combination with FOLFIRI and Avastin (bevacizumab) in patients with KRAS-mutated metastatic Colorectal Cancer (mCRC) (Press release, Trovagene, OCT 1, 2019, View Source [SID1234539987]).

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The trial overview, featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress showed the supportive preclinical data underlying the scientific rationale for the trial, as well as the trial design and primary safety and efficacy endpoints. In addition, early biomarker data demonstrates proof-of-concept that patient response can be monitored by a non-invasive blood test to quantitate the KRAS mutation burden within one week following initial dosing with onvansertib.

"Although early in the trial, the potential to bring a much-needed new treatment option to patients with KRAS-mutated mCRC with the combination of these drugs is promising," said Heinz-Josef Lenz, MD, FACP, Professor of Medicine, J. Terrence Lanni Chair in Gastrointestinal Cancer Research, Co-Director, USC Center for Molecular Pathway and Drug Discovery. "As of September 1, 2019, four patients have been treated and one has successfully completed their first cycle of treatment. We believe onvansertib may provide clinical benefit for patients who are faced with a poor prognosis and for whom therapeutic options are limited."

Colorectal cancer (CRC) is the second leading cause of cancer mortality in the U.S. Despite significant progress in the treatment of mCRC, the majority of patients with metastatic disease succumb to the disease. Therefore, improving the effectiveness of treatments is critical in changing the outcomes for this patient population. Approximately 50% of mCRC has the KRAS mutation. The efficacy of second-line therapy in terms of survival prolongation and response remains very limited, especially in this population, where there is only a 5% response rate.

Presentation Highlights

Metastatic Colorectal Cancer:

Tumor biomarkers drive therapy decisions for 1st and 2nd line mCRC therapy
~50% of mCRC is KRAS-mutated
Standard second-line therapy in KRAS mutated patients is chemotherapy (FOLFOX/FOLFIRI) + Bevacizumab
Second-line therapies have only a ~5% response rate in mCRC
Primary Endpoints:

Phase 1b: Assess the safety and preliminary efficacy of onvansertib in combination with FOLFIRI and bevacizumab and identify the recommended Phase 2 dose (RP2D)
Phase 2: Evaluate the efficacy of onvansertib in combination with FOLFIRI and bevacizumab based on objective response rate (ORR) in patients who receive at least 1 cycle (2 courses) of treatment
About the Phase 1b/2 Clinical Trial of Onvansertib in mCRC
The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, will evaluate the safety and efficacy of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab). Up to 44 patients, with a confirmed KRAS mutation, metastatic and unresectable disease, who have failed/intolerant of treatment with FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab), will be enrolled. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.

About Onvansertib
Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.

Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.

Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.

On October 1, 2019 Audentes Therapeutics, Inc. (Nasdaq: BOLD), a leading AAV-based genetic medicines company focused on developing and commercializing innovative products for serious rare neuromuscular diseases, reported that Natalie Holles, President and Chief Operating Officer, will participate in the following investor conferences in October (Press release, Audentes Therapeutics, OCT 1, 2019, View Source [SID1234539986]):

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Chardan 3rd Annual Genetic Medicines Conference
Fireside Chat: Monday, October 7, 2019, at 10:30am ET
New York, New York

Jefferies Gene Therapy/Editing Summit
Fireside Chat: Tuesday, October 8, 2019, at 9:10am ET
Panel: "Manufacturing, Dose, and Durability in Gene Therapy," Tuesday, October 8, 2019, at 10:20am ET
New York, New York

To access live webcasts of the fireside chats, please visit the Events & Presentations page within the Investors + Media section of the Audentes website. Following each conference, a replay of the live webcast will be available on the Audentes website for approximately 30 days. There is no webcast available for the Manufacturing, Dose, and Durability in Gene Therapy panel at the Jefferies Gene Therapy/Editing Summit.

On October 1, 2019 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported that Carmen Bozic, M.D., has been appointed as the company’s Executive Vice President, Global Medicines Development and Medical Affairs. Dr. Bozic will assume the additional role of Chief Medical Officer on April 1, 2020 when Reshma Kewalramani, M.D., the company’s current Chief Medical Officer, becomes President and Chief Executive Officer of Vertex (Press release, Vertex Pharmaceuticals, OCT 1, 2019, View Source [SID1234539985]). Dr. Bozic has served as Senior Vice President and Head of Global Clinical Development since May of this year.

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Vertex also announced the appointment of Nia Tatsis, Ph.D., currently Vertex’s Senior Vice President, Global Regulatory Affairs, as Senior Vice President, Chief Regulatory Officer, effective immediately.

"The addition of Carmen and Nia to Vertex’s executive team further strengthens our leadership ranks as we work towards completing our CF journey and bringing new therapies into the clinic in a variety of new disease areas," said Jeffrey Leiden, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex.

Dr. Bozic received her M.D. and completed her residency in Internal medicine at McGill University in Montreal, Canada, and then completed a fellowship in Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital in Boston. Since joining Vertex, she has been leading Clinical Development of the company’s cystic fibrosis and alpha-1 antitrypsin deficiency programs, as well as leading Clinical Operations across the pipeline, among other areas. Prior to joining Vertex, Dr. Bozic spent more than 20 years at Biogen, including as Senior Vice President, Global Development. During her tenure at Biogen, she led multiple functions, including Global Clinical Development, Safety, Preclinical Safety, Regulatory, Clinical Operations and Biometrics.

"I am thrilled to take on the leadership of Vertex’s talented Global Medicines Development and Medical Affairs team at such an exciting time for the company," said Dr. Bozic. "Vertex advanced its cystic fibrosis portfolio through the clinic with unprecedented speed and purpose, and now has seven potential therapies in the clinic with the opportunity to transform the treatment of patients with other serious diseases."

Dr. Tatsis received her Ph.D. in Cell and Molecular Biology from the University of Vermont and holds a B.S. in Biology from Temple University. She was a Post-Doctoral Fellow at the Wistar Institute and has held positions of increasing responsibility at pharmaceutical companies including Sanofi, Pfizer, and Wyeth prior to joining Vertex in 2017. Most recently, she was Vice President, Head of Global Regulatory Affairs of the Sanofi Genzyme Business Unit focused on Immunology, Rare Diseases, Multiple Sclerosis and Oncology.

"Vertex is a company that is relentlessly focused on scientific innovation and bringing transformative advances in medicine to patients with serious diseases," said Dr. Tatsis. "We have an outstanding regulatory team and I am honored to lead them in this role as we work to deliver on our mission and strategy."

On October 1, 2019 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that members of its senior management team are scheduled to make the following presentations in October (Press release, CRISPR Therapeutics, OCT 1, 2019, View Source [SID1234539984]):

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Chardan’s 3rd Annual Genetic Medicines Conference
Date: Tuesday, October 8, 2019
Presentation: 10:30 a.m. ET
Location: New York, NY

Jefferies Gene Therapy/Editing Summit
Date: Tuesday, October 8, 2019
Panel Discussion: 1:10 p.m. ET
Location: New York, NY

A live webcast of the events will be available on the "Events & Presentations" page in the Investors section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 14 days following the presentation.

On October 1, 2019, Scilex Pharmaceuticals Inc. ("Scilex"), an indirect subsidiary of Sorrento Therapeutics, Inc. (the "Company"), the Company, U.S. Bank National Association, as trustee (the "Trustee") and collateral agent (the "Agent"), and the beneficial owners of the senior secured notes due 2026 (the "Securities") and the holders of such Securities listed on the signature pages thereto (the "Holders") entered into an omnibus amendment (the "Amendment") to: (i) that certain Indenture, dated September 7, 2018, by and among Scilex, the Company, the Trustee and the Agent (the "Indenture"), and (ii) that certain Irrevocable Standby Letter of Credit issued by the Company to Scilex in the maximum aggregate amount of $35,000,000, with a date of issuance of September 7, 2018 (the "Letter of Credit") (Filing, 8-K, Sorrento Therapeutics, OCT 1, 2019, View Source [SID1234539981]).

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Pursuant to the Indenture, the Company agreed to irrevocably and unconditionally guarantee, on a senior unsecured basis, the punctual performance and payment when due of all obligations of Scilex under the Indenture. A portion of the proceeds from the offering of the Securities were used to fund a segregated reserve account pursuant to the terms of the Indenture. Pursuant to the Indenture, funds in the reserve account were to be released to Scilex upon receipt by the Trustee of an officer’s certificate under the Indenture from Scilex confirming receipt of a marketing approval letter from the United States Food and Drug Administration with respect to ZTlido (lidocaine topical system) 5.4% or a similar product with a concentration of not less than 5% on or prior to July 1, 2023.

Under the terms of the Amendment, among other things, the defined term "Change of Control" was revised to include, in addition to certain events described in the Indenture, (i) prior to the consummation of an initial public offering by Scilex Holding Company, the parent company of Scilex ("Scilex Holding") (the "Scilex Holding IPO"), the Company ceasing to own, directly or indirectly, a majority of the total voting and economic power of the issued and outstanding capital stock that is entitled to vote in the election of the Board of Directors (the "Voting Stock") of Scilex, (ii) at any time following the consummation of the Scilex Holding IPO, Scilex becoming aware of the acquisition by any person or group acquiring, in a single or in a related series of transactions, by way of merger, amalgamation, consolidation or other business combination or purchase of beneficial ownership of a majority of the total voting power of the issued and outstanding Voting Stock of Scilex or Scilex Holding, and (iii) Scilex Holding failing at any time to own 100% of the capital stock of Scilex. The Amendment also provides that Scilex will agree not to engage in or enter into any business other than the research, development, manufacture, sale, distribution, marketing, detailing, promotion, selling and securing of reimbursement of ZTlido (lidocaine topical system) 1.8% and any future iterations, improvements or modifications thereof (the "Product"), on a worldwide basis (exclusive of Japan), and activities that are necessary for, or otherwise relevant to, the same, subject to certain exceptions. The Amendment further provides that, if Scilex Holding fails to contribute $25.0 million of the proceeds of any Scilex Holding IPO to Scilex within three business days following the closing of the issuance and sale of Scilex Holding’s capital stock in the Scilex Holding IPO, such failure shall constitute an "Event of Default" under the Indenture.

In connection with the Amendment, Scilex agreed to repurchase, from each holder of Securities, Securities in a principal amount equal to (i) $20.0 million multiplied by (ii) a fraction the numerator of which will be the then outstanding principal amount of the Securities held by such holder and the denominator of which will be the then outstanding principal amount of all of the outstanding Securities, at a purchase price in cash equal to 100% of the principal amount thereof (such repurchase, the "Effective Date Repurchase"). Pursuant to the Amendment, the Holders agreed to release the funds in the reserve account for the purpose of consummating the Effective Date Repurchase and the remaining funds in the reserve account after the consummation of the Effective Date Repurchase will be released to Scilex by the Trustee and Agent.

The Amendment also modifies the Letter of Credit to provide that one of the conditions that will terminate the Letter of Credit will be the consummation of a Scilex Holding IPO that satisfies certain valuation thresholds.

The Amendment will be effective upon the satisfaction of certain terms and conditions, including the consummation of the Effective Date Repurchase. The Amendment will terminate if the Amendment does not become effective on or prior to October 1, 2020.

The Amendment includes representations and warranties of the parties, indemnification obligations and other terms and conditions customary in agreements of this type. The representations, warranties and covenants contained in the Amendment were made only for purposes of such agreement and as of specific dates, were solely for the benefit of the parties to the Amendment, and may be subject to limitations agreed upon by the contracting parties. Accordingly, the Amendment is incorporated herein by reference only to provide investors with information regarding the terms of the Amendment, and not to provide investors with any other factual information regarding the Company or its business, and should be read in conjunction with the disclosures in the Company’s periodic reports and other filings with the Securities and Exchange Commission.

The foregoing description of the Amendment does not purport to be complete and is qualified in its entirety by reference to the copy of the Amendment filed herewith as Exhibit 10.1. Certain terms of the Amendment have been omitted from this Current Report on Form 8-K and have been omitted from the version of the Amendment filed as Exhibit 10.1 to this Current Report on Form 8-K pursuant to Item 601(b)(10) of Regulation S-K because such terms are both (i) not material and (ii) would likely cause competitive harm to the Company if publicly disclosed.