Entry into a Material Definitive Agreement

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]).

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!

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.

NAVROGEN ENTERS INTO CRADA WITH THE U.S. NATIONAL CANCER INSTITUTE TO DEVELOP AGENTS TO OVERCOME TUMOR-MEDIATED IMMUNO-SUPPRESSION

On October 1, 2019 Navrogen, Inc. reported that it has entered into a Cooperative Research and Development Agreement (CRADA) with researchers at the U.S. National Cancer Institute (NCI) (Press release, Navrogen, OCT 1, 2019, View Source [SID1234539980]). The CRADA is focused on advancing antibody-based experimental medicines to targets associated with tumor-mediated immuno-suppression. Researchers at the NCI, led by Dr. Ira Pastan, NIH Distinguished Investigator and co-chief of NCI Center for Cancer Research’s Laboratory of Molecular Biology, have developed compounds that can uniquely target molecules on inflammatory cells and unlock their immuno-suppressed state within the tumor microenvironment. Under this CRADA, Navrogen is responsible for validating and advancing the preclinical development of these compounds towards clinical trials.

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 have been fortunate to work with some of the leading researchers focused on immune-mediated anti-cancer therapies" stated Luigi Grasso, Ph.D., Chief Scientific Officer of Navrogen. The agents focused within this program have been previously shown in early clinical studies to unlock the immune response within tumors, and we hope to leverage their use with new approaches in tumors that exhibit immune suppression of this pathway."

The CRADA program complements Navrogen’s focus on developing novel agents that can overcome humoral immune suppression which is mediated by tumor-produced humoral immuno-oncology (HIO) factors.

Jounce Therapeutics to Present Two Posters from the JTX-4014 and Vopratelimab Programs at the Society for Immunotherapy of Cancer’s (SITC) 34th Annual Meeting

On October 1, 2019 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that safety and efficacy data for JTX-4014 and a clinical trial in progress description of the vopratelimab Phase 2 EMERGE study will be presented in two poster sessions at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting, being held November 6-10, 2019 in National Harbor, Maryland (Press release, Jounce Therapeutics, OCT 1, 2019, View Source [SID1234539979]).

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!

Poster Details:

Poster Title: Phase 1 First in Human Study of Programmed Cell Death Receptor-1(PD-1) Inhibitor Monoclonal Antibody (mAb) JTX-4014 in Adult Subjects with Advanced Refractory Solid Tumor Malignancies (Safety, efficacy and recommended Phase 2 dose will be presented)
Author: Kyriakos P. Papadopoulos, M.D. Co-Director of Clinical Research, START, San Antonio, Texas
Poster Session Number: P439
Location: Poster Hall (Prince George AB)
Date and Time: Friday, November 8, 2019; 7:00am–8pm ET

Poster Title: Phase 2 Multicenter Trial of ICOS Agonist Vopratelimab and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor Experienced Adult Subjects with Non-Small Cell Lung Cancer or Urothelial Cancer (EMERGE) (This is a trial in progress poster only)
Author: Russell Pachynski M.D., Assistant Professor of Medicine, Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri
Poster Session Number: P438
Location: Poster Hall (Prince George AB)
Date and Time: Saturday, November 9, 2019; 7:00am–8:30pm ET

About JTX-4014
JTX-4014 is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Jounce is developing JTX-4014 for potential use in combination with its pipeline of future product candidates. Jounce completed enrollment in the Phase 1 clinical trial of JTX-4014.

About Vopratelimab
Jounce’s lead product candidate, vopratelimab (formerly JTX-2011), is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab was previously assessed in the Phase 1/2 ICONIC trial and was found to be safe and well-tolerated, alone and in combination with each of the anti-PD-1 antibodies nivolumab and pembrolizumab, and ipilimumab, an antibody that binds to CTLA-4. In June 2018, Jounce reported Response Evaluation Criteria in Solid Tumors (RECIST) responses and other tumor reductions as determined by investigator assessment that were associated with an ICOS pharmacodynamic biomarker, ICOS hi CD4 T cells. In April 2019, Jounce reported data on patients in the ICONIC trial with the emergence of ICOS hi CD4 T cells who had improved progression free survival and overall survival compared to patients with ICOS lo CD4 T cells; this was based on an analysis of a subgroup of patients with multiple solid tumor types including PD-1 inhibitor naive and PD-1 inhibitor experienced patients. Vopratelimab is currently being assessed in the Phase 2 EMERGE clinical trial in combination with ipilimumab in patients with non-small cell lung cancer or urothelial cancer who have progressed on or after PD-1/PD-L1 inhibitor therapies.

Cellectis and Lonza Enter cGMP Manufacturing Service Agreement for Cellectis’ Allogeneic UCART Product Candidates

On October 1, 2019 Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on allogeneic gene-edited CAR T-cells (UCART), and Lonza (SWX: LONN), reported that the companies have entered into a manufacturing service agreement covering clinical manufacturing of Cellectis’ allogeneic UCART product candidates targeting hematological malignancies (Press release, Cellectis, OCT 1, 2019, View Source [SID1234539976]). Lonza is in charge of implementing Cellectis’ manufacturing processes as per current Good Manufacturing Practices (cGMP) in a way that meets the highest quality and safety standards outlined by the FDA. The manufacturing will take place at Lonza’s GMP facility in Geleen, Netherlands.

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!

William Monteith, Executive Vice President, Technical Operations, Cellectis:

"Working with Lonza, a world-class solutions provider with deep experience in the biotech and pharma industries increases our global capabilities and allows Cellectis to further strengthen its manufacturing expertise. This agreement not only bolsters our product supply for clinical trials, but it ensures that we are producing first-rate product candidates so that we can potentially deliver new hope to patients living with certain blood cancers."

Alberto Santagostino, Senior Vice President, Head of Cell & Gene Technologies, Lonza:

"Early-stage innovators with great science, like Cellectis, can find an ideal partner in Lonza as we bring great value in technical development and manufacturing, industrializing processes and enabling the journey to commercialization. We will draw on the experience at our cell and gene therapy center of excellence in the Netherlands, ideally equipped to support Cellectis in bringing their promising pipeline of allogeneic CAR-T therapies to people around the world in need of life-saving products."

Lonza’s supply will complement Cellectis’ ongoing collaboration and in-house manufacturing sites, IMPACT and SMART, which are currently under construction.

The manufacturing process of Cellectis’ allogeneic CAR T-cell product line, Universal CARTs or UCARTs, yields frozen, off-the-shelf, non-alloreactive engineered CAR T-cells. UCARTs are intended to be readily available CAR T-cells for a large patient population. Their production is industrialized with defined pharmaceutical release criteria.

Ziopharm Oncology Announces FDA Clearance of IND for Rapid Personalized Manufacture of CD19-specific CAR-T

On October 1, 2019 Ziopharm Oncology, Inc. ("Ziopharm" or "the Company") (Nasdaq:ZIOP), reported that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug application (IND) for a phase 1 clinical trial to evaluate CD19-specific CAR-T, produced using a process termed rapid personalized manufacture (RPM), as an investigational treatment for patients with relapsed CD19+ leukemias and lymphomas (Press release, Ziopharm, OCT 1, 2019, View Source [SID1234539974]).

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!

The IND clearance builds upon the Company’s experience with two prior generations of immunotherapy trials using the Sleeping Beauty platform, which it believes is the most clinically-advanced non-viral approach to the genetic modification of T cells. With this third-generation trial, DNA from the Sleeping Beauty system is stably inserted into the genome of resting T cells to co-express a chimeric antigen receptor (CAR), membrane-bound IL-15 (mbIL15) and a safety switch, which is designed to reduce cost, simplify production, and preserve the therapeutic potential of the T cells.

"There are currently no effective treatment options for patients who relapse soon after allogeneic bone marrow transplantation (BMT), as evidenced by their low rate of remission and poor long-term survival. This trial expands the range of patients with CD19-expressing malignancies that can be treated using the RPM technology," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of Ziopharm. "We believe RPM is the fastest approach to manufacturing and releasing CD19-specific CAR-T, as T cells from the blood stream are genetically reprogramed with the Sleeping Beauty system and then infused within two days of gene transfer. Existing commercial T-cell products using viral-based manufacturing are costly, time consuming to make and complex to deliver. We are now positioned to not only address those issues, but also to treat a patient group that remains underserved by existing therapies."

Up to 24 patients will be enrolled to evaluate infusion of donor-derived RPM CAR-T in patients with CD19+ leukemias and lymphomas who have relapsed after allogeneic BMT. This study will be conducted at The University of Texas MD Anderson Cancer Center under an investigator-initiated trial expected to begin later this year.

Research reveals three-year survival for adults with CD19+ acute lymphoblastic leukemia after allogeneic BMT ranges from 30% to 65%.1 For patients with other CD19+ cancers, allogeneic BMT can provide a three-year survival rates between 30% to 75%.1 Few patients experience a durable remission who relapse in the months following allogeneic BMT, regardless of the treatment modality, with some having a median survival of only 2 to 3 months.2