On October 31, 2019,Tocagen Inc. (the "Company") reported that it entered into an amendment to its Loan and Security Agreement (the "Second Amendment") with Oxford Finance LLC, as Collateral Agent (the "Agent") and Silicon Valley Bank (the "Lenders"), dated May 18, 2018, as amended, pursuant to which the Lenders lent the Company $26.5 million in term loans (the "Term Loans") (Filing, 8-K, Tocagen, OCT 31, 2019, View Source [SID1234550181]).

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Pursuant to the terms of the Second Amendment, the Lenders (i) agree to waive any prepayment fee otherwise applicable to a prepayment of the Term Loans in connection with any prepayment of the Term Loans on or after the date of the Second Amendment, (ii) consent to the sale of certain specified equipment, so long as the net cash proceeds from the sale of such assets are used to repay the Term Loans, and (iii) release their lien on the specified equipment upon the closing of any such sale.

The Company also has agreed to grant the Agent a security interest in the Company’s intellectual property as additional collateral to secure the Term Loans, pursuant to the Second Amendment for ratable benefit of the Lenders.

In connection with the Second Amendment, the Company made a prepayment of $23.3 million, which amount was used to prepay (A) a portion equal to $21.5 million of the outstanding principal of the Term Loans plus all accrued and unpaid interest thereon through the prepayment date, (B) pro rated portion of the final payment with respect to the portion of such Term Loans being prepaid, plus (C) all outstanding Lenders’ expenses as of the Second Amendment date.

After the date of the Second Amendment and prior to May 31, 2020, the Company may pay down portions of the Term Loans in amounts equal to not less than $500,000,which amount shall be used to prepay all or a portion of the outstanding principal of the Term Loans plus all accrued and unpaid interest thereon through the prepayment date, prorated portion of the final payment due with respect to the portion of such Term Loans being prepaid, plus all outstanding Lenders’ Expenses as of the prepayment date.

The foregoing is only a summary of the material terms of the Second Amendment, does not purport to be complete and is qualified in its entirety by reference to the full text of the Second Amendment, which will be filed as an exhibit to our Quarterly Report on Form 10-Q for the quarter ended September 30, 2019.

On October 31, 2019 The New England Journal of Medicine published detailed results from the Phase 3 ADMIRAL trial, which found that Astellas Pharma Inc.’s (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D. "Astellas") XOSPATA (gilteritinib) demonstrated significantly longer Overall Survival (OS) than salvage chemotherapy in adult patients with relapsed (disease that has returned) or refractory (resistant to treatment) Acute Myeloid Leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation (Press release, Astellas, OCT 31, 2019, View Source [SID1234550086]). Common adverse events from the study of grade 3 or higher in the gilteritinib group were febrile neutropenia (45.9%), anemia (40.7%), and thrombocytopenia (22.8%).1 The results appear in the October 31 print edition of the Journal and are currently available online.1

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"These data show that in a very high-risk leukemia population, single agent FLT3-targeted therapy leads to superior clinical outcomes compared to salvage chemotherapy," said Alexander Perl, MD, associate professor of Hematology-Oncology in the Abramson Cancer Center at the University of Pennsylvania, and the trial’s principal investigator. "This is an important result for patients who previously had quite limited treatment options."

"The detailed findings from our Phase 3 ADMIRAL trial further validate that XOSPATA is a significant addition to the treatments available for people with FLT3 mutation positive relapsed or refractory AML," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas. "We are especially pleased to see the results published in the New England Journal of Medicine, which is widely regarded as one of the most prestigious scientific medical journals."

The U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) in May of 2019 to update the U.S. product labeling for XOSPATA to include final analysis OS data from the ADMIRAL trial.2

XOSPATA was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and commercialize XOSPATA.

XOSPATA was approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations and launched as XOSPATA 40 mg Tablets in 2018.3 In October 2019, the European Commission (EC) approved XOSPATA as a monotherapy for the treatment of adult patients with relapsed or refractory AML with a FLT3 mutation.4 XOSPATA has been designated an orphan medicinal product and also received accelerated assessment from the European Medicines Agency (EMA) earlier this year, which reduced the timeframe for approval.5,6,7 Astellas is currently investigating gilteritinib in various FLT3 mutation-positive AML patient populations through several clinical trials. Visit View Source to learn more about ongoing gilteritinib clinical trials.

On October 31, 2019 Oncolytics Biotech Inc. (NASDAQ:ONCY)(TSX:ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reorted an update on its partner, Adlai Nortye’s, clinical progress and approval by the National Medical Products Administration (NMPA) of China for initiating a phase 3 clinical trial for pelareorep (Press release, Oncolytics Biotech, OCT 31, 2019, View Source [SID1234550111]).

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"We congratulate Adlai on this significant regulatory and business achievement that paves the way for pelareorep’s development in the world’s second largest pharmaceutical market," said Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development. "Since the consummation of this partnership almost two years ago, we’ve been very happy with how Adlai is progressing the development of pelareorep in China, the second largest and rapidly growing pharmaceutical market in the world."

The phase 3 study, initially based on positive results from the randomized phase 2 metastatic breast cancer study IND-213, will be finalized based on data from Oncolytics’ AWARE-1 breast cancer study in combination with Roche’s Tecentriq and BRACELET-1 metastatic breast cancer study in combination with Pfizer’s and Merck KGaA’s Bavencio. These studies provide valuable biomarker data that will help define enrollment criteria to include patients most likely to respond to treatment with pelareorep and increase the likelihood of a positive clinical outcome in this important phase 3 registrational study.

Oncolytics and Adlai Nortye entered into an $86.6 million regional licensing agreement in November 2017, providing Adlai with exclusive development and commercialization rights to pelareorep in China, Hong Kong, Macau, Singapore, South Korea and Taiwan. To date Oncolytics has received $5 million in up front payments and is eligible for $81.6 million in milestone payments.

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On October 31, 2019 Intensity Therapeutics, Inc., a clinical-stage biotechnology company developing proprietary technology and products to kill tumors and increase immune system recognition of solid cancers, reported that the first patient has been dosed with a combination of INT230-6, the Company’s lead investigational product, and Keytruda (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy (Press release, Intensity Therapeutics, OCT 31, 2019, View Source [SID1234550127]). The combination is being studied in a series of cohorts within IT-01, Intensity’s ongoing Phase 1/2 international clinical study (NCT03058289).

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The first part of the combination cohort of IT-01 expects to enroll approximately six patients with different types of advanced solid tumors in order to test safety of the combination. The second part will evaluate the safety and efficacy of the combination in several Phase 2 cohorts of patients with different types of cancer, including cancers that are not immunogenic.

"Bringing INT230-6 into human testing in combination with Keytruda is a major milestone for Intensity Therapeutics," commented Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "Our preclinical and clinical data to date have already demonstrated good safety for INT230-6 as a single agent, with evidence of patient benefit and immune activation in highly refractory cancer patients. We believe the immune activation potential of INT230-6 can be increased when combined with Keytruda, and are excited to have initiated human testing of the combination."

"Our Phase 1/2 study will continue to accrue patients with multiple tumor types in the INT230-6 monotherapy portion while concurrently exploring this combination," said Ian B. Walters, MD, Chief Medical Officer of Intensity Therapeutics. "We are optimistic that our trial design enables us to quickly evaluate safety and efficacy. Tumor types of interest in the Phase 2 cohorts include pancreatic, cholangiocarcinoma, and non and microsatellite unstable colorectal cancer, which are all difficult to treat and historically nonresponsive to a PD1/PDL1 antibody alone. Physicians desperately need improved treatments for these patients and evidence of tumor response in any one of these patient populations would be validation of our approach of releasing tumor antigens derived from the patient’s own tumors to enable an immune attack on the cancer, an effect that can be amplified by blocking a checkpoint signal."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA.

About INT230-6

INT230-6, Intensity’s lead proprietary product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRxSM technology platform. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule that helps disperse the drugs throughout tumors for diffusion into cancer cells. In preclinical studies, INT230-6 eradicated tumors by a combination of direct tumor killing, releasing tumor antigens and recruitment of immune cells to the tumor. Results generated by the National Cancer Institute (NCI) showed treatment with INT230-6 in in vivo models of severe cancer resulted in substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responder animals with long-term, durable protection from multiple re-challenges of the initial cancer and resistance to other cancers. The NCI and Intensity collaborative research, published in July 2019, showed that there was also strong synergy when INT230-6 was combined with anti-PD-1 and anti-CTLA-4 antibodies. INT230-6 is being evaluated in a Phase 1/2 clinical study (NCT03058289) in patients with various advanced solid tumors. There have been no dose limiting adverse events observed in patients to date, even when dosing into deep tumors in the lung and liver. Several patients demonstrated tumor shrinkage, symptomatic improvement, and evidence of cancer cell death and immune cell activation on tumor biopsy.

On October 31, 2019 Eureka Therapeutics, Inc., a clinical stage biotechnology company developing novel T-cell therapies to treat cancers, reported a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting, November 6-10, 2019, in National Harbor, Maryland (Press release, Eureka Therapeutics, OCT 31, 2019, View Source [SID1234550143]). The presentation will highlight the company’s proprietary ARTEMIS antibody T-cell receptor (AbTCR) platform used to develop ET140202 for the treatment of hepatocellular carcinoma (HCC), the most predominant type of liver cancer. ET140202 features ARTEMIS T-cell receptors engineered with a TCR-mimic antibody to target the alpha-fetoprotein (AFP) peptide/ major histocompatibility complex (MHC) on HCC cancer cells.

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SITC Poster Presentation Details:

Title: ET140202 T-cell Therapy for the Treatment of Liver Cancer is Built upon a Novel Antibody-T cell Receptor (AbTCR) ARTEMIS T-cell Platform

Poster Presentation Date: Saturday, November 9, 2019

Poster Presentation Time: 12:35 – 2:05 pm EST and 7:00 – 8:30 pm EST

Presenter: Jun Cui, Ph.D.

Poster Number: P166

Abstract Category: Cellular Therapies

Location: Poster Hall (Prince George AB)