On November 12, 2019 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported financial results and business highlights for the third quarter ended September 30, 2019 (Press release, Tocagen, NOV 12, 2019, View Source [SID1234550957]).

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"Following the topline readout of our Phase 3 Toca 5 trial, we have been conducting a thorough evaluation of the trial data including analysis of the pre-planned subgroups and molecular data in preparation for our presentation at the upcoming Society for Neuro-Oncology Annual Meeting on November 22," said Marty Duvall, chief executive officer of Tocagen. "These data will inform our next steps with regulatory agencies to evaluate a potential path forward for Toca 511 & Toca FC in recurrent high grade glioma."

Third Quarter 2019 and Recent Highlights

Toca 5 final analysis: On September 12, Tocagen announced the pivotal Toca 5 Phase 3 clinical trial evaluating Toca 511 & Toca FC in patients with recurrent high grade glioma (HGG) missed the primary endpoint of overall survival compared to standard of care treatment and all secondary endpoints.

Toca 5 data to be presented in plenary session at SNO: The Phase 3 Toca 5 trial results will be presented on Friday, November 22, 2019 at 11:50 a.m. MT at the Society for Neuro-Oncology Annual Meeting (SNO) by Timothy Cloughesy, M.D., director of the University of California, Los Angeles, neuro-oncology program. Also, a poster will be presented by NRG Oncology outlining the trial design of the planned Phase 2/3 trial of Toca 511 & Toca FC in patients with newly diagnosed glioblastoma. Copies of the presentations will be available on Tocagen’s website following the presentations.

Reported updated Toca 6 data: In November, Tocagen presented updated data, including immune modulation data, from the Phase 1b trial of Toca 6 in advanced solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. The preliminary clinical data in 21 patients with a median 4 lines of prior chemotherapy suggested a signal of activity warranting further investigation. The poster can be found here.

Initiated corporate restructuring: On October 3, Tocagen announced a restructuring to extend its cash position and focus resources on the clinical development of Toca 511 & Toca FC.

Third Quarter 2019 Financial Results

License revenue: License revenue was less than $0.1 million for the quarter ended September 30, 2019, compared to $18.0 million for the quarter ended September 30, 2018. The 2018

revenue was related to upfront payments and milestones earned under our license agreement with Apollobio.

Research and Development (R&D) Expenses: R&D expenses were $13.3 million for the quarter ended September 30, 2019, compared to $12.3 million for the quarter ended September 30, 2018. The R&D expenses in both periods were primarily driven by costs to support the Toca 5 trial and manufacturing of drug product. The increase quarter over quarter is primarily due to increased manufacturing related costs offset by reductions in clinical development expenses due to our Toca 5 trial reaching final analysis.

General and Administrative (G&A) Expenses: G&A expenses were $3.8 million for the quarter ended September 30, 2019, compared to $4.3 million for the quarter ended September 30, 2018. The decrease in G&A expenses was primarily due to non-income tax expense of $1.0 million in 2018 offset by increased contracted services to support commercial readiness activities. Based on our clinical trial results, commercial readiness activities have paused.

Net Loss: Net loss was $18.7 million, or $0.78 per common share (basic and diluted), for the quarter ended September 30, 2019, compared to a net loss of $0.4 million, or $0.02 per common share (basic and diluted), for the quarter ended September 30, 2018. The 2019 calculation is based on 23.9 million average common shares outstanding for the third quarter of 2019, compared to 20.0 million average common shares outstanding for the third quarter of 2018.

2019 Nine-Month Results

License revenue: License revenue was less than $0.1 million for the nine months ended September 30, 2019, compared to $18.0 million for the nine months ended September 30, 2018. The 2018 revenue was related to upfront payments and milestones earned under our license agreement with Apollobio.

R&D Expenses: R&D expenses were $37.7 million for the nine months ended September 30, 2019 compared to $35.5 million for the nine months ended September 30, 2018. The increase in R&D expenses for the nine months ended September 30, 2019 primarily reflect increased manufacturing related activities and personnel related costs offset by a reduction in clinical development expenses due to our Toca 5 trial reaching final analysis.

G&A Expenses: G&A expenses were $13.1 million for the nine months ended September 30, 2019 compared to $9.3 million for the nine months ended September 30, 2018, with the increase primarily driven by higher personnel and related costs, including stock-based compensation, due to additional headcount and increased contracted services to support commercial readiness activities. Based on our clinical trial results, commercial readiness activities have paused.

Net Loss: Net loss for the nine months ended September 30, 2019 was $52.9 million, or $2.25 per common share (basic and diluted), compared to a net loss of $29.4 million, or $1.47 per common share (basic and diluted), for the nine months ended September 30, 2018. This calculation is based on 23.5 million average common shares outstanding for the nine months ended September 30, 2019, compared to 19.9 million average shares outstanding for the same period in 2018.

Cash Position

Cash, cash equivalents and marketable securities were $55.3 million at September 30, 2019 compared to $96.1 million at December 31, 2018. In October 2019, Tocagen made a prepayment of $23.3 million toward its loan agreement. This amount was used to prepay $21.5 million of the outstanding principal plus accrued interest and a pro-rated portion of the final payment. After the prepayment, the remaining principal balance is $5.0 million. Due to the corporate restructuring, Tocagen refined its annual cash burn guidance and estimates the total cash used in 2019 to fund operations and capital expenditures will be approximately $60 million (down from approximately $65 million implied in the guidance provided in February 2019).

About Toca 511 & Toca FC

Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprising an investigational biologic, Toca 511 (vocimagene amiretrorepvec), and an investigational small molecule, Toca FC (flucytosine, extended-release). Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells resulting in anti-cancer immune activation and subsequent tumor killing.

On November 12, 2019 LEO Pharma A/S and HitGen Inc. are reported that HitGen and LEO Pharma expands their collaboration with a license to develop a novel class of drugs for a dermatology indication (Press release, Leo, NOV 12, 2019, View Source [SID1234550956]).

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The licensed compounds were identified using HitGen’s leading technology platform, which involved screening DNA encoded libraries (DEL), containing over 400 billion small molecules with drug-like properties, synthesized on a broad range of structurally diverse scaffolds. A number of novel small molecule leads for an undisclosed target nominated by LEO Pharma are subject of this license.

Under the terms of the collaboration agreement, HitGen will grant exclusive rights to LEO Pharma to develop and commercialize the licensed compounds. HitGen will be eligible for preclinical and clinical milestone payments from LEO Pharma as the project progresses, in addition to an option exercise fee.

Today’s announcement marks a significant milestone in the long lasting partnership between LEO Pharma and HitGen originally initiated in 2015.

"We are delighted to announce this license with LEO Pharma. The success of delivery of these licensed compounds has further demonstrated the power of our DEL platform to discover novel small molecules against a variety of targets, including those previously deemed challenging for small molecule modalities. In this case that target may be characterized as a "protein-protein interaction", a class that has proved "hard-to-drug" for small molecule discovery. The current achievement marks the continued progress and success of the discovery collaboration between the companies, spanning a range of discovery programs. We look forward to announcing future milestones as the programs progress." said Dr. Jin Li, Chairman of the Board and Chief Executive Officer of HitGen.

To date HitGen has initiated screening efforts on multiple LEO Pharma discovery programs related to dermatology. These programs are at various stages of screening, selection, synthesis and validation.

"It is with great pleasure that we expand our collaboration with HitGen to further accelerate LEO Pharma’s ambition to discover promising lead compounds against challenging drug targets in dermatology. This license marks a successful discovery of a promising compound series targeting a novel "protein-protein interaction" and is yet another important milestone in our dedicated efforts to discover and develop oral first-in-class drugs. LEO Pharma is committed to making pioneering advances in dermatology research and to bringing new treatments to patients faster," said Dr. Thorsten Thormann, Vice President of Global Research at LEO Pharma.

On November 12, 2019 AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, reported that data from its ongoing Phase 2 clinical trial in GBM was presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting by Principal Investigator Dr. Daniela Bota (Press release, AIVITA Biomedical, NOV 12, 2019, View Source [SID1234550953]). The oral presentation was titled "Phase II trial of therapeutic vaccine consisting of autologous dendritic cells loaded with autologous tumor cell antigens from self-renewing cancer cells in patients with newly diagnosed glioblastoma."

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Dr. Bota presented interim results from the Phase 2 trial testing AIVITA’s patient-specific immunotherapy AV-GBM-1 in patients with glioblastoma multiforme (GBM). At this time survival is 96% at six months and 91% at twelve months with three patients followed for more than a year. Furthermore, a vast majority of patients displayed an appropriate immune response and a decrease of tumor biomarkers.

AIVITA’s immunotherapy targets tumor-initiating cells. Treatment involves a series of subcutaneous injections. As of the end of October 2019, cell lines had been successfully established for 46/48 patients and dendritic cells produced for 41/42 patients; 38 of the planned 55 patients had been enrolled, 31 had started therapy, and 12 had completed all 8 doses and 184 doses had been injected. Blood tests on the first 16 patients showed induction of a new immune responses that were associated with a decrease in tumor markers.

AIVITA Chief Scientific Officer Gabriel I. Nistor, M.D. acknowledged that the immune response data is highly encouraging. "Once the trial is complete, we’re looking forward to determining the correlation between immune responses and clinical outcome as we previously did in patients with metastatic melanoma treated with a similar patient-specific vaccine," said Dr. Nistor.

"The results are very encouraging," said AIVITA Chief Medical Officer Robert O. Dillman, M.D. "The trial is still in progress and will continue to enroll patients for a few more months with follow up for at least another year. Final analysis likely will occur in early 2021."

CLINICAL TRIAL DETAIL

OVARIAN CANCER

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous cancer stem cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITA’s AVOVA-1 trial patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the cancer stem cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AIVITA’s cancer stem cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.

For additional information about AIVITA’s AV-MEL-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03743298

On November 12, 2019 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, adoptive cell therapies1 and cancer vaccines, reported that it will host an R&D Day on November 15, 2019 (Press release, Agenus, NOV 12, 2019, View Source [SID1234550952]).

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Date: Friday, November 15, 2019

Time: 11:00AM – 2:00PM

Live webcast: View Source

Location: New York, NY (by invitation only)

Agenus has delivered more I-O discoveries to the clinic in the last three years than any large pharma and is on track to file a BLA in 2020 for accelerated approval of its lead candidates Zalifrelimab (anti-CTLA-4) and Balstilimab (anti-PD-1) while also advancing AGEN1181, a potential best-in-class next generation anti-CTLA-4 antibody, and a pipeline of additional antibodies, cell therapies, and vaccines.

The event will be moderated by Dr. Garo Armen, Chairman and Chief Executive Officer, and Dr. Jennifer Buell, Chief Operating Officer, and will include presentations by world experts in I-O, Dr. Steven O’Day, Executive Director of the John Wayne Cancer Institute, and Dr. Manuel Hidalgo, Chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center.

The event will be webcast live and may be accessed by visiting the "Events & Presentations" page within the Investors section of the Agenus website www.agenusbio.com or by using the link below. A replay of the webcast will be available on the Agenus website following the event.

On November 12, 2019 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies for the treatment of cancer patients, reported that Fred Schwarzer, Chief Executive Officer, will present at three upcoming investor conferences (Press release, IGM Biosciences, NOV 12, 2019, View Source [SID1234550951]):

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Stifel 2019 Healthcare Conference on Tuesday, November 19 at 4:45 p.m. ET in New York.
Jefferies 2019 London Healthcare Conference on Thursday, November 21 at 11:20 a.m. GMT in London.
Piper Jaffray 31st Annual Healthcare Conference on Wednesday, December 4 at 3:00 p.m. ET in New York.
A live webcast of the events will be available on the "Events and Presentations" page in the "Investors" section of the Company’s website at View Source A replay of the webcasts will be archived on the Company’s website for 90 days following the presentation.